Uso de testosterona en mujeres: un comentario sobre el consenso global sobre el uso de la terapia de testosterona para mujeres / Global consensus position statement on the use of testosterone therapy for women

Las mujeres han sido tratadas por décadas con testosterona intentando aliviar una gran variedad de síntomas con riesgos y beneficios inciertos. En la mayoría de los países, la testosterona se prescribe "off-label", de modo que las mujeres están utilizando compuestos y dosis ideadas para tratamientos en hombres. En este sentido, varias sociedades médicas de distintos continentes adoptaron recientemente por consenso una toma de posición sobre los beneficios y potenciales riesgos de la terapia con testosterona en la mujer, explorar las áreas de incertidumbre e identificar prácticas de prescripción con potencial de causar daño. Las recomendaciones con respecto a los beneficios y riesgos de la terapia con testosterona se basan en los resultados de ensayos clínicos controlados con placebo de al menos 12 semanas de duración. A continuación se comentan las recomendaciones. (AU)

There are currently no clear established indications for testosterone replacement therapy for women. Nonetheless, clinicians have been treating women with testosterone to alleviate a variety of symptoms for decades with uncertainty regarding its benefits and risks. In most countries, testosterone therapy is prescribed off-label, which means that women are using testosterone formulations or compounds approved for men with a modified dose for women. Due to these issues, there was a need for a global Consensus Position Statement on testosterone therapy for women based on the available evidence from placebo randomized controlled trials (RCTs). This Position Statement was developed to inform health care professionals about the benefits and potential risks of testosterone therapy intended for women. The aim of the Consensus was to provide clear guidance as to which women might benefit from testosterone therapy; to identify symptoms, signs, and certain conditions for which the evidence does not support the prescription of testosterone; to explore areas of uncertainty, and to identify any prescribing practices that have the potential to cause harm. (AU)

Complicaciones digestivas y renales por indometacina e ibuprofeno en prematuros extremos con ductus arterioso permeable / Digestive and Kidney Complications by indomethacin and ibuprofen in extreme preterm infants with patent ductus arteriosus

El ductus arterioso permeable sintomático (DAPs) es frecuente en prematuros extremos (PE), siendo importante su cierre para disminuir la repercusión hemodinámica. Para ello se usa indometacina o ibuprofeno con los riesgos subyacentes. OBJETIVO: Caracterizar las complicaciones digestivas y renales en PE tratados por DAPs. PACIENTES Y MÉTODO: Estudio retrospectivo en PE nacidos entre enero de 2004 y diciembre de 2013. Según diagnóstico se distribuyeron en 3 grupos: sin DAPs, con DAPs tratados con indometacina y con ibuprofeno. Se excluyeron PE con otras complicaciones graves. Se evaluaron complicaciones digestivas y renales graves. Se usó significación estadistica con p ≤ 0,05. RESULTADOS: Se enrolaron 599 PE; 33,1% recibió tratamiento por DAPs, 66,9% no lo requirió. Hubo asociación estadística entre DAPs y menor edad gestacional, depresión neonatal y distrés respiratorio. Del grupo no tratado, el 5% presentó enterocolitis y el 0,25% falla renal; entre los tratados el 2,5% presentó enterocolitis y el 1,0% falla renal. No hubo diferencias estadísticas significativas considerando ambas complicaciones (p = 0,17), sólo enterocolitis (p = 0,11) o sólo falla renal (p = 0,33) entre tratados y no tratados; tampoco las hubo al comparar complicaciones entre tratados con indometacina o ibuprofeno. CONCLUSIONES: Los resultados en nuestra población demuestran que el tratamiento médico del DAPs, en ausencia de otras complicaciones clínicas, no representa un mayor riesgo de complicaciones graves digestivas o renales. No se demostraron ventajas entre la indometacina e ibuprofeno.

The symptomatic patent ductus arteriosus (sPDA) is common in extremely premature infants (EPI). In order to decrease the hemodynamic repercussion and avoid complications it is necessary to close it. Indomethacin or ibuprofen are used for this purpose with its associated risks. OBJECTIVE: Characterize digestive and renal complications in EPI who received indomethacin or ibuprofen as sPDA treatment. PATIENTS AND METHOD: Retrospective study on EPI between January-2004 and December-2013. Three groups were compared: treated with indomethacin or ibuprofen and a non-treated group. EPI with other serious complications were excluded. The primary outcomes on each group were digestive and/or renal complications. Statistical significance was p < 0.05. RESULTS: 599 EPI were included, 33.1% with PDA received treatment and 66.9% did not need it. A statistical association was found between sPDA and lower gestational ages, neonatal depression and respiratory distress. In the non-treated group, 5% presented enterocolitis and 0.25% renal failure; on the treated group, 2.5% presented enterocolitis and 1.0% renal failure. No significant differences were found between the treated and non-treated groups in relation to complications considering enterocolitis (p = 0.11) or renal failure (p = 0.33) alone, or combined (p = 0.17). No difference were detected either between those treated with indomethacin or ibuprofen. CONCLUSIONS: The results show that in absence of other clinical complication, medical treatment of sPDA with indomethacin or ibuprofen, do not increase the risk of serious digestive or renal disorders. There were no advantages of using indomethacin or ibuprofen over the other.

Efeito antimicrobiano da indometacina no biofilme periodontal: estudo em ratos / Antimicrobial effect of indomethacin on periodontal biofilm: study in rats

Introdução: A doença periodontal é uma doença de caráter multifatorial que se desenvolve em decorrência da interação do biofilme bacteriano com a resposta imuno-inflamatória do hospedeiro que pode ser modulada por fatores sistêmicos e ambientais. Objetivo: o presente estudo teve como objetivo avaliar a ação antimicrobiana do anti-inflamatório não esteroidal indometacina sobre o biofilme retido em ligaduras inseridas subgengivalmente para indução de periodontite experimental em ratos. Método: assim, 20 animais foram divididos aleatoriamente em um dos grupos: grupo Indometacina (n=10); grupo água destilada (n=10). Os animais receberam gavagem diária da medicação (5 mg/kg indometacina) ou de água destilada (2 ml), durante 7 dias. As ligaduras ao redor dos dentes foram coletadas e o biofilme foi dispersado, diluído em 10-1, 10-2 e 10-3, semeado em ágar sangue e as placas foram cultivadas em anaerobiose durante 4 dias. As quantificações foram realizadas a partir da contagem das unidades formadoras de colônias (UFC) totais pelo programa Colony counter aplicativo para androide, caracterizadas pela presença de bactérias aeróbias e aeróbias facultativas relacionadas ao processo de saúde, e pela contagem manual de UFC grandes, que melhor caracterizam as bactérias anaeróbias relacionadas ao processo de doença. Resultado: constatou-se um número significativamente maior de UFC grandes no grupo indometacina quando comparado ao grupo água (p=0,004) e um número significativamente menor de UFC totais no grupo indometacina quando comparado ao grupo água (p=0,0013). Conclusão: dentro dos limites do presente estudo pôde-se concluir que a indometaciana agrava o processo infeccioso periodontal devido ao crescimento de UFC anaeróbias e redução de UFC facultativas.

Introduction: Periodontal disease is a multifactorial disease the develop as a result of the interaction of the bacterial biofilm and the immune-inflammatory response of the individual, which, in its turn, is modulate by systemic and environmental factors. Objective: This study aimed to evaluate the antimicrobial effect of indomethacin, a non-steroidal anti-inflammatory, on the biofilm retained in ligatures inserted in the subgingival region to induce experimental periodontitis in rats. Method: 20 animals were randomly assigned to one of the groups: Indomethacin (n = 10); distilled water (n = 10). The animals received daily gavage of drugs (5 mg / kg indomethacin) or distilled water (2 ml) for 7 days. The ligatures around the teeth were collected and the biofilm was dispersed, diluted 10-1, 10-2 and 10-3, seeded in blood agar and the plates were grown anaerobically for 4 days. The measurements were carried out from the counting of total colony forming units (CFU) by Colony counter application program for android, characterized by the presence of facultative aerobic and aerobic bacteria related health process, and the manual counting of large CFU, which better characterized the anaerobic bacteria-related disease process. Result: it was found a significantly higher number of large CFU in indomethacin group compared to the water group (p = 0.004) and a significantly lower number of total CFU in the indomethacin group compared to the water group (p = 0.0 013). Conclusion: within the limits of this study it was concluded that the indomethacin worsens periodontal infectious process due to the growth of anaerobic CFU and the reduction of facultative CFU.

Gastroprotective Activity of Methanol Leaves Extract of Barleria prionitis Linn. on Ethanol and Indomethacin Induced Ulcer in Rats.

Aims: Barleria prionitis L. (Family Acanthaceae) is a medicinal plant found road side in India and whole plant or its various parts like leaves, root, bark, stem and flowers are used traditionally for various treatments like toothache, inflammation, boils, glandular swellings and ulcer. Leaf juice is useful in gastric ulcer. Here, we attempt to prove the use of this plant as gastroprotective agent. Study Design: This study was conducted to evaluate the antiulcer activity of methanol extract obtained from the leaves of Barleria prionitis Linn. Place and Duration of Study: The experiments were conducted at Pharmacology lab of Institute of Pharmaceutical Sciences, Kurukshetra University during the period of July 2012 to December 2012. Material and Methods: Antiulcer activity was performed using the protocols of ulcer induced by ethanol and indomethacin at two different doses (250 and 500mg/kg). Parameters like volume of gastric juice, pH, free acidity, total acidity, aspartate amino transferase (AST) and alanine amino transferase (ALT) were also determined in ethanol induced ulcer model. Results: The reduction in ulcer index in Barleria prionitis treated animals was found to be statistically significant (P=.05), when compared with control groups in both the models. Significant changes were observed in total acidity only at dose 500mg/kg only and changes were significant in AST, ALT levels at both the doses. Other parameters showed non-significant results. Conclusion: The results of the present study show that the methanolic extract of Barleria prionitis L. possess antiulcer activity. This work supports the traditional use of this plant in treating gastric ulcer.

Avaliação da atividade protetora gástrica do extrato hidroalcoólico da semente de girassol em ratas / Evaluation of the gastroprotective activity of hydroalcoholic extract of sunflower seed in rats

JUSTIFICATIVA E OBJETIVOS: Avaliar a proteção gástrica do extrato hidroalcoólico da semente de girassol (EHSG) em relaçãoao estresse, ao uso de indometacina e etanol. MÉTODO: Foi realizado um estudo experimental envolvendo 90 ratas (Rattus norvegicus albinus), da linhagem Wistar, fêmeas, com peso corporal médio de 150-230 g, divididos em 18 grupos distintos os quais receberam os seguintes tratamentos: EHSG:250 mg/kg, 500 mg/kg, 1000 mg/kg e 2000 mg/kg; etanol 0,5mL; cimetidina 60 mg/kg; indometacina 20 mg/kg; água 1 mL. Os dados foram analisados utilizando o programa Grand PadPrism 5 com aplicação de testes estatísticos considerando o nível de significância de 5%. RESULTADOS: O EHSG apresenta proteção contra as lesões gástricas em ratas, nas doses de 250 e 1000 mg, tanto no modelo pelo estresse, quanto na indução por etanol e indometacina. CONCLUSÃO: Os dados obtidos no presente estudo mostram que o EHSG apresenta proteção gástrica em determinadas doses.

BACKGROUND AND OBJECTIVES: To evaluate the gastric protection hidroalcoólico extract the sunflower seed (EHSG) in relation to stress, the use of indomethacin and ethanol. METHOD: We conducted an experimental study involving 90 rats (Rattus norvegicus albinos), Wistar, females, mean body weight of 150-230 g were divided into 18 distinct groups which received the following treatments: EHSG: 250mg/kg , 500 mg/kg, 1000 mg/kg and 2000 mg/kg; 0.5 mL ethanol, cimetidine 60 mg/kg, 20 mg/kg indomethacin; 1 mL water. Data were analyzed using the GrandPad Prism 5 with application of statistical tests, the significance level of 5%. RESULTS: The EHSG has protective against gastric injury in rats at doses 250 mg and 1000, both in the model by stress, as in the induction by ethanol and indomethacin. CONCLUSION: The data obtained in this study show that has EHSG gastric protection in certain doses.

Efecto secuestrador del D-002 sobre radicales hidroxilo en mucosa gástrica / Scavenger effect of D-002 on hydroxyl radicals in the gastric mucosa

Introducción: el agente causal de la ulceración gástrica está asociado al desequilibrio entre factores agresivos y defensivos que actúan sobre la mucosa gástrica. El D-002, mezcla de seis alcoholes alifáticos primarios superiores purificada de la cera de abejas, produce efectos gastroprotectores mediados por múltiples mecanismos y reducción de la peroxidación lipídica en la mucosa gástrica. Objetivo: determinar si el D-002 es capaz de capturar el radical hidroxilo añadido in vitro o generado in vivo en ratas con úlcera gástrica inducida por indometacina. Métodos: En la experiencia in vitro el D-002 se añadió a concentraciones entre 0,9 y 1 000 mg/mL. En la experiencia in vivo las ratas se distribuyeron en seis grupos: un control negativo y cinco que recibieron indometacina: un control positivo tratado con el vehículo, tres con D-002 (5, 25, y 100 mg/kg, respectivamente, p.o.) y otro con omeprazol (20 mg/kg i.p.). Los tratamientos se administraron una hora (vehículo y D-002) o 30 min (omeprazol), respectivamente, antes de inducir las úlceras. En ambas experiencias se tomaron alícuotas de mucosa gástrica, y se determinó el daño a la 2-desoxirribosa por el radical hidroxilo. Resultados: la administración oral del D-002, no in vitro, protegió a la 2-desoxirribosa del daño oxidativo de modo marcado, significativo y dependiente de la dosis con respecto al control positivo. Conclusiones: los resultados indican que la capacidad del D-002 (25 y 100 mg/kg) administrado por vía oral para secuestrar el radical hidroxilo, generado en la mucosa gástrica por la indometacina, pudiera contribuir a sus efectos antioxidantes y gastroprotectores sobre el daño que los antiinflamatorios no esteroideos producen sobre la mucosa gástrica.

Introduction: the etiology of the gastric ulceration is associated to the imbalance between aggressive and defensive factors acting upon the gastric mucosa. D-002, a mixture of 6 higher primary alcohols purified from the beeswax, cause some multiple mechanism-mediated gastroprotective effects and decrease of lipid peroxidation in the gastric mucosa. Objective: to determine whether D-002 can scavenge the in vivo added or in vivo generated hydroxyl radical in rats with indometacin-induced gastric ulcer or not. Methods: For the in vitro experiment, D-002 was added at concentrations 0.9 and 1 000 mg/mL For the in vivo experiment, the rats were randomized into 6 groups: one negative control, and five indometacin-treated groups as follows a positive excipient-treated control, three under D-002 treatment (5, 25 or 100 mg/kg, respectively, p.o.), and another group treated with Omeprazole (20 mg/kg i.p.). These lines of treatment were given 1 hour (excipient and D-002) or 30 min (Omeprazole) prior to inducing the ulcers. In both experiments, aliquots from the gastric mucosa were taken and the damage infringed to 2-deoxiribose by the hydroxyl radical was determined. Results: oral administration of D-002, rather than in vitro addition, significantly protected 2-desoxiribose from the oxidative damage depending on the dosage as compared to the positive control. Conclusions: these results indicate that the ability of the orally administered D-002 (25 and 100 mg/kg) to scavenge the hydroxyl radical endogenously generated on the gastric mucosa by indometacin could contribute to its antioxidant and gastroprotective effects against the damage that the non-steroidal anti-inflammatory drugs carry to the gastric mucosa.

Protective effects of Capparis zeylanica linn. leaf extract on gastric lesions in experimental animals

The aim of the study was to study the anti-ulcer activity of the methanolic extract of the leaves of Capparis zeylanica Linn on experimental animal models. The methanol extract of Capparis zeylanica Linn. leaves was investigated for anti-ulcer activity against aspirin plus pylorus ligation induced gastric ulcer in rats. HCl-Ethanol induced ulcer in mice and Indomethacin induced ulcer in rats at 200 mg/kg body weight p.o. A significant [p<0.01, p<0.001] anti-ulcer activity was observed in all the models. Pylorus ligation showed significant [p<0.01] reduction in gastric volume, free acidity and ulcer index as compared to control. It also showed 88.5% ulcer inhibition in HCl-ethanol induced ulcer and 83.78% inhibition in Indomethacin induced ulcer

Gastroprotective effect of the ethanolic extract of Parkia platycephala Benth. leaves against acute gastric lesion models in rodents

Parkia platycephala Benth. (Leguminosae - Mimosoideae), popularly known as "visgueira", fava bean tree or "fava-de-bolota", is widely found in the Northern and Northeastern regions of Brazil. Its pods are used as cattle food supplement in the drought period. Compounds with a gastroprotective activity were obtained from the genus Parkia. Therefore, this study aimed at investigating the gastroprotective effect of the ethanolic extract of Parkia platycephala Benth. leaves (Pp-EtOH), as well as evaluating its possible mechanisms of action in experimental ulcer induction models. Lesions were induced by absolute ethanol, ethanol-HCl, ischemia-reperfusion and indomethacin in rodents. Pp-EtOH showed a protective effect in the lesion models (66, 48 and 52 percent, respectively), but it was not able to protect gastric mucosa against indomethacin-induced lesions. Results show a possible participation of the NO-synthase pathway in the gastroprotection and an antioxidant activity, by the increase of the catalase activity. The participation of prostaglandins and potassium channels sensitive to ATP in the gastroprotective effect of Pp-EtOH seems less likely to occur. More comprehensive studies, therefore, should be carried out to elucidate the antiulcerative effects of this promising natural product against this gastrointestinal disorder.

Antiulcer activity of ethanolic extract of Encholirium spectabile Mart. ex Schult & Schult f. (Bromeliaceae) in rodents

This study evaluated the antiulcer activity of an ethanolic extract of Encholirium spectabile (ES-EtOH) by using different standard experimental models of induced acute gastric ulceration. ES-EtOH (100 mg/kg p.o) protected the gastric mucosa against ulceration that was induced by absolute ethanol (53 percent), ethanol/HCl (75 percent), ibuprofen (52 percent) and ischemia/reperfusion (43 percent). It also restored catalase activity and non-protein sulfhydryl group concentration in the gastric wall of mice that had been treated with ethanol. The pre-treatment of mice with N-nitro-L-arginine (70 mg/kg i.p.) abolished the protective activity of ES-EtOH, which indicates that prostaglandins, antioxidant compounds and nitric oxide synthase activity are involved in the gastroprotective activity of the extract.

Indomethacin-induced colon perforation in Bartter's syndrome.

Bartter's syndrome (BS) is an inherited renal tubular disorder characterized by hypokalemia, hypochloremic metabolic alkalosis, and hyperaldosteronism with normal blood pressure. A 22-year-old woman was referred at 23 week of gestation. Polyhydramnios was detected and the chloride level of the amniotic fluid was high. The mother was treated with indomethacin from 26 to 31 week of gestation. The newborn was delivered at 34 week of gestation. At 8th day of life, indomethacin was also started for the baby. After three days, a colonic perforation developed. Indomethacin-induced colon perforation is uncommon in antenatal Bartter's syndrome. This patient indicates that administration of indomethacin in both antenatal and/or early postnatal period may be associated with colonic perforation.

Effects of saffron and its active constituents, crocin and safranal, on prevention of indomethacin induced gastric ulcers in diabetic and nondiabetic rats

Saffron is the dried stigmata of the flowers of saffron [Crocus sativus L., Iridaceae]. Saffron is well known for the treatment of gastric disorders in traditional medicine. In the search for new potential antiulcer agents, the effects of the ethanol extract of saffron and its active constituents crocin and safranal as compared with omeprazole against gastric ulcer induced by indomethacin in non-diabetic and streptozocin diabetic rats were studied. The effects of pretreatment with saffron extract [25, 100 or 250 mg/kg, p.o.], crocin [2.5, 5 or 10 mg/kg, p.o.] and safranal [0.25, 2, 5 ml/kg, p.o.] and omeprazole [30 mg/kg, p.o.] 30 min before administration of indomethacin [40 mg/kg, p.o. in non-diabetic rats and 15 mg/kg, p.o. in diabetic rats] on gastric lesions, increase of lipid peroxidation and decrease of glutathione levels induced by indomethacin in non-diabetic and diabetic rats were evaluated. Saffron extract, crocin, safranal and omeprazol prevented the gastric lesions, increase of lipid peroxidation and decrease of glutathione levels induced by indomethacin in non-diabetic and diabetic rats as compared with the control group [P < 0.01]. The effects of saffron extract, crocin and safranal on the gastric ulcer index, lipid peroxidation and glutathione levels were comparable to omeprazole. Saffron, crocin and safranal may prevent the gastric mucosa damage due to their antioxidant properties by increasing the gluthatione levels and diminishing the lipid peroxidation in the rat gastric mucosa

healing effects of Teucrium polium in the repair of indomethacin-induced gastric ulcer in rats

To determine the healing effect of Teucrium polium [T. polium] in indomethacin-induced gastric ulcer in rats. In the fall of 2007, 250 Sprague-Dawley rats provided by the Shiraz University Laboratory Animal Center were divided into 4 equal groups including control [70 rats], and 3 experimental groups [60 rats each], and each group received different doses of T. polium. Ten rats were used to study the induction of gastric ulcer by indomethacin [25 mg/kg/stat]. After 24 hours, their stomachs were evaluated for any mucosal ulcer. The T. polium extract was administered orally, 24 hours after indomethacin administration. In the experimental group, 10 animals were sacrificed after 24, 48, and 72 hours, after administration of T. polium, and at one, 2, and 4 weeks, and in the control group identically after the administration of distilled water. In rats treated with indomethacin, multiple ulcers were evident. After 4 weeks of treatment with T. polium, more re-epithelialization, proliferation, mucosal hyperplasia, migration of the gastric epithelial cells, and decrease in inflammatory cells were observed. The T. polium reduced the ulcer indices by >50% after one week, >80% after 2 weeks, and >90% after 4 weeks. The healing effect of T. polium may be due to antioxidant activity along with the ability to modulate the mucin secretion, prostaglandin synthesis, and epidermal growth factor receptor expression. These results along with the non-toxicity properties of T. polium suggests it as a promising anti-ulcer compound

Omeprazole and misoprostol for preventing gastric mucosa effects caused by indomethacin and celecoxib in rats

OBJETIVO: Avaliar e comparar macro e microscopicamente as lesões agudas da mucosa gástrica de ratos provocadas pelos AINEs celecoxib e indometacina e a citoproteção gástrica com omeprazol e misoprostol. MÉTODOS: A amostragem consistiu 150 ratos machos da raça Wistar, com peso médio de 200g, divididos em quatro grupos, a saber: grupo A, subdividido em grupos A1 e A2 – pré-tratamento com omeprazol (20 mg/rato) durante sete dias, e no oitavo dia receberam o AINEs, sendo A1 (20 ratos) receberam celecoxib (1mg/rato) e A2 (20 ratos) receberam indometacina (12,5mg/rato). O grupo B, subdividido em grupo B1 e B2 – pré-tratamento com misoprostol (20ìg/rato) durante sete dias e no oitavo dia receberam AINEs, sendo B1 (20 ratos) receberam celecoxib (1mg/rato) e B2 (20 ratos) receberam indometacina (12,5mg/rato). O grupo C não recebeu citoproteção durante sete dias e no oitavo dia recebeu AINEs, sendo C1 (20 ratos) receberam celecoxib (1mg/rato) , C2 (20ratos) receberam indometacina (12,5mg/rato), C3 (20 ratos) receberam celecoxib e grupo D – grupo controle, no qual dez ratos foram observados recebendo ração e água ad libitum. A seguir, no 9º dia (de todos os grupos), os estômagos eram removidos e avaliados macro e microscopicamente para a identificação das lesões gástricas. RESULTADOS: Na análise macroscópica, os grupos A2, B2 e C2 apresentaram número de lesões por cm2/animal significativamente elevados, sendo respectivamente 18,55 lesões por cm2/animal, 16,25 lesões por cm2/animal e 13,55 lesões por cm2/animal. Na análise microscópica, a porcentagem da mucosa com lesão mostrou diferença significativa entre os grupos A1, B1, C1 quando comparados com os grupos A2, B2 e C2 (p<0,0001). Os resultados da média da extensão/lesão e da média da profundidade das lesões não mostraram diferenças estatísticas significativas entre os grupos A2, B2 e C2. A média do edema mostrou diferença estatística significativa entre os grupos A2 e D; B2 e C2 e entre C2 e D (p<0,05)...

Effect of licofelone against NSAIDs-induced gastrointestinal ulceration and inflammation.

The present study was aimed to evaluate the effect of licofelone, a dual inhibitor of cycloxygenase1/2-5-lipoxygenase against indomethacin-induced gastric damage in rats and mice in order to assess the role of leukotrienes if any, in non-steroidal anti-inflammatory drugs (NSAIDs)-induced gastrointestinal inflammation. Acute pretreatment with licofelone reversed the indomethacin-induced gastric ulceration, neutrophil adhesion in mesentery venules, neutrophil count in blood, lipid peroxides and vascularity in the stomachs of mice and rats. Further, chronic pretreatment of licofelone also prevented indomethacin-induced gastric morphological changes and cellular infiltration in mesentery venules. Moreover, acute administration of indomethacin elevated leukotriene B4 levels in gastric mucosa, which was reversed by pretreatment with licofelone The results suggest that licofelone offered gastroprotection against NSAIDs-induced gastropathy through its effect on leukotrienes and by inhibiting extravasation of neutrophils.

Study of anti-inflammatory and healing effects of achillea millefolium in the treatment of indomethacin-induced gasthic ulcer in rat

According to numerous sources, the plant "Achillea millefolium" is used for various ailments, mainly for disorders of the gastrointestinal tract or tonically for the healing of wounds. In this research, the effects of hydro-alcoholic extract [8:2V/V] of the plant Achillea millefolium on the treatment of gastric ulcer and possible hepatotoxicity of the plant in rat were studied. Hydro-alcoholic extraction of the plant was carried out using maceration, followed by concentrating under vacuum. Gastric ulcer in rat was induced by oral administration of indomethacin suspension [30mg/kg] in 1% carboxy methyl cellulose following 72 hours of fastin. Hydro-alcoholic extract of the plant was orally administrated as a single dose but in different concentrations of 125, 250, 500, 1000 and 1500 mg/kg for 14 days following induction of gastric ulcer in rats. At the end of the experimental period, animals were killed and the stomachs were examined both macroscopically and microscopically. All different concentration of Achillea millefolium were effective in treating of gastric ulcer specially those with concentrations of 500, 1000 and 1500 mg/kg which showed to be the most effective ones. The extract with concentration of 500 mg/kg was considered to be the most effective dose in treatment as no liver disorder was observed. Achillea millefolium is a suitable preparation in treatment of gastric ulcer

Modulation of ulcerogenicity of Ibuprofen and Indomethacin via blocking the H[2] receptors in the stomach

Among the commonest side effects of NSAIDs are the gastrointestinal manifestations, which could reach gastric erosions, ulcerations, or recurrent liberations in people using NSAID for long durations. This provided idea of accomplishing this work in order to study the possibility of avoiding these side effects, which stand as a strong barrier against the regular use of these drugs. This study aimed at finding a way out from these serious side effects such as gastric ulcers, so that a member of the H[2] receptor antagonists; namely ranitidine, was thought to accompany the treatment with indomethacin being the classic example of the NSAIDs, and ibuprofen; which is one of the most commonly used NSAIDs. The ulcer index was the measure to reach a fair judgment comparing the use and the non-use of ranitidine with indomethacin and ibuprofen therapies. Results were much better when ranitidine was taken as an adjuvant treatment to indomethacin and ibuprofen, a situation indicating the necessity of considering prescribing one of the H[2] receptor antagonists with the NSAIDs therapy, especially in prolonged use

A suspensão súbita ambulatorial de medicações sintomáticas promove melhora da cefaléia em pacientes com migrânea crônica: estudo prospectivo / The abrupt outpatient withdrawal of symptomatic medications improve the headache in chronic migraine patients: a prospective study

Pacientes com migrânea crônica (MC) usam freqüentemente medicações sintomáticas (MS) em caráter excessivo. Estas medicações criam um ciclo de rebote e sintomas de abstinência que podem perpetuar a cefaléia e torná-la diária ou quase diária. Além disso, este perfil de consumo é considerado como responsável pela ausência da eficácia do tratamento preventivo nesses pacientes. Avaliamos prospectivamente 50 (42 M, 8 H) pacientes preenchendo os critérios propostos por Silberstein e col., (1994, 1996) para migrânea crônica (transformada) e uso excessivo de MS. Todos foram clara e enfaticamente orientados quanto à relação entre uso excessivo de MS e cefaléia diária, suspenderam abruptamente suas MS e iniciaram esquema semelhante de drogas preventivas a partir do sétimo dia. Durante os primeiros seis dias de abstinência os pacientes não obtiveram medicamentos regulares para utilizar e poderiam fazer uso de 100mg retal de indometacina no máximo uma vez por semana nas cinco semanas seguintes. Além disso, poderiam acionar esquema permanente para administração parenteral de clorpromazina em ambiente hospitalar. Após cinco semanas foram avaliados os graus de aderência ao tratamento, comportamento da cefaléia e dos sintomas de abstinência durante os primeiros seis dias e consumo de drogas de resgate nesse período. Também foi avaliada a freqüência da cefaléia semana a semana e a redução > 50 por cento da freqüência após cinco semanas de tratamento. Quarenta e um (82 por cento) pacientes retornaram e aderiram ao tratamento proposto. Durante os dias iniciais, houve cefaléia intensa em 68,3 por cento (n=28) dos pacientes, 97,5 por cento (n=40) apresentaram sintomas de abstinência e 46,4 por cento (n=19) pacientes fizeram uso de drogas de resgate. Ao final de cinco semanas, a freqüência da cefaléia encontrava-se significativamente menor (p=0.000), a cefaléia revelou redução média de 43,4 por cento e 63,4 por cento (n=26) dos pacientes apresentavam redução > 50 por cento na freqüência média da dor. Concluímos que a suspensão ambulatorial súbita das MS usadas em excesso por esses pacientes, provoca exacerbação da cefaléia e sintomas de abstinência, mas não compromete a aderência ao tratamento proposto. Além disso, após cinco semanas há redução da freqüência média de cefaléia na maioria dos pacientes.

Indometacina profiláctica en el prematuro extremo / Prophylactic indomethacin in the very low birth weight infant

La indometacina es útil en el cierre del ductus arterioso. Durante los últimos años, se ha utilizado de manera profiláctica precoz, en la disminución de la incidencia de hemorragia intraventricular (HIV) y ductus arterioso persistente (DAP). Diferentes esquemas terapéuticos han sido publicados. Nuestro objetivo es reportar la experiencia clínica de dos protocolos profilácticos comparándolos con un grupo sin profilaxis. Se incluyó recién nacidos (RN) menores de 1 500 gramos y/o edad gestacional inferior a 32 semanas. Se utilizó un grupo histórico sin profilaxis, con RN pareados según peso y edad gestacional, nacidos en el período 1994-1996 (n = 74). Se consideró grupo I a 71 RN con estas características, nacidos entre 1997-1999 y grupo II, 83 RN del período 1999-2001. Se excluyeron en todos los grupos, aquellos con cardiopatías congénitas, asfixia severa, trastornos genéticos y malformaciones mayores. Todos los niños fueron evaluados con ecotomografía encefálica, en los días 3, 10 y 30 de vida, y con ecocardiografía el 7° día de acuerdo a normas de tratamiento similares en los tres periodos. Se registró la incidencia de complicaciones. El grupo I, recibió indometacina en dosis de 0,1 mg/kg, a las 6, 30 y 54 horas de vida; mientras que el grupo II, una dosis única a las 6 horas. En todos los pacientes se administró en infusión continua en 30 minutos. Los tres grupos resultaron comparables. En el grupo sin profilaxis, se observó DAP en 14 pacientes (18,9 por ciento) y HIV en 13 casos (17,5 por ciento). En el grupo I, 6 niños presentaron DAP (8,4 por ciento) y 7 HIV (9,8 por ciento). En el grupo II, se registró DAP en 6 RN (8,4 por ciento), mientras que HIV en 13 pacientes (15,7 por ciento). Así, la incidencia de DAP se puede disminuir utilizando una o tres dosis de indometacina (61,9 por ciento y 55,5 por ciento respectivamente, en relación al grupo sin profilaxis, p < 0,01). Sin embargo, se observó disminución significativa de HIV, sólo con el esquema de tres dosis (disminución de 44 por ciento, p < 0,01 vs 10,28 por ciento en el grupo II, NS). Conclusión: El uso precoz de Indometacina profiláctica, puede disminuir la incidencia de DAP. La dosis única puede ser tan efectiva, como el protocolo de tres. Sin embargo, en la reducción de HIV, sólo éste último demostró utilidad. De esta manera, la elección del esquema a usar debe basarse en los objetivos terapéuticos de cada centro...

Fístula gastrocólica na síndrome de Bartter em uso de indometacina: relato de dois casos / Gastrocolic fistula in Bartter's syndrome caused by indometacin: report of two cases

Os autores relatam dois casos de fístula gastrocólica causada por uso crônico de indometacina em pacientes com síndrome de Bartter, em acompanhamento no Instituto da Criança do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. O diagnóstico foi realizado por meio de trânsito intestinal, que evidenciou passagem de contraste da grande curvatura gástrica para o cólon transverso. O tratamento foi cirúrgico em ambos os casos.

The authors report two cases of gastrocolic fistula caused by chronic therapy with indometacin in patients with Bartter's syndrome followed at the outpatients clinic of "Instituto da Criança do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo", Brazil. The diagnosis was suggested by a barium meal that showed a gastrocolic fistula between the greater curvature of the stomach and the transverse colon. Treatment was surgical in the both cases.