Individualized treatment for allergic rhinitis based on key nasal clinical manifestations combined with histamine and leukotriene D4 levels / Tratamento individualizado para a rinite alérgica baseado nas principais manifestações clínicas nasais e dos níveis de histamina e leucotrieno D4

Abstract Introduction The types of allergic rhinitis are roughly classified based on the causative antigens, disease types, predilection time, and symptom severity. Objective To examine the clinical typing and individualized treatment approach for allergic rhinitis and to determine the optimal treatment method for this disease using various drug combination therapies. Methods A total of 108 participants with allergic rhinitis were divided into three groups based on symptoms. Subsequently, each group was further categorized into four subgroups based on the medications received. The efficacy of the treatments was evaluated using the visual analog scale VAS scores of the total and individual nasal symptoms, decline index of the symptom score, histamine and leukotriene levels, and mRNA and protein expression levels of histamine 1 and cysteinyl leukotriene 1 receptors. Results Loratadine + mometasone furoate and loratadine + mometasone furoate + montelukast significantly improved the sneezing symptom and reduced the histamine levels compared with the other combination therapies (p < 0.05). Meanwhile, montelukast + mometasone furoate and montelukast + mometasone furoate + loratadine considerably improved the nasal obstruction symptom and decreased the leukotriene D4 levels compared with the other combination therapies (p < 0.05). Conclusion Clinical symptom evaluation combined with experimental detection of histamine and leukotriene levels can be an objective and accurate method to clinically classify the allergic rhinitis types. Furthermore, individualized treatment based on allergic rhinitis classification can result in a good treatment efficacy.

Resumo Introdução A rinite alérgica é basicamente classificada de acordo com os antígenos causadores, tipos de doença, peridiocidade e gravidade dos sintomas. Objetivo Avaliar os tipos clínicos e a abordagem terapêutica individualizada para cada tipo de rinite alérgica e determinar o método de tratamento ideal utilizando várias terapias de combinação de fármacos. Método Um total de 108 participantes com rinite alérgica foram divididos em três grupos com base nos sintomas. Posteriormente, cada grupo foi subsequentemente categorizado em quatro subgrupos com base nos medicamentos recebidos. A eficácia dos tratamentos foi avaliada utilizando os escores da escala visual analógica EVA dos sintomas nasais totais e individualmente, índice de declínio do escore de sintomas, níveis de histamina e leucotrienos e níveis de expressão de mRNA e proteína dos receptores de histamina 1 e cisteinil-leucotrieno 1. Resultados As associações entre loratadina + furoato de mometasona, assim como a de loratadina + furoato de mometasona + montelucaste melhoraram significativamente o sintoma de espirros e reduziram os níveis de histamina em comparação às outras terapias combinadas (p < 0,05). Por outro lado, a associação montelucaste + furoato de mometasona, assim como a associação montelucaste + furoato de mometasone + loratadina melhoraram consideravelmente o sintoma de obstrução nasal e diminuíram os níveis de leucotrieno D4 em comparação com as outras combinações (p < 0,05). Conclusão A avaliação clínica dos sintomas combinada com a detecção experimental dos níveis de histamina e leucotrieno pode ser um método objetivo e preciso para classificar clinicamente os tipos de rinite alérgica. Além disso, o tratamento individualizado baseado na classificação da rinite alérgica pode resultar no aumento da eficácia do tratamento.

lncRNA PCGEM1 strengthens anti-inflammatory and lung protective effects of montelukast sodium in children with cough-variant asthma

Montelukast sodium is an effective and well-tolerated anti-asthmatic drug. Long non-coding RNAs (lncRNAs) are involved in the treatment of asthma. Therefore, this study aimed to investigate the effect of montelukast sodium on children with cough-variant asthma (CVA) and the role of lncRNA prostate cancer gene expression marker 1 (PCGEM1) in drug efficacy. The efficacy of montelukast sodium was evaluated by assessing the release of inflammatory factors and pulmonary function in CVA children after a 3-month treatment. An ovalbumin (OVA)-sensitized mouse model was developed to simulate asthmatic conditions. PCGEM1 expression in clinical peripheral blood samples and lung tissues of asthmatic mice was determined. Asthmatic mice experienced nasal inhalation of PCGEM1 overexpression with simultaneous montelukast sodium to investigate the roles of PCGEM1 in asthma treatment. The NF-κB axis after PCGEM1 overexpression was detected to explore the underling mechanisms. Consequently, montelukast sodium contributed to reduced levels of pro-inflammatory factors and improved pulmonary function in CVA children. PCGEM1 was poorly expressed in OVA-sensitized asthmatic mice and highly expressed in CVA children with response to the treatment. PCGEM1 overexpression enhanced the anti-inflammatory effects and promoted effects on pulmonary function of montelukast sodium in CVA children and OVA-sensitized asthmatic mice. Furthermore, PCGEM1 inhibited the activation of the NF-κB axis. This study demonstrated the anti-inflammatory and lung-protective effects of montelukast sodium on CVA, which was strengthened by overexpression of PCGEM1. Findings in this study highlighted a potential anti-asthmatic target of montelukast sodium.

Effect of ethyl acetate extract of usnea longissima on esophagogastric adenocarcinoma in rats

Abstract Purpose: To investigate the effects of the EtOAc extract of U. longissima which is uninvestigated previously on esophagogastric cancer induced in rats with N-methyl-N-nitro-N-nitrosoguanidin (MNNG). Methods: The anticancer activity of EtOAc extract of U. longissima was examined in the esophagogastric adenocarcinoma models induced in rats with MNNG. EtOAc extract of U. longissima, 50 and 100 mg/kg oral doses were administered once daily for six months. MNNG induced differentiated and undifferentiated type adenocarcinomas in the esophageal and gastric tissues of rats. Results: EtOAc extract of U. longissima obtained from U. longissima prevented gastric and esophageal cancerogenesis induced in rats with MNNG. EtOAc extract of U. longissima did not have a lethal effect at doses of 500, 1000 and 2000 mg/kg. The prominent anticarcinogenic activity of EtOAc extract of U. longissima 50 and 100 mg/kg suggests that it is not toxic and it is selective to the cancer tissue. Conclusion: This information may shed light on clinical implementation of EtOAc extract of U. longissima in future.

Anthelmintic effect of thymol and thymol acetate on sheep gastrointestinal nematodes and their toxicity in mice / Efeito anti-helmíntico do timol e acetato de timila sobre nematoides gastrintestinais de ovinos e toxicidade em camundongos

Abstract Thymol is a monoterpene and acetylation form of this compound can reduce the toxicity and enhance its biological effects. The objective of this study was to evaluate the effect of thymol and thymol acetate (TA) on egg, larva and adult Haemonchus contortus and the cuticular changes, acute toxicity in mice and the efficacy on sheep gastrointestinal nematodes. In vitro tests results were analyzed by analysis of variance (ANOVA) and followed by comparison with Tukey test or Bonferroni. The efficacy of in vivo test was calculated by the BootStreet program. In the egg hatch test (EHT), thymol (0.5 mg/mL) and TA (4 mg/mL) inhibited larval hatching by 98% and 67.1%, respectively. Thymol and TA (8 mg/mL) inhibited 100% of larval development. Thymol and TA (800 µg/mL) reduced the motility of adult worms, by 100% and 83.4%, respectively. Thymol caused cuticular changes in adult worm teguments. In the acute toxicity test, the LD50 of thymol and TA were 1,350.9 mg/kg and 4,144.4 mg/kg, respectively. Thymol and TA reduced sheep egg count per gram of faeces (epg) by 59.8% and 76.2%, respectively. In in vitro tests thymol presented better anthelmintic activity than TA. However TA was less toxic and in in vivo test efficacy was similar.

Resumo Timol é um monoterpeno e a acetilação deste composto pode reduzir a toxicidade e potencializar os seus efeitos biológicos. O objetivo deste trabalho foi avaliar o efeito do timol e acetato de timolila (AT) sobre ovos, larvas e adultos de Haemonchus contortus e suas alterações cuticulares, toxicidade aguda em camundongos e a eficácia sobre nematoides gastrintestinais de ovinos. Os resultados dos testes in vitro foram analisados por análise de variância (ANOVA) e comparados pelo testes de Tukey ou Bonferroni. A eficácia do teste de redução da contagem de ovos nas fezes (RCOF) foi calculada pelo programa BootStreet. No teste de inibição da eclosão de ovos (TEO), timol (0,5 mg/mL) e AT (4 mg/mL) inibiram a eclosão das larvas em 98% e 67,1%, respectivamente. Timol e AT (8 mg/mL) inibiram 100% do desenvolvimento larval. Timol e AT (800 μg/mL) reduziram a motilidade dos nematoides adultos, em 100% e 83,4%, respectivamente. O timol provocou alterações cuticulares nos nematoides adultos. No teste de toxicidade aguda, a DL50 do timol e AT foi de 1.350,9 mg/kg e 4.144,4 mg/kg, respectivamente. Timol e AT reduziram a contagem de ovos por gramas de fezes (OPG) dos ovinos em 59,8% e 76,2%, respectivamente. Nos testes in vitro timol apresentou atividade melhor anti-helmíntica do que AT. Entretanto, AT foi menos tóxico do que o timol e no teste in vivo apresentaram eficácia semelhante.

Montelukast reduces seizures in pentylenetetrazol-kindled mice

Cysteinyl leukotrienes (CysLTs) have been implicated in seizures and kindling; however, the effect of CysLT receptor antagonists on seizure frequency in kindled animals and changes in CysLT receptor expression after pentylenetetrazol (PTZ)-induced kindling have not been investigated. In this study, we evaluated whether the CysLT1 inverse agonist montelukast, and a classical anticonvulsant, phenobarbital, were able to reduce seizures in PTZ-kindled mice and alter CysLT receptor expression. Montelukast (10 mg/kg, sc) and phenobarbital (20 mg/kg, sc) increased the latency to generalized seizures in kindled mice. Montelukast increased CysLT1 immunoreactivity only in non-kindled, PTZ-challenged mice. Interestingly, PTZ challenge decreased CysLT2 immunoreactivity only in kindled mice. CysLT1 antagonists appear to emerge as a promising adjunctive treatment for refractory seizures. Nevertheless, additional studies are necessary to evaluate the clinical implications of this research.

Tratamiento de la hipersensibilidad dentinaria post terapia periodontal, mediante el uso de dos dentífricos desensibilizantes / Dentin hypersensitivity treatment post periodontal therapy, using two desensitizing dentifrices

Objetivo: El objetivo de este estudio fue evaluar y comparar la eficacia en la reducción de la hipersensibilidad dentinaria posterior a la terapia periodontal utilizando dentífricos que contienen arginina al 8 por ciento - carbonato de calcio versus acetato de estroncio al 8 por ciento, tras una y tres semanas de uso de las pastas dentales. Materiales y Método: Estudio clínico, aleatorio, ciego y controlado con dos grupos paralelos, y tres semanas de seguimiento, en el cual el universo de trabajo fue de 20 pacientes con diagnóstico de periodontitis crónica generalizada leve o moderada y que hayan presentado hipersensibilidad dentinaria posterior a la terapia periodontal no quirúrgica en al menos un canino y/o premolar, y asociado a recesión gingival. Los pacientes fueron seleccionados aleatoriamente y se distribuyeron al azar en cada grupo de pastas dentales y fueron evaluados tras una y tres semanas de uso de los dentífricos. Se les aplicó aire proveniente de la jeringa triple del equipo dental en la zona cervical con hipersensibilidad, estandarizando la técnica. La cuantificación del dolor se realizó a través de la Escala Visual Análoga (EVA). Resultados: No hubo diferencia estadísticamente significativa entre el uso de los dentífricos que contienen arginina 8 por ciento - carbonato de calcio versus acetato de estroncio al 8 por ciento para la reducción de la hipersensibilidad dentinaria tras una y tres semanas de uso de las pastas dentales. Existió diferencia estadísticamente significativa en la reducción del dolor con el uso de ambos dentríficos a la primera y tercera semana de medición.

Aim: The aim of this clinical study was to evaluate and to compare the efficacy in reducing the dentin hypersensitivity after periodontal therapy using dentifrices which contain 8 percent arginine, calcium carbonate versus 8 percent strontium acetate, after one and three weeks of use of the dentifrices. Methods: A three-week clinical study with 20 subjects with diagnosis of slight to moderate chronic periodontitis with dental hypersensitivity after periodontal therapy, and presence of gingival recession in canines and/or premolars. Patients were randomly selected and assigned to each group and toothpastes were evaluated after one and three weeks of use. Air from a triple syringe was applied into the cervical area with hypersensitivity. The quantification of pain was performed using the Visual Analogue Scale (VAS). Results: There was not statistically significant difference between the use of the dentifrices which contain 8 percent arginine, calcium carbonate versus 8 percent strontium acetate in reducing dentin hypersensitivity after one and three weeks of use of the dentifrices. Nevertheless, there was a statistically significant difference in the reduction of pain using both dentifrices in the first and third week of measurement.

Comparative Efficacy and Outcome Between Metered Dose Inhaled Corticosteroids and Oral Montelukast in Mild Persistent Childhood Asthma.

Asthma is a chronic relapsing inflammatory disorder characterized by hyper reactive airways, leading to episodic, reversible bronchi constriction, owing to increased responsiveness of the tracheobronchial tree to various stimuli1. Specific objectives of the study to compare the clinical efficacy of oral montelukast with metered dose inhaled steroids. The results of the study suggests that metered dose inhaled steroids are superior than oral montelukast in mild persistent childhood asthma.

Protección gonadal de pacientes con malignidades hematológicas durante la quimioterapia: uso del acetato de leuprolide / Gonadal protection in patients with hematological malignancies during chemotherapy: use of leuprolide acetate

Demostrar el papel de los análogos agonistas de hormona liberadora de gonadotropinas en la reserva ovárica de pacientes hemato-oncológicas del Servicio de Hematología del Hospital Universitario de Caracas durante el año 2010, en tratamiento con regímenes de quimioterapia. Estudio de la variable reserva ovárica, mediante la cuantificación periódica de: ritmo menstrual, concentraciones de FSH, volumen ovárico, número de folículos antrales e incidencia de embarazo. Se administró acetato de leuprolide (11,25 mg) cada 3 meses vía intramuscular; se realizaron mediciones trimestrales de las concentraciones de FSH y se practicaron ecosonogramas pélvico o transvaginal cada 6 meses. Posterior al cumplimiento de los análogos de la hormona liberadora de gonadotropinas, se observó la aparición de amenorrea en las pacientes. Las concentraciones de FSH se mantuvieron estables, y siguieron la misma distribución (prueba de Levene p 0,2466) los volúmenes ováricos y el número de folículos antrales se mantienen estables, se rechaza la hipótesis de normalidad del grupo de diferencias al 5 por ciento de significancia. No se registraron embarazos. La reserva ovárica se preserva durante el tratamiento continuo con análogos

To demonstrate the role gonadotropin releasing hormone analogues in ovarian reserve in hematology patients in the hematology service at the Hospital Universitario de Caracas in 2010, treated with chemotherapy regimens. Study of ovarian reserve variable by periodic quantification of: menstrual rhythm, concentrations of FSH, ovarian volume, antral follicle number and incidence of pregnancy. Leuprolide acetate was administered (11.25 mg) intramuscularly every 3 months, were measured quarterly and FSH concentrations were performed pelvic or transvaginal ecosonograms every 6 months. After aGnRH administration, we observed the occurrence of amenorrhea in patients. FSH concentrations were stable, and followed the same distribution (Levene test p 0.2466) ovarian volume and antral follicle numbers were stable, we reject the hypothesis of normality of group differences at 5 percent significance. There were no pregnancies. Ovarian reserve is preserved during continuous treatment with analogs

Bloqueio do receptor de leucotrieno CysLT1 em pacientes com fenômeno de Raynaud: evidência capilaroscópica do papel do leucotrieno / CysLT1 receptor inhibition in patients with Raynaud's phenomenon: capillaroscopic evidence of the role of leukotriene

OBJETIVO: Avaliar a ação do medicamento inibidor do receptor de leucotrieno CysLT1 (montelucaste) nas alterações vasculares das mãos em pacientes com fenômeno de Raynaud. MÉTODOS: Foram selecionadas pacientes com fenômeno de Raynaud secundário à doença inflamatória do tecido conjuntivo, excluindo tabagismo, hipertensão arterial e diabetes mellitus. As pacientes mantiveram a medicação prévia e iniciaram o uso de montelucaste 10 mg/dia por 60 dias. Foi realizada capilaroscopia periungueal dos dedos das mãos antes do uso da medicação e após 30 e 60 dias. A análise estatística foi feita por meio de porcentagem, média, desvio-padrão e teste exato de Fisher, com intervalo de confiança de 95 por cento. RESULTADOS: Foram estudadas cinco pacientes mulheres, brancas, com fenômeno de Raynaud secundário a doenças do tecido conjuntivo, das quais três apresentavam esclerodermia e duas apresentavam doença mista do tecido conjuntivo. A média de idade foi de 42,4 ± 12,4 anos, e a média de tempo de doença foi de 9,6 ± 4,8 anos. As pacientes estavam em uso de até 20 mg/dia de prednisona (pacientes com doença mista do tecido conjuntivo), nifedipina, pentoxifilina. As medicações foram mantidas. Após o uso de inibidor de receptor de leucotrieno por dois meses, o controle com capilaroscopia ungueal demonstrou diminuição do edema e da palidez e normalização do número, tamanho e distribuição dos capilares. CONCLUSÃO: O uso do montelucaste modificou as alterações capilares observadas na capilaroscopia periungueal de pacientes com fenômeno de Raynaud.

OBJECTIVE: To assess the effect of the leukotriene receptor inhibitor (montelukast) on vascular alterations in fingers of patients with Raynaud's phenomenon. METHODS: Patients with Raynaud's phenomenon of the hands secondary to inflammatory connective tissue disease were selected, and those with the following characteristics were excluded: smokers, arterial hypertension, and diabetes mellitus. All patients maintained their previous medications and started the use of montelukast, 10 mg/day, for 60 days. Naifold capillaroscopy of fingers was performed before the use of medication and after 30 and 60 days. Statistical analysis was performed with percentage, media, standard deviation, Fisher exact test, with 95 percent of confidence interval. RESULTS: The study assessed five Caucasian, female patients with Raynaud's phenomenon secondary to inflammatory connective tissue disease (three with scleroderma and two with mixed connective tissue disease), aged 42.4 ± 11.5 years, and with 9.6 ± 4.8 years of disease duration. Patients were on nifedipine and pentoxifylline, and those with mixed connective tissue disease were also on prednisone. The medications were maintained. After using montelukast for two months, nailfold capillaroscopy showed a reduction in edema and pallor, and normalization of capillary number, size, and distribution. CONCLUSION: The use of montelukast modified the capillary abnormalities observed on nailfold capillaroscopy of patients with Raynaud's phenomenon.

Neutrophil predominance in induced sputum from asthmatic patients: Therapeutic implications and role of clara cell 16-KD protein / Predominio de neutrófilos en esputo inducido de asmáticos: Implicancias terapéuticas y rol de la proteína 16-kD de la célula clara

Eosinophil is considered to be a main protagonist in asthma; however, often discordances between clinical manifestations and response to treatment are observed. We aimed to determine the occurrence of neutrophil predominance in asthma and to identify its characteristics on the basis of clinical-functional features, induced sputum cellular pattern and soluble molecules, to guide the appropriated anti-inflammatory therapy. A total of 41 patients were included in randomized groups: 21-40 year-old, with stable mild-to-severe asthma, steroid-naïve and non-smokers. An induced sputum sample was obtained under basal conditions, a second one after treatment with budesonide (400 µg b.i.d.) or montelukast (10 mg/d) for six weeks, and a final one after a 4-week washout period. By cytospin we evaluated eosinophil (EP) or neutrophil predominance (NP), and in supernatant we determined LTE4, and CC16. Peak expiratory flow variability (PEFV) was measured. A total of 23/41 patients corresponded to EP and 18/41 patients to NP. The PEFV was higher in EP than in NP. LTE4 was higher with NP than with EP. No difference was found for CC16. Montelukast reduced the predominant cell in both subsets, whereas budesonide only reduced eosinophils in EP. Budesonide and montelukast reduced PEFV in EP but not in NP. Considering the total treated-samples in each subset, CC16 level increased significantly in EP. In conclusion: a NP subset of asthmatic patients was identified. These patients show a lower bronchial lability; the leukotriene pathway is involved which responds to anti-leukotriene treatment. This phenotype shows a poor recovery of CC16 level after treatment.

El eosinófilo es considerado la célula protagonista principal en el asma; sin embargo, a menudo se observan discordancias entre las manifestaciones clínicas y la respuesta de los pacientes al tratamiento. Nos propusimos determinar la ocurrencia de predominio de neutrófilos en el asma e identificar las características clínico-funcionales, el patrón celular y las moléculas solubles del esputo inducido, para guiar el tratamiento apropiado anti-inflamatorio. Se incluyeron 41 pacientes: 21 a 40 años de edad, con asma estable leve a grave, no tratados con esteroides tópicos ni sistémicos y no fumadores. Se obtuvo una muestra de esputo inducido en condiciones basales, una segunda muestra después del tratamiento al azar con budesonida (400 µg dos veces al día) o el montelukast (10 mg/d) durante seis semanas, y una final después de un período de lavado de 4 semanas. En el frotis por citocentrifugado se evaluó el predominio de eosinófilos (EP) o neutrófilos (NP), y en el sobrenadante se determinó LTE4, y CC16. Se midió la variabilidad del flujo espiratorio máximo (PEFV). Un total de 23/41 pacientes correspondieron al EP y 18/41 pacientes con NP. El PEFV fue mayor en el EP que en NP. LTE4 fue mayor en NP que en EP. No se encontraron diferencias de los niveles de CC16 en ambos grupos. Montelukast redujo la célula predominante en ambos subgrupos, mientras que budesonida sólo redujo los eosinófilos en EP. Tanto budesonida como montelukast redujeron PEFV en EP, pero no en NP. El nivel de CC16 aumentó significativamente en el EP luego del tratamiento antiinflamatorio. En conclusión: se identificó un subgrupo de asmáticos NP que presentan una menor labilidad bronquial, la vía de los leucotrienos parece estar involucrada y responde al tratamiento anti-leucotrienos. Este fenotipo muestra una escasa recuperación del nivel de CC16 posterior al tratamiento.

The effect of montelukast in a model of gouty arthritis induced by sodium monourate crystals / Efecto de montelukast en un modelo de artritis gotosa inducido por cristales de monourato de sodio

Non-steroidal anti-inflammatory drugs (NSAIDS) are the first line of therapy in acute gouty arthritis. NSAIDs inhibit the cyclooxygenase pathway, but not the lipooxygenase activity and can have many adverse effects and thus have a limited effect on the control of inflammation in this disease. In this work we studied the effect of montelukast on the cellular inflammatory infiltrate in a model of murine arthritis induced by sodium monourate crystals (SMU), using a subcutaneous air cavity (air pouch) in BALB/c mice. Seven groups of BALB/c mice (n = 4) were distributed into five experimental groups and two inflammatory control groups, a positive and a negative one. Previous to SMU exposure, the experimental groups received montelukast (1 and 0.01 mg/Kg/w) and/or indomethacine (2.5 mg/Kg/w), followed by administration of SMU in the air pouch. The total and differential counts of inflammatory cells were analyzed after 2, 6, 12 and 24 hours. Montelukast, significantly reduced the total number of cells (p<0.05), with a predominant impact on polymorphonuclear over mononuclear cells, especially after 12 hours of the medication. The montelukast/indometacine combination showed an additive effect. Our data show that montelukast has an anti-inflammatory effect in the model of gouty arthritis. Consequently, anti-leukotrienes could represent a new and effective therapy, either isolated or combined with conventional therapy of gouty arthritis.

En artritis gotosa aguda las drogas antiinflamatorias no esteroideas son la primera línea terapéutica. Este tratamiento no es satisfactorio porque inhibe la ciclooxigenasa sin modificar la actividad de la lipooxigenasa, y puede acompañarse de numerosos efectos adversos. Investigamos el efecto de montelukast sobre el infiltrado celular inflamatorio en un modelo de artritis múrida inducida por cristales de monourato de sodio (MUS) en el modelo experimental de la bolsa de aire (air pouch). Siete grupos de ratones BALB/c (n = 4) fueron distribuidos en cinco grupos experimentales y dos grupos controles inflamatorios: positivo y negativo. Los grupos experimentales recibieron, montelukast (1 y 0,01 mg/Kg/p) y/o indometacina (2,5 mg/Kg/p) por vía oral, previo a la administración de MUS en la bolsa del aire. El conteo absoluto y diferencial de las células inflamatorias fue analizado después de 2, 6, 12 y 24 horas de tratamiento. El tratamiento con montelukast redujo significativamente el número total de células presentes en el infiltrado inflamatorio (p < 0,05), con un efecto mayor sobre polimorfonucleares que sobre las células mononucleares, y con un máximo efecto a las 12 horas después de la administración del medicamento. La combinación montelukast/indometacina mostró un efecto aditivo. Los resultados demuestran que montelukast tiene un efecto antiinflamatorio en el modelo de la artritis gotosa. Por lo tanto, los anti-leucotrienos podrían representar una nueva y eficaz terapia, aislada o en combinación con la terapéutica convencional, para la artritis gotosa.

Esofagitis eosinofílica en niños: características clínicas y endoscópicas / Eosinophilic esophagitis: report of three cases

Eosinophilic esophagitis in adults (EE) is a disease of unknown cause, characterized by symptoms such as reflux and dysphagia that traditionally do not respond to antacid treatment. It affects mostly young men with a strong personal or familial history of a topy asthma and allergies. We repot three male patients aged 10, 14 and 15years, all with symptoms of dysphagia, two of them with chest pain caused by spasm of the esophagus, with heterogeneous endoscopic findings which included from leucoplakia to stenosis that needed endoscopic dilatation. All of them had abnormal findings in immunity studies (prick test or IgE levels). They received treatment based on diet measures, acid suppression and leukotriene inhibitors, with satisfactory clinical, endoscopic and histological response. EE should be suspected in children and adults with esophageal symptoms and personal or family history of allergy and asthma.

Efficacy and safety of montelukast as monotherapy in children with mild persistent asthma.

OBJECTIVE: To study the efficacy and tolerability of montelukast as monotherapy in the treatment of mild persistent bronchial asthma. DESIGN: Open, non-comparative, prospective, 12-month study. SETTING: Asthma clinic in urban multi-speciality trust hospital. METHODS: Children (age 3-11 yrs) with mild persistent asthma, not on any prophylactic drugs were enrolled consecutively (from January to December 2003) and started on 4 mg (2-4 yrs) or 5mg (<4 yrs) montelukast for a period of 12 weeks. Efficacy was assessed by improvements in clinical score, peak expiratory flow rates (PEFR), spirometry measurements and reduction in reliever drug requirement after 4 and 12 weeks of therapy. Side effects were also judged after 12 weeks of therapy. RESULTS: 50 children (mean age 5.41 +/-2.11 years) completed the study. There was association with positive family history (92%), allergic rhinitis (64%), exercise induced asthma (40%), cough variant asthma (24%), seasonal asthma (80%) and high IgE (12%) levels. Clinical scores, viz, activity, wheeze and cough, improved effectively from (1.64 +/-0.5253) at baseline to (0.7 +/-0.7071) and (1.72 +/-0.701) to (0.92 +/-0.6952) and (1.5 +/-0.6145) to (0.88 +/-0.8241) respectively after 12 weeks of therapy. Significant clinical improvement (p >0.001) was also noted after 4 weeks of therapy. Peak expiratory flow rates (done in 19 cases) documented improvement from (120.21 +/-12.23) at baseline to (135.41 +/-23.34) after 12 weeks. FEV1 / FVC (done in 11 cases) improved from (71.44 +/-1.35%) to (87.10 +/-8.34%) after 12 weeks. Mean improvement in all the parameters demonstrated P value less than >.001. A total of 19 of 50 cases showed mild side-effects as anorexia (16%), elevated liver function tests (18%) and headache (10%). CONCLUSION: The clinical outcome showed significant improvement (p < 0.01) after 4 and 12 weeks.

The effects of low dose leukotriene receptor antagonist therapy on airway remodeling and cysteinyl leukotriene expression in a mouse asthma model

Airway structural changes that occur in patients with asthma in response to persistent inflammation are termed airway remodeling. The cysteinyl leukotrienes (LTC4, D4 and E4) are known to play important roles in the pathobiology of asthma. To evaluate the effect of low dose montelukast (MK) on the development of airway remodeling using a chronic murine model of allergic airway inflammation with subepithelial fibrosis, BALB/c mice, after intraperitoneal ovalbumin (OVA) sensitization on days 0 and 14, received intranasal OVA periodically on days 14-75. MK treated mice received montelukast sodium intraperitoneally on days 26-75. The OVA sensitized/challenged mice developed an extensive eosinophil cell inflammatory response, goblet cell hyperplasia, mucus occlusion, and smooth muscle hypertrophy of the airways. In addition, in OVA sensitized/challenged mice, dense collagen deposition/fibrosis was seen throughout the lung interstitium surrounding the airways, blood vessels, and alveolar septae. The cysteinyl leukotriene 1 (CysLT1) receptor antagonist, MK significantly reduced the airway eosinophil infiltration, goblet cell hyperplasia, mucus occlusion, and lung fibrosis except airway smooth muscle hypertrophy in the OVA sensitized/challenged mice. The OVA sensitized/challenged mice had significantly increased epithelial desquamation compared with control mice. MK markedly reduced epithelial desquamation of airways in OVA/MK treated animals compared with OVA sensitized/challenged mice. MK treatment did not affect the levels of CysLT in lung tissue. Our results show that the important role of cysteinyl leukotrienes in the pathogenesis of asthma. Lower dose of CysLT1 receptor antagonism has a significant anti-inflammatory effect on allergen-induced lung inflammation and fibrosis but not airway smooth muscle hypertrophy in an animal model of asthma.

Fibrodysplasia ossificans progressiva: case report

A fibrodisplasia ossificante progressiva (FOP) é doença rara, autossômica dominante, caracterizada por ossificação heterotópica progressiva pós-natal do tecido conjuntivo e malformação congênita dos háluces. Relatamos o caso de menina de nove anos com o quadro clínico-radiológico típico de FOP, nascida com hálux valgo bilateral e que aos 9 anos de idade apresentou massa dolorosa, de consistência endurecida, sem sinais inflamatórios, situada na região cervical. dicionalmente, era possível observar diminuição importante da movimentação em todos os níveis da coluna vertebral e da cintura escapular. A avaliação radiológica revelou a presença de ossificações heterotópicas na região torácica e malformação bilateral dos háluces. A paciente teve outros dois surtos da doença, que foram tratados com corticosteróide oral por quatro dias, (2 mg/kg/dia) seguido por tratamento prolongado com inibidores da Cox-2 (25 mg/dia) e com inibidor de leucotrienos (10 mg/dia).

Montelukast in general pediatric practices.

Allergic diseases, e.g., allergic rhinitis, atopic dermatitis and asthma, are common problems in children. Researches on the pathogenesis of allergic diseases have led to the development of new specific antiinflammatory medications, including Montelukast, which blocks the interaction of cysteinyl leukotrienes to their receptors and resulting downstream events. Several studies have demonstrated the effect of regular Montelukast therapy on asthma, allergic rhinitis, viral-induced wheezing in bronchiolitis and chronic rhinitis symptoms. Evidence base medicine now shows that Montelukast can be used as a monotherapy in mild persistent asthma and can be an add-on drug to inhaled corticosteroid (ICS) in moderate to severe persistent asthma. Even in allergic rhinitis, Montelukast has a role in controlling rhinitis symptoms. Montelukast demonstrated a safety profile similar to placebo and more safety than ICS. Moreover Montelukast can improve quality of life in patients with asthma and comorbid allergic rhinitis.

Montelukast - evaluation in 6 to 14 years old children with persistent asthma - pediatric montelukast study group.

OBJECTIVE: The suffering of children with asthma as a persistent illness is present in approximately 10% of the total population. The prevalent treatment regimens available has been the inhaled coticosteroids and short acting bronchodialators. Though the therapies are rational and well accepted but at the cost of side effects on chronic use. The changing definitions and guidelines with regard to asthma have given a classified slot to newer treatments like leukotriene receptor antagonists (LTRAs). The aim of the present study was to study the efficacy and tolerability of montelukast in the treatment of Indian pediatric patients aged 6 to 14 years with chronic asthma. METHODS: It was a prospective, open, non-comparative multicentric study. 881 Children (Mean age 11.83+/- 3.12 years) were included. Patients fulfilling the inclusion criteria were given one mouth dissolving 5 mg montelukast tablet daily in the evening for 30 days. RESULTS: There was an overall improvement in all the efficacy parameters. The daytime total asthma score decreased from 9.55 +/- 1.52 to 3.59 +/- 2.10. The average number of asthma attacks over the last 4 weeks decreased from 1.14+/- 1.19 to 0.28+/-0.57. The number of nocturnal awakenings fell from 1.54+/-0.78 to 0.43+/-0.54. FEV1 (L) [Predicted] improved by 21.18%). PEFR (L/min.) improved by 34.69%). Approximately 45% physicians rated the treatment as excellent, 30% as very good, 18% as good, 7% as fair and none as poor. CONCLUSION: Montelukast administered once daily improved efficacy end-points and was well tolerated in pediatric patients with chronic persistent asthma establishing itself as a valuable treatment option to current asthma therapies in 6 to 14 years old patients.

A clinical trial of the efficacy and safety of montelukast as monotherapy in patients with chronic stable bronchial asthma.

This study is aimed to evaluate the efficacy and safety of montelukast, as monotherapy, in the treatment of chronic stable bronchial asthma in adults. This was a multicentre, open label, non-comparative, prospective, 4-week study. Eligible patients discontinued all anti-inflammatory medication (steroids, chromoglycate sodium) 2 weeks prior to starting therapy with montelukast (10 mg daily). The primary efficacy criteria were improvements in forced expiratory volume in one second (FEV1), peak exploratory flow rate (PEFR) after 4 weeks of therapy. Secondary efficacy criteria were improvement in the patients' symptoms (assessed on an ordinal scale), decrease in discomfort levels (scored on a scale of 0-100), change in peripheral eosinophil counts, decrease in total daily dose of inhaled beta2 agonist (salbutamol). A total of 148 patients, mean age (+/- SD) 40.21 +/- 13.70 years, were enrolled into the study. At the end of the study there were significant improvements in FEV1 and PEFR (29% and 28% increase respectively from baseline values, p<0.000001). The mean total daily dose of inhaled salbutamol decreased significantly from prestudy values of 461 +/- 332 microg/day to 161 +/- 207 microg/day (p<0.000001). The mean eosinophil counts fell from 5.80 +/- 4.90% (+/- SD) to 4.84 +/- 4.42% (+/- SD) (p=0.02). Symptom scores improved significantly as did subjective assessment of discomfort. A total of 29 (19.6%) adverse events were reported, all of which were of mild to moderate intensity. Monotherapy with montelukast significantly improved parameters of asthma control. It was well tolerated with no reports of serious or severe adverse events.