Analgesicos Mavidol Tr Capsulas, Mavidol

Analgesicos

Mavidol TR capsulas

Mavidol TR® es una combinacion de ketorolaco con tramadol, el cual es un analgesico indicado para el tratamiento a corto plazo del dolor moderado a severo de origen agudo (dorsalgias, fracturas, luxaciones, esguinces, cancer), en el tratamiento del dolor postoperatorio, en el tratamiento del dolor dental, en migrana, cefalea y en el tratamiento del dolor neuropatico.

Mavidol TR® esta contrain­dicado en pacientes con hipersensibilidad a los componentes de la formula, en pacientes con ulcera gas­troduodenal activa, hemorragia digestiva reciente, en intoxicacion con al­co­hol, somniferos y psicotropicos, con insuficiencia renal moderada o grave (creatinina serica > 442 µmol/l), embarazo y lactancia.

Caja con 10 capsulas de 10/25 mg.

Perlinganit, Perlinganit

Perlinganit

Roman name

The composition and the form of

1 bottle of 50 ml for the infusions-50 mg in izotonicescom 5% glucose solution; in a Box 1 flakon.1 peeling from 10 ml to infusions of nitroglycerin 10 mg izotonicescom in 5% glucose solution; in a box 10 pcs. in a contour acheikova pack 1614b age.

Indications

Angina (unstable and vazospastical), acute myocardial infarction, acute malnutrition levojeludochkovaya, hypertonic kriz against heart failure controlled gipotenzia.

Contraindications

Acute circulatory failure (shock collapse Stroke); Expressed gipotenzia (sistolicescoe AD below 95 mm Hg); Cardiogenny shock (while using drugs with a positive inotrope act or balonna contrpulsaciei).

Side-Effects

Headache, drowsiness, weakness, the decline AD tachycardia, nausea, vomiting.

Specific guidance

An infusion system made from polyethylene, polypropylene, polytetrafluoroethylene or glass (but not the PVC and polyurethane, as they adsorb active substance, and may therefore need to increase doses).

Patient interaction

Effect increase gipotenzivee drugs (calcium antagonists, vozodilatatora etc.), alcohol, cyclic antidepressants, digidroergotamin. Decreases effect of heparin.

Storage conditions

List B. In the dark, cool place, away from the fire.

Shelf life

The registration

Indications for use

Instability and vazospastical (caused by the loss of clearance heart veins) stenocardia, acute myocardial infarction, acute malnutrition levojeludochkovaya, hypertonic kriz (quick and dramatic rise in blood pressure) with congestive heart failure controlled gipotenzia (adjustable artificial lowering blood pressure).

Dosing and Administration

Solution perlinganit injected through perfuzing infuzora in nerazvedennom form (1 ml containing 1 mg nitroglycerin), or by Infusion tentatively razveda his izotoniceski solution of sodium chloride, 5% or 10% glucose solution. Solution perlinganit should engage immediately after the opening sealed in aseptic (sterile) conditions. Concentration of 0.1 mg / ml (0.01%). 50 ml 0.1% solution perlinganit (5 vials of 10 ml each) to disengage until 500 ml ready; For the concentration of 0.2 mg / ml. 100 ml of 0.1% solution perlinganit (10 vials of 10 ml each) to disengage until 500 ml ready. Misleading intravenous drip. Initial speed of 1 ml of 0.01% solution for 4 min. Further dose filled in a manner that sistolicescoe (upper pressure-arterial pressure in the phase exile blood) blood pressure was at least 90 mm Hg

Form of

Ampoules and 10 ml 0.1% nitroglycerin solution (10 mg nitroglycerin 1 ml = 1 mg in 1 ml), in a package of 10 pieces.

All products of this group

Histazin, Histazin

????? ?????? (Promethazine Hydrochlorid­­­e) ????? ??????? HISTAZIN

???????? ( ?????????? ???????????? ) ???? ???? ??????????، ???? ??????? ?? ?????? ??????????????. ???????? ??? ???، ?? ???? ????? ?????، ????? ????? ???????? ?????? ?????? ?????? ???????.

???? ?????????? ???? ??? ?? ?????? ??????? ????? ????? ???????? ??? 20 ????? ?? ?????? ?? ???? ????، ?????? ???? 4 – 6 ?????. ????? ?????????? ?? ????? ???? ???? ???? ??? ??? ?????? ، ???? ??????? ????? ?? ???? ???? ???? ??????? ?????. ??? ??????? ?????????? ?????? ????? ??? ???????? ??? ????? ????? ???? ?? ???? ????? ????????.

???? ???????? ?? ??????? ???????: · ???? ????? ????? ???????? ?? ?????? ??????? ?????? ?????? ????? ????? ?????? ????? ???????، ????? ???????? ??? ???????? ??????? ?? ?????????? ???????. · ????? ??? ???? ???????? ???????? ??????? ???????. · ????? ????? ?? ???????? ??????? ??? ???? ?? ??? ???????? ????????. · ??????? ???????? ??? ??????? ?????? ????????? ???????? ????????. · ???? ????? ??? ???????? ????????. · ??????? ??????? ?? ???? ??????. · ????????? ???? ?????: ????? ?????? ????? ??? ???????? ?????? ???????.

??????? ?????? ?????????:

???? ????? ???????? ?? ?????? ?? ????? ???? ???? ???? ?? ???????? ?????. ???? ???? ?????????: · ????????: 25 ???? ???? ????? ????? ????? ?????، ???? ??????? ????? ??? 25 ???? ????? ????? ????? ????.

· ???? ??? ???????? ????????: 50 ???? ???? ?? ?????? ??????? ??????? ????????، ???? ??? ??????? ?????? ?? ???? ??? ?? ??????? ??????? ?? ???????????. · ???? ??? ???????? ???????? ????? ????? ?? ????????: 25 – 50 ????. · ??????? ?? ??????? ?????? ???????? ?????: ???? ?????? 25 ????، ???? ?? 4 – 6 ????? ??? ??????.

· ???? ??????: 25 ???? ???? ?? ?????? ??????? ?????? ????? ?? 6 – 8 ????? ??? ??????. · ????????? ???? ?????: 25 – 50 ???? ???? ????? ????? ????? ?????. ??????? ?? 5 – 10 ?????:

· ????????: 5 – 10 ???? ???? ????? ?????، ?? 10 – 25 ???? ???? ????? ?????. ?????? ??????? ?????? ?? 25 ????.

· ???? ??????: 10 ???? ???? ?? ?????? ??????? ??????، ???? ??? 6 – 8 ????? ??? ??????.

· ????????? ???? ?????: 20 ?? 25 ???? ???? ????? ????? ????? ?????. ??????? ?? 2 – 5 ?????:

· ????????: 5 ???? ???? ????? ?????، ?? 5 – 15 ???? ???? ????? ?????. ?????? ??????? ?????? ?? 15 ????.

· ???? ??????: 5 ???? ???? ?? ?????? ??????? ??????، ???? ??? 6 – 8 ????? ??? ??????. · ????????? ???? ?????: 15 ?? 20 ???? ???? ????? ????? ????? ?????.

· ??? ???????? ??????? ??????????????. · ???????? ?? ???? ?????? ?????? ??????? ??? ?? ???????. · ?????? ????? ??????? ?????? ???????? ???????? ???? 14 ???? ??????? ??? ?????. · ??????? ???? ?? ?????. ???? ?? ???? ??? ????? ????? ?????? ??????? ???? ????. · ??????? ????? ???? ????? ?????? ?????? ??????? ??? ?? ??? ????? ????? ??????.

· ??? ???????? ??????? ??????????????. · ???????? ?? ???? ?????? ?????? ??????? ??? ?? ???????. · ?????? ????? ??????? ?????? ???????? ???????? ???? 14 ???? ??????? ??? ?????. · ??????? ???? ?? ?????. ???? ?? ???? ??? ????? ????? ?????? ??????? ???? ????. · ??????? ????? ???? ????? ?????? ?????? ??????? ??? ?? ??? ????? ????? ??????.

????????? ???? ????? ????? ????????:

?? ???? ?????? ????? ?????? ??????????? ?? ?????? ??????، ??? ???? ??? ???? ?? ?????? ????? ??????، ??? ??? ?? ?????? ??? ?????? ??? ??????? ?? ??????? ???? ??????? ???? ???? ??????، ????????? ?????? ???? ???????? ??????? ???? ?? ???? ?? ????? ??????? ??? ????????? ?? ??????? ??????????؛ ???? ?? ???? ?????????? ???? ???? ????? ??? ??? ???? ??????? ??????? ??? ???? ????? ??????? ??? ??????.

?? ??? ??????? ?? ??? ??? ?????????? ???? ?? ???? ???? ?? ??، ???? ???????? ???? ????? ?????? ??? ?????? ???? ??? ??????? ??????????، ???? ????? ?????? ??? ?????? ?????? ?? ?????? ?? ???????، ??? ????? ???? ???????? ????? ?????? ???? ??????.

· ?????? ?????? ?????? ???????: ?????????? ?? ???? ،???? ?? ???? ?? ??? ???????? ??? ?????? ?????? ???????؛ ???? ????? ??? ????? ??? ???????: ????????/ ???????? (???? ????? ???????????)، ??????? ???????، ????? ??????? ??????، ?????? ???????? ?????? ??????? ???????? ??????? ?? ?????????? ???? ?????? ?? ???? ?? ???? ?????? ???.

· ??? ???? ????? ?????? ????? ???? ?????? ???????????.

· ?????? ???????? ????????: ?? ????? ????? ?? ????? ?????? ???????? ???? ????????? ??? ????????? ???????? ??????????? ?? ??? ?????? ???????? ????????. · ??????? ??????? ????? ????????: ??? ??? ?????? ?????? ??? ????????? ???????? ??????????? ?? ????? ????? ????? ????? ????? ???????? ????ً.

· ?????????: ?? ???? ??????? ?????????? ????? ????????? ?????? ?????؛ ???? ?? ?????? ????????? ????? ???? ????? ?????? ?? ??? ???? ??????????. · ?? ???? ?????????? ?? ??? ????? ?? ???? ????? ????? ????? ??????? ?? ????? ??????. · ?? ???? ?????????? ?? ????? ???????? ?? ????.

· ??? ????? ?????????? ??? 72 ???? ??? ????? ?? ??? ??? ????? ?? ???? ?? ???? ?? ??????? ?????????? ?? ????? ????? ????? ????? ??????.

· ?????? ?????? ???????: ????، ????، ????، ??? ???? ??????، ????، ??????، ?????، ????? ??? ?????????، ??????، ????? ??????. · ?????? ?????? ???????: ?????? ?? ?????? ?? ??? ????، ????? ?? ????? ?? ????? ????? ????????.

· ?????? ??????: ???? ????، ?????، ??? ??????. · ?????? ???????: ???، ?????? ?????، ???? ?? ?????? ??????? ????? ??????. · ?????: ?????? ?????، ???? ???? ????. · ????: ??? ????? ???? ???????، ??? ???????? ??????? ???? ????? ???? ??????? ???????.

????? ????? ??? ?????? ??????. ????? ??? ??????? ???????? ?????? ?? ????????? ، ??????، ??? ????? ??????، ????? ????????، ?? ??? ?? ???? ???????? ????? ?? ???? ??? ??????. ?? ???? ?????? ????? ?? ?? ?? ???????? ????????، ??? ???? ?????? ?????? ????????، ??? ??? ??????? ?? ???? ???? ?? ?????? ?????? - ???????. ???? ??? ?????? ???? ?? ???? ????? ????? ?? ???????? ??????? ??? ??? ????? ??????? ?????. ??? ?????? ???????? ???????? ???????? ?? ?? ?? ?????? ???????? ????????. ??? ?? ?????? ?????? ?????? ??? ??? ??????، ??? ?????? ????? ?????، ?? ??? ??????.

???????? ????: ???? ??? 15 - 30? ، ????? ?? ?????. ???? ???? ?????? ????? ???????. ???????? ?????: ???? ??? 15 - 30 ?

???????? ????: ?? 5 ?? (????? ?????) ????? ??? ?????????? ???????????? ?? ????? ?????????? 5 ???? ?? ????? ??? 125 ??. ???????? ?????: ?? ??? ???? ????? ??? ?????????? ???????????? ?? ????? ?????????? 25 ???? ?? ????? ??? 20 ????ً. ????? ?????????? ?????? ????

?????? ?????? ???? ??? ???? ????????? ????? ????????? ????? ?????. ???? ???? ???? ?????? ?????? ????????? ??????? ????? ???????? ????????? ???? ????? ??. ?? ?????? ?????????? ??? ???????? ??????? ?????? ?????. ?????? ??? ?????? ??????? ?? ?? ????? ????. ?? ???? ??? ?????? ???? ???? ????. ???? ?????? ????? ?? ?????? ???????.

Zombocalypse (3d) - Regular Show Wiki, Zetamax

Zombocalypse (3D)

Zombocalypse (3D) is the name of the movie that Mordecai and Rigby rented from the Movie Shack Hut for the park's scary movie night. As noted by the title, it is a 3D horror film featuring undead zombies. Mordecai and Rigby get the extended version that runs for three hours and twenty-eight minutes.

Plot

The movie focuses on a man who lives through a zombie apocalypse whose wife/girlfriend gets turned into a zombie and has to be put down afterwards. He goes on a mission through the city to stop the undead invasion. After killing a majority of his undead foes, he confronts the ultimate zombie boss, the Zombie Master, and defeats him by ramming him with a sedan. The film ends shortly afterwards.

Trivia

The name of the movie might be a reference to the movie, Zombie Apocalypse.

The double-barrel shotgun on the survivor's back was never seen being used in the movie.

Zombocalypse is an homage/parody of the Bruce Campbell starring movie, Army of Darkness. a s the main character is very similar-looking and uses large amounts of insults and one-liners to zombies, and the two movies' target age is at 17+.

The main character's fate is unknown.

"Zombocalypse" is a portmanteau between "zombie" and "apocalypse".

The tape can only be played by the Zetamax Projectron LLX player, due to it being in Zetamax 3D.

The movie bears a resemblance to the Left 4 Dead video game series. For example, the Man's wife resembles a witch and the boss zombie looks like a cross between a charger and a tank.

Unlike Mordecai and Rigby's situation, the main character of Zombocalypse 3D may not have jumped out of the car and survived, but rather drove the car until it exploded.

The man on the cover seems to be slightly different then the actual zombie slayer.

J. G. Quintel said at WonderCon that there might be a full-length film of this in the future!

The box art looks like the one of a popular, first person shooter game, Doom .

It is also likely to be a spoof of Evil Dead 2 . because of the great resemblance with the main character and the movie plot.

The movie's true format, Zetamax 3D, is a parody of Betamax.

Article Page, Termyl

Thermal enzymes. VIII. Properties of a heat-stable inorganic pyrophosphatase ?

Connell Marsh 2

Walter Militzer

From the Department of Chemistry, University of Nebraska, Lincoln, Nebraska, USA

Received 7 February 1955. Available online 25 November 2004.

Abstract

A highly active inorganic pyrophosphatase from a thermophilic bacterium has been partially purified and studied in some detail.

The enzyme was dependent upon magnesium ions for activation and was activated to a lesser extent by cobalt. Neither calcium nor manganese was effective as an activating ion. The pH-activity curve was quite broad and exhibited a distinct plateau in the range from pH 5.5 to pH 9.5.

The usual Lineweaver-Burk plot of versus ( S ) did not give a straight line. Plotting versus ( S ) 2 gave a straight line from which K s was calculated to be 5 ? 10 ?3. Evidence is presented that the formation of a complex metallosubstrate is necessary for the hydrolysis of pyrophosphate by the enzyme. The energy of activation was found to be 21,000 cal./mole in the range from 45 to 70 °C. and 34,400 cal./mole in the range 30–45 °C.

Apparent thermodynamic values were calculated from heat-inactivation data. The most unusual of these were the entropies of activation, ? S ++. For a 20-min. period of inactivation the mean ? S ++ value was 13.0 cal./mole/deg. After a 40-min. period of inactivation, the ? S ++ value was 45 cal./mole/deg. The low ? S ++ values suggest that there may be inherent structural differences in the thermal enzymes which render them less vulnerable to the denaturing effects of heat.

Aided by a grant from the Division of Research Grants and Fellowships, U. S. Public Health Service, National Institutes of Health.

Copyright © 1956 Published by Elsevier Inc.

Citing articles ( )

Antinociceptive and anti-inflammatory effects of Aloe saponaria Haw on thermal injury in rats

Mariane Arnoldi Silva a

Gabriela Trevisan a

Jonatas Zeni Klafke a

Mateus Fortes Rossato a

Cristiani Isabel Bandero Walker c

Sara Marchesan Oliveira a

Cassia Regina Silva a

Aline Augusti Boligon b

Fernanda Cramer Flores b

Cristiane de Bona Silva b

Margareth Linde Athayde b

Juliano Ferreira a,.

a Programa de Pos Graduacao em Ciencias Biologicas: Bioquimica Toxicologica

b Programa de Pos Graduacao em Ciencias Farmaceuticas, Universidade Federal de Santa Maria, Camobi, Santa Maria 97109-900, RS, Brazil

c Departamento de Saude: Curso de Farmacia, Universidade Federal de Sergipe, Jardim Rosa Elze, Sao Cristovao 49100-000, SE, Brazil

Received 26 September 2012. Revised 13 December 2012. Accepted 29 December 2012. Available online 17 January 2013.

Abstract

Ethnopharmacological relevance

In Brazil, the plant Aloe saponaria Haw, popularly known as “babosa pintadinha”, has been empirically used for its potential effect on thermal injury. Because there are no scientific data confirming its popular use, the aim of the present study was to investigate the effects of Aloe saponaria on nociceptive and inflammatory parameters in a rat model of thermal injury.

Materials and methods

Adult male Wistar rats were subjected to a thermal injury or sham procedure (immersion in water at 70 or 37 °C, respectively, for 5 or 8 s). Burned animals were topically treated with vehicle (base cream), sulfadiazine 1% (positive control) or Aloe saponaria cream (0.3%–30%) once a day for 2 or 6 days. Each day, 30 min before the treatment, we measured nociceptive (static and dynamic mechanical allodynia, thermal allodynia and spontaneous pain) and inflammatory (paw edema) parameters. Moreover, enzymatic indicators of leukocyte infiltration into burned tissue were also determined 2 or 6 days after the thermal injury.

Results

The thermal injury (fist and second-degree) procedure, but not the sham procedure, induced nociception and inflammation from 1 to 6 days after the injury. The topical treatment with Aloe saponaria cream (10%) reduced nociceptive behaviors from day 1 to 6 (peak at day 2), edema at days 5 and 6 (peak at day 6) and myeloperoxidase, N-acetyl-glucosaminidase and eosinoperoxidase activities at day 6. The antinociceptive and anti-inflammatory effects of Aloe saponaria were obtained with doses of 3%–30%, with maximal inhibition obtained with a dose of 10% (reductions of 39±9%, 41±9%, 31±7%, 83±7% and 23±2% for static and dynamic mechanical allodynia, thermal allodynia, spontaneous pain and paw edema, respectively).

Conclusion

Our results demonstrate that topically applied Aloe saponaria presented antinociceptive and anti-inflammatory effects in rats subjected to a thermal injury, which supports its traditional use for burn injuries.

Graphical abstract

Keywords

Analgesic

Burn injury

Inflammation

Medicinal plant

Pain

Silver sulfadiazine

1 Introduction

A thermal injury is a posttraumatic inflammatory wound caused by contact with heat, cold, electricity, chemicals, radiation or friction, and it is accompanied by both local and systemic effects (Evers et al. 2010 ). Most burns are the result of exposure to flame and are induced by scalding (characterized by hot pouring liquids into the body). Burn injuries are accompanied by intense inflammation, tissue damage, infection and a significant incidence of death and disability (Summer et al. 2007 and Parihar et al. 2008 ). Moreover, uncontrolled acute burn pain increases the incidence of chronic pain and associated depression, the need for multiple operative procedures and prolonged hospitalization and rehabilitation, leading to high health care costs (Richardson and Mustard, 2009 ).

According to folk medicine, species from the genus Aloe belong to the Xanthorrhoeaceae Family (The Angiosperm Phylogeny Group, 2009 ), especially Aloe vera . can be used to treat burn wounds and to promote other healing processes (Capasso et al. 1998 ). The Aloe species are most likely native to South and East Africa, although they are widespread throughout the world (Iwu, 1993 ). Pre-clinical studies have demonstrated that some Aloe species, such as Aloe vera . Aloe spicata and Aloe ferox . have anti-inflammatory and burn-healing properties (Chithra et al. 1998. Barros et al. 2007 and Loots et al. 2007 ). Moreover, clinical studies have shown that Aloe vera has an efficacy superior to that of silver sulfadiazine to treat burn injuries (Maenthaisong et al. 2007 and Khorasani et al. 2009 ).

Similar to other Aloe species , Aloe saponaria Haw, popularly known as “babosa-pintadinha”, is also commonly used to treat pain and burn injuries in southern Brazil, where the current study was carried out (Soares et al. 2004 ). However, to the best of our knowledge, there has not been a chemical composition investigation or a pre-clinical study confirming the putative analgesic and anti-inflammatory activities of Aloe saponaria on burn injuries. Thus, the goal of this study was to perform a chemical characterization and to analyze the antinociceptive and anti-inflammatory effects of Aloe saponaria in the treatment of thermal injury.

2 Materials and methods

2.1 Plant material

The plant was collected in July 2008, at Cunhapora, in southern Brazil. A voucher specimen number SMDB 8749 was deposited at the Herbarium of the Botany Department, Federal University of Santa Maria (UFSM), Brazil.

2.2 Extraction and pharmaceutical formulation

Fresh leaves were cut in small pieces and macerated with ethanol (70%) at room temperature for seven days with daily agitation. The crude hydroethanolic extracts from leaves were concentrated to dryness in a rotary evaporator (at a temperature below 50 °C). For the tests, the dry extract (0.3%–30%) or silver sulfadiazine (1%, used as a positive control) were incorporated into Lanette cream (Lanette ® wax 12.0 g; Solid Vaseline 11.0 mL, propylene glycol 7.0 mL; parabens solution preservative 3.3 g; imidazolidinyl urea preservative solution 50%; distilled water for 100 g) manufactured by the Pharmacy of the Federal University of Santa Maria. Lanette cream without drugs was used as the vehicle.

Some of physicochemical characterization of creams was carried out, in relation to pH, viscosity and spreadability. pH values were determined after dispersion of the creams in ultrapure water (10%, w/v) using a calibrated potentiometer (Mettler Toledo, Sao Paulo, Brazil). The viscosity was evaluated using a rotational viscosimeter (Brookfield LVDVII+Pro model, USA) and spindle SC4-25 with a small sample adapter. The spreadability of formulations was determined according to the methodology previously described by Borghetti and Knorst (2006) .

2.3 Animals

Experiments were performed on adult male Wistar rats (weighing 250–300 g) bred in our animal house. The animals were housed in a controlled temperature (22±2 °C) with a 12 h light/dark cycle. They were given standard lab food and water ad libitum. The animals were habituated in the experimental room for at least 30 min before the experiments. The experiments were performed in accordance with the current ethical guidelines for the investigation of experimental pain in conscious animals from Zimmermann (1983). Animals were randomly assigned to individual treatment groups and all subsequent behavioral tests were performed blindly. Moreover, to verify the reproducibility of our data, the experiments were performed at least in two blocks. The intensities of the noxious stimuli were previously defined by pilot stimuli–response curves. The used noxious stimuli and number of animals were the minimum necessary to demonstrate the consistent and statistically significant effects of the procedures and the drug treatments. The Committee on the Use and Care of Laboratory Animals at our university approved this study (no. 117/2010).

2.4 Reagents, equipment and general procedures for HPLC-DAD

All chemicals were of analytical grade. Methanol, acetic acid, gallic acid and caffeic acid were purchased from Merck (Darmstadt, Germany). Quercetin, rutin and kaempferol were acquired from Sigma Chemical Co. (St. Louis, MO, USA). High performance liquid chromatography (HPLC-DAD) was performed with a Shimadzu Prominence Auto Sampler (SIL-20A) HPLC system (Shimadzu, Kyoto, Japan) equipped with Shimadzu LC-20AT reciprocating pumps connected to a DGU 20A5 degasser with a CBM 20A integrator, SPD-M20A diode array detector and the LC solution 1.22 SP1 software.

2.4.1 Quantification of compounds by HPLC-DAD

Reverse phase chromatographic analyses were carried out under gradient conditions using a C 18 column (4.6 mm?250 mm) packed with 5 ?m diameter particles. The mobile phase was water containing 2% acetic acid (A) and methanol (B), and the composition of the gradient was 5% of B for 2 min and increased to obtain 25%, 40%, 50%, 60%, 70% and 100% B at 10, 20, 30, 40, 50 and 100 min, respectively (Evaristo and Leitao, 2001 ). The extract of the plant was dissolved in ethanol at a concentration of 8 mg/mL and analyzed. The presence of six phenolic compounds, namely, gallic, chlorogenic and caffeic acids and the flavonoids quercetin, rutin and kaempferol, was investigated. Identification of these compounds was performed by comparing their retention times and UV absorption spectra with those of commercial standards. The flow rate was 0.6 mL/min, the injection volume was 40 ?l and the wavelengths were 254 nm for gallic acid, 325 nm for caffeic acid, and 365 nm for quercetin, rutin and kaempferol. All of the samples and mobile phases were filtered through 0.45 ?m membrane filters (Millipore) and then degassed with an ultrasonic bath prior to use. Stock solutions of the reference standards were prepared in the HPLC mobile phase at a concentration range of 0.031–0.250 mg/ml for kaempferol, quercetin and rutin and 0.006–0.250 mg/ml for gallic and caffeic acids. The chromatography peaks were confirmed by comparing the retention times with those of the reference standards and by the DAD spectra (200–500 nm). The calibration curves are as follows: gallic acid, Y =12407 x +1059.8 ( r =0.9993); caffeic acid, Y =16862 x +1126.3 ( r =0.9997); rutin, Y =18973 x +1575.7 ( r =0.9989); quercetin, Y =20134 x +1492.2 ( r =0.9995); and kaempferol, Y =17923 x +1853.9 ( r =0.9978). All chromatography operations were carried out at ambient temperature and in triplicate.

2.5 Experimental design

To investigate the effects of Aloe saponaria on thermal injury, adult male Wistar rats were subjected to a thermal injury or sham procedure (immersion in water at 70 or 37 °C, respectively, for 5 and 8 s (s)). Burned animals were topically treated with vehicle (base cream) or Aloe saponaria (0.3%–30%) immediately after thermal procedure and once a day for 2 or 6 days. The doses range used in our study were based in previous studies using Aloe vera leaf extract topical formulations to treat burns that ranged from 0.5% to 50% (Khorasani et al. 2009. Lv et al. 2006 and Bunyapraphatsara et al. 1996 ). As a positive control, we have treated a separated group of animals with silver sulfadiazine (1%). Each day, we measured nociceptive (static and dynamic mechanical allodynia, thermal allodynia and spontaneous pain) and inflammatory (paw edema) parameters 30 min before the treatment. Moreover, enzymatic indicators of leukocyte infiltration into the burned tissue were also determined 6 days after the burn.

2.6 Thermal injury models

Rats received a scald burn as described previously by Gao et al. (2010). Following the measurement of baseline responses, the animals were anaesthetized with 2% isofluorane, and the right hind paw was placed and held in 70 °C water for 5 or 8 s. In the sham procedure group, the right hind paw was exposed to 37 °C water for 5 or 8 s. After the stimulus was applied, the rat was returned to the individual testing compartment and allowed to recover from anesthesia within 2–3 min. Hot-water immersion for 5 and 8 s was considered first and second-degree burn, respectively (Gao et al. 2010 ). Since second-degree thermal injury produced a more severe tissue lesion than the first-degree injury, we assessed nociception and inflammation for two and six days after burn, respectively, to avoid unnecessary discomfort of animals.

2.7 Nociception assessment

2.7.1 Static mechanical allodynia

Static mechanical allodynia was measured as described previously by Chaplan et al. (1994). Rats were individually placed in clear Plexiglas boxes (9 cm?7 cm?11 cm) on elevated, wire mesh platforms to access the ventral surface of the hind paws. The paws were touched with a series of seven von Frey hairs (6–100 g). The von Frey hairs were applied perpendicular to the plantar surface of the paws with sufficient force to cause a slight buckling against the paws and were held for approximately 2 s. The 50% withdrawal threshold was determined using the up-and-down method of Dixon (1980). In this paradigm, testing was initiated with the 15-g hair. Stimuli were always presented consecutively; either ascending or descending. Withdrawal thresholds were verified at several time points after thermal injury (from1 to 6 days) and were compared with the baseline values (before thermal injury).

2.7.2 Dynamic mechanical allodynia

The dynamic response to a non-noxious mechanical stimulus was measured with modifications as described previously by Jaggi and Singh (2011). The response to a smooth paintbrush has been described as allodynia because naive rats rarely withdraw from this stimulus. Rats were placed in a cylinder with a wire mesh floor and a smooth paintbrush stimulus was used to rub the plantar area of hind paw from the heel to the toes for a maximum of 15 s. A paw withdrawal response within 15 s was considered dynamic mechanical allodynia.

2.7.3 Thermal allodynia

We employed the paw immersion test to observe the response of rats to non-noxious heat, as described previously by Takahashi et al. (2003). Briefly, after the environmental habituation period, rats were gently handled, and their right paw was dipped into a bath containing water at 30 °C. This low-intensity stimulus yields baseline latencies (15 s) that are long enough to observe hyperalgesia or analgesia. The latency to withdraw the paw from the non-noxious bath was recorded with a stopwatch. Each rat was tested twice before the administration of drugs to obtain baseline withdrawal latencies and several times after drug treatments. If after 15 s the animals did not withdrawal their paw, the stimulus as the test was suspended. The paw withdrawal response within 15 s was considered to be a nociceptive behavior.

2.7.4 Spontaneous nociception

Inspection of rat behavior was performed during the time they stayed on the wire mesh floor, as described previously by Weissman-Fogel et al. (2008). A number of measurements were observed: gait/weight bearing disturbance, guarding, hind paw lifting and grooming. The time spent demonstrating any one of these behaviors was measured for 5 min with a chronometer and defined as spontaneous pain. Spontaneous pain was verified at several time points after the thermal injury (from 1 to 6 days) and was compared to the control group (sham). A spontaneous pain response was verified before the measurement of allodynia.

2.8 Inflammation assessment

2.8.1 Edema formation

The edema induced by a thermal burn was considered as the increase in paw thickness measured with a digital caliper (Mytutoio, Japan) as described previously by Silva et al. (2010). Paw thickness was verified at several time points (1 to 6 days) after thermal injury and compared to baseline values (before thermal injury).

2.8.2 Leukocyte infiltration markers

To estimate the inflammatory cell infiltration in the paw after a thermal injury, paw skin samples were collected to estimate the activities of myeloperoxidase (MPO), N-acetyl - ? - d - glucosaminidase (NAGase) and eosinoperoxydase (EPO), markers of neutrophil, macrophage and eosinophil infiltration, respectively (Lloret and Moreno, 1995. Suzuki et al. 1983 and Kang et al. 2008 ). Firstly, the samples were homogenized in acetate buffer (8 mM, pH 5.5) containing 0.5% HTAB and centrifuged at 16,000 g at 4 °C for 20 min, and the supernatant was collected.

For the MPO activity measurement, 10 ?l of supernatant was added to 200 ?l of acetate buffer (200 mM, pH 5.4) and 20 ?l of 3,3?,5,5? tetramethyl-benzidine (TMB-18.4 mM) in a 96-well plate and incubated at 37 °C for 3 min in duplicate. To stop the reaction, the microplates were incubated in an ice bath, and 30 ?l of acetic acid was added. The color formed was assessed at 630 nm.

For the measurement of NAGase activity, 25 ?L of the supernatant was incubated with 25 ?L of 4-nitrophenyl N-acetyl - ? - d - glucosaminide (2.24 nM) and 100 ?L of citrate buffer (50 mM, pH 4.5) at 37 °C for 1 h. After incubation, 100 ?L of glycine buffer (0.2 ?M, pH 10.4) was added to stop the reaction and to allow for the development of color, and it was measured at 405 nm.

For the measurement of EPO activity, 100 ?l of a substrate solution consisting of 0.1 mM of o-phenylenediamine in Tris–HCl buffer (0.05 M, pH 8.0) with 0.1% Triton X-100 and 1 mM H 2 O 2 was added to 100 ?l of supernatant. The reaction mixture was incubated for 30 min at 37 °C, and then the reaction was stopped by the addition of 50 ?l of 4 M H 2 SO 4 . The enzyme activity was evaluated colorimetrically at 490 nm.

The absorbance of all reactions was measured in a Fisher Biotech Microkinetics Reader BT 2000 microplate reader. The values are expressed as optical densities, corrected for the protein content, which was measured by the method of Bradford (1976) .

2.9 Histology

To confirm the leukocyte infiltration in the tissues of the right hind paws of the animals that received or did not receive a thermal injury, we carried out histological analyses. Samples were collected 6 days after the incision or sham procedure. Rats were sacrificed, and their paws were removed and fixed in alfac solution (16:2:1 mixture of ethanol 80%, formaldehyde 40% and acetic acid) and then decalcified. Each sample was embedded in paraffin wax, sectioned at 5 ?m and stained with toluidine blue. A representative area was selected for qualitative light microscopic analysis of the inflammatory cellular response with a 10? and 100? objective (Oliveira et al. 2011 ). To minimize any source of bias, the investigator analyzing the samples did not know the identity of the group that he was analyzing.

2.10 Statistical analyses

The results are expressed as the means±S. E.M. All data were analyzed by Student's t - test, one-way or two-way analysis of variance (ANOVA) followed by Bonferroni's or Student–Newman–Keuls' (SNK) post hoc tests when appropriate. P values of less than 0.05 ( P <0.05) were considered significant. The I max (maximal inhibition) were calculated based on the responses of the control (sham) group. To meet the ANOVA assumptions, the mechanical allodynia data were subjected to Log transformation before statistical analysis.

3 Results

3.1 HPLC analysis of the Aloe saponaria extract and physicochemical characterization of creams

The HPLC fingerprinting demonstrated that flavonoids (quercetin, rutin and kaempferol) and phenolic acids (gallic and caffeic acids) are present in the extract of Aloe saponaria . The quantitative analysis of Aloe saponaria extract revealed the presence of gallic acid ( t R =13.97 min; 1.05%; peak 1), caffeic acid ( t R =27.15 min; 0.47%; peak 2), rutin ( t R =41.54 min; 2.13%; peak 3), quercetin ( t R =50.83 min; 1.09%; peak 4) and kaempferol ( t R =69.06 min; 0.38%; peak 5) (Fig. 1 and Table 1 ).

Fig. 1. Representative high performance liquid chromatography spectrum of Aloe saponaria . detection UV was at 325 nm. Gallic acid (peak 1), caffeic acid (peak 2), rutin (peak 3), quercetin (peak 4) and kaempferol (peak 5). Chromatographic conditions are described in the Methods section.

Table 1. Phenolics and flavonoids composition of Aloe saponaria .

Results are expressed as mean±standard deviations (SD) of three determinations.

P <0.05 compared to the gallic acid concentration (one-way ANOVA followed by the Newman–Keuls test).

For the tests, the dry extract was incorporated into Lanette cream and some of physicochemical characterization of formulations was carried out. Regarding the spreadability, no difference ( P >0.05; Student's t - test) was observed between base cream and Aloe saponaria 10% cream (spreadability factor=3.02±0.47 and 2.36±0.45 mm 2 /g, respectively). At 0.22 s ?1 (shear rate), the viscosity was 230,831 and 94,060 mPa s for base cream and Aloe saponaria 10% cream, respectively. Moreover, the formulations exhibited a non-Newtonian behavior, because the viscosity varied according to the change in the shear rate. The pH values obtained were 5.87 and 4.91 for base cream and Aloe saponaria 10% cream, respectively, and were compatible with topical application.

3.2 Effects of Aloe saponaria treatment on mechanical allodynia induced by a thermal injury

Compared to animals that received the sham procedure, animals that received a first-degree thermal injury and were not treated developed static mechanical allodynia, which was characterized by a significant reduction in the paw withdrawal threshold in response to von Frey filaments (24.7±0.9 g at baseline for the sham group vs. to 6.1±0.5 g for the thermal injury group P <0.01, Student's t - test) (Fig. 2 A–B). Furthermore, compared to rats that received the sham procedure, rats that received a first-degree thermal injury also presented dynamic mechanical allodynia characterized by a significant reduction in the paw withdrawal latencies in response to a paintbrush (14±3 s at baseline to 2.0±0.5 s, P <0.01, Student's t - test) (Fig. 3 A–B). The topical treatment with the vehicle did not alter either static or dynamic allodynia caused by the burn. On the other hand, the treatment with Aloe saponaria (10%) or sulfadiazine (1%, used as a positive control) was able to reduce the static and dynamic mechanical allodynia induced by the thermal injury, an effect that started at 1 day, peaked at 2 days and was maintained up to 6 days after injury (Fig. 2 and Fig. 3 A). The dose–response curve demonstrated that Aloe saponaria treatment at the doses of 10% and 30%, but not at 0.3% and 1%, was capable of reducing static and dynamic allodynia with a maximal inhibition of 68±11% and 36±5%, respectively (at the dose of 10%), demonstrating an efficacy similar to that of sulfadiazine (inhibition of 70±11% and 38±10%, respectively) (Fig. 2 and Fig. 3 B).

Fig. 2. Time-course (A) and dose–response curves (B) for the Aloe saponaria extract, no treatment (N/treat) and Sulfadiazine 1% (Sulfa) effects on static mechanical allodynia (A and B) induced by a first-degree thermal injury. The dose–response curves for allodynia were assessed at 48 h after thermal injury. Data are presented as the means±SEM from 7 rats. * P <0.05; ** P <0.01 and *** P <0.001 compared to the no treatment group (Two-way ANOVA followed by Bonferroni's test).

Fig. 3. Time-course (A) and dose–response curves (B) for the Aloe saponaria extract, no treatment (N/treat) and Sulfadiazine 1% (Sulfa) effects on dynamic mechanical allodynia (A and B) induced by a first-degree thermal injury. The dose–response curves for allodynia were assessed at 48 h after thermal injury. Data are presented as the means±SEM from seven rats. * P <0.05; ** P <0.01 and *** P <0.001 compared to the no treatment group (Two-way ANOVA followed by Bonferroni's test).

Similar to the first-degree, animals submitted to second-degree thermal injury developed static and dynamic mechanical allodynia (Suppl. Fig. 1A–B). The topical treatment with Aloe saponaria (10%) or sulfadiazine (1%, used as a positive control), but not with vehicle, was able to reduce static (inhibitions of 57±12% and 72±6%, respectively) and dynamic (10±5% and 15±9%, respectively) mechanical allodynia with similar efficacy (Suppl. Fig. 1A–B).

3.3 Effect of Aloe saponaria treatment on heat allodynia induced by a thermal injury

Animals that received a first-degree thermal injury and were not treated developed thermal allodynia characterized by a significant reduction in the latency to non-noxious heat compared with the sham procedure (13±0.6 s at baseline to 2.8±0.7 s, respectively, P <0.01, Student's t - test) (Fig. 4 A–B). Topical treatment with vehicle did not alter thermal allodynia caused by the first-degree burn. On the other hand, it was observed that treatment with Aloe saponaria (10%) or sulfadiazine (1%, used as a positive control) was able to reduce the thermal allodynia induced by the thermal injury, an effect that started at 1 day, peaked at 2 days and was maintained up to 6 days after injury (Fig. 4 A). The dose–response curve demonstrated that Aloe saponaria treatment at the doses of 10% and 30%, but not at 0.3% and 1%, was capable of reducing thermal allodynia with maximal inhibition of 29±6% (at the dose of 10%) demonstrating an efficacy similar to that of 1% sulfadiazine (inhibition of 38±6%) (Fig. 4 B).

Fig. 4. Time-course (A) and dose–response curves (B) for the Aloe saponaria extract, no treatment (N/treat) and Sulfadiazine 1% (Sulfa) effects on thermal allodynia (A and B) induced by a first-degree thermal injury. The dose–response curves for allodynia were assessed at 48 h after thermal injury. Data are presented as the means±SEM from 7 rats. * P <0.05; ** P <0.01 and *** P <0.001 compared to the no treatment group (Two-way ANOVA followed by Bonferroni's test).

Similarly to the first-degree injury, animals submitted to second-degree thermal injury developed thermal allodynia (Suppl. Fig. 1 C). The topical treatment with Aloe saponaria (10%) or sulfadiazine (1%), but not with vehicle, was capable of reducing thermal allodynia induced by the thermal injury, an effect that started at 1 day, peaked at 2 days after injury (with inhibitions of 87±4% and 82±4%, respectively) (Suppl. Fig. 1 C)

3.4 Effect of Aloe saponaria treatment on spontaneous nociception induced by a thermal injury

Animals that received a first-degree thermal injury and were not treated presented spontaneous pain characterized by the presence of gait/weight bearing disturbance, guarding, hind paw lifting and grooming compared to the sham procedure group (58±11 s, P <0.01, Student's t - test) (Fig. 5 A–B). Topical treatment with vehicle did not alter the spontaneous pain caused by the first-degree burn. On the other hand, it was observed that treatment with Aloe saponaria (10%) or sulfadiazine (1%, used as a positive control) was able to reduce the spontaneous pain induced by the thermal injury, an effect that started at 1 day, peaked at 2 days and was maintained up to 6 days after injury (Fig. 5 A). The dose–response curve demonstrated that Aloe saponaria treatment at the doses of 10% and 30%, but not at 0.3% and 1%, were capable of reducing spontaneous pain with maximal inhibition of 83±7% (at the dose of 10%), demonstrating an efficacy similar to that of sulfadiazine 1% (inhibition of 81±8%) (Fig. 5 B).

Fig. 5. Time-course (A) and dose–response curves (B) for the Aloe saponaria extract, no treatment (N/treat) and Sulfadiazine 1% (Sulfa) effects on spontaneous pain (A and B) induced by a first-degree thermal injury. The dose–response curves for spontaneous pain were assessed at 48 h after thermal injury. Data represented as the means±SEM from 7 rats * P <0.05; ** P <0.01 and *** P <0.001 compared to the no treatment group (Two-way ANOVA followed by Bonferroni?s test).

Furthermore, rats submitted to second-degree thermal injury (second-degree model) presented spontaneous pain (Suppl. Fig. 1 E). The topical treatment with the vehicle did not alter spontaneous pain caused by the second-degree thermal injury, but the treatment with Aloe saponaria (10%) or sulfadiazine (1%, used as a positive control) was able to reduce the spontaneous pain induced by the thermal injury (71±3% and 61±4%, respectively), an effect that started at 1 day, peaked at 2 days after injury (Suppl. Fig. 1 E).

3.5 Effects of Aloe saponaria treatment on paw edema induced by a thermal injury

Compared to animals that received the sham procedure, animals that received the first-degree thermal injury procedure and were not treated presented edema characterized by an increase in paw thickness (4±0.1 mm at baseline compared to 11.15±0.09 mm, respectively, P <0.01, Student's t - test) (Fig. 6 A–B). Topical treatment with the vehicle did not alter edema formation caused by the first-degree burn. On the other hand, it was observed that treatment with Aloe saponaria (10%) or sulfadiazine (1%, used as a positive control) was able to reduce the thermal injury-induced edema, an effect that started at day 4 and was maintained up to 6 days (peaked) after injury (Fig. 6 A). The dose–response curve demonstrated that Aloe saponaria treatment at the doses of 10 and 30%, but not at 0.3% and 1%, was capable of reducing the edema formation with maximal inhibition of 62±2% (at the dose of 10%), demonstrating an efficacy similar to that of 1% sulfadiazine (inhibition of 51±2%) (Fig. 6 B).

Fig. 6. Time-course (A) and dose–response curves (B) for the Aloe saponaria extract, no treatment (N/treat) and Sulfadiazine 1% (Sulfa) effects on paw edema (A and B) induced by a first-degree thermal injury. The dose–response curve for paw edema was assessed at 144 h after thermal injury. Data represented as the means±SEM from seven rats. * P <0.05; ** P <0.01 and *** P <0.001 compared to the no treatment group (Two-way ANOVA followed by Bonferroni's test).

Animal submitted to a second-degree thermal injury developed paw edema, which was inhibited by the topical treatment with Aloe saponaria (10%) or sulfadiazine (1%) (reductions of 28±5% and 35±9% at 2 days after injury, respectively) (Suppl. Fig. 1 D).

Furthermore, we have tested the treatments in animals submitted to sham procedure (that not received thermal injury). During 6 days, none of the treatments (vehicle, sulfadiazine 1% or Aloe saponaria 10%) caused edema or nociception in animals (data not shown), indicating that they not produced skin irritation in animals.

3.6 Aloe saponaria Haw attenuated leukocyte infiltration induced by the thermal burn injury

To investigate whether the treatment with Aloe saponaria altered neutrophil, macrophage and eosinophil infiltration induced by injury, we assessed the activities of MPO, NAGase and EPO in the injured tissue (Fig. 7 A – C). Six days after the first-degree thermal injury, we detected increases of 100%, 66±14% and 100% in the MPO, NAGase and EPO activities, respectively, compared with the sham-injured group. The increases in the MPO, NAGase and EPO activities were inhibited by the A. saponaria (10%) treatment (100%, 60±3% and 83±6%, respectively). Similarly, the silver sulfadiazine treatment (1%, used as positive control) also inhibited the increases in the MPO, NAGase and EPO activities caused by the thermal injury (inhibitory effects of 68±14%, 79±10% and 55±4%, respectively).

Fig. 7. Effect of the treatment with Aloe saponaria 10% extract or silver sulfadiazine 1% after 6 days treatment on MPO (A), NAG (B) and EPO (C) levels in the paw tissue of rats subjected to a thermal burn. Data are presented as the means±SEM from seven rats. * P <0.05 and ** P <0.01 compared to the no treatment group. # P <0.01 compared to the control group. (Two-way ANOVA followed by Bonferroni's test).

Furthermore, we confirmed our enzymatic leukocyte infiltration detection with histological analyses. In accordance with the enzymatic results, the first-degree thermal injury-induced leukocyte infiltration observed in histological slides compared with the sham procedure submitted group (Suppl. Fig. 2 A–B). The treatment with sulfadiazine 1% or Aloe saponaria 10%, but not with vehicle, caused a reduction in leukocytes infiltration compared with no treatment group (Suppl. Fig. 2 C–E).

Finally, we also assessed the activities of MPO and EPO in the injured tissue that animals that received the second-degree thermal injury. Two days after injury, we detected an increased of MPO and EPO activities that were reduced by either Aloe saponaria (10%) (inhibitions of 18±3% and 33±12%, respectively) or silver sulfadiazine (1%) treatment (inhibitions of 16±4% and 37±3%, respectively) (Suppl. Fig. 3 A–B).

4 Discussion

Aloe saponaria has been empirically used worldwide as a folk medicine for various skin disorders, including thermal injuries, and this treatment is based on anecdotal evidence or on research conducted almost exclusively with Aloe vera (Soares et al. 2004 ). Thus, we investigated the antinociceptive and anti-inflammatory effects of Aloe saponaria for the treatment of both first and second-degree thermal injuries, which has yet to be studied. The results of this study demonstrate that burn-induced nociception and inflammation is ameliorated by topical treatment with Aloe saponaria.

A preliminary HPLC analysis of Aloe saponaria showed several chromatographic peaks, revealing great chemical diversity. Among the substances present, flavonoids (rutin, quercetin and kaempferol) and phenolic acids (gallic and caffeic acids) were found. These flavonoids and phenolics are widely distributed in medicinal plants. Our results are in accordance with previous findings for the same genus, which detected phenols and flavonoids in leaf extracts of Aloe ferox, Aloe secundiflora and Aloe vera (Rebecca et al. 2003 and Wintola and Afolayan, 2011 ). Moreover, several studies have shown that the flavonoids and phenolics found in Aloe saponaria possess antinociceptive and anti-inflammatory effects in models of inflammatory pain in rodents (Lapa et al. 2009. Hajhashemi et al. 2012 and Mehrotra et al. 2011 ). Thus, these biological activities could be responsible, at least in part, for the effects of Aloe saponaria observed in our study.

To evaluate the antinociceptive and anti-inflammatory activities of Aloe saponaria . we used a thermal injury model (Gao et al. 2010 ) in which the animals received a scald burn to the paw. In a scald burn, pain is the most frequent complaint of the injured patient. Patients present mechanical allodynia, thermal hyperalgesia and spontaneous pain of the skin (Summer et al. 2007 ). Moreover, in humans, burns cause edema and leukocyte infiltration (Kowal-Verne et al. 1997 ). Because we detected the same signs and symptoms in our study, this model seems to be relevant to study the anti-inflammatory and antinociceptive effects of Aloe saponaria after a thermal burn.

The hyperalgesia induced by mechanical stimulation of the injured site is the major source of severe pain after a burn injury (Summer et al. 2007 ). In accordance, our study showed that first and second-degree thermal injury model decreased the threshold of static mechanical allodynia and decreased the latency in dynamic mechanical allodynia and thermal allodynia in rats. Furthermore, burn-injured patients also describe spontaneous components of breakthrough pain. Spontaneous pain is commonly reported by patients in qualitative terms such as “stinging”, “pricking”, “shooting”, and “pounding” (Summer et al. 2007 ). Spontaneous nociception after a burn could also be observed in rats subjected to the thermal injury model. Our findings showed that topical treatment with Aloe saponaria had an antinociceptive effect in various broad parameters of pain, such as dynamic and static mechanical allodynia, thermal allodynia and spontaneous nociception. Our findings are in agreement with a previous study that showed that systemic administration of an ethanol extract of Aloe saponaria presented antinociceptive effects in a model of neuropathic pain caused by successive treatment with cisplatin (Yoo et al. 2008 ).

A skin burn results in local tissue damage, which induces a painful inflammatory process (Sener et al. 2003 ). In fact, we observed that thermal injury-induced edema formation, an effect that was reduced by Aloe saponaria treatment. Other species from the genus Aloe have been previously described to have topical anti-edematogenic effects. For instance, Aloe vera treatment reduces edema produced by bacteria infection (Rishi et al. 2008 ). Similar to Aloe saponaria . the treatment with 1% silver sulfadiazine (positive control) had antinociceptive and anti-inflammatory effects in the thermal burn model. Silver sulfadiazine is the most commonly used topical treatment for burn injury, and several studies have shown it to be effective to treat burn injuries (Maenthaisong et al. 2007 and Khorasani et al. 2009 ). Because Aloe saponaria presented efficacy similar to sulfadiazine and Aloe vera (Bunyapraphatsara et al. 1996 and present study), the antinociceptive and anti-inflammatory effects of this plant could be beneficial in the treatment of first and second-degree burns, apart being as effective as the reference treatments. The similar efficacy of Aloe saponaria and silver sulfadiazine could be due to their resemblance with regard to its properties. In fact, sulfadiazine is primarily used for burns because of its antimicrobial action (Khorasani et al. 2009 ) and a study indicated that Aloe saponaria also possesses antibacterial action (Tian et al. 2003 ). Furthermore, we also observed that Aloe saponaria extract 10% was more effective than 30% to produce antinociceptive and antiinflammatory effects. This finding is not unexpected since the relationship of the flux of a drug from ointments to skin and the drug dose follows usually an inverted-U shaped curve (Troy, 2005 ). In fact, the evaporation of more volatile components of a cream (such as water) may lead to the early precipitation of drugs, reducing their access to skin, which may explain why the Aloe saponaria dose of 30% is less effective than of 10%.

In addition to edema, burn wounds are also susceptible to infiltration by a variety of cell types including macrophages and neutrophils (Sener et al. 2003 and Evers et al. 2010 ). The MPO, NAGase and EPO activities in injured tissue were used as a marker of neutrophil, macrophage and eosinophil infiltration, respectively (Lloret and Moreno, 1995 and Kang et al. 2008 ). Our observation demonstrated that the MPO, NAGase and EPO activities were increased in paw tissue samples after a thermal injury, indicating neutrophil, macrophage and eosinophil infiltration into this tissue, which could contribute to injury in a thermal injury. Concomitant with its antinociceptive and anti-edematogenic effects, Aloe saponaria has a preventive effect in a thermal injury through inhibition of the infiltration of neutrophils, macrophages and eosinophils. In accordance with our findings, it has been found that Aloe vera reduced leukocyte adhesion in the endothelium of burn-wounded rats (Duansak et al. 2003 ). Furthermore, Yoo et al. (2008) showed that the incubation of Aloe saponaria extract with cultured macrophages in vitro suppressed nitric oxide production and inhibited the lipopolysaccharide (LPS)-induced mRNA increases in nitric oxide synthase, granulocyte-macrophage colony-stimulating factor and cyclooxygenase 2. Thus, the reduction in leukocyte infiltration and activation in injured tissue seems to contribute to the beneficial effects of Aloe saponaria on thermal injury.

Finally, changes in the physicochemical characteristics of the cream after extract incorporation could facilitate its anti-inflammatory action. In fact, the incorporation of the Aloe saponaria extract into Lanette cream reduced its pH and viscosity, but not its spreadability. It is important to relate that the efficacy of topical therapy depends on the patient spreading the formulation on the skin, and their distribution on the applied region, as well as the viscosity and composition (Garg et al. 2002 ). In this case, the formulations had similar values and the incorporation of the Aloe extract into the base cream did not influence its spreadability. Apart to be lower than base cream, the pH value of the Aloe saponaria cream was still compatible with topical application and with the slightly acidic mantle of skin pH between 4.6 and 5.8. Furthermore, the low pH of the cream Aloe may be favorable in the healing process, since the acid mantle has a number of functions, including antimicrobial defense and restriction of inflammation by inhibiting the release of pro-inflammatory cytokines (Prow et al. 2011 ).

In conclusion, the results presented in this study show that treatment with Aloe saponaria Haw has antinociceptive and anti-inflammatory effects in an animal that received first or second-degree model of thermal injuries. Taken together, our results support the traditional use of this plant in the treatment of burns.

Acknowledgments

This study was supported by the Conselho Nacional de Desenvolvimento Cientifico (CNPq), Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES), Instituto do Milenio, Instituto Nacional de Ciencia e Tecnologia (INCT) em Medicina Molecular. We thank CNPq and CAPES for their fellowship support.

Appendix A Supplementary materials

References

Barros et al. 2007

F. M.C. Barros. K. N. Pereira. G. D. Zanetti. B. M. Heinzmann

Plantas de Uso Medicinal no Municipio de Sao Luiz Gonzaga, RS, Brasil

Latin American Journal of Pharmacy. Volume 26. 2007. pp. 652–662

Borghetti and Knorst, 2006

G. S. Borghetti. M. T. Knorst

Desenvolvimento e avaliacao da estabilidade fisica de locoes O/A contendo filtros solares

Revista Brasileira de Ciencias Farmaceuticas. Volume 42. Issue 4. 2006. pp. 531–537

Bradford, 1976

M. M. Bradford

A rapid and sensitive method for the quantification of microgram quantities of protein utilizing the principle of protein—dye binding

Analytical Biochemistry. Volume 72. 1976. pp. 248–254

Bunyapraphatsara et al. 1996

N. Bunyapraphatsara. S. Jirakulchaiwong. S. Thirawarapan. J. Manonukul

The efficacy of Aloe vera cream in the treatment of first, second and third degree burns in mice

Phytomedicine: International Journal of Phytotherapy and Phytopharmacology. Volume 2. Issue 3. 1996. pp. 247–251

Capasso et al. 1998

F. Capasso. F. Borrelli. R. Capasso. G. Di Carlo. A. A. Izzo. L. Pinto. N. Mascolo. S. Castaldo. R. Longo

Aloe and its therapeutic use

Phytotherapy Research. Volume 12. 1998. pp. 124–127

Chaplan et al. 1994

S. R. Chaplan. F. W. Bach. J. W. Pogrel. J. M. Chung. T. L. Yaksh

Quantitative assessment of tactile allodynia in the rat paw

Journal of Neuroscience Methods. Volume 53. 1994. pp. 55–63

Chithra et al. 1998

P. Chithra. G. B. Sajithlal. G. Chandrakasan

Influence of aloe vera on the healing of dermal wounds in diabetic rats

Journal of Ethnopharmacology. Volume 59. 1998. pp. 195–201

Dixon, 1980

W. J. Dixon

Efficient analysis of experimental observations

Annual Review of Pharmacology and Toxicology. Volume 20. 1980. pp. 441–462

Duansak et al. 2003

D. Duansak. J. Somboonwong. S. Patumraj

Effects of Aloe vera on leukocyte adhesion and TNF-alpha and IL-6 levels in burn wounded rats

Clinical Hemorheologic Microcirculation. Volume 29. 2003. pp. 239–246

Evaristo and Leitao, 2001

I. M. Evaristo. M. C. Leitao

Identificacao e Quantificacao por DAD-HPLC, da Fraccao Fenolica Contida em Folhas de Quercussuber L

Silva Lusitana. Volume 9. 2001. pp. 135–141

Evers et al. 2010

L. H. Evers. D. Bhavsar. P. Mailander

The biology of burn injury

Experimental Dermatology. Volume 19. 2010. pp. 777–783

Gao et al. 2010

Y. Gao. C. S. Xu. K. Yu. G. Li. F. Wan. S. Liu. J. Lin. H. Liu. J. Zhang. X. Li. S. D. Liang

Effect of tetramethylpyrazine on DRG neuron P2?3 receptor involved in transmitting pain after burn

Burns: Journal of the International Society for Burn Injuries. Volume 36. 2010. pp. 127–134

Garg et al. 2002

A. Garg. D. Aggarwal. S. Garg. A. Singela

Spreading of semisolid formulations

Pharmaceutical Technology. Volume 26. 2002. pp. 84–105

Hajhashemi et al. 2012

V. Hajhashemi. B. Zolfaghari. A. Yousefi

Antinociceptive and anti-inflammatory activities of Saturejahortensis seed essential oil, hydroalcoholic and polyphenolic extracts in animal models

Medical Principles and Practice. Volume 21. 2012. pp. 178–182

Iwu, 1993

Iwu, M. M. 1993. Handbook of African Medicinal Plants. Library of Congress Edition, Florida, pp. 114–117.

Jaggi and Singh, 2011

A. S. Jaggi. N. Singh

Exploring the potential of telmisartan in chronic constriction injury-induced neuropathic pain in rats

European Journal of Pharmacology. Volume 667. 2011. pp. 215–221

Kang et al. 2008

H. S. Kang. J. Y. Lee. C. J. Kim

Anti-inflammatory activity of arctigenin from Forsythiae Fructus

Journal of Ethnopharmacology. Volume 116. 2008. pp. 305–312

Khorasani et al. 2009

G. Khorasani. S. J. Hosseinimehr. M. Azadbakht. A. Zamani. M. R. Mahdavi

Aloe versus silver sulfadiazine creams for second-degree burns: a randomized controlled study

Surgery Today. Volume 39. 2009. pp. 587–591

Kowal-Verne et al. 1997

A. Kowal-Verne. J. M. Walenga. M. Sharp–Pucci. D. Hoppensteadt. R. L Gamelli

Postburn edema and related changes in interleukin-2, leukocytes, platelet activation, edothelin-1, and C1 esterase inhibitor

The Journal of Burn Care & Rehabilitation. Volume 18. 1997. pp. 99–103

Lapa et al. 2009

F. R. Lapa. V. M. Gadotti. F. C. Missau. M. G. Pizzolatti. M. C.A. Marques. A. L. Dafre. M. Farina. A. L.S. Rodrigues. A. R.S. Santos

Antinociceptive properties of the hydroalcoholic extract and the flavonoid rutin obtained from Polygala paniculata L. in mice

Basic & Clinical Pharmacology & Toxicology. Volume 104. 2009. pp. 306–315

Lloret and Moreno, 1995

S. Lloret. J. J. Moreno

Effects of an-anti-inflammatory peptide antiflammin 2 on cell influx, eicosanoid biosynthesis and oedema formation by arachidonic acid and tetradecanoylphorbol dermal application

Biochemical Pharmacology. Volume 50. 1995. pp. 347–353

Loots et al. 2007

D. T. Loots. F. Van Der Westhuizen. L. Botes

Aloe ferox leaf gel phytochemical content, antioxidant capacity, and possible health benefits

Journal of Agricultural and Food Chemistry. Volume 55. 2007. pp. 6891–6896

Lv et al. 2006

R. L. Lv. B. Y. Wu. X. D. Chen. Q. Jiang

The effects of aloe extract on nitric oxide and endothelin levels in deep-partial thickness burn wound tissue in rat

Zhonghua shao shang za zhi=Zhonghua shaoshang zazhi=Chinese Journal of Burns. Volume 22. 2006. pp. 362–365

Maenthaisong et al. 2007

R. Maenthaisong. N. Chaiyakunapruk. S. Niruntraporn. C. Kongkaew

The efficacy of Aloe vera used for burn wound healing: a systematic review

Burns. Journal of the International Society for Burn Injuries. Volume 33. 2007. pp. 713–718

Mehrotra et al. 2011

A. Mehrotra. R. Shanbhag. M. R. Chamallamudi. V. P. Singh. J. Mudgal

Ameliorative effect of caffeic acid against inflammatory pain in rodents

European Journal of Pharmacology. Volume 666. 2011. pp. 80–86

Oliveira et al. 2011

S. M. Oliveira. C. C. Drewes. C. R. Silva. G. Trevisan. S. L. Boschen. C. G. Moreira. D. A. Cabrini. C. Cunha. J. Ferreira

Involvement of mast cells in a mouse model of postoperative pain

European Journal of Pharmacology. Volume 672. 2011. pp. 88–95

Parihar et al. 2008

A. Parihar. M. S. Parihar. S. Milner. B. Bhat

Oxidative stress and anti-oxidative mobilization in burn injury

Burns: Journal of the International Society for Burn Injuries. Volume 34. 2008. pp. 6–17

Prow et al. 2011

T. W. Prow. J. E. Grice. L. L. Lin. R. Faye. M. Butler. W. Becker. E. M. Wurm. C. Yoong. T. A. Robertson. H. P. Soyer. M. S. Roberts

Nanoparticles and microparticles for skin drug delivery

Advanced Drug Delivery. Volume 63. 2011. pp. 470–491

Rebecca et al. 2003

W. Rebecca. O. Kayser. H. Hagels. K. H. Zessin. M. Madundo. N. Gamba

Main phenolic compounds from the leaf exudate of Aloe secundiflora by high-performance liquid chromatography-mass spectroscopy

Phytochemical Analysis. Volume 14. 2003. pp. 83–86

Richardson and Mustard, 2009

P. Richardson. L. Mustard

The management of pain in the burns unit

Burns: Journal of the International Society for Burn Injuries. Volume 35. 2009. pp. 921–936

Rishi et al. 2008

P Rishi. A Rampuria. R Tewari. A. Koul

Phyromodulatory potentials of Aloe vera against Salmonella OmpR-mediated inflammation

Phytotherapy Research. Volume 22. 2008. pp. 1075–1082

Sener et al. 2003

G. Sener. H. Satiroglu. A. O. Sehirli. A. Kacmaz

Protective effect of aqueous garlic extract against oxidative organ damage in a rat model of thermal injury

Life Sciences. Volume 73. 2003. pp. 81–91

Silva et al. 2010

M. A. Silva. J. Z. Klafke. M. F. Rossato. C. Gewehr. G. P. Guerra. M. A. Rubin. J. Ferreira

Role of peripheral polyamines in the development of inflammatory pain

Biochemical Pharmacology. Volume 82. 2010. pp. 269–277

Soares et al. 2004

E. L.C. Soares. G. S. Vendrusculo. S. M. Eisinger. R. A. Zachia

Estudo etonobotanico do uso dos recursos vegetais em Sao Joao do Polesine, RS, Brasil, no periodo de outubro de 1999 a junho de 2001. I-Origem e fluxo do conhecimento

Revista Brasileira de Plantas Medicinais. 2004. pp. 69–95

Summer et al. 2007

G. J. Summer. K. A. Puntillo. C. Miaskowski. P. G. Green. J. D. Levine

Burn injury pain: the continuing challenge

The Journal of Pain. Volume 8. 2007. pp. 533–548

Suzuki et al. 1983

K. Suzuki. H. Ota. S. Sasagawa. T. Sakatani. T. Fujikura

Assay method formyeloperoxidase in human polymorphonuclear leukocytes

Analytical Biochemistry. Volume 132. 1983. pp. 345–352

Takahashi et al. 2003

K. Takahashi. J. Sato. K. Mizumura

Responses of C-fiber low threshold mechanoreceptors and nociceptors to cold were facilitated in rats persistently inflamed and hypersensitive to cold

Neuroscience Research. Volume 47. 2003. pp. 409–419

The Angiosperm Phylogeny Group, 2009

The Angiosperm Phylogeny Group

An update of the angiosperm phylogeny group classification for the orders and families of flowering plants: APG III

Botanical Journal of the Linnean Society. Volume 161. 2009. pp. 105–121

Tian et al. 2003

B. Tian. Y. J. Hua. X. Q. Ma. G. L. Wang

Relationship between antibacterial activity of aloe and its anthaquinone compounds

Zhongguo Zhong Yao ZaZhi. Volume 28. 2003. pp. 1034–1037

Troy, 2005

Troy, D. B. 2005. Remington: The Science and Practice of Pharmacy, 21st ed. Lippincott Williams and Wilkins, Baltimore, pp. 871–888.

Weissman-Fogel et al. 2008

I. Weissman-Fogel. A. Dashkovsky. Z. Rogowski. D. Yarnitsky

Vagal damage enhances polyneuropathy pain: additive effect of two algogenic mechanisms

Pain. Volume 138. 2008. pp. 153–162

Wintola and Afolayan, 2011

O. A. Wintola. A. J. Afolayan

Phytochemical constituents and antioxidant activities of the whole leaf extract of Aloe ferox Mill

Pharmacognosy Magazine. Volume 28. 2011. pp. 325–333

Yoo et al. 2008

E. A. Yoo. S. D. Kim. W. M. Lee. H. J. Park. S. K. Kim. J. Y. Cho. W. Min. M. H. Rhee

Evaluation of antioxidant, antinociceptive, and anti-inflammatory activities of ethanol extracts from Aloe saponaria Haw

Phytotherapy Research. Volume 22. 2008. pp. 1389–1395

Zimmermann, 1983

M. Zimmermann

Ethical guidelines for investigations of experimental pain in conscious animals

Pain. Volume 16. 1983. pp. 109–110

?

Correspondence to: Departamento de Quimica, Universidade Federal de Santa Maria, Avenida Roraima 1000, Camobi, ZIP CODE 97105-900, Santa Maria, RS, Brazil. Tel. +55 55 3220 8053; fax: +55 55 3220 8031.

Copyright © 2013 Elsevier Ireland Ltd.

Citing articles ( )

Buy Zerocoler Ezetimibe Simvastatin Online Without Prescriptions, Zerocoler

Vytorin is used for treating high cholesterol along with a cholesterol-lowering diet. Vytorin is a combination of 2 medicines. Ezetimibe works by reducing the amount of cholesterol that your body absorbs from your diet. Simvastatin is an HMG-CoA reductase inhibitor or "statin." It works by blocking an enzyme that is necessary for your body to make cholesterol. Lowering cholesterol levels in the blood reduces the chance of heart disease, heart attacks, and strokes. Vytorin has not been shown to reduce heart attacks or strokes more than simvastatin alone.

Use Vytorin as directed by your doctor.

Take Vytorin by mouth with or without food, preferably in the evening, unless directed otherwise by your doctor.

Taking Vytorin at the same time each day will help you remember to take it.

If you also take a bile acid sequestrant (eg, cholestyramine, colestipol, colesevelam), do not take it within 2 hours before or 4 hours after taking Vytorin. Check with your doctor if you have questions.

For best results, Vytorin should be used along with exercise, a low-cholesterol/low-fat diet, and a weight-loss program if you are overweight. Follow the diet and exercise program given to you by your health care provider.

Eating grapefruit or drinking grapefruit juice may increase the amount of Vytorin in your blood, which may increase your risk for serious side effects. The risk may be greater with large amounts of grapefruit or grapefruit juice. Avoid large amounts of grapefruit or grapefruit juice (eg, more than one quart daily). Talk with your doctor or pharmacist if you have questions about including grapefruit or grapefruit juice in your diet while you are taking Vytorin.

Most people with high cholesterol do not feel sick. Continue to take Vytorin even if you feel well. Do not miss any doses.

If you miss a dose of Vytorin, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

Ask your health care provider any questions you may have about how to use Vytorin.

Store Vytorin at room temperature, between 68 and 77 degrees F (20 and 25 degrees C). Store away from heat, moisture, and light. Do not store in the bathroom. Keep Vytorin out of the reach of children and away from pets.

Active Ingredients: Ezetimibe, Simvastatin.

Do NOT use Vytorin if:

you are allergic to any ingredient in Vytorin

you have liver problems or ongoing abnormal liver function test results

you are taking another medicine that contains simvastatin or ezetimibe

you are taking an HIV protease inhibitor (eg, nelfinavir, lopinavir, ritonavir), itraconazole, ketoconazole, a macrolide or ketolide antibiotic (eg, clarithromycin, erythromycin, troleandomycin), mibefradil, or nefazodone

you are pregnant or breast-feeding.

Contact your doctor or health care provider right away if any of these apply to you.

Some medical conditions may interact with Vytorin. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

if you are pregnant, planning to become pregnant, or are breast-feeding

if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement

if you have allergies to medicines, foods, or other substances

if you are a woman of childbearing age

if you have kidney problems, muscle problems, or a family history of muscle problems; low blood pressure; uncontrolled seizures; or serious metabolic, endocrine, or electrolyte problems

if you are scheduled for major surgery, have recently had a major trauma, or have a severe infection or history of alcohol abuse

if you have had an organ transplant and are taking medicine to suppress a rejection reaction.

Some medicines may interact with Vytorin. Tell your health care provider if you are taking any other medicines, especially any of the following:

Amiodarone, angiotensin-converting enzyme (ACE) inhibitors (eg, enalapril), azole antifungals (eg, itraconazole, ketoconazole), cyclosporine, danazol, delavirdine, diltiazem, fibrates (eg, clofibrate, fenofibrate), fluconazole, gemfibrozil, HIV protease inhibitors (eg, ritonavir), imatinib, macrolide antibiotics (eg, erythromycin), macrolide immunosuppressives (eg, tacrolimus), mibefradil, nefazodone, niacin, nicotinic acid, streptogramins, telithromycin, verapamil, or voriconazole because side effects, such as muscle pain, may occur

Bosentan, carbamazepine, cholestyramine, hydantoins (eg, phenytoin), rifampin, or St. John's wort because they may decrease Vytorin's effectiveness

Anticoagulants (eg, warfarin) because the risk of their side effects may be increased by Vytorin.

This may not be a complete list of all interactions that may occur. Ask your health care provider if Vytorin may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

Important safety information:

Vytorin may cause dizziness, drowsiness, or changes in vision. These effects may be worse if you take it with alcohol or certain medicines. Use Vytorin with caution. Do not drive or perform other possible unsafe tasks until you know how you react to it.

It may take several weeks for Vytorin to work.

Proper dental care is important while you are taking Vytorin. Brush and floss your teeth and visit the dentist regularly.

Vytorin may harm your liver. Your risk may be greater if you drink alcohol while you are using Vytorin. Talk to your doctor before you take Vytorin or other fever reducers if you drink more than 3 drinks with alcohol per day.

Vytorin may cause injury to your muscles, especially when taken at higher doses or when taken with certain other medicines. Contact your doctor right away if you experience muscle pain, tenderness, or weakness, especially with a fever.

Some patients taking Vytorin have reported poor memory or trouble sleeping. If you experience these effects, check with your doctor.

Lab tests, including blood cholesterol levels, liver function tests, or muscle tests, may be performed while you use Vytorin. These tests may be used to monitor your condition or check for side effects. Be sure to keep all doctor and lab appointments.

Vytorin should be used with extreme caution in children younger 10 years; safety and effectiveness in these children have not been confirmed.

Pregnancy and breast-feeding: Do not use Vytorin if you are pregnant. Avoid becoming pregnant while you are taking it. If you think you may be pregnant, contact your doctor right away. It is not known if Vytorin is found in breast milk. Do not breastfeed while taking Vytorin.

All medicines may cause side effects, but many people have no, or minor, side effects.

Check with your doctor if any of these most common side effects persist or become bothersome:

Diarrhea; flu-like symptoms; headache; pain in the arms or legs; tiredness; upper respiratory tract infection.

Seek medical attention right away if any of these severe side effects occur:

Severe allergic reactions (rash; hives; itching; difficulty breathing or swallowing; tightness in the chest; swelling of the mouth, face, lips, or tongue); blurred vision or vision changes; change in the amount of urine; chest pain; dark urine; depression; fast heartbeat; fever; loss of appetite; muscle tenderness, pain, or weakness; nausea; numbness, tingling, burning, or weakness in the arms, hands, feet, or legs; pale stools; stomach tenderness; unexplained pain in the stomach or mid-upper back; unusual bruising or bleeding; unusual tiredness; vomiting; yellowing of the skin or eyes.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider.

Customers who bought this product also bought

Copyright © 2004-2016 All Rights Reserved

Comprar Barato Online Cilovas, Cilovas

Comprar Cilovas

August Gastropec Manfred Stauber, Thomas Weyerstahl Dieses Medicammentos ist nur fur den personlichen Gebrauch bestimmt und darf in keiner Form an Dritte weitergegeben werden. Triagynon wie Reproduktionsmedizin, pranatale Medizin medicamentos cilovas (ciplox) Onkologie konfrontieren den Arzt haufig cilovas (ciplox) pastillas mas baratas ethischen Konflikten, mit denen er nicht selten uberfordert ist.

Tags relacionados: Cilovas Cilovas (ciplox) 500 mg pastillas sin receta Cilovas los precios mas baratos Cilovas (ciplox) 500 mg comprar pela internet Comprar barato online cilovas (ciplox) 500 mg Cilovas (ciplox) 500 mg comprar sin receta Cilovas 500 mg comprar online Descuento de precios cilovas Cilovas precios de los medicamentos Costo promedio cilovas (ciplox) Cilovas (ciplox) venta en mexico Pastillas cilovas 500 mg Pastillas cilovas (ciplox) Cilovas 500 mg venta en mexico Farmacias en venta cilovas Cilovas compra venta online Cilovas (ciplox) precios de pastillas Baratos sin receta generic cilovas (ciplox) Baratos sin receta generic cilovas (ciplox) 500 mg Farmacia online de genericos cilovas (ciplox) 500 mg Cilovas (ciplox) 500 mg de bajo coste Medicamentos cilovas 500 mg Cilovas (ciplox) 500 mg comprar espana Cilovas (ciplox) 500 mg el mejor precio Cilovas 500 mg el mejor precio Farmacia online de genericos cilovas (ciplox) Cilovas (ciplox) el mejor precio Cilovas venta en farmacias Cilovas (ciplox) baratos sin receta generic Cilovas (ciplox) 500 mg venta en farmacias Cilovas (ciplox) precios de la pildora Cilovas el mejor precio Compara precios de medicamentos cilovas (ciplox) Costo promedio cilovas Cilovas (ciplox) venta en farmacias Cilovas 500 mg precios baratos Cilovas (ciplox) 500 mg a bajo precio Compra cilovas Cilovas (ciplox) el precio mas bajo Cilovas (ciplox) comprar por internet

Articulos de interes:

Buscar/Search/Chercher:

Donde/Where/Ou

Bendit, planchas de asar.

Mosen Cinto Verdaguer, 3 25100 Almacelles (Lleida) Tel. (34) 973 26 93 96 [email protected] es www. bendit. es

Pharmacy Prodorol, Prodorol

Pharmacy / Prodorol/ Pur-bloka

Question Dear Doctor, I am a 29 year old female, very fit and in-shape, no allergies, a smoker. and I have been prescriber Pur-bloka for a tremor in my left hand. My doctor said that I do have corpal tunnel syndrome (not sure about the spelling) but the tremors in my hands and arms are apparently something else which she has not diagnosed as such. In any case, I started taking the pur-bloke twice a day and felt no ill effects and I could even have a few drinks and not feel strange. When I went to the pharmacist for my new prescription of pur-bloka, he gave me prodorol and said its the same thing as pur-bloka. When I have a glass of wine, I felt VERY strange and drunk. I want to know what the dangers are of drinking while on this pill, please. Can I get a heart attack? What if I only take the second pill right before I go to sleep after I had a few glasses of wine? Will I die? Also, what will happen if I suddenly stop taking the prodorol/pur-bloka instead of going off it gradually? I've been researching the internet about these things, but I can't find any specific answers. I would really appreciate it if you could get back to me as I don't want to damage my heart while on these pills and I don't just want to stop taking them either.

Thank you very much for your time. Kind Regards, Marike

Answer Hi Marike, Pur-bloka and Prodrol contain the same active ingredient which is propranolol. This is a beta blocker which is used to treat angina, prevent some migraine headaches and essential tremor. Taking this medication with alcohol can cause either an increase or decrease in propranool levels. The effect is not predictable. You have to watch for changes in hear rate. When taken for angina propranolol should not be stopped abruptly. When taken for essential tremor you do not need to gradually wean off of it. Thank you for using Allexperts Sincerely, Eric Brandt, B. Sc. Pharm

Magic Of Manatee - Bradenton, Fl, Adelone

Magic of Manatee is an extraordinary group of women who gather together in Bradenton, FL, to sing and celebrate the art form known as barbershop harmony. We are a chapter of Sweet Adelines International .

Our director is the wonderful Lois Van Beek, who inspires us to reach new heights with each performance. We can be heard throughout the year, singing for civic and charitable organizations, private groups, churches, community events, and fundraisers.

Magic of Manatee Rehearsals .

Tuesdays 7:30 pm

3304 43rd Street West

Do you sing? Do you want to be part of a special group of women?

We love to entertain by putting on our own musical events each year for the community, our friends, and families. Please contact us to sing at your next special event!

8 Things You Might Not Know About Pantip Plaza, Pantip

8 things you might not know about Pantip Plaza

Pantip Plaza is Bangkok’s most infamous IT-related shopping center. Located in a drab, five-story building on Petchaburi Road, it houses hundreds of shops selling computer hardware, software –- both pirated and legit -- accessories and other tech-related gadgets.

Nearly every Bangkok resident, not to mention tech-loving tourists who have done even a tiny bit of research, knows that if you need new gear for cheap, go to Pantip. But while the shopping center is well-known to many, the fluorescent and neon-lit space still holds a few surprises.

Here are some of Pantip Plaza’s lesser-known qualities.

1. There actually is a method to the madness. Kind of

On first glance, the tangle of shops and stalls appears chaotic. But there is a semblance of logic. The ground floor has mostly cell phone-related items and various plastic toys, like radio-controlled helicopters and electronic fly swatters. There are also some software, game, and movie vendors here.

The first (mezzanine) floor is home to the large Data IT shop -- you’ll see its prominent yellow sign -- which offers a wide variety of legitimate, brand-name electronics.

The second floor has a handful of vendors selling various pirated software, movies, and porn CDs. The touts offering “sexy movies” can be somewhat aggressive.

The third floor has computer and camera shops, as well as hardware like external hard drives, CPUs, and RAM for sale. Some shops specialize in assembling computers from parts you pick out. The fourth floor has yet more computers and repair shops.

There’s just one shop on the 5th floor: IT City, which has more expensive goods like brand name computers, printers, headphones and hard drives. This can be a good place to shop if you want to find a wide variety of items in one store.

2. There’s good grub

The front of the building -- where taxis, motorbikes and buses sit and spew exhaust -- might not offer a particularly welcoming atmosphere, but you’ll find fruit, grilled meat, iced coffee and more.

Inside, avoid Pantip's acronym-heavy franchises -- -- S&P, KFC and A&W -- and head up to the second floor. There's a food court with typical Thai dishes, as well as a relative rarity in Bangkok: a decent khao soi vendor. Chiang Mai’s signature noodle dish is pretty good here, considering that tasty bowls of khao sois are so hard to find away from the north.

Unless you’re an especially adventurous eater, stay clear of the Crepes by Boss offerings, which feature combinations like banana and shredded pork crepes, tuna and ham.

3. Beer drinking is encouraged

If you’re in the mood for some suds, order a Heineken or Singha at the small stall in the food court serving drinks.

Reports suggest that well after closing, the steps of Pantip are also a popular place for local folks to linger, drink and snack.

4. Pantip is Apple friendly

There’s a common misperception that iPhones and iPads can only be purchased at Bangkok’s high-end shopping malls like Emporium and Paragon. But there’s actually an iStudio and an iShop on Pantip’s third floor, as well as official Apple service center on the fourth floor.

5. There isn’t just one Pantip Plaza

There are also Pantips in Chiang Mai, Nonthaburi, and Bangkapi. Full details on shops, hours and locations on the official Pantip website.

6. The best time to go is midday

Pantip’s official hours are 10 a. m. to 9 p. m. but some shops open later in the morning, while others close as evening approaches, as early as 6 p. m.

7. It’s official: Pantip is a “notorious market”

Many of the pirated goods available in Pantip are the intellectual property of U. S. film studios and software companies. So I asked Walter Braunohler, spokesperson at the U. S. embassy in Bangkok, if the U. S. government has an official policy on Pantip.

The United States “respects intellectual property rights and encourages all nations to do so,” he said. Braunohler pointed out an April, 2010 report from the Office of the U. S. Trade Representative, that -- unsurprisingly -- classes Pantip Plaza as a “notorious market,” along with other international markets, for “openly selling pirated and counterfeit goods.”

The report notes, however, that Thai authorities have targeted Pantip for “increased raids.”

8. Pantip is featured in the chorus of a popular Thai rock song

Several years ago, Thai band Loso -- as in, the opposite of “high so,” or “high society” -- recorded a popular tune called “Pantip.” In the chorus, the singer says he’ll go shopping with his girlfriend anywhere in Bangkok -- except Pantip, since an ex-girlfriend works there.

Check out the video by clicking here. An English translation of the lyrics can be found at www. ethaimusic. com .

Getting there: Pantip Plaza is at 604/3 Petchaburi Road. The closest BTS station is Ratchatewi.

Newley Purnell is a freelance journalist in Bangkok. His work has appeared in the New York Times, on AFP, ABC News Radio, ABCNews. com, Travel + Leisure Southeast Asia, and more. He has been blogging at http://newley. com since 2002.

Oxibutinina Medlineplus Medicinas, Reteven

Oxibutinina

?Para cuales condiciones o enfermedades se prescribe este medicamento?

La oxibutinina se utiliza para tratar la vejiga hiperactiva (una condicion en la que los musculos de la vejiga se contraen sin control y causan miccion frecuente, necesidad urgente de orinar e incapacidad de controlar la miccion) para controlar la miccion urgente, frecuente o sin control en personas que tienen vejiga hiperactiva (una condicion en la que los musculos de la vejiga tienen espasmos sin control). La oxibutinina tambien se usa para controlar los musculos de la vejiga en adultos y ninos mayores de 6 anos de edad con espina bifida (una discapacidad que ocurre cuando la medula espinal no se cierra adecuadamente antes de nacer) u otras condiciones del sistema nervioso que afectan los musculos de la vejiga. La oxibutinina es una clase de medicamentos llamados anticolinergicos/antimuscarinicos. Funciona relajando los musculos de la vejiga.

?Como se debe usar este medicamento?

La oxibutinina viene como tableta, un jarabe y una tableta de liberacion prolongada (accion prolongada) para tomar por via oral. Las tabletas y jarabe usualmente se toman de dos a cuatro veces al dia. Usualmente la tableta de liberacion prolongada se toma una vez al dia, con o sin alimentos. Tome la oxibutinina aproximadamente a la misma hora todos los dias. Siga cuidadosamente las instrucciones que se encuentran en la etiqueta de su receta medica y pida a su medico u otro proveedor de atencion medica que le explique cualquier parte que no comprenda. Tome la oxibutinina exactamente como se indica. No tome mas ni menos cantidad del medicamento ni lo tome con mas frecuencia de lo que indica la receta de su medico.

Trague las tabletas de liberacion prolongada enteras con abundante agua u otro liquido. No parta, mastique ni triture las tabletas de liberacion prolongada. Informe a su medico si no puede tragar las tabletas.

Utilice una cuchara o taza para medir la dosis de liquido en la cantidad correcta para cada dosis, no use una cuchara casera.

Es posible que su medico le indique que inicie con una dosis baja de oxibutinina y que incremente gradualmente su dosis, no mas de una vez a la semana.

La oxibutinina puede controlar sus sintomas, pero no curara su condicion. Continue tomando oxibutinina aunque se sienta bien. No deje de tomar la oxibutinina sin hablar con su medico.

Puede observar alguna mejora en sus sintomas en las primeras 2 semanas de su tratamiento. Sin embargo, puede tomar de 6 a 8 semanas para que sienta el beneficio completo de la oxibutinina. Hable con su medico si despues 8 semanas no mejoran sus sintomas.

?Que otro uso se le da a este medicamento?

Este medicamento algunas veces se receta para otros usos; pida mas informacion a su medico o farmaceutico.

?Cuales son las precauciones especiales que debo seguir?

Antes de tomar oxibutinina,

indique a su medico y farmaceuta si es alergico a la oxibutinina o a cualquier otro medicamento o a cualquier ingrediente que contienen las tabletas, tabletas de liberacion prolongada o jarabe de oxibutinina. Pida a su medico o farmaceutico una lista de los ingredientes.

Informe a su medico y farmaceutico que medicamentos con y sin receta medica, vitaminas, suplementos nutricionales y productos de hierbas esta tomando o tiene planificado tomar. Asegurese de mencionar cualquiera de los siguientes: amiodarona (Cordarone, Pacerone), ciertos antibioticos como claritromicina (Biaxin), eritromicina (E. E.S, E-Mycin, Erythrocin) y tetraciclina (Bristamycin, Sumycin, Tetrex), ciertos antimicoticos como itraconazol (Sporanox),miconazol (Monistat) y ketoconazol (Nizoral), antihistaminicos; aspirina y otros medicamentos antiinflamatorios no esteroides (AINE) como ibuprofeno (Advil, Motrin) y naproxeno (Aleve, Naprosyn, otros), cimetidina (Tagamet), diltiazem (Cardizem, Dilacor, Tiazac), fluvoxamina, ipratropio (Atrovent), suplementos de hierro; ciertos medicamentos para la infeccion del virus de inmunodeficiencia humana (VIH), como indinavir (Crixivan), nelfinavir (Viracept) y ritonavir (Norvir, en Kaletra), medicamentos para la enfermedad de intestino irritable, mareo por el movimiento, enfermedad de Parkinson, ulceras o problemas urinarios, medicamentos para osteoporosis (una condicion en la que los huesos son debiles, fragiles y pueden romperse con facilidad) como alendronato (Fosamax), ibandronato (Boniva) y risedronato (Actonel), nefazodona; suplementos de potasio, quinidina y verapamilo (Calan, Covera, Tarka, Verelan). Es posible que su medico deba cambiar las dosis de sus medicamentos o supervisarle cuidadosamente para ver si sufre efectos secundarios.

Informe a su medico si tiene o ha tenido glaucoma de angulo estrecho (una condicion grave de los ojos que puede provocar perdida de la vista), cualquier condicion que impida que su vejiga se vacie completamente o cualquier condicion que ocasiona que su estomago se evacue lenta o incompletamente. Su medico podria indicarle que no tome oxibutinina.

informe a su medico si tiene o ha tenido la colitis ulcerosa (un trastorno que causa inflamacion y ulceras en el revestimiento del colon [intestino grueso] y el recto), enfermedad de reflejo gastroesofagico (GERD, condicion en la que el contenido del estomago regresa al esofago y puede ocasionar dolor y acidez), hernia hiatal (condicion en la que una parte de la pared del estomago se inflama hacia afuera y puede ocasionar dolor y acidez), hipertiroidismo (condicion en la cual hay demasiada hormona tiroidea en el cuerpo); miastenia gravis (un trastorno del sistema nervioso que ocasiona debilidad muscular), ritmo cardiaco irregular o rapido, hipertension arterial; hipertrofia prostatica benigna (BPH, agrandamiento de la prostata, un organo reproductivo masculino) o enfermedad del corazon, hepatica o renal.

Informe a su medico si esta embarazada, si planea quedar embarazada o esta amamantando. Si queda embarazada mientras toma oxibutinina, llame a su medico.

Hable con su medico sobre los riesgos y beneficios de tomar tabletas o jarabe de oxibutinina si es mayor de 65 anos de edad. Los adultos mayores usualmente no deberan tomar tabletas o jarabe de oxibutinina debido a que no son seguros y puede ser que no sean tan efectivos como otros medicamentos que se pueden usar para tratar la misma condicion.

Si va a someterse a una cirugia, incluso una cirugia dental, informe a su medico o dentista que esta tomando oxibutinina.

Debe saber que este medicamento le puede ocasionar somnolencia o vision borrosa. No conduzca un vehiculo ni opere maquinaria hasta que sepa como le afecta este medicamento.

Consulte a su medico sobre el consumo seguro de bebidas alcoholicas mientras toma este medicamento. El alcohol puede empeorar los efectos secundarios de la oxibutinina.

Debe saber que la oxibutinina puede dificultar la capacidad de su cuerpo de enfriarse cuando hay mucho calor. Evite la exposicion a calor extremo y llame a su medico u obtenga tratamiento medico de emergencia si tiene fiebre u otros signos de insolacion como mareos, nausea, dolor de cabeza, confusion y pulso rapido despues de estar expuesto al calor.

?Que dieta especial debo seguir mientras tomo este medicamento?

Hable con su medico sobre comer toronja y tomar jugo de toronja mientras toma este medicamento.

?Que tengo que hacer si me olvido de tomar una dosis?

Si toma tabletas o jarabe, tome la dosis que omitio tan pronto como lo recuerde. Sin embargo, si ya casi es hora de la proxima dosis, omita la dosis y continue con su dosificacion regular. No duplique la dosis para compensar la dosis omitida.

Si toma tabletas de liberacion prolongada y recuerda mas de 8 horas antes de que sea la hora de la siguiente dosis, tome la dosis que omitio de inmediato. Sin embargo, si su proxima dosis es en menos de 8 horas, omita la dosis que omitio y continue con su horario de dosificacion regular. No duplique la dosis para compensar la dosis omitida.

?Cuales son los efectos secundarios que podria provocar este medicamento?

La oxibutinina puede ocasionar efectos secundarios. Informe a su medico si cualquiera de estos sintomas es grave o no desaparece:

boca seca

vision borrosa

ojos, nariz o piel seca

dolor de estomago

estrenimiento

diarrea

nausea

acidez

flatulencia

cambio en la capacidad para saborear los alimentos

dolor de cabeza

mareos

debilidad

confusion

somnolencia

dificultad para conciliar el sueno o para mantenerse dormido

nerviosismo

rubor

inflamacion de las manos, brazos, pies, tobillos o parte inferior de las piernas

dolor de espalda o de las articulaciones

Algunos efectos secundarios pueden ser graves. Si experimenta algunos de los siguientes sintomas, llame a su medico inmediatamente o busque tratamiento medico de emergencia:

sarpullido

urticaria

inflamacion de los ojos, el rostro, los labios, la lengua o la garganta

ronquera

dificultad para respirar o tragar

miccion frecuente, urgente o dolorosa

ritmo cardiaco rapido, irregular o fuerte

Si desarrolla un efecto secundario grave, usted o su doctor puede enviar un informe al programa de divulgacion de efectos adversos 'MedWatch' de la Administracion de Alimentos y Medicamentos (FDA, por su sigla en ingles) en la pagina de Internet (http://www. fda. gov/Safety/MedWatch ) o por telefono al 1-800-332-1088.

La oxibutinina puede ocasionar otros efectos secundarios. Llame a su medico si tiene cualquier problema inusual mientras toma este medicamento.

?Como debo almacenar o desechar este medicamento?

Mantenga este medicamento en su envase original, cerrado hermeticamente y fuera del alcance de los ninos. Almacenelo a temperatura ambiente y lejos del exceso de calor y humedad (no en el bano). Deseche cualquier medicamento que este vencido o que ya no necesite. Hable con el farmaceutico sobre la forma adecuada para desechar el medicamento.

?Que debo hacer en caso de una sobredosis?

En caso de una sobredosis, llame a la oficina local de control de envenenamiento al 1-800-222-1222. Si la victima esta inconsciente, o no respira, llame inmediatamente al 911.

Los sintomas de sobredosis pueden incluir los siguientes:

agitacion

temblor incontrolable de una parte del cuerpo

irritabilidad

convulsiones

confusion

alucinaciones (ver cosas o escuchar voces que no existen)

rubor

fiebre

ritmo cardiaco irregular

vomitos

dificultad para orinar

dificultad para respirar o respiracion lenta

incapacidad para movilizarse

coma (perdida del conocimiento por un periodo de tiempo)

perdida de la memoria

agitacion

pupilas dilatadas (circulos negros en el centro de los ojos)

piel seca

?Que otra informacion de importancia deberia saber?

Asista a todas las citas con su medico.

No deje que nadie mas tome su medicamento. Haga a su farmaceutico cualquier pregunta que tenga sobre como volver a surtir su receta medica.

Si toma tabletas de liberacion prolongada, puede observar algo que parece una tableta en sus heces. Esto es simplemente la cubierta de la tableta vacia y no significa que no obtuvo su dosis completa de medicamento.

Es importante que Ud. mantenga una lista escrita de todas las medicinas que Ud. esta tomando, incluyendo las que recibio con receta medica y las que Ud. compro sin receta, incluyendo vitaminas y suplementos de dieta. Ud. debe tener la lista cada vez que visita su medico o cuando es admitido a un hospital. Tambien es una informacion importante en casos de emergencia.

Marcas comerciales

Ceftin - Fda Prescribing Information, Side Effects And Uses, Cefadin

Ceftin

Pharyngitis/Tonsillitis

Ceftin ® tablets are indicated for the treatment of adult patients and pediatric patients (13 years and older) with mild-to-moderate pharyngitis/tonsillitis caused by susceptible strains of Streptococcus pyogenes .

Ceftin for oral suspension is indicated for the treatment of pediatric patients aged 3 months to 12 years with mild-to-moderate pharyngitis/tonsillitis caused by susceptible strains of Streptococcus pyogenes .

Limitations of Use

• The efficacy of Ceftin in the prevention of rheumatic fever was not established in clinical trials. • The efficacy of Ceftin in the treatment of penicillin‑resistant strains of Streptococcus pyogenes has not been demonstrated in clinical trials.

Acute Bacterial Otitis Media

Ceftin tablets are indicated for the treatment of pediatric patients (who can swallow tablets whole) with acute bacterial otitis media caused by susceptible strains of Streptococcus pneumoniae. Haemophilus influenzae (including β - lactamase–producing strains), Moraxella catarrhalis (including β - lactamase–producing strains), or Streptococcus pyogenes.

Ceftin for oral suspension is indicated for the treatment of pediatric patients aged 3 months to 12 years with acute bacterial otitis media caused by susceptible strains of Streptococcus pneumoniae. Haemophilus influenzae (including β - lactamase–producing strains), Moraxella catarrhalis (including β - lactamase–producing strains), or Streptococcus pyogenes.

Acute Bacterial Maxillary Sinusitis

Ceftin tablets are indicated for the treatment of adult and pediatric patients (13 years and older) with mild-to-moderate acute bacterial maxillary sinusitis caused by susceptible strains of Streptococcus pneumoniae or Haemophilus influenzae (non - β‑lactamase–producing strains only).

Ceftin for oral suspension is indicated for the treatment of pediatric patients aged 3 months to 12 years with mild-to-moderate acute bacterial maxillary sinusitis caused by susceptible strains of Streptococcus pneumoniae or Haemophilus influenzae (non - β‑lactamase–producing strains only).

Limitations of Use

The effectiveness of Ceftin for sinus infections caused by β-lactamase–producing Haemophilus influenzae or Moraxella catarrhalis in patients with acute bacterial maxillary sinusitis was not established due to insufficient numbers of these isolates in the clinical trials [see Clinical Studies (14.1)].

Acute Bacterial Exacerbations of Chronic Bronchitis and Secondary Bacterial Infections of Acute Bronchitis

Ceftin tablets are indicated for the treatment of adult patients and pediatric patients (aged 13 and older) with mild-to-moderate acute bacterial exacerbations of chronic bronchitis and secondary bacterial infections of acute bronchitis caused by susceptible strains of Streptococcus pneumoniae. Haemophilus influenzae (β‑lactamase–negative strains), or Haemophilus parainfluenzae (β‑lactamase–negative strains).

Uncomplicated Skin and Skin‑structure Infections

Ceftin tablets are indicated for the treatment of adult patients and pediatric patients (aged 13 and older) with uncomplicated skin and skin-structure infections caused by susceptible strains of Staphylococcus aureus (including β-lactamase–producing strains) or Streptococcus pyogenes.

Uncomplicated Urinary Tract Infections

Ceftin tablets are indicated for the treatment of adult patients and pediatric patients (aged 13 and older) with uncomplicated urinary tract infections caused by susceptible strains of Escherichia coli or Klebsiella pneumoniae .

Uncomplicated Gonorrhea

Ceftin tablets are indicated for the treatment of adult patients and pediatric patients (aged 13 and older) with uncomplicated gonorrhea, urethral and endocervical, caused by penicillinase-producing and non‑penicillinase–producing susceptible strains of Neisseria gonorrhoeae and uncomplicated gonorrhea, rectal, in females, caused by non‑penicillinase–producing susceptible strains of Neisseria gonorrhoeae .

Early Lyme Disease (erythema migrans)

Ceftin tablets are indicated for the treatment of adult patients and pediatric patients (aged 13 and older) with early Lyme disease (erythema migrans) caused by susceptible strains of Borrelia burgdorferi .

Impetigo

Ceftin for oral suspension is indicated for the treatment of pediatric patients aged 3 months to 12 years with impetigo caused by susceptible strains of Staphylococcus aureus (including β - lactamase–producing strains) or Streptococcus pyogenes .

Usage

To reduce the development of drug‑resistant bacteria and maintain the effectiveness of Ceftin and other antibacterial drugs, Ceftin should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

Ceftin Dosage and Administration

Important Administration Instructions

• Ceftin tablets and Ceftin for oral suspension are not bioequivalent and are therefore not substitutable on a milligram-per-milligram basis [see Clinical Pharmacology (12.3)]. • Administer Ceftin tablets or oral suspension as described in the appropriate dosage guidelines [see Dosage and Administration (2.2, 2.3, 2.4)]. • Administer Ceftin tablets with or without food. • Administer Ceftin for oral suspension with food. • Pediatric patients (aged 13 years and older) who cannot swallow the Ceftin tablets whole should receive Ceftin for oral suspension because the tablet has a strong, persistent bitter taste when crushed [see Dosage and Administration (2.2)].

Dosage for Ceftin Tablets

Administer Ceftin tablets as described in the dosage guidelines table below with or without food.

Table 1. Adult Patients and Pediatric Patients Dosage Guidelines for Ceftin Tablets

a Recommended daily dose given twice daily divided in equal doses

Preparation and Administration of Ceftin for Oral Suspension

Prepare a suspension at the time of dispensing as follows:

1. Shake the bottle to loosen the powder. 2. Remove the cap. 3. Add the total amount of water for reconstitution (Table 3) and replace the cap. 4. Invert the bottle and vigorously rock the bottle from side to side so that water rises through the powder. 5. Once the sound of the powder against the bottle disappears, turn the bottle upright and vigorously shake it in a diagonal direction.

Table 3. Amount of Water Required for Reconstitution of Labeled Volumes of Ceftin for Oral Suspension

Amount of Water Required for Reconstitution

• Shake the oral suspension well before each use. • Replace cap securely after each opening. • Store the reconstituted suspension refrigerated between 2° and 8°C (36° and 46°F). • Discard the reconstituted suspension after 10 days.

Dosage in Patients with Impaired Renal Function

A dosage interval adjustment is required for patients whose creatinine clearance is <30 mL/min, as listed in Table 4 below, because cefuroxime is eliminated primarily by the kidney [see Clinical Pharmacology (12.3)].

Table 4. Dosing in Adults with Renal Impairment

Creatinine Clearance (mL/min)

No dosage adjustment

Standard individual dose given every 24 hours

˂10 (without hemodialysis)

Standard individual dose given every 48 hours

A single additional standard dose should be given at the end of each dialysis

Dosage Forms and Strengths

Ceftin tablets are white, capsule‑shaped, film‑coated tablets available in the following strengths:

• 250 mg of cefuroxime (as cefuroxime axetil) with "GX ES7" engraved on one side and blank on the other side. • 500 mg of cefuroxime (as cefuroxime axetil) with "GX EG2" engraved on one side and blank on the other side.

Ceftin for oral suspension is provided as dry, white to off‑white, tutti‑frutti–flavored powder. When reconstituted as directed, the suspension provides the equivalent of 125 mg or 250 mg of cefuroxime (as cefuroxime axetil) per 5 mL.

Contraindications

Ceftin is contraindicated in patients with a known hypersensitivity (e. g. anaphylaxis) to Ceftin or to other β-lactam antibacterial drugs (e. g. penicillins and cephalosporins).

Warnings and Precautions

Anaphylactic Reactions

Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients on β-lactam antibacterials. These reactions are more likely to occur in individuals with a history of β-lactam hypersensitivity and/or a history of sensitivity to multiple allergens. There have been reports of individuals with a history of penicillin hypersensitivity who have experienced severe reactions when treated with cephalosporins. Ceftin is contraindicated in patients with a known hypersensitivity to Ceftin or other β-lactam antibacterial drugs [see Contraindications (4)]. Before initiating therapy with Ceftin, inquire about previous hypersensitivity reactions to penicillins, cephalosporins, or other allergens. If an allergic reaction occurs, discontinue Ceftin and institute appropriate therapy.

Clostridium difficile - associated Diarrhea

Clostridium difficile - associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including Ceftin, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile .

C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin-producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over 2 months after the administration of antibacterial agents.

If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile. and surgical evaluation should be instituted as clinically indicated.

Potential for Microbial Overgrowth

The possibility of superinfections with fungal or bacterial pathogens should be considered during therapy.

Development of Drug-resistant Bacteria

Prescribing Ceftin either in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug‑resistant bacteria.

Phenylketonuria

Ceftin for oral suspension 125 mg/5 mL contains phenylalanine 11.8 mg per 5 mL (1 teaspoonful) of reconstituted suspension. Ceftin for oral suspension 250 mg/5 mL contains phenylalanine 25.2 mg per 5 mL (1 teaspoonful) of reconstituted suspension.

Interference with Glucose Tests

A false-positive result for glucose in the urine may occur with copper reduction tests, and a false-negative result for blood/plasma glucose may occur with ferricyanide tests in subjects receiving Ceftin [see Drug Interactions (7.4)] .

Adverse Reactions

The following serious and otherwise important adverse reaction is described in greater detail in the Warnings and Precautions section of the label:

Anaphylactic Reactions [see Warnings and Precautions [5.1)]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Multiple ‑ dose Dosing Regimens with 7 to 10 Days’ Duration: In multiple-dose clinical trials, 912 subjects were treated with Ceftin (125 to 500 mg twice daily). It is noted that 125 mg twice daily is not an approved dosage. Twenty (2.2%) subjects discontinued medication due to adverse reactions. Seventeen (85%) of the 20 subjects who discontinued therapy did so because of gastrointestinal disturbances, including diarrhea, nausea, vomiting, and abdominal pain. The percentage of subjects treated with Ceftin who discontinued study drug because of adverse reactions was similar at daily doses of 1,000, 500, and 250 mg (2.3%, 2.1%, and 2.2%, respectively). However, the incidence of gastrointestinal adverse reactions increased with the higher recommended doses.

The adverse reactions in Table 5 are for subjects (n = 912) treated with Ceftin in multiple‑dose clinical trials.

Table 5. Adverse Reactions (≥1%) after Multiple‑dose Regimens with Ceftin Tablets

The following adverse reactions occurred in less than 1% but greater than 0.1% of subjects (n = 912) treated with Ceftin in multiple-dose clinical trials.

Immune System Disorders: Hives, swollen tongue. Metabolism and Nutrition Disorders: Anorexia. Nervous System Disorders: Headache. Cardiac Disorders: Chest pain. Respiratory Disorders: Shortness of breath. Gastrointestinal Disorders: Abdominal pain, abdominal cramps, flatulence, indigestion, mouth ulcers. Skin and Subcutaneous Tissue Disorders: Rash, itch. Renal and Urinary Disorders: Dysuria. Reproductive System and Breast Disorders: Vaginitis, vulvar itch. General Disorders and Administration Site Conditions: Chills, sleepiness, thirst. Investigations: Positive Coombs’ test.

5-Day Regimen: In clinical trials using Ceftin 250 mg twice daily in the treatment of secondary bacterial infections of acute bronchitis, 399 subjects were treated for 5 days and 402 subjects were treated for 10 days. No difference in the occurrence of adverse reactions was found between the 2 regimens.

Early Lyme Disease with 20-Day Regimen: Two multicenter trials assessed Ceftin 500 mg twice daily for 20 days. The most common drug‑related adverse experiences were diarrhea (10.6%), Jarisch‑Herxheimer reaction (5.6%), and vaginitis (5.4%). Other adverse experiences occurred with frequencies comparable to those reported with 7 to 10 days’ dosing.

Single ‑ dose Regimen for Uncomplicated Gonorrhea: In clinical trials using a single 1,000-mg dose of Ceftin, 1,061 subjects were treated for uncomplicated gonorrhea.

The adverse reactions in Table 6 were for subjects treated with a single dose of 1,000 mg Ceftin in US clinical trials.

Table 6. Adverse Reactions (≥1%) after Single‑dose Regimen with 1,000-mg Ceftin Tablets for Uncomplicated Gonorrhea

The following adverse reactions occurred in less than 1% but greater than 0.1% of subjects (n = 1,061) treated with a single dose of Ceftin 1,000 mg for uncomplicated gonorrhea in US clinical trials.

Infections and Infestations: Vaginal candidiasis. Nervous System Disorders: Headache, dizziness, somnolence. Cardiac Disorders: Tightness/pain in chest, tachycardia. Gastrointestinal Disorders: Abdominal pain, dyspepsia. Skin and Subcutaneous Tissue Disorders: Erythema, rash, pruritus. Musculoskeletal and Connective Tissue Disorders: Muscle cramps, muscle stiffness, muscle spasm of neck, lockjaw-type reaction. Renal and Urinary Disorders: Bleeding/pain in urethra, kidney pain. Reproductive System and Breast Disorders: Vaginal itch, vaginal discharge.

In clinical trials using multiple doses of Ceftin, pediatric subjects (96.7% were younger than 12 years) were treated with Ceftin (20 to 30 mg/kg/day divided twice daily up to a maximum dose of 500 or 1,000 mg/day, respectively). Eleven (1.2%) US subjects discontinued medication due to adverse reactions. The discontinuations were primarily for gastrointestinal disturbances, usually diarrhea or vomiting. Thirteen (1.4%) US pediatric subjects discontinued therapy due to the taste and/or problems with drug administration.

The adverse reactions in Table 7 are for US subjects (n = 931) treated with Ceftin in multiple‑dose clinical trials.

Table 7. Adverse Reactions (≥1%) after Multiple‑dose Regimens with Ceftin for Oral Suspension

Dislike of taste

Skin and subcutaneous tissue disorders

The following adverse reactions occurred in less than 1% but greater than 0.1% of US subjects (n = 931) treated with Ceftin for oral suspension in multiple‑dose clinical trials.

Infections and Infestations: Gastrointestinal infection, candidiasis, viral illness, upper respiratory infection, sinusitis, urinary tract infection.

Blood and Lymphatic System Disorders: Eosinophilia.

Psychiatric Disorders: Hyperactivity, irritable behavior.

Gastrointestinal Disorders: Abdominal pain, flatulence, ptyalism.

Skin and Subcutaneous Tissue Disorders: Rash.

Musculoskeletal and Connective Tissue Disorders: Joint swelling, arthralgia.

Reproductive System and Breast Disorders: Vaginal irritation.

General Disorders and Administration Site Conditions: Cough, fever.

Investigations: Elevated liver enzymes, positive Coombs’ test.

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of Ceftin. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Blood and Lymphatic System Disorders

Hemolytic anemia, leukopenia, pancytopenia, thrombocytopenia.

Pseudomembranous colitis [see Warnings and Precautions (5.2)] .

Hepatic impairment including hepatitis and cholestasis, jaundice.

Immune System Disorders

Anaphylaxis, serum sickness‑like reaction.

Increased prothrombin time.

Nervous System Disorders

Renal and Urinary Disorders

Skin and Subcutaneous Tissue Disorders

Angioedema, erythema multiforme, Stevens‑Johnson syndrome, toxic epidermal necrolysis, urticaria.

Drug Interactions

Oral Contraceptives

Cefuroxime axetil may affect the gut flora, leading to lower estrogen reabsorption and reduced efficacy of combined oral estrogen/progesterone contraceptives. Counsel patients to consider alternate supplementary (non-hormonal) contraceptive measures during treatment.

Drugs that Reduce Gastric Acidity

Drugs that reduce gastric acidity may result in a lower bioavailability of Ceftin compared with administration in the fasting state. Administration of drugs that reduce gastric acidity may negate the food effect of increased absorption of Ceftin when administered in the postprandial state. Administer Ceftin at least 1 hour before or 2 hours after administration of short-acting antacids. Histamine-2 (H 2 ) antagonists and proton pump inhibitors should be avoided.

Probenecid

Concomitant administration of probenecid with cefuroxime axetil tablets increases serum concentrations of cefuroxime [see Clinical Pharmacology (12.3)]. Co-administration of probenecid with cefuroxime axetil is not recommended.

Drug/Laboratory Test Interactions

A false‑positive reaction for glucose in the urine may occur with copper reduction tests (e. g. Benedict's or Fehling's solution), but not with enzyme‑based tests for glycosuria. As a false‑negative result may occur in the ferricyanide test, it is recommended that either the glucose oxidase or hexokinase method be used to determine blood/plasma glucose levels in patients receiving cefuroxime axetil. The presence of cefuroxime does not interfere with the assay of serum and urine creatinine by the alkaline picrate method.

USE IN SPECIFIC POPULATIONS

Pregnancy

Pregnancy Category B. There are no adequate and well‑controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, Ceftin should be used during pregnancy only if clearly needed.

Reproduction studies have been performed in mice at doses up to 3,200 mg/kg/day (14 times the recommended maximum human dose based on body surface area) and in rats at doses up to 1,000 mg/kg/day (9 times the recommended maximum human dose based on body surface area) and have revealed no evidence of impaired fertility or harm to the fetus due to cefuroxime axetil.

Nursing Mothers

Because cefuroxime is excreted in human milk, caution should be exercised when Ceftin is administered to a nursing woman.

Pediatric Use

The safety and effectiveness of Ceftin have been established for pediatric patients aged 3 months to 12 years for acute bacterial maxillary sinusitis based upon its approval in adults. Use of Ceftin in pediatric patients is supported by pharmacokinetic and safety data in adults and pediatric patients, and by clinical and microbiological data from adequate and well‑controlled trials of the treatment of acute bacterial maxillary sinusitis in adults and of acute otitis media with effusion in pediatric patients. It is also supported by postmarketing adverse events surveillance. [See Indications and Usage (1), Dosage and Administration (2), Adverse Reactions (6), Clinical Pharmacology (12.3).]

Geriatric Use

Of the total number of subjects who received Ceftin in 20 clinical trials, 375 were aged 65 and older while 151 were aged 75 and older. No overall differences in safety or effectiveness were observed between these subjects and younger adult subjects. Reported clinical experience has not identified differences in responses between the elderly and younger adult patients, but greater sensitivity of some older individuals cannot be ruled out.

Cefuroxime is substantially excreted by the kidney, and the risk of adverse reactions may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

Renal Impairment

Reducing the dosage of Ceftin is recommended for adult patients with severe renal impairment (creatinine clearance <30 mL/min) [see Dosage and Administration (2.5), Clinical Pharmacology (12.3)] .

Overdosage

Overdosage of cephalosporins can cause cerebral irritation leading to convulsions or encephalopathy. Serum levels of cefuroxime can be reduced by hemodialysis and peritoneal dialysis.

Ceftin Description

Ceftin tablets and Ceftin for oral suspension contain cefuroxime as cefuroxime axetil. Ceftin is a semisynthetic, cephalosporin antibacterial drug for oral administration.

The chemical name of cefuroxime axetil (1‑(acetyloxy) ethyl ester of cefuroxime) is ( RS )-1-hydroxyethyl (6 R ,7 R ) - 7 - [2 - (2 - furyl)glyoxyl - amido] - 3 - (hydroxymethyl) - 8 - oxo - 5 - thia - 1 - azabicyclo[4.2.0] - oct - 2 - ene - 2 - carboxylate, 7 2 -( Z )-( O - methyl-oxime), 1-acetate 3-carbamate. Its molecular formula is C 20 H 22 N 4 O 10 S, and it has a molecular weight of 510.48.

Cefuroxime axetil is in the amorphous form and has the following structural formula:

Tablets are film‑coated and contain the equivalent of 250 or 500 mg of cefuroxime as cefuroxime axetil. Tablets contain the inactive ingredients colloidal silicon dioxide, croscarmellose sodium, hydrogenated vegetable oil, hypromellose, methylparaben, microcrystalline cellulose, propylene glycol, propylparaben, sodium benzoate, sodium lauryl sulfate, and titanium dioxide.

Oral suspension, when reconstituted with water, provides the equivalent of 125 mg or 250 mg of cefuroxime (as cefuroxime axetil) per 5 mL. Oral suspension contains the inactive ingredients acesulfame potassium, aspartame, povidone K30, stearic acid, sucrose, tutti‑frutti flavoring, and xanthan gum.

Ceftin - Clinical Pharmacology

Mechanism of Action

Ceftin is an antibacterial drug [see Clinical Pharmacology (12.4)].

Pharmacokinetics

After oral administration, cefuroxime axetil is absorbed from the gastrointestinal tract and rapidly hydrolyzed by nonspecific esterases in the intestinal mucosa and blood to cefuroxime. Serum pharmacokinetic parameters for cefuroxime following administration of Ceftin tablets to adults are shown in Table 8.

Table 8. Pharmacokinetics of Cefuroxime Administered in the Postprandial State as Ceftin Tablets to Adults a

a Mean values of 12 healthy adult volunteers.

b Drug administered immediately after a meal.

Food Effect: Absorption of the tablet is greater when taken after food (absolute bioavailability increases from 37% to 52%). Despite this difference in absorption, the clinical and bacteriologic responses of subjects were independent of food intake at the time of tablet administration in 2 trials where this was assessed.

All pharmacokinetic and clinical effectiveness and safety trials in pediatric subjects using the suspension formulation were conducted in the fed state. No data are available on the absorption kinetics of the suspension formulation when administered to fasted pediatric subjects.

Lack of Bioequivalence: Oral suspension was not bioequivalent to tablets when tested in healthy adults. The tablet and oral suspension formulations are NOT substitutable on a milligram-per-milligram basis. The area under the curve for the suspension averaged 91% of that for the tablet, and the peak plasma concentration for the suspension averaged 71% of the peak plasma concentration of the tablets. Therefore, the safety and effectiveness of both the tablet and oral suspension formulations were established in separate clinical trials.

Cefuroxime is distributed throughout the extracellular fluids. Approximately 50% of serum cefuroxime is bound to protein.

The axetil moiety is metabolized to acetaldehyde and acetic acid.

Cefuroxime is excreted unchanged in the urine; in adults, approximately 50% of the administered dose is recovered in the urine within 12 hours. The pharmacokinetics of cefuroxime in pediatric subjects have not been studied. Until further data are available, the renal elimination of cefuroxime axetil established in adults should not be extrapolated to pediatric subjects.

Renal Impairment: In a trial of 28 adults with normal renal function or severe renal impairment (creatinine clearance <30 mL/min), the elimination half-life was prolonged in relation to severity of renal impairment. Prolongation of the dosage interval is recommended in adult patients with creatinine clearance <30 mL/min [see Dosage and Administration (2.5)] .

Pediatric Patients: Serum pharmacokinetic parameters for cefuroxime in pediatric subjects administered Ceftin for oral suspension are shown in Table 9.

Table 9. Pharmacokinetics of Cefuroxime Administered in the Postprandial State as Ceftin for Oral Suspension to Pediatric Subjects a

a Mean age = 23 months.

b Drug administered with milk or milk products.

Geriatric Patients: In a trial of 20 elderly subjects (mean age = 83.9 years) having a mean creatinine clearance of 34.9 mL/min, the mean serum elimination half‑life was prolonged to 3.5 hours; however, despite the lower elimination of cefuroxime in geriatric patients, dosage adjustment based on age is not necessary [see Use in Specific Populations (8.5)] .

Concomitant administration of probenecid with cefuroxime axetil tablets increases the cefuroxime area under the serum concentration versus time curve and maximum serum concentration by 50% and 21%, respectively.

Microbiology

Mechanism of Action

Cefuroxime axetil is a bactericidal agent that acts by inhibition of bacterial cell wall synthesis. Cefuroxime axetil has activity in the presence of some β-lactamases, both penicillinases and cephalosporinases, of gram-negative and gram-positive bacteria.

Mechanism of Resistance

Resistance to cefuroxime axetil is primarily through hydrolysis by β-lactamase, alteration of penicillin-binding proteins (PBPs), decreased permeability, and the presence of bacterial efflux pumps.

Susceptibility to cefuroxime axetil will vary with geography and time; local susceptibility data should be consulted, if available. Beta-lactamase‑negative, ampicillin-resistant (BLNAR) isolates of H. influenzae should be considered resistant to cefuroxime axetil.

Cefuroxime axetil has been shown to be active against most isolates of the following bacteria, both in vitro and in clinical infections [see Indications and Usage (1)] :

• Gram‑positive bacteria Staphylococcus aureus (methicillin-susceptible isolates only) Streptococcus pneumoniae Streptococcus pyogenes • Gram‑negative bacteria Escherichia coli a Klebsiella pneumoniae a Haemophilus influenzae Haemophilus parainfluenzae Moraxella catarrhalis Neisseria gonorrhoeae a Most extended spectrum β-lactamase (ESBL)‑ producing and carbapenemase-producing isolates are resistant to cefuroxime axetil. • Spirochetes Borrelia burgdorferi The following in vitro data are available, but their clinical significance is unknown. At least 90 percent of the following microorganisms exhibit an in vitro minimum inhibitory concentration (MIC) less than or equal to the susceptible breakpoint for cefuroxime axetil of 1 mcg/mL. However, the efficacy of cefuroxime axetil in treating clinical infections due to these microorganisms has not been established in adequate and well-controlled clinical trials. • Gram‑positive bacteria Staphylococcus epidermidis (methicillin-susceptible isolates only) Staphylococcus saprophyticus (methicillin-susceptible isolates only) Streptococcus agalactiae • Gram‑negative bacteria Morganella morganii Proteus inconstans Proteus mirabilis Providencia rettgeri • Anaerobic bacteria Peptococcus niger

Susceptibility Test Methods

When available, the clinical microbiology laboratory should provide the results of in vitro susceptibility tests for antimicrobial drug products used in local hospitals and practice areas to the physician as periodic reports that describe the susceptibility profile of nosocomial and community-acquired pathogens. These reports should aid the physician in selecting an antibacterial drug product for treatment.

Dilution Techniques: Quantitative methods are used to determine antimicrobial MICs. These MICs provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. The MICs should be determined using a standardized test method (broth or agar). 1,2 The MIC values should be interpreted according to criteria provided in Table 10. 2,3

Diffusion Techniques: Quantitative methods that require measurement of zone diameters also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. The zone size provides an estimate of the susceptibility of bacteria to antimicrobial compounds. The zone size should be determined using a standardized test method. 4 This procedure uses paper disks impregnated with 30 mcg cefuroxime axetil to test the susceptibility of microorganisms to cefuroxime axetil. The disk diffusion interpretive criteria are provided in Table 10. 3

Table 10. Susceptibility Test Interpretive Criteria for Cefuroxime Axetil

a For Enterobacteriaceae. Haemophilus spp. and Moraxella catarrhalis. susceptibility interpretive criteria are based on a dose of 500 mg every 12 hours in patients with normal renal function.

b Haemophilus spp. includes only isolates of H. influenzae and H. parainfluenzae .

Susceptibility of staphylococci to cefuroxime may be deduced from testing only penicillin and either cefoxitin or oxacillin.

Susceptibility of Streptococcus pyogenes may be deduced from testing penicillin. 3

A report of “Susceptible” indicates that the antimicrobial drug is likely to inhibit growth of the pathogen if the antimicrobial drug reaches the concentration usually achievable at the site of infection. A report of “Intermediate” indicates that the result should be considered equivocal, and if the microorganism is not fully susceptible to alternative, clinically feasible drugs, the test should be repeated. This category implies possible clinical applicability in body sites where the drug is physiologically concentrated or in situations where a high dosage of drug can be used. This category also provides a buffer zone that prevents small uncontrolled technical factors from causing major discrepancies in interpretation. A report of “Resistant” indicates that the antimicrobial drug is not likely to inhibit growth of the pathogen if the antimicrobial drug reaches the concentrations usually achievable at the infection site; other therapy should be selected.

Quality Control: Standardized susceptibility test procedures require the use of laboratory controls to monitor and ensure the accuracy and precision of supplies and reagents used in the assay, and the techniques of the individual performing the test. 1,2,4 The QC ranges for MIC and disk diffusion testing using the 30-mcg disk are provided in Table 11. 3

Table 11. Acceptable Quality Control (QC) Ranges for Cefuroxime Axetil

ATCC = American Type Culture Collection.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

Although lifetime studies in animals have not been performed to evaluate carcinogenic potential, no mutagenic activity was found for cefuroxime axetil in a battery of bacterial mutation tests. Positive results were obtained in an in vitro chromosome aberration assay; however, negative results were found in an in vivo micronucleus test at doses up to 1.5 g/kg. Reproduction studies in rats at doses up to 1,000 mg/kg/day (9 times the recommended maximum human dose based on body surface area) have revealed no impairment of fertility.

Clinical Studies

Acute Bacterial Maxillary Sinusitis

One adequate and well‑controlled trial was performed in subjects with acute bacterial maxillary sinusitis. In this trial, each subject had a maxillary sinus aspirate collected by sinus puncture before treatment was initiated for presumptive acute bacterial sinusitis. All subjects had radiographic and clinical evidence of acute maxillary sinusitis. In the trial, the clinical effectiveness of Ceftin in treating acute maxillary sinusitis was comparable to an oral antimicrobial agent containing a specific β‑lactamase inhibitor. However, microbiology data demonstrated Ceftin to be effective in treating acute bacterial maxillary sinusitis due only to Streptococcus pneumoniae or non-β‑lactamase–producing Haemophilus influenzae. Insufficient numbers of β-lactamase–producing Haemophilus influenzae and Moraxella catarrhalis isolates were obtained in this trial to adequately evaluate the effectiveness of Ceftin in treating acute bacterial maxillary sinusitis due to these 2 organisms.

This trial randomized 317 adult subjects, 132 subjects in the United States and 185 subjects in South America. Table 12 shows the results of the intent‑to‑treat analysis.

Table 12. Clinical Effectiveness of Ceftin Tablets in the Treatment of Acute Bacterial Maxillary Sinusitis

a 95% confidence interval around the success difference [‑0.08, +0.32].

b 95% confidence interval around the success difference [‑0.10, +0.16].

c Control was an antibacterial drug containing a β-lactamase inhibitor.

In this trial and in a supporting maxillary puncture trial, 15 evaluable subjects had non-β‑lactamase–producing Haemophilus influenzae as the identified pathogen. Of these, 67% (10/15) had this pathogen eradicated. Eighteen (18) evaluable subjects had Streptococcus pneumoniae as the identified pathogen. Of these, 83% (15/18) had this pathogen eradicated.

Early Lyme Disease

Two adequate and well‑controlled trials were performed in subjects with early Lyme disease. All subjects presented with physician-documented erythema migrans, with or without systemic manifestations of infection. Subjects were assessed at 1 month posttreatment for success in treating early Lyme disease (Part I) and at 1 year posttreatment for success in preventing the progression to the sequelae of late Lyme disease (Part II).

A total of 355 adult subjects (181 treated with cefuroxime axetil and 174 treated with doxycycline) were randomized in the 2 trials, with diagnosis of early Lyme disease confirmed in 79% (281/355). The clinical diagnosis of early Lyme disease in these subjects was validated by 1) blinded expert reading of photographs, when available, of the pretreatment erythema migrans skin lesion, and 2) serologic confirmation (using enzyme-linked immunosorbent assay [ELISA] and immunoblot assay [“Western” blot]) of the presence of antibodies specific to Borrelia burgdorferi. the etiologic agent of Lyme disease. The efficacy data in Table 14 are specific to this “validated” patient subset, while the safety data below reflect the entire patient population for the 2 trials. Clinical data for evaluable subjects in the “validated” patient subset are shown in Table 13.

Table 13. Clinical Effectiveness of Ceftin Tablets Compared with Doxycycline in the Treatment of Early Lyme Disease

(1 Month after 20 Days of Treatment) a

a 95% confidence interval around the satisfactory difference for Part I (-0.08, +0.05).

b 95% confidence interval around the satisfactory difference for Part II (-0.13, +0.07).

c n’s include subjects assessed as unsatisfactory clinical outcomes (failure + recurrence) in Part I (Ceftin ‑ 11 [5 failure, 6 recurrence]; doxycycline - 8 [6 failure, 2 recurrence]).

d Satisfactory clinical outcome includes cure + improvement (Part I) and success + improvement (Part II).

Ceftin and doxycycline were effective in prevention of the development of sequelae of late Lyme disease.

While the incidence of drug-related gastrointestinal adverse reactions was similar in the 2 treatment groups (cefuroxime axetil - 13%; doxycycline - 11%), the incidence of drug-related diarrhea was higher in the cefuroxime axetil arm versus the doxycycline arm (11% versus 3%, respectively).

Secondary Bacterial Infections of Acute Bronchitis

Four randomized, controlled clinical trials were performed comparing 5 days versus 10 days of Ceftin for the treatment of subjects with secondary bacterial infections of acute bronchitis. These trials enrolled a total of 1,253 subjects (Study 1 n = 360; Study 2 n = 177; Study 3 n = 362; Study 4 n = 354). The protocols for Study 1 and Study 2 were identical and compared Ceftin 250 mg twice daily for 5 days, Ceftin 250 mg twice daily for 10 days, and AUGMENTIN ® (amoxicillin/clavulanate potassium) 500 mg 3 times daily for 10 days. These 2 trials were conducted simultaneously. Study 3 and Study 4 compared Ceftin 250 mg twice daily for 5 days, Ceftin 250 mg twice daily for 10 days, and CECLOR ® (cefaclor) 250 mg 3 times daily for 10 days. They were otherwise identical to Study 1 and Study 2 and were conducted over the following 2 years. Subjects were required to have polymorphonuclear cells present on the Gram stain of their screening sputum specimen, but isolation of a bacterial pathogen from the sputum culture was not required for inclusion. Table 14 demonstrates the results of the clinical outcome analysis of the pooled trials Study 1/Study 2 and Study 3/Study 4, respectively.

Table 14. Clinical Effectiveness of Ceftin Tablets 250 mg Twice Daily in Secondary Bacterial Infections of Acute Bronchitis: Comparison of 5 versus 10 Days’ Treatment Duration

Study 1 and Study 2 a

a 95% confidence interval around the success difference [‑0.164, +0.029].

b 95% confidence interval around the success difference [‑0.061, +0.103].

The response rates for subjects who were both clinically and bacteriologically evaluable were consistent with those reported for the clinically evaluable subjects.

REFERENCES

1. Clinical and Laboratory Standards Institute (CLSI). Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically; Approved Standard - Tenth Edition. 2015. CLSI document M07-A10, Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA. 2. Clinical and Laboratory Standards Institute (CLSI). Methods for Antimicrobial Dilution and Disk Susceptibility Testing for Infrequently Isolated or Fastidious Bacteria: Approved Guidelines - Second Edition. 2010. CLSI document M45-A2, Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA. 3. Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Susceptibility Testing; Twenty-fifth Informational Supplement. 2015. CLSI document M100-S25, Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA. 4. Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Disk Diffusion Susceptibility Tests; Approved Standard – Twelfth Edition. 2015. CLSI document M02-A12, Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA.

How Supplied/Storage and Handling

Ceftin tablets, 250 mg of cefuroxime (as cefuroxime axetil), are white, capsule‑shaped, film‑coated tablets engraved with "GX ES7" on one side and blank on the other side as follows:

20 Tablets/Bottle NDC 0173-0387-00

Ceftin tablets, 500 mg of cefuroxime (as cefuroxime axetil), are white, capsule‑shaped, film‑coated tablets engraved with "GX EG2" on one side and blank on the other side as follows:

20 Tablets/Bottle NDC 0173-0394-00

Store the tablets between 15° and 30°C (59° and 86°F). Replace cap securely after each opening.

Ceftin for oral suspension is provided as dry, white to off‑white, tutti‑frutti–flavored powder. When reconstituted as directed, the suspension provides the equivalent of 125 mg or 250 mg of cefuroxime (as cefuroxime axetil) per 5 mL. It is supplied in amber glass bottles as follows:

100‑mL Suspension NDC 0173-0740-00

50‑mL Suspension NDC 0173-0741-10 100‑mL Suspension NDC 0173-0741-00

Before reconstitution, store dry powder between 2° and 30°C (36° and 86°F).

After reconstitution, immediately store suspension refrigerated between 2° and 8°C (36° and 46°F). DISCARD AFTER 10 DAYS.

Patient Counseling Information

Inform patients that Ceftin is a cephalosporin that can cause allergic reactions in some individuals [see Warnings and Precautions (5.1)] .

Clostridium difficile - associated Diarrhea

Inform patients that diarrhea is a common problem caused by antibacterials, and it usually ends when the antibacterial is discontinued. Sometimes after starting treatment with antibacterials, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as 2 or more months after having taken their last dose of the antibacterial. If this occurs, advise patients to contact their physician as soon as possible.

Inform patients and caregivers that Ceftin for oral suspension contains phenylalanine (a component of aspartame) [see Warnings and Precautions (5.6)] .

Instruct patients to swallow the tablet whole, without crushing the tablet. Patients who cannot swallow the tablet whole should receive the oral suspension.

Instruct patients to shake the oral suspension well before each use, store in the refrigerator, and discard after 10 days. The oral suspension should be taken with food.

Inform patients that antibacterial drugs, including Ceftin, should only be used to treat bacterial infections. They do not treat viral infections (e. g. the common cold). When Ceftin is prescribed to treat a bacterial infection, inform patients that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may: (1) decrease the effectiveness of the immediate treatment, and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by Ceftin or other antibacterial drugs in the future.

Ceftin and AUGMENTIN are registered trademarks of the GSK group of companies.

The other brands listed are trademarks of their respective owners and are not trademarks of the GSK group of companies. The makers of these brands are not affiliated with and do not endorse the GSK group of companies or its products.

Research Triangle Park, NC 27709

©2015, the GSK group of companies. All rights reserved.

PRINCIPAL DISPLAY PANEL

Ceftin ® Tablets

(cefuroxime axetil tablets)

Replace cap securely after each opening.

Each tablet contains cefuroxime axetil equivalent to 250 mg of cefuroxime.

See package insert for Dosage and Administration.

Store between 15º and 30ºC (59º and 86ºF).

Made in England

10000000136237 Rev. 9/15

PRINCIPAL DISPLAY PANEL

Ceftin ® Tablets

(cefuroxime axetil tablets)

Each tablet contains cefuroxime axetil equivalent to 500 mg of cefuroxime.

See package insert for Dosage and Administration.

Store between 15º and 30ºC (59º and 86ºF). Replace cap securely after each opening.

Research Triangle Park, NC 27709

Made in England

10000000131083 Rev. 12/14

PRINCIPAL DISPLAY PANEL

Ceftin ® for Oral Suspension

(cefuroxime axetil for oral suspension)

For Oral Use Only

125 mg per 5 mL

100 mL (when reconstituted)

Contains 3.0 g of cefuroxime axetil equivalent to 2.5 g of cefuroxime.

Phenylketonurics: Contains Phenylalanine 11.8 mg per 5 mL (1 teaspoonful) constituted suspension.

See package insert for Dosage and Administration.

Directions for Mixing Oral Suspension. Prepare the suspension at time of dispensing. Shake the bottle to loosen the powder. Remove the cap. Add 37 mL of water for reconstitution and replace the cap. Invert bottle and vigorously rock it from side to side so that water rises through the powder. Once the sound of powder against the bottle disappears, turn thebottle upright and vigorously shake it in a diagonal direction.

Before reconstitution, store dry powder between 2º and 30ºC (36º and 86ºF).

After reconstitution, store suspension between 2º and 8ºC (36º and 46ºF), in a refrigerator. SHAKE WELL BEFORE EACH USE. Replace cap securely after each opening. Discard after 10 days.

Research Triangle Park, NC 27709

Made in England

10000000136641 Rev. 8/15

PRINCIPAL DISPLAY PANEL

Ceftin ® for Oral Suspension

(cefuroxime axetil for oral suspension)

For Oral Use Only

250 mg per 5 mL

50 mL (when reconstituted)

Contains 3.6 g of cefuroxime axetil equivalent to 3 g of cefuroxime.

Phenylketonurics: Contains Phenylalanine 25.2 mg per 5 mL (1 teaspoonful) constituted suspension.

See package insert for Dosage and Administration.

Directions for Mixing Oral Suspension. Prepare the suspension at time of dispensing. Shake the bottle to loosen the powder. Remove the cap. Add 19 mL of water for reconstitution and replace the cap. Invert bottle and vigorously rock it from side to side so that water rises through the powder. Once the sound of powder against the bottle disappears, turn thebottle upright and vigorously shake it in a diagonal direction.

Before reconstitution, store dry powder between 2º and 30ºC (36º and 86ºF).

After reconstitution, store suspension between 2º and 8ºC (36º and 46ºF), in a refrigerator. SHAKE WELL BEFORE EACH USE. Replace cap securely after each opening. Discard after 10 days.

Made in England

10000000136681 Rev. 8/15

Fort Frances General Supply -Cleaning Supplies, Kilbac

KILBAC Surface Disinfectant & Air Deodorizing Spray

1492 Germicidal Detergent (Part #231694) Comes in: 4L Jug, Case of 4 Jugs

Bactericidal - Fungicidal - Mildewicidal - Virucidal

Extensive labratory testing confirms killing of a wide range of Gram-Positive and Gram-Negative bacteria; fungi; mildew; and viruses - Herpes simplex (Type 1), Influenza A2 (Hong Kong), Vaccinia, Parainfluenza (Type 3), Canine Distemper and Feline Pnewmonitis when used as 12mL per Litre. MSDS Sheet

Directions: To clean, disinfect and deoderize all water washable surfaces: Use 1 part in 80 parts warm water (12mL per L). To disinfect heavily soiled surfaces: First clean using 1:80 hot water solution of 1492. Rinse, then reapply 1492 at 1:80 dilution. Where Pseudomonas is suspected: Use 1 part in 40-50 parts of warm water (20-25mL per L). To disinfect immersible items: Use 1 part in 80 parts of warm water and soak 10 minutes or longer. For metals, add 1 part Sodium Nitrate to 100 parts of useable > solution. In food processing plants: Use as directed above. Keep away from direct contact with foodstuffs. Contains alkul phenoxy polyethoxy ethanol. Food contact surfaces cleaned with this product must be thoroughly rinsed with potable > water.

W-400 Liquid Disinfectant Cleaner (Part #231204) Comes in: 4L Jug, Case of 4 Jugs

W-400 is a heavy duty disinfectant cleaner. At 1:20 dilution (50mL/L) of water, W-400 is a germicide and disinfectant against: Staphylococcus aureus, Salmonella typhosa, Trichophyton interdigitale, Salmonella choleraesuis, Escherichia coli and Enterobacter aerogenes. At 1:60 dilution (16mL/L) of water, W-400 is a very good sanitizer and deoderizer because it destroys odour causing bacteria. Directions: To clean and sanitize floors, walls, sinks, toilets, etc. use one part W-400 per 60 parts water (16mL/L). To clean and disinfect all water-washable hard surfaces, use one part W-400 per 20 parts of water (50mL/L). Note: To ensure disinfection allow 10 inutes wet contact time. MSDS Sheet

FULLTROL PLUS Disinfectant Cleaner (Part #111) Comes in: 4L Jug, Case of 4 Jugs

For use in hospitals, schools, institutions and food processing industries. Directions: For general disinfecting 1:60 For general sanitizing 1:320 Food establishments: Equipment and surfaces subjected to direct food contact must be thoroughly rinsed with potable water after cleaning with this product. Avoid contamination of food during use. Do not store in food processing or food storage area. MSDS Sheet

P. T.M. Disinfectant Cleanser (Part #9134) Comes in: 909mL bottle, Case of 12 Bottles

Safe for use on all porcelain, ceramic tile, marble, plastic, fiberglass, acrylic, arborite, stainless steel, metal and enamel surfaces. Non-abrasive - will not scratch. Clings to vertical surfaces. Acid-free for safety. Use as a non-acid bowl and urinal cleaner. Leaves a pleasant scent. No mixing necessary. Economical dispenser cap. Directions: Shake well before using. Apply with damp cloth and rinse. Food establishments: Equipment and surfaces subjected to direct food contact must be thoroughly rinsed with potable water after cleaning with this product. Avoid contamination of food during use. Do not store in food processing or food storage area. MSDS Sheet

DISINFECTANT SPRAY Surface Disinfectant and Air Deoderant (Part #501) Comes in: 440g aerosol can, Case of 12 Cans

Kills household germs - Inhibits mildew and mould - Stops offensive odours - Kills herpes virus Disinfects and deoderizes surfaces through effective bactericidal and fungicidal activity. Kills most Staph. and Strep. organisms, Pseudomonas aeruginosa, Tubercle bacilli, Salmonella choleraesuis and Trichophyton interdigitate (athlete's foot fungi) on hard surfaces and controls odours. Kills influenza A2 virus on environmental hard surfaces. Kills Herpes Simplex Virus types 1 and 2 on hard, non-porous surfaces.

Directions for use: Use for empty garbage cans, diaper pails, clothes hampers, storage areas, refuse containers, toilet seats, sinks and basins, telephones and animal areas. Also useful for shower stalls and wall tile around bathtubs. 1. Hold can as nearly upright as possible, approximately 15-20cm from surface to be sprayed. 2. Spray until covered with fine mist. For disinfection, spray, wait 10 minutes and then wipe. Do not saturate. Inhibits mould and mildew on hard non-porous surfaces for one week. Use on porcelain and painted surfaces, and all metallic surfaces except copper. Use caution on varnished, shellacked or natural finished woods - do not over spray on polished wood. Do not spray directly on clothing or rayon fabrics. To eliminate cooking, smoke, tobacco, bathroom and other unpleasany odours, spray centre of room 1 to 2 seconds. MSDS Sheet

KILBAC Surface Disinfectant & Air Deodorizing Spray (Part #255494) Comes in: 425g aerosol can, Case of 12 Cans

For disinfection in: 1. Hospitals on inanimate hard surfaces such as dressing carts, hampers, linen carts, wheel chairs, metal springs, toilet seats, telephones, light switches, wash basins, urinals, door knobs, air ducts and other similar germ laden hard surfaces. 2. Food plants on inanimate objects in those areas where food is manufactured, prepared or stored. Kills Staphylococcus aureus, Salmonella choleraeusuis, Pseudomonas aeruginosa, Escherichia coli, Trichophyton interdigitale and Mycobacterium tuberculosis.

Directions for use: Shake well before spraying: Hold can about 10-20cm from surface, spray evenly until a fine mist covers surface. All soiled surfaces must be cleaned prior to disinfection. Hospital disinfection: Cover entire clean surface with mist. For effective germ killing action, maintain wetted surfaces for 10 minutes. Food plant disinfection: Cover or remove exposed food. Spray on pre-cleaned surfaces. Maintain wetted surfaces for 10 minutes. Avoid contamination of food in the application and storage of the product.

Caution: All food contact surfaces must be rinsed with potable water before re-use. To eliminate odours: Spray upward into room for 2-3 seconds. Do not use on polished wood furniture or rayon fabrics. MSDS Sheet

KILBAC Germicidal Foaming Cleaner (Part #255496) Comes in: 539g aerosol can, Case of 12 Cans

Directions: Shake well before using. Hold can 10-20cm from surface to be cleaned, spray evenly to cover entire surface. Wipe off in a few seconds with a clean cloth or sponge. For heavy build-up, allow product to penetrate and then wipe clean. Hospital disinfection: To disinfect, cover entire surface completely, wait ten minutes then wipe. Food plant disinfection: Spray on pre-cleaned surfaces. Allow foam to wet surface completely. Wait ten minutes then wipe. When cleaning food contact areas follow with a thorough rinse of potable water. Cover all food prior to spray cleaning.

Live Bat in your fireplace? Toss in a FFGS Mouse Glue Trap in flat position and let nature take its course. The bat will stick to the glue board, then reach in and remove the little varmint. Wear a FFGS glove for added protection.

Buy Woman S Health - Polibiotic (Brand Name Flagyl Er) Online - Order Metronidazole - Purchase Woman

METRONIDAZOLE is an antiinfective. This medicine is used to treat many kinds of infections, like respiratory, skin, gastrointestinal, and bone and joint infections. It will not work for colds, flu, or other viral infections.

What should my health care professional know before I take this medicine?

They need to know if you have any of these conditions: anemia or other blood disorders disease of the nervous system fungal or yeast infection if you drink alcohol containing drinks liver disease seizures an unusual or allergic reaction to metronidazole, or other medicines, foods, dyes, or preservatives pregnant or trying to get pregnant breast-feeding

How should I take this medicine?

Take this medicine by mouth with a full glass of water. Take your medicine at regular intervals. Do not take your medicine more often than directed. Take all of your medicine as directed even if you think you are better. Do not skip doses or stop your medicine early.

Talk to your pediatrician regarding the use of this medicine in children. Special care may be needed.

If you think you have taken too much of this medicine contact a poison control center or emergency room at once.

NOTE: This medicine is only for you. Do not share this medicine with others.

What if I miss a dose?

If you miss a dose, take it as soon as you can. If it is almost time for your next dose, take only that dose. Do not take double or extra doses.

What may interact with this medicine?

Do not take this medicine with any of the following: alcohol or any product that contains alcohol amprenavir oral solution disulfiram paclitaxel injection ritonavir oral solution sertraline oral solution sulfamethoxazole-trimethoprim injection

This medicine may also interact with the following: cimetidine lithium phenobarbital phenytoin warfarin

This list may not describe all possible interactions. Give your health care providers a list of all the medicines, herbs, non-prescription drugs, or dietary supplements you use. Also tell them if you smoke, drink alcohol, or use illegal drugs. Some items may interact with your medicine.

What should I watch for while taking this medicine?

Tell your doctor or health care professional if your symptoms do not improve or if they get worse.

You may get drowsy or dizzy. Do not drive, use machinery, or do anything that needs mental alertness until you know how this medicine affects you. Do not stand or sit up quickly, especially if you are an older patient. This reduces the risk of dizzy or fainting spells.

Avoid alcoholic drinks while you are taking this medicine and for three days afterward. Alcohol may make you feel dizzy, sick, or flushed.

If you are being treated for a sexually transmitted disease, avoid sexual contact until you have finished your treatment. Your sexual partner may also need treatment.

What side effects may I notice from this medicine?

Side effects that you should report to your doctor or health care professional as soon as possible: allergic reactions like skin rash or hives, swelling of the face, lips, or tongue confusion, clumsiness dark or white patches in the mouth fever, infection numbness, tingling, pain or weakness in the hands or feet pain when passing urine seizures if you are unusually weak or tired vaginal irritation or discharge

Side effects that usually do not require medical attention (report to your doctor or health care professional if they continue or are bothersome): diarrhea headache metallic taste nausea stomach pain or cramps

This list may not describe all possible side effects.

Where can I keep my medicine?

Keep out of the reach of children.

Store at room temperature below 25 degrees C (77 degrees F). Protect from light. Keep the container tightly closed. Throw away any unused medicine after the expiration date.

Comprar Oxilepsi (Trileptal) Sin Receta, Oxilepsi

compra Oxilepsi (Trileptal) en linea sin receta

Oxilepsi (Trileptal) Explicacion

Oxilepsi se utiliza en lo que respecta a hacer frente a determinados tipos de convulsiones en los enfermos, junto con la epilepsia. Puede ser utilizado por si mismo o incluso en combinacion con algunos otros medicamentos. Esto tambien puede suministrar para algunas otras circunstancias.

Oxilepsi es definitivamente un anticonvulsivo. Funciones a traves de la disminucion de los nervios irregular insta dentro de la mente.

Oxilepsi tambien puede ser referido como oxcarbazepina, Trexapin.

titulo general asociada con Oxilepsi es en realidad oxcarbazepina.

Marca asociada con Oxilepsi Oxilepsi es en realidad.

Oxilepsi (Trileptal) Dosis

Oxilepsi viene en:

150mg Baja Dosis material de friccion

300mg material de friccion regular Dosis

600mg Mejora Dosis material de friccion

Oxilepsi puede ser utilizado con o sin comidas.

Es muy importante conseguir casi todas las dosis de inmediato para mantener la cantidad de medicamento en el torrente sanguineo continuo. Obten dosis en periodos igualmente repartidas. Por lo general no lo hacen por las dosis de pase.

El uso de Oxilepsi exactas mismas ocasiones cada dia le ayudara a asegurarse de llevarlo.

Aun asi obtener Oxilepsi a pesar de que usted realmente se siente muy bien.

Por lo general, no se salte ninguna clase de dosis. Oxilepsi es mas eficaz si encuentra un grado continuo de Oxilepsi dentro de su cuerpo.

Si usted desea lograr mejores resultados por lo general no dejar de usar Oxilepsi, de repente. En caso de Oxilepsi es en realidad se detuvo, esta se llevara a cabo lentamente. La posibilidad de que las convulsiones se podria mejorar en caso Oxilepsi es en realidad, de repente, se detuvo.

Oxilepsi (Trileptal) Careciendo asocia con dosis

Por lo general, no reciben doble dosis. En caso de que salte la dosis que necesita para llevar una vez se tiene en cuenta en lo que respecta a su deficiente. Cuando es hora de la dosis que necesita para llevar a cabo su propia rutina de dosificacion normal.

Oxilepsi (Trileptal)

En el caso de que una sobredosis de Oxilepsi y que tambien se evita gran usted necesita comprobar hacia fuera su medico o incluso el medico de inmediato.

Oxilepsi (Trileptal) Espacio de almacenamiento

Tienda en temperaturas de espacio entre 10 y 30 niveles de D (59, asi como ochenta y seis niveles F) de la humedad, la iluminacion, asi como la temperatura. Mantener cuadro de texto firmemente cerrada. Haga compras en el cuadro de texto inicial. Utilizado en siete semanas varios asociados con la primera a partir del contenedor real. Fortalecer cualquier tipo de medicamento sin tocar a partir del dia de vencimiento. Mantener colocado de forma segura fuera del camino de los ninos.

Oxilepsi (Trileptal) Efectos negativos

Oxilepsi ofrece los efectos negativos. El mas tipico tienden a ser:

material de los brotes de acne friccion

material de friccion congestion

material de friccion fatiga

friccion somnolencia materiales

seca material de friccion area de la boca

material de friccion dolor de cabeza

material de friccion de reflujo acido

nauseas o vomitos friccion de material

Material vientre molestias friccion

material de friccion fatiga

material de friccion hormigueo

material de los problemas de sueno de friccion

friccion raro paseo materiales

vomitando material de friccion

Mucho menos tipica y severos efectos negativos en toda utilizando Oxilepsi:

respuestas de reaccion alergica (urticaria, inhalando y exhalando cuestiones, alergia, asi como la erupcion) material de friccion

torrente sanguineo dentro de material de friccion heces Material

problemas cardiacos friccion

pis oscuro material de friccion

redujo pis material de friccion

problemas para hablar material de friccion

material de friccion de doble vista

dentro de la vista, o incluso inconsciente movimiento material de friccion ojos

embotado sensacion asociada con material de friccion de contactos

material de la temperatura, escalofrios, o aun amigdalas doloridos friccion

la falta de material de friccion destreza

sal inferior grado? a €

un material de friccion € ?

material de friccion dolor

mentales / estado de animo material de friccion modificaciones

material de friccion hemorragia nasal

de color rojo, inflamado. ampollas, o incluso poros viejos y material de friccion de la piel

Material vientre molestias friccion Material

convulsiones friccion

Sistemas de ganglios inflamados material de friccion

problemas paseando material de friccion

de control muscular acciones de masas de material de friccion

sangrado infrecuente o material de friccion moretones

raro que algun material de friccion debilidad

coloracion amarillenta de los poros y la piel o incluso material de friccion ojo

Los efectos negativos son indicaciones se basan en medicamentos que podrian estar utilizando pero, ademas, se basan en su condicion de bienestar y otros aspectos.

Oxilepsi (Trileptal) Contraindicaciones

Por lo general no reciben Oxilepsi en caso de que son sensibles con el fin de elementos Oxilepsi.

Por lo general no reciben Oxilepsi en caso de que se espera, va a quedar embarazada, y / o en periodo de lactancia.

Para aquellos que tienen una breve historia asociada con las convulsiones, es posible que todo de una conciencia cobertizo repentina cuando se utiliza Oxilepsi. Evitar acciones donde la falta de conciencia podria ser perjudicial para usted o incluso otras personas (conduccion, natacion va, subiendo, asi como la maquinaria de trabajo pesado).

pastillas de anticoncepcion de chatarra podrian no actuar como muy bien cuando usted esta utilizando Oxilepsi. Para evitar estar embarazada, el uso de tipo anticonceptivo adicional (condones).

Oxilepsi puede causar que usted de vuelta definitivamente a ser quemada por el sol mas facil. Mantengase alejado de la luz del sol, las lamparas solares o incluso cabinas para el bronceado si no se entiende como una persona responde a Oxilepsi. Hacer uso de un protector solar o incluso poner en la proteccion de la ropa en caso de que usted debe estar al aire libre durante un momento.

Oxilepsi debe reducirse lentamente cada vez que se detuvo. Hable con su medico acerca de la forma mas conveniente para evitar Oxilepsi.

Alerte a su proveedor de servicios medicos en caso de convulsiones administrar empeora.

Los examenes de diagnostico, como el torrente sanguineo cantidades de sal, pueden llevarse a cabo como usted utiliza Oxilepsi. Este tipo de evaluaciones se podrian utilizar para realizar un seguimiento de su problema o incluso buscar efectos negativos. Asegurese de mantener casi todo medico, asi como visitas de laboratorio.

Oxilepsi no debe ser utilizado en ninos mas jovenes en comparacion con una edad. Seguridad, asi como la utilidad durante estos ninos nunca han sido verificados.

Evite las bebidas alcoholicas.

Puede ser danino para evitar el uso de Oxilepsi, de repente.

Oxilepsi (Trileptal) Preguntas comunes

Queen: Exactamente ?que implica Oxilepsi?

El: Oxilepsi se utiliza en lo que respecta a hacer frente a determinados tipos de convulsiones en los enfermos junto con la epilepsia. Puede ser utilizado por si mismo o incluso en combinacion con algunos otros medicamentos. Esto tambien se puede suministrar por alguna otra circumstances. A

Queen: ?Que son exactamente los de marca, asi como las marcas generales asociados con Oxilepsi?

El: titulo general asociada con Oxilepsi es en realidad oxcarbazepina. Marca asociada con Oxilepsi es en realidad Oxilepsi. A

Reina: ?Como se puede realmente funcionar Oxilepsi?

El: Oxilepsi es definitivamente un anticonvulsivo. Funciones a traves de la disminucion de los nervios dentro de la irregular insta mind. a

comprar Oxilepsi (Trileptal) en linea, Oxilepsi (Trileptal) comprar en linea sin receta, Oxilepsi (Trileptal) comprar sin receta, comprar barato Oxilepsi (Trileptal), Oxilepsi (Trileptal) comprar sin receta, comprar Oxilepsi (Trileptal) de Canada, comprar Oxilepsi (Trileptal) Canada, Para Oxilepsi (Trileptal) en linea, Para Oxilepsi (Trileptal) Generico Sin Receta Medica, Oxilepsi (Trileptal) orden sin receta, Pildora por via oral Oxilepsi (Trileptal)

Busqueda

Las Personas Tambien Buscan

Sebact Mr 100mg Capsules, Sebact

SEBACT MR 100MG CAPSULES

Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

+ iMedi. co. uk

Sebact mr 100mg capsules

Sebact MR 100mg Capsules

Font size 10 pt

Please read all of this leaflet carefully before you start taking this medicine. It is an important source of information about your medicine and how to take it safely.

• Keep this leaflet. You may need to read it again.

• If you have further questions, please ask your doctor or your pharmacist.

• This medicine has been prescribed for you personally and you should not pass it on to others. It may harm them, even if their symptoms are the same as yours.

• If any of the side effects gets serious, or you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

In this leaflet:

1. What Sebact MR is and what it is used for

2. Before you take Sebact MR

3. How to take Sebact MR

4. Possible side effects

5. How to Store Sebact MR

6. Further information

1. What Sebact MR is and what it is used for

The name of your medicine is Sebact MR 100mg Capsules (referred to as Sebact MR throughout this leaflet).

The active ingredient in your medicine is minocycline.

Minocycline is one of a group of antibiotics called Tetracyclines.

Sebact MR is used for the treatment of acne. It is thought that acne is partly due to, or made worse by, infection with a type of bacteria called Propionibacterium Acnes. Treating acne with Sebact MR is intended to reduce the infection with this bacterium and so help in the overall treatment of acne.

2. Before you take Sebact MR Do not take Sebact MR if:

• You are allergic (hypersensitive) to minocycline or any of the other ingredients of Sebact MR (these are listed below

• You are allergic to any medicines from the group of antibiotics called Tetracyclines (e. g. oxytetracycline, tetracycline, doxycycline)

• You have kidney failure

• You are pregnant, think you might be pregnant or are trying to become pregnant. Sebact MR may cause harm to the foetus

• You are breastfeeding. Medicines from the Tetracycline group (as Sebact MR) passes through the breast milk

• You are less than 12 years old The use of Sebact MR during tooth development (last half of pregnancy, breastfeeding infants and children under the age of 12 years) may cause dental staining and/or incomplete development of the hard tooth surface leading to pitted, small or mis-shaped sensitive teeth prone to tooth decay (enamel hypoplasia).

Sebact MR may or may not be suitable for you if:

• You have liver problems

• You have had, or think you might have, kidney disease

• You have a condition called Myasthenia Gravis i. e. serious weakness in the muscles

• You have Systemic Lupus Erythematosus (SLE) i. e. swelling and tissue damage due to the immune system attacking the body’s cells and tissues

Tell your doctor or pharmacist if you have any of the above conditions before you start taking Sebact MR.

If you have any questions or are not sure about anything, ask your doctor before you start to take Sebact MR.

Take special care with Sebact MR:

If you are having tests on your urine for substances called Catecholamines (sometimes measured to look for problems with the adrenal gland), you should tell the doctor ordering the test that you are taking minocycline because it may interfere with the test and give the wrong result.

Taking Sebact MR with food and drink:

It is advisable not to drink too much alcohol while taking Sebact MR. Drink alcohol only in moderation and within the Government’s recommended limits. Sebact MR can be taken with food or drink.

Pregnancy and breast-feeding: Do not take Sebact MR if you are pregnant or beastfeeding. If you become pregnant while taking

Sebact MR stop taking it immediately and

tell your doctor (For further information see above 'Do not take Sebact MR if').

Driving and using machines: It is advisable not to drive or operate machinery if you notice headaches, dizziness, lightheadedness, vertigo (a feeling of unsteadiness), tinnitus (ringing in the ears) or effects on hearing whilst you are taking Sebact MR.

Taking other medicines: Please inform your doctor or pharmacist if you are taking or have recently taken any other medicines, even those not prescribed, before you start taking Sebact MR. It is especially important that you tell your doctor or pharmacist if you are taking any of the following:

• Quinapril (ACE inhibitor)- a medicine used to treat heart disease and high blood pressure

• Ranitidine bismuth citrate, sucralfate and tripotassium dicitratobismuthate (ulcer healing drugs)

• Antacids such as calcium carbonate, sodium bicarbonate, aluminium or magnesium compounds

• Vitamins or any preparations containing iron, calcium, aluminium, magnesium, bismuth or zinc salt

• Kaolin (to treat diarrhoea or stomach upset)

• Strontium ranelate (to treat osteoporosis)

• Ergotamine and methysergide (ergot alkaloids)- medicines used to treat migraines.

• Any medicines that can damage your liver (hepatotoxic drugs). For example: Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) such as aspirin, diclofenac and Ibuprofen (to treat pain, fever and inflammation); isoniazide (to treat tuberculosis), phenytoin (to treat epilepsy). It is imperative that you check with your doctor or pharmacist first to see if this applies to any medicine you are taking

• Antibiotics called beta-lactams (to treat infections). For example, penicillins (e. g. ampicillin, amoxicillin) and cephalosporins (e. g. cefalexin, cefaclor, cefadroxil)

• Medicines to thin your blood (e. g. warfarin). The dose of these medicines may need to be reduced whilst you are taking Sebact MR

• Diuretics (to regulate body water content), for example, thiazides, furosemide or amiloride.

• Isotretinoin (sometimes used to treat severe acne) should not be taken shortly before, during or shortly after a course of Sebact MR

• Oral contraceptives (the “pill”). Taking Sebact MR may make oral contraceptives less effective. It is very important that you do not become pregnant while taking Sebact MR and you should take advice from your doctor on extra precautions needed to avoid pregnancy

3. How to take Sebact MR

• Always take Sebact MR exactly as your doctor has instructed you. You should check with your doctor or pharmacist if you are unsure.

Dosage and frequency of administration:

• The usual dose for children over the age of 12 years and for adults is one

capsule of Sebact MR taken at about the same time each day.

• Some elderly people may need a lower dose. Your doctor will advise you about this.

Method of administration:

• Sebact MR capsules should be swallowed whole with a drink of water. They should not be sucked or chewed. The capsules should be taken while you are sitting upright or standing to prevent irritation of your gullet.

• It does not matter whether you take Sebact MR on an empty stomach or after food. However, the capsules should not be taken within 3 hours of some types of antacids, vitamins and other medicines.

• Do not remove a capsule from the pack until you are due to take it.

Duration of treatment:

Acne responds quite slowly to antibiotics and it may be several weeks (e. g. six weeks or more) before you see any improvement in your acne. If, however, your acne has not improved after a treatment period of six months, you should return to your doctor to have your treatment reviewed. Your doctor may decide to continue your treatment with Sebact MR for longer than 6

Font size 10 pt

months, and will ask to see you on a regular basis, usually at least once every 3 months. These regular visits will enable your doctor to examine you for any possible side effects related to the liver or unusual skin colouration or a condition called Systemic Lupus Erythematosus (SLE) which can include pain or stiffness of joints, rash or fever.

Your doctor will also take blood tests to measure your blood count and to assess how your liver and kidneys are working.

If you take more Sebact MR than you should: Never take more capsules than the doctor has told you to, it will not help you get better any faster and it could be harmful to you.

If you have accidentally taken too many capsules of Sebact MR (more capsules than the doctor has told you to take) you should get medical help immediately, either by calling your doctor or by going to the nearest hospital accident and emergency department. Always take the labelled medicine container with you, whether there are any Sebact MR capsules left or not.

If you forget to take Sebact MR: If you do

miss a dose you should take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take a double dose to make up for a missed dose.

4. Possible side effects

Like all medicines Sebact MR can cause side effects.

Do not be alarmed by the list of possible side effects. You may not experience any of them. Your doctor has judged the benefits of Sebact MR outweigh the risk of side effects.

If any of the following happen, stop taking Sebact MR and tell your doctor immediately or go to the emergency department at your nearest hospital.

• Severe allergic reactions that cause symptoms such as sudden onset of wheezing, shortness of breath, tightness in chest, swelling of the face, eyelids, mouth, lips, tongue or body and a drop in blood pressure resulting in loss of consciousness. These allergic responses might sometimes be linked to an increase in blood cells called eosinophils

• Swelling of the heart muscle or area around the heart resulting in symptoms such as fever, chest pain or difficulty breathing

• Swelling of the blood vessels resulting

in symptoms such as muscle pain, cramps, unusual tiredness or weakness, spitting blood

• Headaches, occasionally with eyesight problems including blurred vision, "blind" spots, permanent loss of vision or double vision

• Joint pains, stiffness or swelling or other joint problems together with fever, muscle pain and/or rashes

• Allergic skin reactions such as:

skin rashes that may blister and peel, often with involvement of the mouth, eyes and genital areas (Stevens-Johnson Syndrome) or redness and scaling of the skin (exfoliative dermatitis). Sometimes these types of reactions can occur with inflammation of one or more major body organs and with fever and swelling of the glands

• Severe and/or bloody diarrhoea

• Swelling of the pancreas or pancreatitis, is very serious condition resulting in symptoms such as severe upper abdominal pain, spreading to the back, and often with nausea and vomiting

Contact your doctor immediately if you notice any of the following side effects:

• Any staining or discoloration (slight blue/black/grey or muddy-brown) on your body or of secretions so that your treatment can be reviewed. Staining can appear on your skin, teeth or nails, inside of the mouth, eyes, in body secretions (e. g. tears, breast milk or sweat). Staining of some internal tissues such as the thyroid gland and bones can also occur

Staining may appear at any time during treatment with Sebact MR but is more common during long-term treatment. Staining usually disappears a few months after discontinuation of the drug, although some muddy-brown skin pigmentation may persist, particularly in areas exposed to the sun.

• Diarrhoea, sickness or unexpected bleeding while taking a contraceptive pill. Your "pill" may not work. You should use a different or additional means of birth control (e. g. a condom or diaphragm/cap) to ensure you are protected. See also Section 2 of this leaflet.

Other possible side effects of Sebact MR are:

Common (more than 1 in every 100 people)

• Dizziness or feeling light-headed

Rare (less than 1 in every 1,000 people but more than 1 in every 10,000 people)

• Loss of appetite

• Hearing problems such as loss of hearing ringing in the ears or unsteadiness

• Increased sensitivity of the skin to sunlight

• Numbness or tingling feelings (like pins and needles)

• Increasing frequency of infections or unexplained or unusual bruising or bleeding (as a result of drop in numbers of white blood cells) or in small cells called platelets)

• Increased sensitivity to stimulation such as pain etc.

Very rare (less than 1 in every 10,000 people)

• Worsening of asthma

• Incomplete development of the hard tooth surface leading to pitted, small or miss-shaped sensitive teeth prone to tooth decay

• Heartburn or difficulty in swallowing, sometimes due to swelling of the gullet or ulcers in the gullet

• Itching around the anus

• Anaemia resulting in tiredness, paleness and blood test showing red blood cells breaking up

• Swelling of the area around the tip of the penis

• Abnormal function of the thyroid gland (show up only in blood test results)

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

5. How to store Sebact MR

Store the capsules in the original package. Do not use this medicine after the expiry date stated on the label.

Keep out of the reach and sight of children.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

6. Further information What Sebact MR contains

Each capsule contains 100mg of the active substance minocycline as minocycline hydrochloride.

Sebact MR also contains the following other ingredients: microcrystalline cellulose, croscarmellose sodium, povidone, iron oxide red (E172), iron oxide yellow (E172), silica colloidal anhydrous, magnesium stearate, hypromellose phthalate, triethyl citrate, carnauba wax, gelatin, Opadry OY-S-24932 pink which contains hypromellose 2910, macrogol 6000, titanium dioxide (E171), talc, iron oxide red (E172).

What Sebact MR looks like and content of the pack

Sebact MR is a modified release brown and cream coloured, hard gelatin capsule. These MR capsules are intended to provide “modified release” of the active substance minocycline so that some is released in the stomach and some in the small intestine.

Sebact MR is available in packs of 56 capsules, in foil blister strips.

Marketing authorisation holder and manufacturer is Dexcel®-Pharma Ltd. 1 Cottesbrooke Park, Heartlands Business Park, Daventry, Northants NN11 8YL, United Kingdom.

This leaflet was last approved in 08/2009.

If after reading this leaflet you have any questions, please ask your doctor or pharmacist or contact NHS Direct on 0845 46 47.

A B C D E F G H

SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

3 PHARMACEUTICAL FORM

4 CLINICAL PARTICULARS

5 PHARMACOLOGICAL PROPERTIES

6 PHARMACEUTICAL PARTICULARS

7 MARKETING AUTHORISATION HOLDER

8 MARKETING AUTHORISATION NUMBER(S)

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

10 DATE OF REVISION OF THE TEXT

Camirox, Camirox

Cefaclor

Chemical Name

5-tia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid, 7-[(aminophenylacetyl)amino]-3-chloro-8-oxo-, [6R-[6?,7?(R*)]]-

Foreign Names

Cefaclorum (Latin)

Cefaclor (German)

Cefaclor (French)

Cefaclor (Spanish)

Generic Names

Cefaclor (OS: USAN, JAN, BAN)

Cefacloro (OS: DCIT)

Cefeaclor (OS: DCF)

Cephaclor (IS)

Compound 99638 (IS: Lilly)

Cefaclor (PH: JP XVI, USP 38)

Cephaclor-1-Wasser (IS)

S 6472 (IS)

Cefaclor (PH: BP 2016, Ph. Eur. 8, USP 38)

Cefaclor (PH: Ph. Eur. 8)

Cefaclor-Monohydrat (PH: Ph. Eur. 8)

Cefaclorum (PH: Ph. Eur. 8)

Brand Names

Click for further information on drug naming conventions and International Nonproprietary Names .

Important Notice: The Drugs. com international database is in BETA release. This means it is still under development and may contain inaccuracies. It is not intended as a substitute for the expertise and judgement of your physician, pharmacist or other healthcare professional. It should not be construed to indicate that the use of any medication in any country is safe, appropriate or effective for you. Consult with your healthcare professional before taking any medication.

Was this page helpful?

Why register with MediGuard?

We are a free monitoring service designed for patients like you who want to be in the driver seat of your medical treatment. We have a community of more than 2.6 million members and offer the services below.

Medication Information Personalized Risk Rating Easy to understand overview Serious Side Effects Printable Medication List

Information you can understand Overview on Safety Alerts & Recalls Overview of Medications & Conditions

Community of patients Members’ Feedback Members Treatment Satisfaction

Health condition information Easy to understand overview Commonly Used Medications

Safety checks Safety Alerts & Recalls Drug - Drug Interaction Drug - Condition Interaction

Research participation Option to participate in medical surveys & studies*

Cefaclor (Cefaclor)

What is your Risk Rating for this medicine?

The risk of serious side effects for taking this medicine can be different if you take other medicines or if you suffer from a condition. Get your Risk Rating by creating a profile in a few steps.

Benefits:

We monitor your health and alert you to any safety updates and recalls.

You get to talk directly to other members about their experience.

You can create profiles for you and your loved ones.

Create my Profile Learn more about Risk Ratings

Other Names

Expand to see all

Share your story! Tell us how MediGuard has helped you or someone you love. Download the MediGuard Mobile App to manage your prescription and over-the-counter medications, for free. Taking multiple medications puts you at risk for possible drug-drug interactions Monitor the medical treatment of you and your loved ones.

DISCLAIMER: MediGuard is not intended to be a substitute for professional medical advice. MediGuard cannot and does not take into consideration every possible interaction or account for individual responses to medicine. Different individuals may respond to medication in different ways. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective, or appropriate for any given patient. Always seek the advice of a qualified health provider with any questions you may have before making any changes to your treatment. The use of the MediGuard site and its content is at your own risk. The MediGuard site and the information contained in it is intended for users in the United States and information in other countries may be different.

© Quintiles 2016

Naproxen, Aleve Side Effects, Dosage, And Interactions, Naproxenum

naproxen, Anaprox, Naprelan, Naprosyn, Aleve

GENERIC NAME: naproxen

BRAND NAME: Anaprox, Naprelan, Naprosyn, Aleve, Mediproxen

DRUG CLASS AND MECHANISM: Naproxen belongs to a class of drugs called nonsteroidal anti-inflammatory drugs (NSAIDs ). Other members of this class include ibuprofen (Motrin ), indomethacin (Indocin ), nabumetone (Relafen) and several others. These drugs are used for the management of mild to moderate pain. fever. and inflammation. They work by reducing the levels of prostaglandins, chemicals that are responsible for pain. fever. and inflammation. Naproxen blocks the enzyme that makes prostaglandins (cyclooxygenase), resulting in lower concentrations of prostaglandins. As a consequence, inflammation, pain and fever are reduced. Naproxen was approved by the FDA in December 1991.

PRESCRIBED FOR: Naproxen is used for the treatment of

SIDE EFFECTS: The most common side effects from naproxen are:

Medically Reviewed by a Doctor on 8/6/2015

Quick Guide Migraine or Headache? Migraine Symptoms, Triggers, Treatment

Report Problems to the Food and Drug Administration

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.

Ibuklaph, Ibuklaph

Ibuklaph

Important Notice: The Drugs. com international database is in BETA release. This means it is still under development and may contain inaccuracies. It is not intended as a substitute for the expertise and judgement of your physician, pharmacist or other healthcare professional. It should not be construed to indicate that the use of any medication in any country is safe, appropriate or effective for you. Consult with your healthcare professional before taking any medication.

Was this page helpful?

Arthritis - Ibuklaph (Brand name: motrin)

Motrin is used for treating rheumatoid arthritis, osteoarthritis, menstrual cramps, or mild to moderate pain. Motrin is an NSAID. NSAIDs treat the symptoms of pain and inflammation. They do not treat the disease that causes those symptoms.

Use Motrin as directed by your doctor.

Take Motrin by mouth with or without food. It may be taken with food if it upsets your stomach. Taking it with food may not lower the risk of stomach or bowel problems (eg, bleeding, ulcers). Talk with your doctor or pharmacist if you have persistent stomach upset.

Take Motrin with a full glass of water (8 oz/240 mL) as directed by your doctor.

If you miss a dose of Motrin and you are taking it regularly, take it as soon as possible. If it is almost time for your next dose, skip the missed dose. Go back to your regular dosing schedule. Do not take 2 doses at once.

Ask your health care provider any questions you may have about the proper use of Motrin .

Store Motrin at room temperature, between 68 and 77 degrees F (20 and 25 degrees C). Store away from heat, moisture, and light. Do not store in the bathroom. Keep Motrin out of the reach of children and away from pets.

Active Ingredient: Ibuprofen.

Do NOT use Motrin if:

you are allergic to any ingredient in Motrin

you have had a severe allergic reaction (eg, severe rash, hives, trouble breathing, growths in the nose, dizziness) to aspirin or an NSAID (eg, ibuprofen, celecoxib)

you have recently had or will be having bypass heart surgery

you are in the last 3 months of pregnancy.

Contact your doctor or health care provider right away if any of these apply to you.

Some medical conditions may interact with Motrin. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

if you are pregnant, planning to become pregnant, or are breast-feeding

if you are taking any prescription or nonprescription medicine, herbal product, or dietary supplement

if you have allergies to medicines, foods, or other substances

if you have a history of kidney or liver disease, diabetes, or stomach or bowel problems (eg, bleeding, perforation, ulcers)

if you have a history of swelling or fluid buildup, lupus, asthma, or growths in the nose (nasal polyps), or mouth inflammation

if you have high blood pressure, blood disorders, bleeding or clotting problems, heart problems (eg, heart failure), or blood vessel disease, or if you are at risk for any of these diseases

if you have poor health, dehydration or low fluid volume, or low blood sodium levels, you drink alcohol, or you have a history of alcohol abuse.

Some medicines may interact with Motrin. Tell your health care provider if you are taking any other medicines, especially any of the following:

Anticoagulants (eg, warfarin), aspirin, corticosteroids (eg, prednisone), heparin, or selective serotonin reuptake inhibitors (SSRIs) (eg, fluoxetine) because the risk of stomach bleeding may be increased

Probenecid because it may increase the risk of Motrin 's side effects

Cyclosporine, lithium, methotrexate, or quinolones (eg, ciprofloxacin) because the risk of their side effects may be increased by Motrin

Angiotensin-converting enzyme (ACE) inhibitors (eg, enalapril) or diuretics (eg, furosemide, hydrochlorothiazide) because their effectiveness may be decreased by Motrin.

This may not be a complete list of all interactions that may occur. Ask your health care provider if Motrin may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

Important safety information:

Motrin may cause dizziness or drowsiness. These effects may be worse if you take it with alcohol or certain medicines. Use Motrin with caution. Do not drive or perform other possible unsafe tasks until you know how you react to it.

Serious stomach ulcers or bleeding can occur with the use of Motrin. Taking it in high doses or for a long time, smoking, or drinking alcohol increases the risk of these side effects. Taking Motrin with food will NOT reduce the risk of these effects. Contact your doctor or emergency room at once if you develop severe stomach or back pain; black, tarry stools; vomit that looks like blood or coffee grounds; or unusual weight gain or swelling.

Do not take more than the recommended dose or use for longer than prescribed without checking with your doctor.

Motrin has ibuprofen in it. Before you start any new medicine, check the label to see if it has ibuprofen in it too. If it does or if you are not sure, check with your doctor or pharmacist.

Do not take aspirin while you are using Motrin unless your doctor tells you to.

Lab tests, including kidney function, complete blood cell counts, and blood pressure, may be done to monitor your progress or to check for side effects. Be sure to keep all doctor and lab appointments.

Use Motrin with caution in the elderly; they may be more sensitive to its effects, including stomach bleeding and kidney problems.

Motrin should be used with extreme caution in children; safety and effectiveness in children have not been confirmed.

Pregnancy and breast-feeding: Motrin may cause harm to the fetus. Do not take it during the last 3 months of pregnancy. If you think you may be pregnant, contact your doctor. You will need to discuss the benefits and risks of taking Motrin while you are pregnant. It is not known if Motrin is found in breast milk. Do not breastfeed while taking Motrin .

All medicines can cause side effects, but many people have no, or minor, side effects.

Check with your doctor if any of these most common side effects persist or become bothersome:

Constipation; diarrhea; dizziness; gas; headache; heartburn; nausea; stomach pain or upset.

Seek medical attention right away if any of these severe side effects occur:

Severe allergic reactions (rash; hives; itching; trouble breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); bloody or black, tarry stools; change in the amount of urine produced; chest pain; confusion; dark urine; depression; fainting; fast or irregular heartbeat; fever, chills, or persistent sore throat; mental or mood changes; numbness of an arm or leg; one-sided weakness; red, swollen, blistered, or peeling skin; ringing in the ears; seizures; severe headache or dizziness; severe or persistent stomach pain or nausea; severe vomiting; shortness of breath; stiff neck; sudden or unexplained weight gain; swelling of hands, legs, or feet; unusual bruising or bleeding; unusual joint or muscle pain; unusual tiredness or weakness; vision or speech changes; vomit that looks like coffee grounds; yellowing of the skin or eyes.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider.

Xenocin Export By The Flagellar Type Iii Pathway In Xenorhabdus Nematophila, Xenoxin

Xenocin Export by the Flagellar Type III Pathway in Xenorhabdus nematophila

ABSTRACT

The xenocin operon of Xenorhabdus nematophila consists of xciA and ximB genes encoding a 64-kDa xenocin and 42-kDa immunity protein to kill competing microbes in the insect larva. The catalytic domain of xenocin has RNase activity and is responsible for its cytotoxicity. Under SOS conditions, xenocin is produced with immunity protein as a complex. Here, we show that xenocin and immunity protein complex are exported through the flagellar type III system of X. nematophila. Secretion of xenocin complex was abolished in an flhA strain but not in an fliC strain. The xenocin operon is not linked to the flagellar operon transcriptionally. The immunity protein is produced alone from a second, constitutive promoter and is targeted to the periplasm in a flagellum-independent manner. For stable expression of xenocin, coexpression of immunity protein was necessary. To examine the role of immunity protein in xenocin export, an enzymatically inactive protein was produced by site-directed mutagenesis in the active site of the catalytic domain. Toxicity was abolished in D535A and H538A variants of xenocin, which were expressed alone without an immunity domain and secreted in the culture supernatant through flagellar export. Secretion of xenocin through the flagellar pathway has important implications in the evolutionary success of X. nematophila.

INTRODUCTION

Xenorhabdus nematophila is a Gram-negative gammaproteobacterium that resides in the gut of the soil nematode Steinernema carpocapsae as a symbiont (1 ). The bacterium produces potent cytotoxins (2. –. 5 ) and orally toxic proteins to kill larval stages of insect pests (6. 7 ). After the death of the larva, the bacterium secretes a variety of antibiotic molecules (8. –. 10 ) to kill putrefying microbes for optimum growth of the nematode. In addition, a number of effector proteins are also released by the bacterium to communicate with and manipulate its hosts (11 ); however, secretion pathways of very few have been elucidated to date. We have described an insect-toxic outer membrane vesicle complex from the culture supernatant of X. nematophila containing multiple virulence factors (12 ), and an extracellular lipase, XlpA, was shown to be exported through the flagellum by this bacterial pathogen (13 ).

Bacteriocins are antimicrobial peptides produced by bacteria under environmental stress conditions, e. g. high population density and nutrient depletion (14 ). A cognate immunity protein (IP) is coinduced from an SOS-responsive promoter to protect the producer cell from the lethal effect of the bacteriocin (15 ). The bacteriocin and IP remain associated as a complex until the toxin enters the target cell (16. 17 ). In operons encoding nuclease bacteriocins, two different promoters regulate IP synthesis: an inducible SOS promoter and a constitutive promoter that allows constant production of IP to ensure inactivation of the incoming bacteriocins (15. 18 ).

Earlier we described a gene pair constituting the xenocin operon of X. nematophila (19 ). The first locus, xciA (XNC1_3261), encoded a 64-kDa xenocin with RNase activity followed by ximB encoding the cognate immunity protein. The 42-kDa IP is constituted by a 10-kDa immunity domain in the N terminus and a C-terminal 32-kDa putative hemolysin domain (Fig. 1 ). The two genes were transcribed as a single mRNA by an SOS inducible promoter located upstream of the xciA gene. Additionally, ximB was transcribed alone from a constitutive promoter present in the 5?-untranslated sequence of the gene (19 ) (Fig. 1 ). Generally, bacteriocin-IP complexes are released from the producer cell with the help of a lysis or lysis-inducing protein located in the same operon in group A members (15 ) or through an ABC transporter in group B members (20 ). Since none of the genes mentioned above was present in the proximity of the xenocin operon, it was presumed that secretion of xenocin occurred though an atypical pathway.

Schematic representation of xenocin operon xciA and ximB genes. P1, inducible promoter; P2, constitutive promoter; T, translocation domain; R, receptor binding domain; C, catalytic domain; I, immunity domain; H, hemolysin domain.

Bacteria have adopted a variety of mechanisms to translocate effector proteins across the cell envelop. The secretion systems have been classified as types I to VII (21 ). In addition to the well-established pathways, secretion of toxins also occurs commonly through membrane blebs in many pathogenic bacteria (22 ). There are two protein export machineries exclusive and inbuilt into bacterial organelle biogenesis system, the chaperon-usher system for translocation and assembly of pilin subunits (23 ) and flagellar biogenesis on the cell surface. In both the cases the nascent subunit proteins are exported through a dedicated system in a sequential manner for assembly of the mature organelle. The export of flagellar subunits directly from the cytoplasm to the cell surface resembles the contact-dependent type III secretion of Gram-negative bacteria. Some of the common features, e. g. homology in the sequence of the subunits and secretion of substrates without modification, reflects functional similarities between the two systems. The flagellar secretory system exports a number of effector proteins/virulence factors in addition to flagellar components out of the cell (13. 24. –. 26 ). However, data regarding recognition and targeting of potential substrates to the flagellar secretory machinery are conflicting and not very well defined (27. –. 29 ).

Screening of the X. nematophila genome for secretion systems revealed the total absence or redundancy of major protein secretory pathways in this insect pathogen and predicted that flagellar export apparatus and type Vb systems identified in the genome play a wider role in effector protein export (30 ). Thus, in the light of the clues obtained from genomic analysis of X. nematophila. this study was conducted to explore the involvement of the flagellar type III secretory system in xenocin export. Our results demonstrate that under SOS conditions, xenocin-IP is translocated as a complex through the flagellar pathway in X. nematophila.

MATERIALS AND METHODS

Bacterial strains, media, and culture conditions. Bacterial strains and plasmids used in this study are listed in Table 1. X. nematophila 19061 and xciA . flhA . fliA . and fliC mutant strains of X. nematophila were maintained on LB medium containing appropriate antibiotics. Ampicillin was used at 50 ?g/ml, kanamycin at 25 ?g/ml, and chloramphenicol at 25 ?g/ml as required. All of the Xenorhabdus strains were grown for 24 h at 30°C, and E. coli strains were grown for 14 to 16 h at 37°C with shaking at 200 rpm for procedures requiring general growth. For secretion-related experiments, strains were grown without shaking in 2? LB medium at 30°C for 16 to 18 h. The plasmid pJQ200SK+ was maintained in E. coli DH5?, which was grown in LB medium with 5 ?g/ml gentamicin. Escherichia coli S-17.1 was used to conjugally transfer the plasmids to X. nematophila. E. coli strain pLysS was used as the indicator strain for bactericidal activity. The plasmid vector pGEM-T Easy, from Promega (Madison, WI), was used for PCR cloning. pCR-XL-TOPO and pBCSK(+) were used for cloning and complementation studies. The data presented here are representative of experiments performed at least 2 to 3 times with all the strains.

Strains and plasmids used in the study

Preparation of cytosolic and extracellular proteins from Xenorhabdus strains. X. nematophila strains were grown at 30°C as static cultures until the optical density at 600 nm (OD 600 ) reached 0.4 to 0.5 and induced with 0.25 ?g/ml mitomycin C for 2 to 3 h for xenocin expression. After induction, samples were collected at different time points and centrifuged, and the supernatant was passed through a nonpyrogenic 0.22-?m-pore-size filter. Extracellular proteins were precipitated with 10% (wt/vol) ice-cold trichloroacetic acid at 4°C for 3 h and centrifuged, and the pellet was resuspended in 50 mM Tris-HCl buffer, pH 8.0. The cell pellet from 1 to 2 ml of culture was boiled for 5 min in sample loading dye and centrifuged, and the supernatant was loaded in the gel.

Cellular fractionation. Different cellular fractions of X. nematophila containing cytoplasmic, outer membrane, and periplasmic proteins were prepared as described earlier (7 ) and were analyzed by Western blotting using antibodies of xenocin and immunity protein. All of the subcellular fractions were checked for the respective markers; alkaline phosphatase as a periplasmic marker, glyceraldehyde-3-phosphate dehydrogenase (32 ) and GroES as cytoplasmic markers, and OpnP as an outer membrane marker were used to validate the fractions.

Preparation of flagella. Flagella were isolated from cells grown in LB medium as described before (33 ) and induced with mitomycin C for 2 h. The cells were harvested by centrifugation and suspended in 100 mM Tris-HCl buffer (pH 7.5), vortexed for 5 min, and centrifuged to remove the cells. The supernatant containing the flagella was filtered to remove floating cells. The supernatant was centrifuged at 75,000 rpm for 40 min. The pellet was washed repeatedly and resuspended in 100 mM Tris-HCl buffer, pH 7.5, with 1 mM phenylmethylsulfonyl fluoride.

Immunoprecipitation. The protein fractions from wild-type X. nematophila were incubated with anti-IP serum for 1 h at room temperature, followed by addition of protein A-Sepharose beads for an hour at room temperature. The beads were centrifuged, washed thoroughly, boiled in SDS-PAGE sample buffer, and resolved by gel electrophoresis. Western blotting was performed with antibodies against xenocin and a nontarget protein, GroES.

Bacteriostatic activity of different cellular fractions. Growth-inhibitory activity of the preparations was determined in indicator plates prepared by overlying 3 ml of soft nutrient agar, containing E. coli indicator cells, grown in M9 medium on LB agar plates. The cellular fractions were filter sterilized and applied on sterile filter paper discs placed on the surface. The plates were incubated at 37°C overnight, and the clearance zone was recorded.

RT-PCR of flagellar genes. X. nematophila cultures were induced with mitomycin C as described above for 2.5 h. The culture was centrifuged and total RNA was isolated from the cells using an RNeasy kit (Qiagen) as described before (19 ). The RNA was treated with DNase and checked by PCR for DNA contamination. A 50-?l reaction mixture was set up with 800 ng of purified RNA using a Qiagen one-step reverse transcription-PCR (RT-PCR) kit and primers shown in Table S1 in the supplemental material. The reaction was amplified for 25 cycles.

Construction of xciA - null strain of X. nematophila. The 1.7-kb xciA gene was amplified by PCR using X. nematophila genomic DNA as the template and primers 1 and 3 (see Table S1 in the supplemental material) as described before (19 ). The PCR-amplified fragment was cloned in the pGEM-T Easy vector, producing p xciA . Similarly, a 1.5-kb kanamycin cassette was amplified using plasmid pJH101 (34 ) as the template and cloned in pGEM-T Easy vector. The kanamycin cassette was excised and ligated at the unique BglII site in the p xciA - generating pPSA. The 3.2-kb fragment containing the disrupted xciA gene was excised from pPSA with BamHI and SalI and ligated to plasmid pJQ200SK+ at complementary sites. The resulting plasmid, pPSB, was electroporated into E. coli S-17.1, producing strain PSB. pPSB in E. coli S17.1 was conjugally transferred into X. nematophila as described earlier (35 ). The allelic replacement in Km r Cm s exconjugants was verified by PCR amplification and Southern analysis.

To complement the xciA mutant, a 3.7-kb DNA fragment containing both xciA and ximB genes with the native promoter was amplified using primers XciAB F (879 bp upstream of the start codon of the xciA locus) and primer 2 and was cloned in the pCR-XL-TOPO(+) vector, producing pAB. pAB DNA was digested with BamHI and PstI, and the released fragment was ligated in pBCSK(+) at complementary sites, producing pXAB construct, which was chemically transformed in the xciA mutant as described earlier (36 ). The xciA mutant was also complemented with the xciA gene alone. A 2.6-kb DNA fragment containing xciA with 5?-untranslated promoter sequence was amplified using primer XciAB F and primer 3 and cloned into pGEM-T Easy vector. The DNA was digested with BamHI and HindIII, and the fragment was subcloned in pBCSK(+) vector. The construct pXA was chemically transformed in the xciA mutant as described earlier (36 ).

SDS-PAGE and Western blot analysis. Ten to 20 ?g of total protein from different strains was loaded in the gel, and all the lanes in one gel contained the same amount of protein. The proteins were resolved by SDS-PAGE followed by Western blotting. The blots were developed with polyclonal antibodies raised against the proteins. Xenocin and IP antibodies were used at a dilution of 1:4,000 and 1:5000, respectively, and the proteins were detected with nitroblue tetrazolium-5-bromo-4-chloro-3-indolylphosphate substrate.

Cloning of ximB with 5? untranslated sequence and expression of immunity protein in E. coli DH5? cells. ximB sequence with 300 bp of the 5?-untranslated region (UTR) containing its promoter was PCR amplified using primers ximB-UTR and ximB RP and cloned in pGEM-T Easy vector. The resulting plasmid pimm was transformed in E. coli DH5? cells and IP synthesis was examined in different cellular fractions of an overnight grown culture, without induction.

Construction of xenocin variants in a heterologous vector and expression in X. nematophila. A heterologous ptac-pBCSK vector was produced by ligating the tac promoter at the XbaI and BamHI site of pBCSK(+) (Stratagene). The tac promoter was obtained from pGEX-4T1 (GE Health Care Life Sciences) vector by PCR amplification, using TacF and TacR primers. The DNAs encoding different protein variants (see Fig. 8A ) were amplified by PCR using primers shown in Table S1 in the supplemental material, cloned at BamHI and HindIII sites of ptac-pBCSK vector, and transformed in E. coli DH5? cells. The plasmid DNAs pPS1 to pPS4 were prepared from E. coli and transformed into a chemically competent xciA mutant strain of X. nematophila (Table 1 ). All of the strains were grown as static cultures in 2? LB medium at 30°C, and log-phase cells (OD 600 of 0.4 to 0.5) were induced with 1 mM isopropyl-? - d - thiogalactopyranoside (IPTG) for 2 h. Samples were taken and processed as described above and analyzed by Western blotting.

Mutation of active-site residues of xenocin. A homology model was generated based on the structure of bacteriocin E3 of E. coli (37 ) using http://www. fundp. ac. be/urbm/bioinfo/esypred/. Six key residues (D535, H538, E542, H551, K564, and R570) in the active site of RNase (xenocin) were altered to alanine by site-directed mutagenesis to produce nontoxic xenocin. For mutagenesis, the 1.7-kb xciA DNA was used as the template with primers (see Table S1 in the supplemental material), and the altered DNAs were expressed in E. coli cells. These strains were tested for growth, and the variant proteins were analyzed by CD spectra. The nontoxic variants D535A and H538A of xciA were able to grow like the vector control, and the wild-type genes were subcloned in ptac-pBCSK vector and transformed in the xciA knockout strain of X. nematophila. The proteins were induced by 1 mM IPTG for 2 h as described above and examined by Western blotting.

RESULTS

Detection of xenocin and IP in cellular fractions after induction of X. nematophila. To determine the secretion pathway of the xenocin-IP complex, different cellular and extracellular fractions were examined. Induction of SOS response in the wild-type X. nematophila cells with mitomycin C resulted in synthesis and release of both xenocin and immunity proteins in the soluble fraction (obtained after ultracentrifugation of the culture supernatant), while GroES, a cytosolic protein marker, was not detected (Fig. 2A ). The OD 600 and CFU/ml in the induced culture was not very different (0.40 and 3 ? 10 7. respectively) from those of the uninduced culture (0.42 and 5 ? 10 7. respectively) after 2.5 h; in addition, release of an intracellular enzyme, glyceraldehydes-3-phosphate dehydrogenase, in the culture supernatant was negligible relative to intracellular levels (2.1 U/mg protein). This suggested that xenocin was exported by a specific pathway and not by cell lysis. Neither xenocin nor immunity protein was detected in the outer membrane or outer membrane vesicles (Fig. 2B ). The IP was present alone in the periplasmic fraction of both induced and uninduced cells. No xenocin was detected in the periplasm under either condition (Fig. 2C ). The presence of IP in the periplasm of uninduced cells indicated that it is produced constitutively and released in the culture supernatant by a yet-unknown mechanism. We have shown earlier (19 ) that the xenocin operon had two promoters: the SOS-inducible P1, upstream of the xciA gene, produced a bicistronic transcript, and P2, upstream of ximB . constitutively produced a smaller RNA (Fig. 1 ). To demonstrate specific targeting of constitutively produced IP to the periplasm, a plasmid containing the ximB locus with its constitutive, upstream promoter sequence in the pGEM-T Easy vector was produced and transformed in E. coli DH5? cells. Examination of proteins localized in different cellular fractions showed the presence of IP in the cytosol and periplasm but not in the flagella of transformed cells grown overnight. No protein was detected in the untransformed host cells (Fig. 3 ). Immunoprecipitation of the cytoplasmic and culture supernatant proteins of wild-type X. nematophila with antibody against IP demonstrated that xenocin and IP were present as a complex in both fractions (Fig. 2D ).

Secretion analysis of xenocin and IP in wild-type X. nematophila by Western blotting. (A) The cells were induced with 0.25 ?g/ml mitomycin C for 2 to 3 h, and total secreted proteins were separated from the cell pellet and precipitated with 10% TCA. The cell pellet and culture supernatant fractions were analyzed using antibodies against xenocin, IP, and GroES. (B) Total culture supernatant proteins were fractionated, and xenocin and IP were detected in different fractions with their respective antibodies. OMV, outer membrane vesicles. (C) Xenocin and IP were detected in the periplasmic fraction with their respective antibodies. (D) Cytosolic and culture supernatant proteins from induced culture of X. nematophila were immunoprecipitated with antiserum against IP and protein A-Sepharose beads, followed by SDS-PAGE and blotting with anti-xenocin antibodies or anti-GroES as a nontarget control. (E) Flagella were prepared from cells grown in LB broth, induced, and incubated under stationary conditions. Xn, purified xenocin; IP, purified IP; U, uninduced; I, induced. Lane M, low-range, prestained molecular mass markers (in kDa; Bio-Rad).

Export of constitutively expressed immunity protein. E. coli DH5? cells containing the ximB locus with an 5?-upstream promoter sequence in pGEM-T Easy vector was grown overnight. Cytosolic, periplasmic, and flagellar proteins were prepared without induction. The fractions were analyzed with antibody against IP. Lane M, low-range, prestained molecular mass markers (in kDa).

Bioinformatic analysis of xenocin polypeptide sequence showed neither a leader sequence nor any motifs involved in protein export (38. 39 ). To get an idea of the probable export pathway, we proceeded to determine the N-terminal sequence of the processed protein, purified from the culture supernatant of recombinant M15 E. coli by ammonium sulfate precipitation, followed by SP Sepharose column chromatography. However, attempts to purify xenocin protein repeatedly failed due to copurification of FliC protein of E. coli (identified by its N-terminal sequence). This suggested an association of xenocin with the flagella as a possible route of export. Hence, to examine the involvement of the flagellar system in xenocin export, flagella were prepared from wild-type X. nematophila cells after induction with mitomycin C. Protein analysis by Western blotting identified both xenocin and IP in the flagella from induced cells only (Fig. 2E ); none of the proteins were detected in the flagella of uninduced cells (Fig. 2E ). The association of xenocin and IP with flagella is not due to cosedimentation during high-speed centrifugation of flagella, as immunogold labeling of Xenorhabdus cell or isolated flagella with xenocin antibody showed negligible binding by transmission electron microscopy (unpublished results), suggesting the presence of the proteins within the flagellar fiber. Antibacterial activity was also detected in the flagellar preparation from induced cells; none of the proteins or bioactivity was observed in the flagella from uninduced cells, demonstrating close association of xenocin complex with the flagella of X. nematophila.

Flagellar genes are not regulated by mitomycin C. To examine the effect of mitomycin C on the flagellar operon, total RNA from mitomycin-induced X. nematophila cells was subjected to semiquantitative RT-PCR, and relative abundances of flhC . fliA . fliC . and xciA genes were measured. The results showed that mitomycin C specifically upregulated xciA transcription only, and none of the flagellar genes were affected in that time period, demonstrating independent control of the two gene clusters (Fig. 4 ).

RT-PCR analysis of flagellar genes after induction with mitomycin C. Total RNA was prepared from X. nematophila cells after induction, and mRNA levels were analyzed. U, uninduced; I, induced. Arrow shows the xciA amplicon.

Analysis of protein secretion by xciA mutant. To ascertain that xenocin is indeed responsible for the observed antibacterial activity and is secreted through the flagellar system, the xciA gene was insertionally inactivated by allelic exchange. After induction of the SOS response with mitomycin C for 2.5 h, the OD 600 and CFU/ml counts in the culture (0.46 and 4.5 ? 10 7. respectively) were similar to those of uninduced culture (0.53 and 5.2 ? 10 7. respectively). The cells produced no xenocin in the culture supernatant (Fig. 5A ). However, IP was produced alone, with or without induction, and was detected in the cytosol, periplasmic fraction, and culture supernatant, similar to the wild-type strain (Fig. 5B ). In the uninduced cells, IP was synthesized from the constitutive promoter P2 (not affected by polar effect due to disruption of xciA ) and targeted to the periplasm and the culture supernatant (Fig. 5B ). After induction, amounts of IP in the fractions described above were similar to those of uninduced conditions (Fig. 5B ), indicating no additional synthesis from the inducible promoter, P1. Unlike the case for the wild-type strain, IP was not detected in the flagella under any condition, with or without induction, in the xciA null mutant strain (Fig. 5B ). These results suggest that (i) due to disruption of the xciA gene, no IP was produced from the inducible P1 promoter; and (ii) for localization of IP in the flagellum, either a P1 mRNA or a xenocin-IP complex is required. The IP synthesized constitutively from P2 is expressed but not targeted to the flagella (Fig. 3 ). Similarly, consistent with the absence of xenocin and IP from the flagellar preparation, no antibacterial activity was observed after induction with mitomycin C (Table 2 ). Complementation of the mutant with xciA-ximB sequence restored xenocin protein expression in the culture supernatant (Fig. 5C ) and bactericidal activity in the flagella (Table 2 ). However, complementation with xciA alone was toxic for the cell. The cell density was very low compared to that of the noncomplemented strain after 20 h of growth, and no xenocin could be detected in the induced cells (data not shown). Early detection of only IP in the culture supernatant at 1.5 h, ahead of xenocin, appears to be due to constitutive synthesis of the protein in both the xciA mutant and the complemented strains.

Secretion analysis of xciA and xciA - complemented mutant strains by Western blotting. (A and B) xciA cells were induced with mitomycin C for 2.5 h, and samples were taken at different time points. The cell pellets were separated from the supernatant and precipitated with TCA, and the proteins were analyzed. (C) Protein fractions from xciA + cells were isolated as described in the text and analyzed. Xn protein, purified xenocin. Cytosolic proteins refers to proteins at 2.5 h of induction of the respective strains. Lane M, low-range, prestained molecular mass markers (in kDa).

Exogenous antibacterial activity and proteins in flagellar preparation from different strains

Secretion of xenocin requires FlhA. To confirm secretion of xenocin-IP complex through the flagellar type III system of X. nematophila. an flhA mutant strain (13 ) lacking FlhA, a membrane component of the basal body necessary for export of flagellar subunits, was employed. Induction of SOS response in this strain with mitomycin C did not affect cell density, and OD 600 and CFU/ml counts in the culture were 0.41 and 3.1 ? 10 7. respectively, similar to those of uninduced culture (0.44 and 3.2 ? 10 7. respectively) after 2.5 h. The cellular protein profile of the mutant showed the presence of both xenocin and IP in the cytoplasmic fraction of the induced cells (Fig. 6A ), but no xenocin was detected in the culture supernatant (Fig. 6A ). However, IP alone was detected in the culture supernatant of the flhA mutant, suggesting that IP can be exported through a route other than that of the flagellum (Fig. 6A ). The major flagellar subunit FliC was produced in the cells normally but was not exported. Unlike the case in E. coli and Salmonella. FliC expression in Xenorhabdus occurs in the absence of flhA . as reported earlier (13 ), leading to normal levels of FliC synthesis in the flhA strain. Complementation of the flhA mutant with flhA - flhB sequence restored secretion of both xenocin complex and FliC proteins, as expected (Fig. 6B ).

Secretion analysis of flhA and flhA - complemented mutant strains by Western blotting. The samples were taken after induction as described in the text, and proteins in the culture supernatant were separated from the cells. The proteins were precipitated with TCA and analyzed. Cytosolic proteins indicates proteins at 2.5 h of induction of the respective strains. Lane M, low-range, prestained molecular mass markers (in kDa).

Analysis of fliA and fliC mutants for xenocin-IP complex secretion. To determine if the xenocin operon was coregulated by FliA (?28), a transcription factor that regulates class III flagellar genes, an fliA mutant strain of X. nematophila was used. There was no difference between the synthesis and secretion of xenocin complex in the fliA mutant strain and those in the wild-type cells (Fig. 7A ), indicating that xenocin complex was transcribed independently and secreted through the flagella, unlike the fliA - regulated class III flagellar component, FliC, which was not produced in this strain. The growth rate of the fliC mutant strain was found to be lower than that of the wild-type strain. Xenocin-immunity protein complex was produced and secreted normally after mitomycin C induction in the absence of flagellar filament as shown in Fig. 7B. indicating that absence of flagellar filament does not affect xenocin export.

Secretion analysis of fliA and fliC mutants by Western blotting. (A) Wild-type and fliA mutant cultures were induced with mitomycin C and samples taken after 2.5 h. Proteins in the culture supernatant were precipitated and analyzed. WT, wild type. (B) Cytosolic and culture supernatant proteins of the fliC mutant strain were induced with mitomycin C, and samples were taken at different time points and processed as described in the text. Cytosolic proteins were analyzed at 2.5 h; flagellin control indicates purified flagellin. Lane M, low-range, prestained molecular mass markers (in kDa).

Secretion of xenocin variants in X. nematophila. To determine the minimum essential sequence necessary for secretion through the flagella, DNA sequences encoding xenocin variants were cloned and expressed in the xciA strain of X. nematophila under an IPTG-inducible promoter. The results show that xenocin and IP were produced in the cytosol and exported to the flagella and outside the pPS1 plasmid, containing only the coding sequences of the proteins (Fig. 8B ). This implied that the 5?-UTR of the xciA gene is not necessary for targeting the complex to flagellar export. To examine the role of IP in export of the complex, pPS2 containing the xciA sequence without ximB was tested. The wild-type xenocin, when expressed in the absence of IP, was less abundant, suggesting that IP is required for xenocin stability in the cytoplasm. Since the cells harboring the plasmid eventually lysed, flagellar localization could not be examined (Fig. 8C ). It is puzzling as to why the constitutively produced IP could not neutralize the toxicity of xenocin. We suspect that the amount of constitutively produced IP is not enough to inactivate xenocin produced from a multicopy plasmid, as it has been observed earlier that more than a 3 times molar excess of IP was required to neutralize xenocin under in vitro conditions (19 ). Alternatively, the constitutively produced IP, in isolation, may not be readily accessible for complex formation, or it may be chemically/structurally distinct from the inducible IP, not amenable to complex formation. Further work will be needed to answer these interesting questions.

(A) Schematic representation of xciA-ximB constructs. Filled boxes represent the DNA sequences present in the constructs. An asterisk denotes the altered amino acid. Arrows and numbers above them indicate the positions of the primers. For secretion analysis, different DNA constructs were tested in the xciA mutant by Western blotting. Strains were induced with IPTG for 2 to 3 h, cells were separated, and flagella were prepared. Proteins in the culture supernatant were precipitated with 10% TCA. All of the cell pellets and supernatant fractions were probed with anti-GroES antibodies as controls for cell lysis. Lane M, low-range, prestained molecular mass markers (in kDa). (B) Xenocin operon. (C) Xenocin variants D535A and H538A.

To neutralize xenocin toxicity, we produced enzymatically inactive protein by introducing point mutations in the active site. Growth profiles of the E. coli strains containing xenocin variants D535A and H538A (pPS3 and pPS4) were similar to that of the vector control and showed minimal inhibition in growth compared to the wild-type protein (data not shown). Far-UV circular dichroism spectra of the nontoxic variant indicated that the secondary structure of the latter was not disturbed (data not shown). The plasmids pPS3 and pPS4, when transformed in the xciA mutant, allowed variant xenocin expression in the absence of IP without causing cell lysis when induced with mitomycin C, in contrast to cells containing the wild-type xciA variant. Analysis of expression by Western blotting with anti-xenocin antibody showed the presence of variant xenocin in the cytoplasmic fractions, flagella, and the culture supernatant (Fig. 8C ). The level of expression of xenocin alone was lower than that when it was produced as a complex with IP, which could be due to the higher proteolytic susceptibility of the unprotected protein. The individual domains of xenocin, e. g. translocation, translocation-receptor binding, and catalytic domains, were not expressed very stably in the cytosol, hence their export could not be evaluated with a reasonable degree of confidence (data not shown).

DISCUSSION

Previously, we have described an antibacterial protein xenocin of X. nematophila that has activity against several bacterial species colonizing the larval gut (19 ). Bacteriocins need to be transported out of the cell to be functionally active, which occurs by a well-established mechanism of cell lysis orchestrated by a lysis-inducing gene (15 ). In this study, we demonstrate that the xenocin-IP complex of X. nematophila is released in the extracellular medium through the flagellar type III pathway, which has not been reported before for a bacteriocin.

In bacterial cultures, as the nutrients are depleted due to overcrowding, bacteriocins are induced and released by cell lysis to eliminate the competitor strains. As a consequence, most of the producer population is killed, leaving a small number to withstand the unfavorable conditions (15 ). In X. nematophila. since antimicrobials are produced in a nutrient-rich insect carcass to control putrefying competitors (40. 41 ), it may be counterproductive to reduce its own population, considering the requirement of high population density for efficient nematode reproduction (42. –. 44 ). This might have driven xenocin export by an alternate route without lysing the cell, as it would be beneficial for the evolutionary success of the symbiotic relationship. In a similar case in Pseudomonas aeruginosa. effector toxins were delivered directly in the target cells by a type VI secretion system, thereby minimizing the fitness cost associated with self-targeting, and further, to prevent self-intoxication, the cognate immunity proteins were localized in the periplasm (45 ). In X. nematophila. we do not know if xenocin is delivered directly to the target cell; however, its direct export outside without cell lysis/self-targeting would surely help in sustaining mutualism, which is vital to its survival in nature.

Our study reveals a unique feature of the immunity protein export in X. nematophila. Synthesis of IP alone, constitutively from the second promoter, P2, and with xenocin from the inducible promoter P1 is in agreement with our earlier observation of two transcripts of 1.2 and 2.9 kb (19 ). The results of this study show that IP produced from different promoters is exported through different routes. This has never been reported before and raises important questions about, e. g. the specific role of the constitutively produced IP in the periplasm in light of the C-terminal hemolysin domain in the protein (19 ). The 5?-UTR or the coding sequence of IP appears to contain a signal for targeting it only to the periplasm, as it is never seen alone in the flagella. The nature of the signal sequence/motif and mode of subsequent release of IP in the medium are not known and will be addressed in the future. The presence of IP in the periplasm has been reported for strains producing bacteriocins that act on the murein layer, e. g. colicin M and pesticin, and require an IP to neutralize the incoming bacteriocins (46. –. 49 ). Since bacteriocins displaying nuclease activity, like xenocin, contain tightly bound IP both in the intracellular and released form (37. 47 ), presence of free IP in the periplasm is unexpected, and its function entails further investigation. The results suggest that function of the inducible IP is to neutralize lethal activity of xenocin by forming a complex until it is exported out of the producer cell and to protect it from proteolytic degradation. It does not appear to be involved in translocation of the complex, as the nontoxic xenocin variants were exported through the flagellum alone. Under the circumstances, the constitutively produced IP that is present in the cell could not have substituted for inducible IP in xenocin export, because if it were so, the wild-type xenocin (when expressed alone) would be stable and harmless to the cell (Fig. 8C ). Based on the observations described above, it can be concluded that xenocin alone has the necessary information for export.

In the absence of a dedicated lysis-inducing system in the proximity of the xenocin operon, we searched for genes implicated in bacteriocin secretion in the genome of X. nematophila (http://www. xenorhabdus. org ; RefSeq NC_014228.1) with no significant results. No secretion signal could be identified in the N terminus of xenocin. This is in contrast to the export of the flagellin protein FliC in E. coli and Salmonella. the N terminus of which contains the signal for export through flagella (50. –. 52 ). Similarly, in Campylobacter jejuni. targeting of FlaA and FlaB was mediated by their amino termini (53 ), while in Y. enterocolitica the signal for export of YopQ through the type III system was reported to be in the mRNA (54 ), reflecting the lack of consensus in the recognition motif of substrates. Primary sequence comparison of xenocin to other effector proteins secreted through the flagellar route, e. g. a lipase of X. nematophila (13 ), phospholipase of Yersinia enterocolitica (26 ), and flagellar subunits FliC and FliD, did not reveal any common, conserved motif. Thus, it is evident that characteristics of recognition and targeting signals of substrates to the flagellar and type III secretory machinery are yet to be established (27 ).

It is intriguing that an ?100-kDa protein complex travels through the narrow 20- to 30-A-diameter channel of the flagellar filament (55 ). Flagellar subunits, including the major 55-kDa FliC, are synthesized in the cytoplasm and translocated to the distal end of the growing flagella through a 2- to 3-nm channel (56 ); it is suggested that the flagellin transits partially unfolded through this channel to its tip, where it refolds before inserting into the growing filament (57. 58 ). A 41-kDa lipase encoded by xlpA . contiguous to the xciA locus, is also exported through the flagella in X. nematophila (13 ); however, since it is transcribed divergently by an FliA-dependent promoter, their cotranslocation seems unlikely. Incidentally, Photorhabdus luminescens. another closely related, insect-pathogenic bacterium carried by entomopathogenic nematodes, contains a bacteriocin cluster adjacent to the flagellar operon (59 ) and could be a substrate for export via flagella. Several pathogenic bacteria are known to export effector proteins and virulence factors through the flagellar type III apparatus (60 ), but molecular details of translocation have not been elucidated.

Thus, despite the facts that (i) IP is synthesized and exported alone via the periplasm, (ii) the constitutively produced IP, though present, is unable to protect the cell, and (iii) IP apparently is not required for xenocin export through the flagellum, the existence and export of xenocin alone, not in complex with IP, is suicidal for the producer cell. While the combined evidence, e. g. transcription of xciA and ximB as a single transcript and detection of xenocin and IP together in the cytosol by immunoprecipitation and in the flagella only after mitomycin C induction, strongly argue for transport of xenocin-IP together. At this stage, it is not clear if the proteins travel by themselves or if they are assisted by another protein/chaperone, which is common in type III secretory systems (61 ).

In conclusion, the physiological significance of bacteriocin export through the flagellar route and not by cell lysis could be that it enables X. nematophila to maintain high population density, and it may provide a growth advantage over competing species. Also, secretion through flagella would ensure its effective dissemination in the environment through cellular motility. Another function that may benefit X. nematophila that needs to be explored is whether the flagella can directly deliver xenocin to the target species, as reported for EtpA of enterotoxigenic E. coli (62 ). Thus, in the absence of a dedicated (nonflagellar) type III secretory system (13 ), the flagellar pathway could be employed for efficient, targeted killing of competing microbes by X. nematophila.

ACKNOWLEDGMENTS

We thank Jitendra Singh for his participation in the early stages of the study.

This work was supported by in-house funding from ICGEB, New Delhi, India.

Nicardia Generic Name Nifedipine Online, Nicardia

Nicardia General Information

Nicardia - Pharmacology:

Nicardia inhibits the influx of extracellular calcium through myocardial and vascular membrane pores by physically plugging the channel. The decrease in intracellular calcium inhibits the contractile processes of smooth muscle cells, causing dilation of the coronary and systemic arteries, increased oxygen delivery to the myocardial tissue, decreased total peripheral resistance, decreased systemic blood pressure, and decreased afterload.

Nicardia for patients

Nicardia, known as a calcium channel blocker, is used to treat high blood pressure and some forms of chest pain known as angina. This medication works by relaxing blood vessels and decreasing the pressure on the heart. This can lead to dizziness, headache, lightheadedness, flushing and swelling of the legs. You should report this to your physician because it can often be easily treated with a diuretic (water-pill). This medication is available in an extended-release form allowing for once a day dosing. Some brands must be taken on an empty stomach. Other brands are made in porous capsule which slowly releases the medication. You may notice the empty capsule in your stool. Extended release medications should not be crushed, cut or split because this destroys the slow release mechanism. If you are taking this for high blood pressure, you should have your blood pressure checked regularly to make sure the medication is working.

This description is suitable for active ingredient Nifedipine

Nicardia Interactions

Beta-adrenergic Blocking Agents: Experience in over 1400 patients in a non-comparative clinical trial has shown that concomitant administration of nifedipine and beta-blocking agents is usually well tolerated, but there have been occasional literature reports suggesting that the combination may increase the likelihood of congestive heart failure, severe hypotension or exacerbation of angina.

Long Acting Nitrates: Nicardia may be safely co-administered with nitrates, but there have been no controlled studies to evaluate the antianginal effectiveness of this combination.

Digitalis: Immediate Release Capsules: Since there have been isolated reports of patients with elevated digoxin levels, and there is a possible interaction between digoxin and nifedipine, it is recommended that digoxin levels be monitored when initiating, adjusting, and discontinuing nifedipine to avoid possible over - or under-digitalization. Extended Release Tablets: Administration of nifedipine with digoxin increased digoxin levels in 9 of 12 normal volunteers. The average increase was 45%. Another investigator found no increase in digoxin levels in 13 patients with coronary artery disease. In an uncontrolled study of over 200 patients with congestive heart failure during which digoxin blood levels were not measured, digitalis toxicity was not observed. Since there have been isolated reports of patients with elevated digoxin levels, it is recommended that digoxin levels be monitored when initiating, adjusting, and discontinuing nifedipine to avoid possible over - or under-digitalization.

Quinidine: Immediate Release Capsules: There have been rare reports of an interaction between quinidine and nifedipine (with a decreased plasma level of quinidine).

Coumarin Anticoagulants: There have been rare reports of increased prothrombin time in patients taking coumarin anticoagulants to whom nifedipine was administered. However, the relationship to nifedipine therapy is uncertain.

Cimetidine: A study in 6 healthy volunteers has shown a significant increase in peak nifedipine plasma levels (80%) and area-under-the-curve (74%) after a 1 week course of cimetidine at 1000 mg per day and nifedipine at 40 mg per day. Ranitidine produced smaller, non-significant increases. The effect may be mediated by the known inhibition of cimetidine on hepatic cytochrome P-450, the enzyme system probably responsible for the first-pass metabolism of nifedipine. If nifedipine therapy is initiated in a patient currently receiving cimetidine, cautious titration is advised.

Nicardia Contraindications

Chemical Of The Day - Today S Chemical, Hydantin

The biggest concern that DMDM Hydantoin carries is that it can release or be contaminated with the carcinogen formaldehyde. It actually works as a preservative by releasing formaldehyde. It is also a strong skin, eye, and lung irritant. It has also been known to trigger an immune response that can include burning, itching, blistering, or scaling of skin.

Types of products it's in:

Shampoo, bodywash, sunscreen, hand lotion, facial moisturizers, baby wipes

Brands that use this chemical:

These are the brands we are currently aware of as of the date of this post. If you see a correction is needed or if you have other companies you would like to mention using this ingredient please post it in the "comments" at the bottom of this Chemical of the Day.

Bumble & Bumble (Not Bubble & Bee!)

Steph's Opinion: Isn't it interesting that these brands have built a reputation for being gentle and safe but they'll use a preservative like DMDM Hydantion. Think of this the next time you see their commercial. yes, Dove may not leave soap scum, but it'll outgas formaldehyde! And in baby wipes! It's just sad when there are other safer preservatives that don't leave traces of carcinogens.

I was using a product line from Whole Foods by Surya Brasil called Color Fixation Restorative Line (shampoo, conditioner etc.) that contains DMDM Hydanation & I informed the regional manager who said that this was unacceptable. Several months later they still carry this product line. WHAT. I was so disappointed. I figure "Whole Foods" is still "Corporate" & the goal of many corporations is $$$$. Period. I am fortunate to have a Co-op market which is for the people & they would & have never carried things of this nature. My opinion is support a Co-op Market if you have one & your local farmer's market for produce etc. They don't have "greed" in there eyes. Also, maybe order from small natural businesses online or find a natural food store other than Whole Food & never go to any other grocery store because they are even worse (i. e. Vons, Ralphs etc.). I appreciate these types of websites so. Thank you.

I have asthma and it was only about a year ago, when I was constantly having trouble breathing that I came across info on chemicals that triggered it. The one I narrowed it down to, for me, was DMDM. It was in a new, organic shampoo that I had been using (and sadly, loving!) I cannot remember the name at this time - possibly Bio Infusions? Yesterday I was having major trouble again. Finally realized it was a different lotion than I normally used. JERGENS lotion. It is also in V05 shampoo. I normally use Curel lotion and have never had a problem with it, my bottle does not list it as an ingredient.

Thanks for your informative help with chemicals in our products. DMDM Hydantoin is in TRESemme, Luxurious Moisture Shampoo and Conditioner. I received a sample of each in today's mail. I did call and gave feedback about it. I hope people do politely let manufacturers know that we need safer products. Lee S.

Just bought V05 Repair and protect conditioner today and decided to look up the ingredients to make sure it doesn't contain silicones. It doesn't contain silicones but it does contain dmdm hydantoin! I will have a look around your site while I'm here. I have very sensitive dry skin and have been using Dove soap per my doctors recommendation. I believe I need to examine all of my products! Glad I found this site. Thanks for the information.

I just purchased Mary Kay Timewise night solution and its disappointing to read the ingredients. There's not only DMDM Hydantoin but methylparaben and titanium dioxide. The terrific part is, Mary Kay is supported with "The Good Housekeeping Seal of Approval". I think GHSofA better research these ingredients before they label moisturizers that disrupt our hormones, are known to cause cancer in animals, banned in European products and the negative list goes on and on. Makes you consider your life insurance policy.

Hotel Shandranj - Tezero, Italiya, Tesero

Hotel Shandranj

Отель Shandranj, окруженный Доломитовыми Альпами, находится в небольшом районе Става, в 5 минутах езды от города Тезеро. К услугам гостей полностью оборудованный спа-центр и ресторан традиционной кухни региона Трентино. Номера оформлены в традиционном …

Отель Shandranj, окруженный Доломитовыми Альпами, находится в небольшом районе Става, в 5 минутах езды от города Тезеро. К услугам гостей полностью оборудованный спа-центр и ресторан традиционной кухни региона Трентино.

Номера оформлены в традиционном альпийском стиле и обставлены мебелью из светлого дерева. В числе стандартных удобств — спутниковое телевидение и собственная ванная комната с феном.

В спа-центре можно посетить сауну, турецкую баню и гидромассажную ванну. В распоряжении гостей светлый крытый бассейн.

В обильный завтрак «шведский стол» входят закуски и сладости. В хорошую погоду завтрак могут сервировать в меблированном саду. В ресторане подают блюда классической итальянской кухни и фирменные блюда региональной кухни.

На территории 4-звездочного отеля Shandranj есть бесплатная открытая парковка и платный гараж. В 3 км расположен горнолыжный центр «Латемар».

Гостям выдается бесплатная карта FiemmE-Motion, предоставляющая право на бесплатный проезд в общественном транспорте и бесплатное посещение некоторых развлекательных мероприятий, музеев и природных парков. Свяжитесь с администрацией отеля для получения более подробной информации, поскольку вышеописанные услуги зависят от сезона.

Cartril-S, Cartril-S

Cartril - S

CCM Pharmaceuticals Sdn Bhd provides a wide range of antirheumatic / antiarthritic / anti-gout products which includes cartril - S. It is a glucosamine sulfate sodium equivalent to glucosamine sulfate capsule/granules. It is in white to off white form. Size: 1 red / white, cartril-S and 1 red / red, cartril-S / 500. Packing: 100's/10 x 10's/30 x 4 mg. Contact us for more information.

Dosage: 250 mg/500 mg/1500 mg

Contact CCM Pharmaceuticals

CCM Pharmaceuticals

Address Lot 2 & 4 Jalan P/7 Section 13, Bangi Industrial Estate 43650 Bandar Baru Bangi, Selangor Darul Ehsan Malaysia +603-8924 2188 http://www. ccmberhad. com/f Visit profile

Nyefax, Nyefax

Indication

Action

-Nifedipine is a calcium channel blocker. It inhibits the slow inward calcium ion channels - It is a relaxant of vascular smooth muscle and an inhibitor of coronary artery spasm thus improving myocardial oxygen supply. - It inhibits the influx of calcium ions causing relaxation and peripheral vasodilatation, which in turn reduces the afterload against which the heart works. - It directly decreases myocardial oxygen consumption. - Reduction in blood pressure is mediated by relaxation of vascular smooth muscle and resultant decrease in peripheral vascular resistance.

Dose advice

-Hypertension: Initial dose is 10-20 mg twice daily. Dose can be increased to 40 mg twice daily if needed. - Recommended dose interval is about 12 hours - Patients with hepatic impairment should commence therapy at 10 mg twice daily with careful supervision - In cases of severe overdosage a. disturbances of consciousness, drop in blood pressure, tachycardic/bradycardic rhythm disturbance, hyperglycaemia, metabolic acidosis, cardiogenic shock with pulmonary oedema can occur.

Schedule

Common side effects

-Peripheral oedema - Hypotension - Dizziness - Flushing - Numbness - Tingling - Tiredness - Nausea - Vomiting - Heartburn - Dyspepsia - Headache

Uncommon side effects

-Auditory – tinnitus - Cardiovascular – tachycardia, chest pain, ischaemia - Gastrointestinal a. abdominal pain, diarrhoea, gum alterations - Dermatological a. exfoliative dermatitis, pruritus, urticaria - Nervous system a. acute psychosis, tremor, myalgia, - Others a. allergic hepatitis, hyperglycaemia, thrombocytopaenia, anaemia, leucopenia, gynaecomastia, transaminase increases, intrahepatic cholestasis, polyuria, glomerulonephritis, nephrotic syndrome, increased asthmatic symptoms after cessation of therapy in patients with chronic obstructive lung disease.

For further information talk to your doctor.

Nitroglycerin Infusion During Cardiac Surgery - Full Text View, Millisrol

Nitroglycerin Infusion During Cardiac Surgery

Further study details as provided by Tri-Service General Hospital:

Primary Outcome Measures:

Plasma lactate level [ Time Frame: one year ] [ Designated as safety issue: No ]

Perioperative blood loss [ Time Frame: one year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Mean arterial blood pressure [ Time Frame: one year ] [ Designated as safety issue: No ]

To keep mean blood pressure 50-80 mmHg during cardiopulmonary bypass.

Inotropic doses [ Time Frame: one year ] [ Designated as safety issue: No ]

Time to extubation [ Time Frame: one year ] [ Designated as safety issue: No ]

Other Outcome Measures:

Brain oximetry values [ Time Frame: one year ] [ Designated as safety issue: No ]

Values decreasing to 50 or less need interventions.

Yentreve (Duloxetine) Report For Patients Like You, Yentreve

Yentreve treatment report

See 1 evaluation from 1 patient with major perceived effectiveness

See 1 evaluation from 1 patient with moderate perceived effectiveness

See 2 evaluations from 2 patients with slight perceived effectiveness

See 0 evaluations from 0 patients with none perceived effectiveness

See 0 evaluations from 0 patients with unknown perceived effectiveness

This item is relevant to you: Depressed mood

See 0 evaluations from 0 patients with major perceived effectiveness

See 0 evaluations from 0 patients with moderate perceived effectiveness

See 0 evaluations from 0 patients with slight perceived effectiveness

See 0 evaluations from 0 patients with none perceived effectiveness

See 0 evaluations from 0 patients with unknown perceived effectiveness

See 0 evaluations from 0 patients with major perceived effectiveness

See 0 evaluations from 0 patients with moderate perceived effectiveness

See 0 evaluations from 0 patients with slight perceived effectiveness

See 1 evaluation from 1 patient with none perceived effectiveness

See 0 evaluations from 0 patients with unknown perceived effectiveness

See 0 evaluations from 0 patients with major perceived effectiveness

See 0 evaluations from 0 patients with moderate perceived effectiveness

See 0 evaluations from 0 patients with slight perceived effectiveness

See 0 evaluations from 0 patients with none perceived effectiveness

See 0 evaluations from 0 patients with unknown perceived effectiveness

See 0 evaluations from 0 patients with major perceived effectiveness

See 0 evaluations from 0 patients with moderate perceived effectiveness

See 0 evaluations from 0 patients with slight perceived effectiveness

See 0 evaluations from 0 patients with none perceived effectiveness

See 0 evaluations from 0 patients with unknown perceived effectiveness

See 0 evaluations from 0 patients with major perceived effectiveness

See 0 evaluations from 0 patients with moderate perceived effectiveness

See 1 evaluation from 1 patient with slight perceived effectiveness

See 0 evaluations from 0 patients with none perceived effectiveness

See 0 evaluations from 0 patients with unknown perceived effectiveness

See 1 patient that have taken Yentreve

What is duloxetine?

Duloxetine is an antidepressant in a group of drugs called selective serotonin and norepinephrine reuptake inhibitors (SSNRIs). Duloxetine affects chemicals in the brain that may become unbalanced and cause depression.

Duloxetine is used to treat major depressive disorder and general anxiety disorder. It is also used to treat a chronic pain disorder called fibromyalgia, and to treat pain caused by nerve damage in people with diabetes (diabetic neuropathy).

Duloxetine may also be used for other purposes not listed in this medication guide.

Precautions

Do not use duloxetine together with thioridazine (Mellaril), or an MAO inhibitor such as isocarboxazid (Marplan), tranylcypromine (Parnate), phenelzine (Nardil), rasagiline (Azilect), or selegiline (Eldepryl, Emsam). Serious and sometimes fatal reactions can occur when these medicines are taken with duloxetine. You must wait at least 14 days after stopping an MAO inhibitor before you can take duloxetine. After you stop taking duloxetine, you must wait at least 5 days before you start taking an MAOI.

Do not use this medication if you are allergic to duloxetine, or if you have untreated or uncontrolled glaucoma.

Before taking duloxetine, tell your doctor if you are allergic to any drugs, or if you have:

liver or kidney disease;

seizures or epilepsy;

a bleeding or blood clotting disorder;

glaucoma;

bipolar disorder (manic depression); or

a history of drug abuse or suicidal thoughts.

If you have any of these conditions, you may need a dose adjustment or special tests to safely take duloxetine.

You may have thoughts about suicide when you first start taking an antidepressant, especially if you are younger than 24 years old. Tell your doctor if you have worsening symptoms of depression or suicidal thoughts during the first several weeks of treatment, or whenever your dose is changed.

Your family or other caregivers should also be alert to changes in your mood or symptoms. Your doctor will need to check you at regular visits for at least the first 12 weeks of treatment.

FDA pregnancy category C. Duloxetine may be harmful to an unborn baby, and may cause problems in a newborn baby if the mother takes the medication late in pregnancy (during the third trimester). Tell your doctor if you are pregnant or plan to become pregnant during treatment.

Duloxetine can pass into breast milk and may harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

Older adults may be more sensitive to the side effects of this medication.

Do not give duloxetine to anyone younger than 18 years old without the advice of a doctor.

Avoid drinking alcohol while taking duloxetine. Alcohol may increase the risk of damage to your liver.

Duloxetine can cause side effects that may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be awake and alert.

Tell your doctor if you regularly use other medicines that make you sleepy (such as cold or allergy medicine, narcotic pain medicine, sleeping pills, muscle relaxers, and medicine for seizures or anxiety). They can add to sleepiness caused by duloxetine.

Instructions

Seek emergency medical attention if you think you have taken too much of this medication. Overdose symptoms may include nausea, vomiting, diarrhea, agitation, confusion, hallucinations, fast heart rate, feeling light-headed, or fainting.

Take the missed dose as soon as you remember. However, if it is almost time for the next regularly scheduled dose, skip the missed dose and take the next one as directed. Do not take extra medicine to make up the missed dose.

Side effects

Get emergency medical help if you have any of these signs of an allergic reaction: skin rash or hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have any new or worsening symptoms such as: mood or behavior changes, anxiety, panic attacks, trouble sleeping, or if you feel impulsive, irritable, agitated, hostile, aggressive, restless, hyperactive (mentally or physically), more depressed, or have thoughts about suicide or hurting yourself.

Call your doctor at once if you have any of these serious side effects:

nausea, stomach pain, low fever, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes);

painful or difficult urination;

easy bruising or bleeding, nosebleeds;

black, bloody, or tarry stools;

very stiff (rigid) muscles, high fever, vomiting, diarrhea, sweating, fast or uneven heartbeats, tremors, overactive reflexes;

headache, trouble concentrating, memory problems, confusion, hallucinations; or

weakness, feeling unsteady, loss of coordination, fainting, seizure, shallow breathing or breathing that stops.

Less serious side effects may include:

dry mouth, blurred vision;

drowsiness, dizziness, spinning sensation;

mild nausea, constipation, gas;

sleep problems (insomnia);

joint or muscle pain;

weight changes; or

decreased sex drive, impotence, or difficulty having an orgasm.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. You may report side effects to FDA at 1-800-FDA-1088.

Interactions

Talk to your doctor before taking any medicine for pain, arthritis, fever, or swelling. This includes aspirin, ibuprofen (Advil, Motrin), naproxen (Aleve, Naprosyn), diclofenac (Voltaren), indomethacin, piroxicam (Feldene), nabumetone (Relafen), etodolac (Lodine), and others. Taking any of these drugs with duloxetine may cause you to bruise or bleed easily.

Before taking duloxetine, tell your doctor if you are using any of the following medicines:

a blood thinner such as warfarin (Coumadin);

cimetidine (Tagamet);

a diuretic (water pill);

fluvoxamine (Luvox);

linezolid (Zyvox);

lithium (Lithobid, Eskalith);

St. John's wort;

tramadol (Ultram);

tryptophan (sometimes called L-tryptophan);

an antibiotic such as ciprofloxacin (Cipro) or enoxacin (Penetrex);

almotriptan (Axert), frovatriptan (Frova), sumatriptan (Imitrex), naratriptan (Amerge), rizatriptan (Maxalt), or zolmitriptan (Zomig); or

any other antidepressant such as desipramine (Norpramin), fluoxetine (Prozac, Sarafem), paroxetine (Paxil), and others.

This list is not complete and there may be other drugs that can interact with duloxetine. Tell your doctor about all the prescription and over-the-counter medications you use. This includes vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start using a new medication without telling your doctor.

Other Names

Cymbalta and duloxetine

Disclaimer

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

Copyright 1996-2004 Cerner Multum, Inc. Version 2.05. Revision date 8/23/04

Last updated: September 21, 2016

What is the most important information I should know about duloxetine?

Do not take duloxetine together with thioridazine (Mellaril), or a monoamine oxidase inhibitor (MAOI) such as isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam), or tranylcypromine (Parnate). You must wait at least 14 days after stopping an MAOI before you can take duloxetine. After you stop taking duloxetine, you must wait at least 5 days before you start taking an MAOI.

You may have thoughts about suicide when you first start taking an antidepressant, especially if you are younger than 24 years old. Your doctor will need to check you at regular visits for at least the first 12 weeks of treatment.

Call your doctor at once if you have any new or worsening symptoms such as: mood or behavior changes, anxiety, panic attacks, trouble sleeping, or if you feel impulsive, irritable, agitated, hostile, aggressive, restless, hyperactive (mentally or physically), more depressed, or have thoughts about suicide or hurting yourself.

Avoid drinking alcohol while taking duloxetine. Alcohol may increase the risk of damage to your liver.

Duloxetine can cause side effects that may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be awake and alert.

Warning

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Metrocream Topical Reviews And User Ratings Effectiveness, Ease Of Use, And Satisfaction, Metrocream

User Reviews & Ratings - MetroCream topical

« MetroCream topical Information

Current Rating: 5

Comment: After three weeks of using this cream on again and off again, I am very satisfied. I saw noticeable results after one week of applying pretty much 2X/day. General redness on cheeks is now noticeably reduced. The red bumps on my cheeks and chin are almost gone. There still are some flat red spots on my cheeks and redness on my chin, but I have missed a few applications this third week because I was. Show Full Comment

Comment: After three weeks of using this cream on again and off again, I am very satisfied. I saw noticeable results after one week of applying pretty much 2X/day. General redness on cheeks is now noticeably reduced. The red bumps on my cheeks and chin are almost gone. There still are some flat red spots on my cheeks and redness on my chin, but I have missed a few applications this third week because I was so improved I didn't apply the cream twice a day. Hide Full Comment

1 person found this review helpful. Was this review helpful? Yes | No

Condition: Acne Rosacea

12/31/2012 7:08:09 AM

Reviewer: 25-34 Female on Treatment for 1 to less than 2 years (Patient)

Current Rating: 2

Current Rating: 5

Current Rating: 2

Comment: I don't notice much change pertaining to the redness. I could take it or leaving

Comment: I don't notice much change pertaining to the redness. I could take it or leaving Hide Full Comment

3 people found this review helpful. Was this review helpful? Yes | No

Condition: Acne Rosacea

7/3/2011 4:26:33 PM

Reviewer: lars, 25-34 Male on Treatment for less than 1 month (Patient)

Current Rating: 4

Current Rating: 5

Current Rating: 5

Comment: Applied cream to both cheeks each night before bed. It took about 4 or 5 days, but the lumps went away and the redness was cut it half. Most effective cream that i've used for rosecea.

Comment: Applied cream to both cheeks each night before bed. It took about 4 or 5 days, but the lumps went away and the redness was cut it half. Most effective cream that i've used for rosecea. Hide Full Comment

3 people found this review helpful. Was this review helpful? Yes | No

Condition: Acne Rosacea

4/18/2011 12:48:31 AM

Reviewer: watch tower, 45-54 Female on Treatment for less than 1 month (Patient)

Current Rating: 1

Current Rating: 1

Current Rating: 1

Comment: i had a servere reaction to this cream face turned red and swelled had to go to hospital to get meds for swelling

Comment: i had a servere reaction to this cream face turned red and swelled had to go to hospital to get meds for swelling Hide Full Comment

7 people found this review helpful. Was this review helpful? Yes | No

Condition: Acne Rosacea

5/17/2010 8:20:24 AM

Reviewer: JD, 45-54 Male on Treatment for 1 to 6 months (Patient)

Current Rating: 5

Current Rating: 5

Current Rating: 5

Comment: I had severe Acne rosacea on the left side of my face and nose. This has pretty much taken care of the problem. I am extremely happy with the results.

Comment: I had severe Acne rosacea on the left side of my face and nose. This has pretty much taken care of the problem. I am extremely happy with the results. Hide Full Comment

8 people found this review helpful. Was this review helpful? Yes | No

Valette Restaurant - Healdsburg, Ca, Valette

OpenTable

OpenTable

Valette

Contemporary American: Portraying what Sonoma County has to offer with refined elegance and simplicity.

We will showcase what the region has to offer by focusing on the amazing network of farmers and artisan producers in the area. The relationships we have formed with our purveyors have given us the opportunity to work with what is available while providing the flexibility of changing our menu weekly.

We are determined to provide warm and personable service by dedicated professionals who love what they do. Every guest will feel as if we were inviting them into our own homes.

The wine program is inspired by the incredible history and diversity of the region that surrounds us. Here you can explore classic varieties made by the pioneers whose dedication has made Northern California one of the most exciting wine growing regions in the world.

Dining Style: Casual Elegant

Cuisines: Contemporary American

Hours of Operation: Dinner Nightly Monday - Sunday 5:30pm - 9:30pm

Cross Street: North Street

Dress Code: Smart Casual

Price Range: $31 to $50

Payment Options AMEX, MasterCard, Visa

Phone Number: (707) 473-0946

Executive Chef: Dustin Valette

Additional: Bar Dining, Beer, Farm to Table, Full Bar, Non-Smoking, Wine

Happy (San Francisco)

· Dined 3 days ago

This restaurant is simply wonderful. They really know hospitality! They have it all dialed in. Great food. Great service. Group of five and all left exceedingly happy after a lovely night out. We arrived early but had no issues with walking around Healdsburg Square for a few minutes. Nice table. Pretty restaurant. Happy servers. Happy chefs. Happy customers!

Tags: Comfort Food, Local Ingredients, Healthy, Good for Groups, Romantic, Good for a Date

Was this review useful to you? Yes · No ·

busybev (San Francisco)

· Dined 5 days ago

After hearing great things about Valette on TV we immediately made reservations for dinner the next night. We drove from Palo Alto to Healdsburg to dine there and we were not disappointed. The drive was worth it. We will be back. with friends.

Tags: Worth the Drive, Special Occasion, Good for Anniversaries, Gluten Free Options, Fit for Foodies

Was this review useful to you? Yes · No ·

Jchag (San Francisco)

· Dined on September 14, 2016

It was my first experience at a restaurant I'd wanted to try for a long time. The service was excellent, food well prepared and tasty. Prices are on the high side as are many Healdsburg restaurants these days. As a resident, I will go back, but only for a special occasion.

Tags: Special Occasion, Tasting Menu, Local Ingredients

Was this review useful to you? Yes · No ·

OpenTable Diner Since 2001 (San Francisco)

· Dined on September 13, 2016

Perfect combination of excellent, creative food, attentive staff, exemplary service and the charm of a small-town family-owned business. Valette made our anniversary celebration truly memorable. We had the "Trust Us" tasting menu. you should trust them. It was exceptional, every course.

Tags: Good for a Date, Good for Birthdays, Tasting Menu, Special Occasion, Business Meals, Seasonal, Creative Cuisine

Was this review useful to you? Yes · No ·

Cc32 (Los Angeles)

· Dined on September 11, 2016

The tasting menu was a phenomenal experience. Everything and every bite was delicious. Between the six-courses, my wife and I got to try 12 different dishes. 11/12 (save for one OK desert) were a stellar hit. We wanted a great multi-course wine country dining experience, with inventive good, great service, and great wine, and we found it here. There are so many restaurants to choose from in Sonoma/Napa let alone Healdsburg and we are glad we made Valette our one dinner experience for our weekend away. We did not think we would have such a memorable experience, but it definitely was!

Tags: Handcrafted Cocktails, Notable Wine List, Authentic, Tasting Menu, Special Occasion, Fun

Was this review useful to you? Yes · No ·

· Dined on September 6, 2016

exceptional experience will be returning on our next trip to the area. Food was as good as it gets with very good service.

Tags: Good for Anniversaries, Authentic, Fun, Neighborhood Gem, Business Meals, Local Ingredients, Fit for Foodies, Special Occasion, Good for a Date, Creative Cuisine, Worth the Drive, Notable Wine List, Good for Birthdays

Was this review useful to you? Yes · No ·

LindaW (San Francisco)

· Dined on September 5, 2016

We had a great experience with both food and service. We ordered the 6-course tasting menu, which was a great way to sample both on and off the menu dishes. Everything was well prepared and delicious. I loved the beef tartare, seared foie gras special and the Librety Farms duck. The scallop en croute was presented beautifully, and the scallop inside was perfectly cooked, although the sauce was a tad salty for me. I also wished the lobster-stuffed halibut had more lobster and was a bit less cooked. Service was attentive and pacing was quick -- just the way we like it. They were also quite accommodating towards our 3-year-old son, offering to bring a booster seat (he didn't need one) and bringing him bread, apple juice and an extra share plate. If we had ordered a la carte, I may have thought the the entree prices were a little high, but we thought that $90 for such an expertly executed 6-course tasting menu was an excellent value.

Tags: Open Kitchen, Local Ingredients, Tasting Menu, Hot Spot, Special Occasion, Bar Seating, Creative Cuisine, Neighborhood Gem, Fit for Foodies

Was this review useful to you? Yes · No ·

OpenTable Diner Since 2016 (San Francisco)

· Dined on September 5, 2016

Best duck my wife has had. Excellent lamb and the server chose a great wine for us that went well with both. Restaurant grown tomato salad was fantastic. Wish we lived closer so we could eat there more often.

Tags: Local Ingredients, Good for a Date, Creative Cuisine, Special Occasion

Was this review useful to you? Yes · No ·

poundpod (New York Area)

· Dined on September 2, 2016

An outstanding restaurant in a town where anything less could not survive. A beautiful room. A warm welcome. Comfortable seating. A menu offering and delivering big flavor, careful preparation and plating, and innovative combinations.

My lamb was tender, seasoned and grilled perfectly, and served with crisp, flavorful potatoes and greens. The salads were crisp, flavorful, and dressed perfectly.

The wine list is strong on local wines, but not too narrow.

This is a GREAT restaurant experience.

Crimson (San Francisco)

· Dined on September 2, 2016

My husband and I celebrated our anniversary at Valette on Thursday evening. We were warmly greeted with a special occasion glass of rose.' The menu was so interesting that it was hard to make a decision. Instead, we chose the 4 course "Trust Me" tasting menu priced at $15 per course. Looking back, this was a bargain. Our personable and very professional waiter suggested that we allow him to arrange for each course to be different for each of us, so that we could experience 8 different menu items. Great idea! The 2 appetizer courses were slightly smaller than when ordered off of the menu, but the main courses were full size, as were the desserts. Our main courses were local lamb three ways and prime New York steak. We could have expressed food preferences when ordering. The food components were fresh, colorful, creatively plated and delicious. It was an impressive meal and we will return. We asked our server to match the wines to the courses as we did not know what we would be eating. And he accommodated us by allowing us to each have a half pour of each wine. It worked very well. All in all, a memorable evening. Highly recommended.

Tags: Seasonal, Organic, Good for Anniversaries, Local Ingredients, Good Vegetarian Options, Worth the Drive

Was this review useful to you? Yes · No ·

Jimdjock (San Francisco)

· Dined on September 2, 2016

I've dined at some marvelous restaurants. Valette ranks with the best of them. The cocktails were favorful, complex and amazing. The food was perfectly prepared and infused with wonderful herbaceous aromas and flavors. This was a birthday dinner, which I mentioned when I made my reservation. They presented my date with a hand-written birthday card just after we were seated. She was impressed. Superb service continued from that point forward. Prices were reasonable for a high-end gourmet restaurant. We'll be back.

Tags: Good for Groups, Creative Cuisine

Was this review useful to you? Yes · No ·

OpenTable Diner Since 2008 (Chicago)

· Dined on September 1, 2016

Excellent meal---one of the best I've had in Sonoma County! Presentation was outstanding and the service was superb. Obviously the chef and the staff love preparing good food and delight in having patrons enjoy it. Wait staff are knowledgeable and funny. made us feel like old friends coming in for dinner. Don't miss it!

Tags: Molecular Gastronomy, Creative Cuisine, Good for Birthdays, Local Ingredients, Worth the Drive, Fit for Foodies, Special Occasion, Good for Anniversaries

Was this review useful to you? Yes · No ·

RubyElite (San Francisco)

· Dined on August 31, 2016

We live an hour away. "Hey let's treat ourselves " we were seated upon arrival. Cocktails were ordered and received promptly. For dinner I had the arugula wrapped salmon. It was very good. My husband had the Day Boat Scallops and the Coriander Crusted Liberty Duck. It was very tender and nicely presented-tasted great. We shared a bottle of 2013 Rochioli pinot noir which was wonderful. Great wine list. For desert we shared a blackberry panna cotta. french press coffee helped us get thru the hour drive home. Wonderful time. Great meal.

Tags: Good for a Date, Fit for Foodies

Was this review useful to you? Yes · No ·

OpenTable Diner Since 2012 (Minneapolis)

· Dined on August 30, 2016

Nice space, well done in "modern rustic". First and foremost: the food was excellent. Appetizers of "Day Boat Scallops" (very creatively presented) and the "Hand Made Semolina Pasta" were outstanding. Entrees included "Maine Lobster-Stuffed Halibut", "Joe Valera's Healdsburg Lamb Trio" and the "Char-Grilled NY Prime Steak". All were well executed and very tasty. Only downside was an inattentive waiter, given to distraction, but he made it up when he became aware of our, shall we say, awareness, and compensated at the end with a tasty "Dry Creek Peach Tarte Tatin" which was fabulous. So. the bottom line: this is an excellent restaurant with first rate food. Don't miss it if you are staying in wine country.

Tags: Fireplace, Handcrafted Cocktails, Special Occasion, Creative Cuisine

Was this review useful to you? Yes · No ·

OpenTable Diner Since 2010 (San Francisco)

· Dined on August 28, 2016

We celebrated our 26th anniversary at Valette. It was one of the best meals we have had in Sonoma County. Everything from the service, ambiance, and food was outstanding. Will go back for all special occasions.

Tags: Vibrant Bar Scene, Hot Spot, Handcrafted Cocktails, Good for Anniversaries

Was this review useful to you? Yes · No ·

OpenTable Diner Since 2010 (San Francisco)

· Dined on August 27, 2016

Perfect evening. The right balance of energy and conversation without being loud. The food is incredible and dependably so, making this one of the hottest and most desired reservations in Sonoma County. We always recommend this place to diners from out of town

Tags: Local Ingredients, Good for a Date, Open Kitchen, Tasting Menu, Bar Seating, Wood Oven, Fun, Hot Spot, Worth the Drive, Modern Decor, Healthy, Vibrant Bar Scene, Seasonal, Paleo Friendly, Notable Wine List, Special Occasion, People Watching, Romantic, Fit for Foodies

Was this review useful to you? Yes · No ·

SandyT (San Francisco)

· Dined on August 27, 2016

Valette is a wonderful restaurant and the food was incredible. Don't pass up the homemade buns - they are served freshly made and warm. Our server (sorry I forgot her name) really knew the menu and answered all of our questions about how the food was prepared. We will definitely go back to this restaurant.

Tags: Creative Cuisine, Good for Birthdays, Worth the Drive, Good for a Date, Neighborhood Gem, Casual, Quiet Conversation, Good for Anniversaries, Special Occasion

Was this review useful to you? Yes · No ·

Micheal (San Francisco)

· Dined on August 24, 2016

This restaurant was amazing! A great night out. Food was superb. From the moment we walked in we were greeted and seated right away, waiter was spot on and very friendly. The wine list was extensive and the menu was entising. From the wine to appetizers, main course and dessert. It was a lovely experience and we'll definitely return !

Tags: People Watching, Business Meals, Healthy, Good for a Date, Fun, Notable Wine List, Worth the Drive, Fit for Foodies, Creative Cuisine, Local Ingredients, Special Occasion, Happy Hour, Neighborhood Gem, Good for Birthdays, Organic, Handcrafted Cocktails

Was this review useful to you? Yes · No ·

· Dined on August 19, 2016

I was so excited to eat at Valette on my trip to Healdsburg. The food was decent, but each dish seemed just a little off. Some had to much seasoning, some didn't have enough and both entrees were over cooked (steak and halibut). We were celebrating a birthday and mentioned it in our reservation, but they never even acknowledged it. Our dinner at Scopa the night before was 10x better.

Was this review useful to you? Yes · No ·

Uniretic (Moexipril Hcl Hydrochlorothiazide Tablets) Side Effects, Interactions, Warning, Dosage & U

See full prescribing information for complete boxed warning.

When pregnancy is detected, discontinue uniretic ® as soon as possible.

Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus. See WARNINGS. Fetal Toxicity

DRUG DESCRIPTION

Uniretic® (moexipril hydrochloride/hydrochlorothiazide) is a combination of an angiotensinconverting enzyme (ACE) inhibitor, moexipril hydrochloride, and a diuretic. hydrochlorothiazide. Moexipril hydrochloride is a fine white to off-white powder. It is soluble (about 10% weight-tovolume) in distilled water at room temperature. It has the empirical formula C 27 H 34 N 2 O 7 ·HCl and a molecular weight of 535.04. It is chemically described as [3S-[2[R*(R*)],3R*]]-2-[2-[[1(Ethoxycarbonyl)-3-phenyl-propyl]amino]-1-oxopropyl]-1,2,3,4-tetrahydro-6,7-dimethoxy-3isoquino-linecarboxylic acid, monohydrochloride. Moexipril hydrochloride is a non-sulfhydryl containing precursor of the active ACE inhibitor moexiprilat and its structural formula is:

Hydrochlorothiazide is a white, or practically white, crystalline powder. It is slightly soluble in water, freely soluble in sodium hydroxide solution, in n-butylamine and in dimethylformamide. Hydrochlorothiazide has the empirical formula C 7 H 8 CIN 3 O 4 S 2 and a molecular weight of 297.75. It is chemically described as 2H-1,2,4-Benzothiadiazine-7-sulfonamide,6-chloro-3,4-dihydro-,1,1dioxide. Hydrochlorothiazide is a thiazide diuretic and its structural formula is:

Uniretic® is available for oral administration in three tablet strengths. The inactive ingredients in all strengths are lactose, magnesium oxide, crospovidone, magnesium stearate and gelatin. The film coating in all strengths contains hydroxypropyl cellulose, hypromellose, polyethylene glycol 6000, magnesium stearate and titanium dioxide. In addition, the film coating for uniretic® 7.5 mg / 12.5 mg and uniretic® 15 mg / 25 mg contains ferric oxide.

What are the possible side effects of hydrochlorothiazide and moexipril (Uniretic)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; severe stomach pain; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have a serious side effect such as:

eye pain, vision problems;

high potassium (slow heart rate, weak pulse, muscle weakness, tingly feeling);

low potassium (confusion, uneven heart rate, extreme thirst, increased urination, leg discomfort, muscle weakness or limp feeling);

dry mouth, thirst, nausea.

What are the precautions when taking moexipril hcl hydrochlorothiazide tablets (Uniretic)?

Before taking this product, tell your doctor or pharmacist if you are allergic to either moexipril or hydrochlorothiazide; or to other ACE inhibitors (e. g. captopril, lisinopril); or to other thiazides (e. g. chlorothiazide); or if you have any other allergies (including an allergic reaction after exposure to certain membranes used for blood filtering). This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

This medication should not be used if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if you have: a history of an allergic reaction that included swelling of the face/lips/tongue/throat (angioedema), an inability to make.

Last reviewed on RxList: 9/24/2012 This monograph has been modified to include the generic and brand name in many instances.

Buy Wontac - Ranitidine - Online Without Prescriptions, Wontac

Ranitidine (Wontac)

Ranitidine is used for treating certain conditions that cause your body to make too much stomach acid (eg, Zollinger-Ellison syndrome). It is also used to treat ulcers of the small intestine that have not responded to other treatment. It may be used as a short-term alternative to oral ranitidine, in patients who are not able to take medicine by mouth. Ranitidine is an H 2 - receptor blocker. It works by blocking the action of histamine in the stomach. This reduces the amount of acid the stomach makes. Reducing stomach acid helps to reduce heartburn, heal irritation of the esophagus, and heal ulcers of the stomach or intestines.

Use Ranitidine as directed by your doctor.

Do not take the medication in larger amounts, or take it for longer than recommended by your doctor. Follow the directions on your prescription label.

You may take antacids while you are using Ranitidine if you are directed to do so by your doctor.

Continue to use Ranitidine even if you feel well. Do not miss any dose.

If you miss a dose of Ranitidine, use it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not use 2 doses at once.

Ask your health care provider any questions you may have about how to use Ranitidine.

Store Ranitidine between 68 and 77 degrees F (20 and 25 degrees C). Brief storage at temperatures between 59 and 86 degrees F (15 and 30 degrees C) is permitted. Store away from heat, moisture, and light. Do not store in the bathroom. Keep Ranitidine out of the reach of children and away from pets.

Do NOT use Ranitidine if:

you are allergic to any ingredient in Ranitidine

you have a history of the blood disease porphyria

you are taking dasatinib.

Contact your doctor or health care provider right away if any of these apply to you.

Some medical conditions may interact with Ranitidine. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

if you are pregnant, planning to become pregnant, or are breast-feeding

if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement

if you have allergies to medicines, foods, or other substances

if you have a history of kidney or liver problems

if you have abnormal blood electrolyte levels or a history of irregular heartbeat.

Some medicines may interact with Ranitidine. Tell your health care provider if you are taking any other medicines, especially any of the following:

Certain benzodiazepines (eg, midazolam, triazolam), glipizide, procainamide, or warfarin because the risk of their side effects may be increased by Ranitidine

Dasatinib, delavirdine, gefitinib, certain HIV protease inhibitors (eg, atazanavir), itraconazole, or ketoconazole because their effectiveness may be decreased by Ranitidine.

This may not be a complete list of all interactions that may occur. Ask your health care provider if Ranitidine may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

Important safety information:

Ranitidine may rarely cause drowsiness, dizziness, or blurred vision. These effects may be worse if you take it with alcohol or certain medicines. Use Ranitidine with caution. Do not drive or perform other possible unsafe tasks until you know how you react to it.

Ranitidine may interfere with certain lab tests, including urine protein tests. Be sure your doctor and lab personnel know you are taking Ranitidine.

Lab tests, including liver function, may be performed while you use Ranitidine. These tests may be used to monitor your condition or check for side effects. Be sure to keep all doctor and lab appointments.

Ranitidine should be used with extreme caution in children younger than 1 month old; safety and effectiveness in these children have not been confirmed.

Pregnancy and breast-feeding: If you become pregnant, contact your doctor. You will need to discuss the benefits and risks of using Ranitidine while you are pregnant. Ranitidine is found in breast milk. Do not breastfeed while taking Ranitidine.

All medicines may cause side effects, but many people have no, or minor, side effects.

Check with your doctor if any of these most common side effects persist or become bothersome:

Constipation; diarrhea; headache; nausea; stomach upset.

Seek medical attention right away if any of these severe side effects occur:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue; unusual hoarseness); change in the amount of urine produced; confusion; dark urine; depression; fast, slow, or irregular heartbeat; fever, chills, or sore throat; hallucinations; severe or persistent headache or stomach pain; unusual bruising or bleeding; yellowing of the eyes or skin.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider.

Customers who bought this product also bought

Isoniazid (Nydrazid, Laniazid) Drug Side Effects & Dosing, Rimifon

home / skin center / skin a-z list / isoniazid, inh index / isoniazid (discontinued brands: nydrazid, laniazid, inh, rimifon, stanozide, hyzyd, dow-isoniazid) drug monograph

isoniazid (Discontinued brands: Nydrazid, Laniazid, INH, Rimifon, Stanozide, Hyzyd, Dow-Isoniazid)

Omudhome Ogbru, PharmD

Dr. Ogbru received his Doctorate in Pharmacy from the University of the Pacific School of Pharmacy in 1995. He completed a Pharmacy Practice Residency at the University of Arizona/University Medical Center in 1996. He was a Professor of Pharmacy Practice and a Regional Clerkship Coordinator for the University of the Pacific School of Pharmacy from 1996-99.

Jay W. Marks, MD

Jay W. Marks, MD, is a board-certified internist and gastroenterologist. He graduated from Yale University School of Medicine and trained in internal medicine and gastroenterology at UCLA/Cedars-Sinai Medical Center in Los Angeles.

GENERIC NAME: isoniazid

BRAND NAMES: None

DISCONTINUED BRANDS: Nydrazid, Laniazid, INH, Rimifon, Stanozide, Hyzyd, Dow-isoniazid

GENERIC AVAILABLE: Yes

Isoniazid is used to prevent active tuberculosis in persons who have an abnormal skin test for tuberculosis (latent tuberculosis) or in combination with other drugs for the treatment of active tuberculosis.

When isoniazid is broken down by the liver. one of the products is acetylhydrazine, a potent toxin for the liver. When taken over a long period of time at standard doses, isoniazid can cause important and even fatal liver injury (hepatitis ) in approximately 1 out of every 100 patients. Isoniazid-associated hepatitis usually occurs during the first three months of treatment but can occur at any time during therapy or even many months after starting treatment. Elevated blood liver tests occur in between 1 in 20 and 1 in 10 patients. Usually, enzyme levels return to normal despite continuation of the isoniazid, but in some cases progressive liver damage and even death occurs.

The risk of developing hepatitis is age-related. It occurs in less than 1 per 1,000 patients under 20 years of age, 3 per 1,000 patients 20-34 years of age, 12 per 1,000 patients 35-49 years of age, 23 per 1,000 patients 50-64 years of age, and 8 per 1,000 patients over 65 years of age. The risk of hepatitis is increased by daily consumption of alcohol. Among individuals who complete a full course of prophylaxis (prevention of tuberculosis), the hepatitis-related death rate (mortality) is 23-58 patients per 100,000 patients, far lower than the frequency of hepatitis. The mortality rate among individuals who develop symptoms of isoniazid-induced hepatitis (not just minor abnormalities of liver tests) is approximately 10%. In one U. S. Public Health Service Surveillance Study involving 13,838 persons taking isoniazid, there were 8 deaths among 174 cases of hepatitis, a mortality rate of 5%.

There seems to be an increased risk of fatal hepatitis among women, particularly African-American and Hispanic women. The risk also may be increased during postpartum or immediately after pregnancy. Because of the risk of hepatitis, patients taking isoniazid should have their blood liver tests monitored monthly and should notify their physicians immediately if symptoms or signs of hepatitis arise. These symptoms and signs include:

Medically Reviewed by a Doctor on 6/27/2016

Quick Guide Infectious Mononucleosis (Mono): Symptoms and Treatment

Report Problems to the Food and Drug Administration

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.

Cifloc, Cifloc

Ciprofloxacin

Antibacterial: Fluoroquinolone (gyrase inhibitor)

Chemical Name

3-Quinolinecarboxylic acid, 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-

Foreign Names

Generic Names

Ciprofloxacin (OS: BAN, USAN, JAN)

Ciprofloxacine (OS: DCF)

Bay q 3939 (IS)

Ciprofloxacin Betaine (IS)

Ciprofloxacin (PH: BP 2016, Ph. Eur. 8, Ph. Int. 4, USP 38)

Ciprofloxacine (PH: Ph. Eur. 8)

Ciprofloxacinum (PH: Ph. Eur. 8, Ph. Int. 4)

Ciprofloxacin Hydrochloride (OS: USAN, BANM, JAN)

Bay o 9867 monohydrate (IS: Bayer)

UNII-4BA73M5E37 (IS)

Ciprofloxacin Hydrochloride (PH: BP 2016, Ph. Int. 4, USP 38)

Ciprofloxacin hydrochloride (PH: Ph. Eur. 8)

Ciprofloxacine (chlorhydrate de) (PH: Ph. Eur. 8)

Ciprofloxacinhydrochlorid (PH: Ph. Eur. 8)

Ciprofloxacini hydrochloridum (PH: Ph. Eur. 8, Ph. Int. 4)

Ciprofloxacin sulfate (IS)

Ciprofloxacin Lactate (OS: BANM)

Brand Names

Click for further information on drug naming conventions and International Nonproprietary Names .

Important Notice: The Drugs. com international database is in BETA release. This means it is still under development and may contain inaccuracies. It is not intended as a substitute for the expertise and judgement of your physician, pharmacist or other healthcare professional. It should not be construed to indicate that the use of any medication in any country is safe, appropriate or effective for you. Consult with your healthcare professional before taking any medication.

Was this page helpful?

Mefenamic Acid, Acidum Mefenamicum

Mefenamic Acid

Click for further information on drug naming conventions and International Nonproprietary Names .

Important Notice: The Drugs. com international database is in BETA release. This means it is still under development and may contain inaccuracies. It is not intended as a substitute for the expertise and judgement of your physician, pharmacist or other healthcare professional. It should not be construed to indicate that the use of any medication in any country is safe, appropriate or effective for you. Consult with your healthcare professional before taking any medication.

Was this page helpful?

Benfotiaminum, Benfotiaminum

Benfotiamine prevents complications of neuropathy, retinopathy and nephropathy by inhibiting the build-up of glucose in the vessels. This means that the occurrence of diabetic complications might be slowed or prevented.

As a dietary supplement, take two capsules daily, with or without food. If you miss a dose of Benfotiamine, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

Use directly as prescribed by the doctor.

Most people get excellent results in 14-21 days time using two 150mg. capsules twice per day (two in the morning and two in the evening). Benfotiamine need not be taken with meals. Some people get better results increasing the dosage to 900mg. or 1200mg. per day after the first two weeks. The point here is that benfotiamine is safe at any reasonable daily usage level. An individual should merely find the level that produces the maximum beneficial effect without reaching a point of diminishing return beyond which the excess amount is wasted.

Store Benfotiamine at room temperature, between 68 and 77 degrees F (20 and 25 degrees C). Store away from heat, moisture, and light. Keep Benfotiamine out of the reach of children and away from pets.

Benfotiamine is a synthetic derivative of thiamine (vitamin B1).

Before taking saw palmetto, talk to your doctor, pharmacist, herbalist, or other healthcare provider. You may not be able to use this product if you have:

liver disease;

heart disease;

a heart rhythm disorder;

a history of stomach ulcer; or

asthma or other breathing disorder.

Do NOT use this medication if you are allergic to Saw Palmetto, or have certain conditions. Be sure your doctor knows if you have:

a bleeding or blood clotting disorder (such as hemophilia);

stomach ulcer with active bleeding; or

ulcerative colitis or Crohn's disease.

Do not take Benfotiamine without telling your doctor if you are pregnant or plan to become pregnant during treatment. It may be harmful to an unborn baby. It is not known whether Benfotiamine passes into breast milk or if it could harm a nursing baby. Do not use this product without telling your doctor if you are breast-feeding a baby. Do not give any herbal/health supplement to a child without the advice of a doctor.

No side effects were observed.

Buy Panto Basics Pantoprazole Online Without Prescriptions, Panto Basics

Protonix blocks the production of stomach acid. It is prescribed to heal a condition called erosive esophagitis (a severe inflammation of the passage to the stomach) brought on by a persistent backflow of stomach acid (gastroesophageal reflux disease). Later, it may be prescribed to maintain healing and prevent a relapse. It is also used in the treatment of conditions marked by constant overproduction of stomach acid, such as Zollinger-Ellison syndrome. Protonix is a member of the "proton pump inhibitor" class of acid blockers.

Use Protonix as directed by your doctor.

Protonix may be taken with or without food. Do not chew, crush, or split the tablets. If you are taking antacids you may continue to do so.

If you miss a dose of Protonix, use it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not use 2 doses at once.

Ask your health care provider any questions you may have about how to use Protonix.

Store Protonix at 77 degrees F (25 degrees C). Brief storage at temperatures between 59 and 86 degrees F (15 and 30 degrees C) is permitted. Store away from heat, moisture, and light. Do not store in the bathroom. Keep Protonix out of the reach of children and away from pets.

Active Ingredient: Pantoprazole sodium.

Do NOT use Protonix if:

you are allergic to any ingredient in Protonix

you are taking dasatinib or an HIV protease inhibitor (eg, atazanavir).

Contact your doctor right away if any of these apply to you.

Some medical conditions may interact with Protonix. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

if you are pregnant, planning to become pregnant, or are breast-feeding

if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement

if you have allergies to medicines, foods, or other substances

if you have liver problems or stomach or bowel cancer

if you have low blood zinc levels.

Some medicines may interact with Protonix. Tell your health care provider if you are taking any other medicines, especially any of the following:

Clarithromycin or voriconazole because they may increase the risk of Protonix's side effects

Anticoagulants (eg, warfarin) or digoxin because the risk of their side effects may be increased by Protonix

Ampicillins, azole antifungals (eg, ketoconazole), clopidogrel, dasatinib, HIV protease inhibitors (eg, atazanavir), or iron because their effectiveness may be decreased by Protonix

This may not be a complete list of all interactions that may occur. Ask your health care provider if Protonix may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

Important safety information:

Protonix may cause drowsiness or dizziness. These effects may be worse if you take it with alcohol or certain medicines. Use Protonix with caution. Do not drive or perform other possible unsafe tasks until you know how you react to it.

Contact your doctor if you have any symptoms of a bleeding ulcer, such as black, tarry stools or vomit that looks like coffee grounds, or if you experience throat pain, chest pain, severe stomach pain, or trouble swallowing.

Protonix may interfere with certain lab tests. Be sure your doctor and lab personnel know you are taking Protonix.

Protonix should be used with caution in Asian patients; the risk of side effects may be increased in these patients.

Protonix should be used with extreme caution in children younger 18 years; safety and effectiveness in these children have not been confirmed.

Pregnancy and breast-feeding: If you become pregnant, contact your doctor. You will need to discuss the benefits and risks of using Protonix while you are pregnant. Protonix is found in breast milk. Do not breastfeed while taking Protonix.

All medicines may cause side effects, but many people have no, or minor, side effects.

Check with your doctor if any of these most common side effects persist or become bothersome:

Diarrhea; headache; nausea; stomach pain; vomiting.

Seek medical attention right away if any of these severe side effects occur:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue; unusual hoarseness); chest pain; dark urine; fast or irregular heartbeat; fever, chills, or sore throat; red, swollen, blistered, or peeling skin; unusual bruising or bleeding; unusual tiredness; vision changes; yellowing of the skin or eyes.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider.

Customers who bought this product also bought

Copyright © 2004-2016 All Rights Reserved

Protonix blocks the production of stomach acid. It is prescribed to heal a condition called erosive esophagitis (a severe inflammation of the passage to the stomach) brought on by a persistent backflow of stomach acid (gastroesophageal reflux disease). Later, it may be prescribed to maintain healing and prevent a relapse. It is also used in the treatment of conditions marked by constant overproduction of stomach acid, such as Zollinger-Ellison syndrome. Protonix is a member of the "proton pump inhibitor" class of acid blockers.

Use Protonix as directed by your doctor.

Protonix may be taken with or without food. Do not chew, crush, or split the tablets. If you are taking antacids you may continue to do so.

If you miss a dose of Protonix, use it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not use 2 doses at once.

Ask your health care provider any questions you may have about how to use Protonix.

Store Protonix at 77 degrees F (25 degrees C). Brief storage at temperatures between 59 and 86 degrees F (15 and 30 degrees C) is permitted. Store away from heat, moisture, and light. Do not store in the bathroom. Keep Protonix out of the reach of children and away from pets.

Active Ingredient: Pantoprazole sodium.

Do NOT use Protonix if:

you are allergic to any ingredient in Protonix

you are taking dasatinib or an HIV protease inhibitor (eg, atazanavir).

Contact your doctor right away if any of these apply to you.

Some medical conditions may interact with Protonix. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

if you are pregnant, planning to become pregnant, or are breast-feeding

if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement

if you have allergies to medicines, foods, or other substances

if you have liver problems or stomach or bowel cancer

if you have low blood zinc levels.

Some medicines may interact with Protonix. Tell your health care provider if you are taking any other medicines, especially any of the following:

Clarithromycin or voriconazole because they may increase the risk of Protonix's side effects

Anticoagulants (eg, warfarin) or digoxin because the risk of their side effects may be increased by Protonix

Ampicillins, azole antifungals (eg, ketoconazole), clopidogrel, dasatinib, HIV protease inhibitors (eg, atazanavir), or iron because their effectiveness may be decreased by Protonix

This may not be a complete list of all interactions that may occur. Ask your health care provider if Protonix may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

Important safety information:

Protonix may cause drowsiness or dizziness. These effects may be worse if you take it with alcohol or certain medicines. Use Protonix with caution. Do not drive or perform other possible unsafe tasks until you know how you react to it.

Contact your doctor if you have any symptoms of a bleeding ulcer, such as black, tarry stools or vomit that looks like coffee grounds, or if you experience throat pain, chest pain, severe stomach pain, or trouble swallowing.

Protonix may interfere with certain lab tests. Be sure your doctor and lab personnel know you are taking Protonix.

Protonix should be used with caution in Asian patients; the risk of side effects may be increased in these patients.

Protonix should be used with extreme caution in children younger 18 years; safety and effectiveness in these children have not been confirmed.

Pregnancy and breast-feeding: If you become pregnant, contact your doctor. You will need to discuss the benefits and risks of using Protonix while you are pregnant. Protonix is found in breast milk. Do not breastfeed while taking Protonix.

All medicines may cause side effects, but many people have no, or minor, side effects.

Check with your doctor if any of these most common side effects persist or become bothersome:

Diarrhea; headache; nausea; stomach pain; vomiting.

Seek medical attention right away if any of these severe side effects occur:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue; unusual hoarseness); chest pain; dark urine; fast or irregular heartbeat; fever, chills, or sore throat; red, swollen, blistered, or peeling skin; unusual bruising or bleeding; unusual tiredness; vision changes; yellowing of the skin or eyes.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider.

Customers who bought this product also bought

Copyright © 2004-2016 All Rights Reserved

Danfoss Products, Denfos

Danfoss

Filter Results

Category Products

Quantity: Add to Cart Add to Quote

Danfoss 1/2" FIP non-electric, side mounted angle-pattern, thermostatic radiator valve with a 1/2" male union nut and nipple. Side mount valves are for use with built-in operators, which also contain a temperature sensor. Although the inlet to outlet connection is an angle pattern, the sensor mounts off to the side of the valve to prevent ambient temperature from rising up into the operator.

Online Price: $43.14

Regular Price: $44.00

Quantity: Add to Cart Add to Quote

Danfoss 1/2" FIP non-electric, angle-pattern, top mount, thermostatic radiator valve with a 1/2" male union nut and nipple. This valve is for use with remote operators, which prevent ambient temperature from rising into the operators.

Online Price: $43.14

Regular Price: $44.00

Quantity: Add to Cart Add to Quote

Danfoss 1/2" FIP non-electric, straight-pattern, flex mount, thermostatic radiator valve with a 1/2" male union nut and nipple. This valve is for use with both remote and built-in operators, which prevent ambient temperature from rising into the operators. When using a built-in operator turn the valve so that the sensor is on the side rather than the top.

Online Price: $43.14

Regular Price: $44.00

Quantity: Add to Cart Add to Quote

Danfoss 3/4" FIP non-electric, side mounted, angle-pattern, thermostatic radiator valve with a 3/4" male union nut and nipple. Side mount valves are for use with built-in operators, which also contain a temperature sensor. Although the inlet to outlet connection is an angle pattern, the sensor mounts off to the side of the valve to prevent ambient temperature from rising up into the operator.

Online Price: $47.06

Regular Price: $48.00

Quantity: Add to Cart Add to Quote

Danfoss 3/4" FIP non-electric, angle-pattern, top mount, thermostatic radiator valve with a 3/4" male union nut and nipple. This valve is for use with remote operators, which prevent ambient temperature from rising into the operators.

Online Price: $47.06

Regular Price: $48.00

Quantity: Add to Cart Add to Quote

Danfoss 3/4" FIP non-electric, straight-pattern, flex mount, thermostatic radiator valve with a 3/4" male union nut and nipple. This valve is for use with both remote and built-in operators, which prevent ambient temperature from rising into the operators. When using a built-in operator turn the valve so that the sensor is on the side rather than the top.

Online Price: $47.06

Regular Price: $48.00

Quantity: Add to Cart Add to Quote

Danfoss 3/4" double solder union, non-electric straight-pattern thermostatic radiator valve. This valve is for use with both remote and built-in operators, which prevent ambient temperature from rising into the operators. When using a built-in operator turn the valve so that the sensor is on the side rather than the top.

Online Price: $64.71

Regular Price: $66.00

Quantity: Add to Cart Add to Quote

Danfoss 1" FIP non-electric, side mounted, angle-pattern, thermostatic radiator valve with a 1" male union nut and nipple. Side mount valves are for use with built-in operators, which also contain a temperature sensor. Although the inlet to outlet connection is an angle pattern, the sensor mounts off to the side of the valve to prevent ambient temperature from rising up into the operator.

Online Price: $68.63

Regular Price: $70.00

Quantity: Add to Cart Add to Quote

Customer Service & Sales

About State Supply

Shop With Confidence

Ampen, De Lighting Designers & Suppliers, Ampen

64 Ampen, DE Lighting Designers and Suppliers

A well-lit home is essential for both functional and aesthetic reasons. Lighting designers will analyze your Ampen, DE home's layout, structure and needs to create an effective lighting plan throughout your home. Though electrical engineers or interior designers can take on the task of outfitting your home with the appropriate lighting, a professional lighting designer explores lighting as a technique. More

Manuel Moreno und sein Team realisieren seit uber 20 Jahren ausgefallene und individuelle Lichtkonzepte. Fur. Read More

List your business here for free - Learn More

What Is a Lighting Plan Designer?

Lighting designers often have a knowledge of physics, optics, ergonomics and environmental issues along with an eye for construction and design, allowing them to devise lighting plans that not only improve visibility but create hierarchies, dynamics and a mood within a space. Often working in conjunction with an architect or interior designer, lighting designers will work to incorporate reflective surfaces and integrate daylight. Here are some related professionals and vendors to complement the work of lighting showrooms & sales: Interior Designers & Decorators. Design-Build Firms. Electricians.

Think about how you plan to use each area of your Ampen, DE home. It's important to communicate to your lighting designer which space will be used as an office and which will be a media room, for example, as these will require very different lighting methods. In addition, consider how you'd prefer to control the lights. Lighting technology today includes dimmers, sensors, photocells (that let lights react to the amount of daylight in a space), programmable scene controls (that let you program different settings for varied lighting) and whole-house lighting controls (that let you control all or a portion of your home's lights from one source), allowing you to tailor your lighting controls however you wish.

Be wary of electricians or sales reps posing as lighting designers. Identify professional lighting designers by finding out whether they're involved in lighting programs or associations such as the International Association of Lighting Designers, and confirming that they have LC (Lighting Certification) or CLC (Certified Lighting Consultant) credentials.

Questions to ask a prospective lighting designer:

How long have you been in the business?

How many projects like mine have you completed?

Can you provide me with references?

Are you licensed and insured?

Are you a participant of any professional programs or associations?

How do you charge, and what does that include?

Can you give me a written estimate?

What do your services include?

When can the job get done?

What happens when the cost exceeds the budget? What about when there are changes to materials or labor pricing?

What will I need to provide?

Are there any important considerations or concerns you foresee with this project?

Find a lighting designer on Houzz. Narrow your search in the Professionals section of the website to Ampen, DE lighting designer. You can also look through Ampen, DE photos by style to find a lighting design you like, then contact the designer.

Professional Categories in Ampen

Professional Metro Areas

Sucralfate - Side Effects, Dosage, Interactions, Sucral

Sucralfate

Sucralfate is the generic form of the brand-name drug Carafate. It's a prescription medicine used to treat ulcers of the upper gastrointestinal tract.

Sucralfate is used to treat peptic ulcer disease and to prevent ulcers from recurring after they heal. It may also be used to treat or prevent ulcers caused by non-steroidal anti-inflammatory drugs (NSAIDs), to treat people with gastroesophageal reflux disease (GERD). and to prevent ulcers associated with physical stress in hospitalized patients.

The medicine works by forming a barrier or coating over the ulcer, which protects it from acid in the stomach and allows it to heal.

Sucralfate comes in a tablet and a liquid form. The drug was approved by the Food and Drug Administration in 1981 and is manufactured by Aptalis Pharma US, Inc.

What Are the Key Things I Need to Know About Sucralfate?

You should tell your doctor or pharmacist before taking sucralfate if you have a medical history of kidney problems, swallowing problems, stomach/intestine problems, tube feeding, or use of a breathing tube.

The medication contains aluminum, which is normally removed by the kidneys. Elderly patients may be at a higher risk for developing high aluminum levels while taking sucralfate because kidney function declines as you age.

Although some data suggests concern about the effects of aluminum during pregnancy might be warranted, human studies have shown no negative effects on the fetus. Sucralfate is generally considered safe during pregnancy. Although there are no data, the medicine is also considered safe for use by breast-feeding mothers.

Sucralfate Side Effects

Cefabiotic, Cefabiotic

Uruguay

CEFABIOTIC

ComposiciпїЅn.

Cada frasco ampolla contiene ceftazidima pentahidrato estпїЅril equivalente a 1g de ceftazidima base con 118mg de carbonato de sodio estпїЅril.

Indicaciones.

CEFABIOTIC estпїЅ indicado en infecciones producidas por gпїЅrmenes sensibles en: infecciones de las vпїЅas respiratorias. Infecciones de piel y anexos. Infecciones de las vпїЅas urinarias. Infecciones del hueso y articulaciones. Infecciones de oпїЅdo, nariz y garganta. Infecciones intraabdominales. Infecciones ginecolпїЅgicas. Infecciones severas en general (meningitis, septicemia, quemaduras infectadas, infecciones en pacientes inmunodeprimidos). Debido a su amplio espectro de acciпїЅn, puede ser usado como antibiпїЅtico пїЅnico de primera elecciпїЅn mientras no se tengan resultados de ensayo de sensibilidad. En infecciones graves con riesgo de vida o en pacientes inmunocomprometidos. CEFABIOTIC puede ser utilizado simultпїЅneamente con otros antibiпїЅticos, como aminoglucпїЅsidos, clindamicina o vancomicina.

PresentaciпїЅn.

Env. con 1 fco. amp. de 1g.

Ceftazidima

AcciпїЅn terapпїЅutica.

Propiedades.

La ceftazidima es una cefalosporina de tercera generaciпїЅn semisintпїЅtica inyectable de espectro amplio. Desarrolla su acciпїЅn con preferencia sobre gпїЅrmenes grampositivos, gramnegativos y seudomonas. Luego de una administraciпїЅn IV de 0,5g y 1g durante 5 minutos, en adultos voluntarios normales, se obtuvieron picos sпїЅricos de 45 m g y 90 m g/ml, respectivamente. Luego de la infusiпїЅn IV de 500mg, 1g y 2g durante 30 minutos, en voluntarios sanos, se obtuvieron picos de concentraciпїЅn sпїЅrica de 42,69 m g y 170 m g/ml. La absorciпїЅn y la eliminaciпїЅn de la ceftazidima fue directamente proporcional a la magnitud de la dosis. La vida media despuпїЅs de una administraciпїЅn IV fue de alrededor de 2 horas. Aproximadamente 80% a 90% de las dosis IM o IV de ceftazidima se excretan inmodificadas por la orina, durante un perпїЅodo de 24 horas.

Indicaciones.

Infecciones de los tractos respiratorio y genitourinario. Infecciones otorrinolaringolпїЅgicas, y de piel y tejidos blandos. Infecciones osteoarticulares. Peritonitis y otras infecciones intraabdominales. Septicemias bacterianas. Enfermedad inflamatoria pпїЅlvica, endometritis y otras infecciones del aparato genital femenino. Infecciones enterocпїЅcicas. Infecciones del sistema nervioso central.

DosificaciпїЅn.

La ceftazidima debe administrarse por vпїЅa IM o IV luego de su reconstituciпїЅn. Las dosis totales diarias son las mismas para ambas vпїЅas. En forma IV puede administrarse como infusiпїЅn intermitente (disuelta en cloruro de sodio a 0,9%, dextrosa a 5% o 10%, soluciпїЅn de Ringer-lactato con dextrosa a 5% y soluciпїЅn de Ringer-lactato con dextrosa a 5% y cloruro de sodio a 0,9%) o como inyecciпїЅn IV. Las dosis para adultos fluctпїЅan de acuerdo con la gravedad de la infecciпїЅn entre 1g y 2g, divididas en administraciones cada 8 a 12 horas.

Reacciones adversas.

Trastornos gastrointestinales, nпїЅuseas, vпїЅmitos y diarrea. Reacciones dermatolпїЅgicas por hipersensibilidad. Igual que con otros betalactпїЅmicos, con el uso prolongado puede aparecer neutropenia reversible. SпїЅntomas derivados del SNC: cefaleas, vпїЅrtigo y parestesias.

Precauciones y advertencias.

Hipersensibilidad a las penicilinas. En insuficiencia renal grave reducir las dosis a la mitad, en especial si se usan dosis elevadas o en combinaciпїЅn con agentes nefrotпїЅxicos. La vida media de la ceftazidima estпїЅ levemente disminuida durante la hemodiпїЅlisis. Embarazo y lactancia.

Interacciones.

Su acciпїЅn puede inhibirse por la administraciпїЅn simultпїЅnea de agentes bacteriostпїЅticos (tetraciclinas, cloramfenicol, sulfamidas). Con el uso concomitante puede aumentar la nefrotoxicidad de los aminoglucпїЅsidos y de los diurпїЅticos potentes como la furosemida. Puede antagonizar los efectos del cloranfenicol. Puede dar reacciones falsamente positivas cuando se administra junto con los test de glucosuria.

Contraindicaciones.

Hipersensibilidad a las cefalosporinas.

CEFABIOT ® (acetoxietil cefuroxima o axetil cefuroxima) es un antimicrobiano cefalosporínico bactericida, resistente a la mayoría de las betalactamasas y activo contra una extensa variedad de microorganismos grampositivos y gramnegativos. Está indicado para el tratamiento de infecciones causadas por gérmenes sensibles, entre éstas figuran las siguientes:

Infecciones del tracto respiratorio superior: Otitis media, sinusitis, amigdalitis, faringitis. Infecciones del tracto respiratorio inferior: Neumonía, bronquitis aguda, crónica y crónica exacerbada. Infecciones del tracto genitourinario: Pielonefritis, cistitis y uretritis. Uretritis y cervicitis gonocócica no complicada. Infecciones de la piel y tejidos blandos: Furunculosis, pioderma e impétigo. Tratamiento de adultos y ni­ños mayores de 12 años en la etapa temprana de la enfermedad de Lyme y prevención del progreso a etapas tardías de la misma. CEFABIOT ® tiene buena estabilidad ante las beta-lactamasas bacterianas y, por consiguiente, es activa contra muchas cepas resistentes a la ampicilina o amoxicilina. La cefuroxima generalmente es activa in vitro contra los siguientes ­microorganismos: Aerobios gramnegativos: Haemophilus influenzae (incluyendo cepas resistentes a la ampicilina), Haemophilus parainfluenzae . Moraxella (Branhamella) ca­tarrhalis . Neisseria gonorrhoeae (incluso cepas pro­ductoras y no productoras de penicilinasa), Neisseria meningitidis . Escherichia coli . Klebsiella spp, Proteus mirabilis, Providencia spp y Proteus rettgeri. Aerobios grampositivos: Staphylococcus aureus y S. epidermidis (incluyendo cepas resistentes a la penicilina, pero no incluye cepas meticilino-resistentes), Streptococcus pyogenes (y otros estreptococos beta-hemolíticos), Streptococcus pneumoniae y Streptococcus grupo B ( Streptococcus agalactiae ). Anaerobios: Cocos grampositivos y gramnegativos (incluyendo especies de Peptococcus y Peptostreptococcus ), bacilos grampositivos (incluyendo especies de Clostridium ) y gramnegativos (incluyendo especies de Bacteroides y Fusobacterium ) y Propionibacterium spp . No son susceptibles a la cefuroxima in vitro . los siguientes microorganismos: Clostridium difficile, Pseudomonas spp, Campylobacter spp, Acinetobacter calcoaceticus, las cepas de Staphylococcus aureus y epidermidis resistentes a la meticilina, Legionella spp y Listeria monocytogenes . Algunas cepas de los siguientes géneros tampoco son susceptibles in vitro a la cefuroxima: Streptococcus faecalis . Morganella morganii, Proteus vul­garis, Enterobacter spp, Citrobacter spp, Serratia spp, Bacteroides fragilis.

FARMACOCIN?TICA Y FARMACODINAMIA

Después de su administración oral, CEFABIOT ® se absorbe en el tracto gastrointestinal y es rápidamente hidrolizada en la mucosa intestinal y en la sangre, para liberar cefuroxima a la circulación. La absorción óptima tiene lugar cuando la acetoxietil cefuroxima es administrada después de los alimentos. Los niveles máximos en suero (2-3 mg/l después de una dosis de 125 mg, 4-6 mg/l después de una dosis de 250 mg, 5-8 mg/l después de una dosis de 500 mg y de 9-14 mg/l después de una dosis de 1 g), se alcanzan entre 2 a 3 horas después de la administración.

La unión a las proteínas séricas es del 33 al 50%, dependiendo de la metodología empleada. CEFABIOT ® no se metaboliza y es excretada por filtración glomerular y secreción tubular. La tasa de absorción de CEFABIOT ® de la suspensión, al compararse con las tabletas, es ligeramente menor, lo que produce menores niveles sé­ricos y en consecuencia una biodisponibilidad 4-17% menor. La administración concomitante de probenecid incrementa el área bajo la curva en 50%. Los niveles de cefuroxima sérica son reducidos por diálisis.

CEFABIOT ® es un antibiótico bactericida que actúa al inhibir la síntesis de la pared celular bacteriana, al unirse a proteínas esenciales.

DOSIS Y V?A DE ADMINISTRACI?N

Oral. La duración normal del tratamiento es de 7 días, pero puede variar de 5 a 10 días de acuerdo con la severidad del proceso infeccioso. Para una absorción óptima, CEFABIOT ® debe ser ingerido después de los alimentos.

En adultos: Casi todas las infecciones: 250 mg cada 12 horas. Infecciones de vías urinarias, infecciones leves a moderadas de vías respiratorias bajas, por ejemplo, bronquitis, y pielonefritis, infecciones de vías respiratorias bajas, graves o en sospecha de neumonía: 500 mg cada 12 horas. Gonorrea: 1 g dosis única. Enfermedad de Lyme en adultos y niños de 12 años en adelante: 500 mg cada 12 horas durante 20 días.

MANIFESTACIONES Y MANEJO DE LA SOBREDOSIFICACI?N O INGESTA ACCIDENTAL

La sobredosificación de cefalosporinas puede producir irritación cerebral, lo cual resulta en convulsiones. Hasta el momento no han habido reportes de sobredosificación con CEFABIOT ®. Las concentraciones séricas de cefuroxima pueden ser reducidas por hemodiálisis o diálisis peri­toneal.

[ 1 2 3 4 5 6 7 8 9 10 15 ]