Efficacy of montelukast sodium combined with methylprednisolone in the treatment of allergic purpura in children and its effects on inflammatory factors and immune function / 中国基层医药

Objective:To investigate the efficacy of montelukast sodium combined with methylprednisolone in the treatment of pediatric allergic purpura and its effects on inflammatory factors and immune function.Methods:A total of 94 children with allergic purpura who received treatment in Taizhou Women and Children's Hospital and Taizhou Hospital Medical Center (Group) Enze Hospital from March 2019 to March 2021 were included in this study. They were randomly divided into observation and control groups ( n = 47/group). The control group was treated with methylprednisolone. The observation group was treated with montelukast sodium combined with methylprednisolone. The course of treatment was 2 weeks in both groups. Efficacy and changes in inflammatory factors and immune function post-treatment relative to those pre-treatment were compared between the two groups. Results:Total response rate in the observation group [93.62% (44/47)] was significantly higher than that in the control group [74.47% (35/47), Z = 2.15, P < 0.05)]. After treatment, interleukin (IL-4), IL-6, and IL-18 levels in each group were significantly decreased compared with those before treatment ( tobservation group = 21.19, 22.26, 27.20, tcontrol group = 11.10, 13.21, 14.86, all P < 0.05). After treatment, IL-4, IL-6, and IL-8 levels in the observation group were (48.98 ± 5.21) ng/L, (34.10 ± 6.42) ng/L, and (53.29 ± 5.67) ng/L, respectively, which were significantly lower than (65.38 ± 7.08) ng/L, (47.83 ± 4.71) ng/L, (67.83 ± 7.10) ng/L in the control group ( t = 12.79, 11.82, 10.97, all P < 0.05). After treatment, CD3 +, CD4 +, and CD4 +/CD8 + in each group were significantly increased compared with those before treatment ( tobservation group = 14.27, 14.41, 17.61, tcontrol group = 6.90, 5.12, 7.40, all P < 0.05). After treatment, CD3 +, CD4 +, and CD4 +/CD8 + in the observation group were (68.94 ± 2.89)%, (39.94 ± 2.15)%, and (1.79 ± 0.13), respectively, which were significantly higher than (63.86 ± 3.28)%, (35.65 ± 2.31)%, and (1.53 ± 0.16) in the control group ( t = 7.96, 9.32, 8.64, all P < 0.05). After treatment, serum IgG and IgM levels in each group were significantly decreased compared with those before treatment ( tobservation group = 21.00, 7.99, tcontrol group = 8.38, 5.76, both P < 0.05). After treatment, serum IgG and IgM levels in the observation group were (1.43 ± 0.19) g/L and (9.74 ± 0.78) g/L, respectively, which were significantly lower than (1.95 ± 0.37) g/L and (10.89 ± 0.85) g/L in the control group ( t = 8.57, 6.83, both P < 0.05). Conclusion:Montelukast sodium combined with methylprednisolone is highly effective on allergic purpura in children. The combined therapy can reduce inflammatory responses and improve immune function in children.

Efficacy of inhalation therapy with montelukast sodium, budesonide and formoterol in combination in the treatment of bronchial asthma in adult patients and its effects on cytokines / 中国基层医药

Objective:To investigate the efficacy of combination treatment with montelukast sodium, budesonide and formoterol in the treatment of bronchial asthma in adults and its effects on cytokines.Methods:A total of 100 adult patients with bronchial asthma who received treatment in The First People's Hospital of Yongkang from January 2019 to December 2020 were included in this study. They were randomly assigned to receive either budesonide inhalation alone (control group, n = 50) or combination inhalation of montelukast sodium, budesonide and formoterol (observation group, n = 50) for 12 weeks. Efficacy was compared between the two groups. Lung function [forced expiratory volume in one second (FEV 1), peak expiratory flow (PEF) and FEV 1/forced vital capacity (FVC) ratio], cytokines [interleukin (IL)-2, IL-4, IL-6], Asthma Quality of Life Questionnaire (AQLQ) score, and Asthma Control Test (ACT) score measured before and 12 weeks after treatment were compared between the two groups. Results:Total response rate in the observation group was significantly higher than that in the control group [92.00% (46/50) vs. 72.00% (36/50), χ2 = 6.77, P < 0.05). After 12 weeks of treatment, FEV 1, PEF and FEV1/FVC in the observation group were (2.17 ± 0.23) L, (246.56 ± 17.86) L/s, and (83.86 ± 3.98)%, respectively, which were significantly higher than (1.86 ± 0.17) L, (203.12 ± 20.10) L/s, (74.82 ± 5.67)% in the control group ( t = 7.66, 11.42, 9.22, P < 0.05). Serum IL-2 level in the observation group was significantly higher than that in the control group [(10.85 ± 0.86) ng/L vs. (8.94 ± 1.03) ng/L, t = 10.06, t < 0.05]. Serum IL-4 and IL-6 in the observation group were (24.98 ± 3.08) ng/L and (98.46 ± 9.76) μg/L, respectively, which were significantly lower than (36.75 ± 4.34) ng/L and (125.84 ± 13.19) μg/L in the control group ( t =15.63, 11.79, both P < 0.05). AQLQ score and ACT score in the observation group were (121.03 ± 8.69) points and (22.08 ± 1.35) points, respectively, which were significantly higher than (110.93 ± 7.86) points and (19.74 ± 1.76) points in the control group ( t = 6.095, 7.460, both P < 0.05). Conclusion:Inhalation therapy with montelukast sodium, budesonide and formoterol produces obvious therapeutic effects on bronchial asthma in adult patients and the combined therapy can reduce inflammatory reactions.

Reacciones adversas a montelukast: de la teoría a la práctica. Serie de casos / Adverse drug reactions of montelukast: from theory to practice. Case report

El montelukast se utiliza ampliamente en el tratamiento de sibilancias recurrentes y/o asma. Están descritas numerosas reacciones adversas medicamentosas (RAM) en niños relacionadas con montelukast; se destacan las neuropsiquiátricas. Realizamos un estudio observacional, retrospectivo, descriptivo, sobre RAM relacionadas con montelukast. Entre enero de 2012 y diciembre de 2017, en la Unidad de Neumonología Pediátrica se trataron con Montelukast 348 pacientes; de ellos, 20 presentaron RAM. Los síntomas más frecuentes fueron insomnio (n = 7), hiperactividad (n = 4), pesadillas (n = 3), dolor abdominal (n = 2) y parestesias en extremidades (n = 2). Se presentaron desde días hasta meses tras iniciar el tratamiento, y desaparecieron tras su suspensión. Se destacan dos pacientes con parestesias en extremidades, síntoma no descrito antes en niños. El 5,7 % de los pacientes tratados con montelukast presentaron RAM que requirieron suspender el tratamiento. Los trastornos del sueño fueron los más frecuentes.

Montelukast is widely used in recurrent wheezing and/or asthma treatment. Several adverse drug reactions (ADRs) have been described in children related to montelukast. Neuropsychiatric reactions are one of the most important. We designed an observational, retrospective, descriptive study on ADRs related to montelukast in the Pediatric Pulmonology Unit, Hospital Universitario Miguel Servet, Zaragoza, Spain. Between January 2012 and December 2017, in the Pediatric Pulmonology Unit, 348 patients were treated with Montelukast; of them, 20 presented RAM. The main symptoms described were insomnia (n = 7), hyperactivity (n = 4), nightmares (n = 3), abdominal pain (n = 2) and paraesthesia in extremities (n = 2). They appeared from the first days to months after the start of treatment and disappeared after stopping it. Two patients presented limb paresthesia, not described previously in children. The 5.7 % of our patients treated with montelukast had ADRs that required treatment discontinuation. Sleep disorders were the most frequent.

Efectos adversos neuropsiquiátricos de montelukast / Neuropsychiatric adverse effects of montelukast / Reações psiquiátricas adversas do montelucaste

Resumen: En la última década se ha registrado un aumento en la prescripción de antileucotrienos, en particular montelukast. A partir del año 2007 comenzaron los primeros reportes efectos adversos de esfera neuropsiquiátrica en la edad pediátrica. Los efectos reportados incluían trastornos del sueño y del humor hasta una posible asociación con ideación suicida y suicidio consumado. En el presente trabajo se realiza una revisión de la seguridad de montelukast tema con objetivo de establecer o descartar una eventual asociación entes los fenómenos mencionados y la administración de antileucotrienos.

Summary: In the last decade there has been an increase in the prescription of antileukotrienes, specifically montelukast. The first pediatric reports discussing adverse neuropsychiatric effects go back to 2007. The reported effects included a range from sleep and mood disorders, to even a possible association with suicidal ideation and consummated suicide. In the present paper we carry out a review of the safety of using montelukast in order to confirm or rule out an eventual association between such adverse effects and the administration of antileukotrienes.

Resumo: Na última década, houve um aumento na prescrição de antileucotrienos, em particular do montelucaste. A partir de 2007, começaram a surgir os primeiros reportes relativos aos efeitos neuropsiquiátricos adversos na idade pediátrica. Os efeitos relatados incluíram desde distúrbios do sono e do humor até uma possível associação com ideação suicida e suicídio consumado. No presente paper realizamos uma revisão da segurança no uso do montelucaste com o objetivo de confirmar ou descartar uma eventual associação entre os seus efeitos adversos e a administração de antileucotrienos.

Clinical effect of mometasone furoate nasal spray combined with montelukast in the treatment of children with obstructive sleep apnea hypopnea syndrome / 中国基层医药

Objective@#To explore the clinical effect of mometasone furoate nasal spray combined with montelukast in the treatment of children with obstructive sleep apnea hypopnea syndrome (OSAHS), and to analyze its feasibility and clinical application value.@*Methods@#From August 2017 to March 2019, 64 children with OSAHS who were treated in the People's Hospital of Jinhua were selected in the study.According to the random number table method, they were divided into the observation group and the control group, with 32 cases in each group.The observation group was treated with mometasone furoate nasal spray combined with montelukast for 12 weeks.The control group was treated with surgical treatment to remove hypertrophic tonsils and/or adenoids.The clinical symptom scores, polysomnography(PSG) monitoring index, adenoid and tonsil size index, and the efficacy after 12 weeks of treatment were compared between the two groups.@*Results@#There were no statistically significant differences in symptom scores and minimum arterial oxygen saturation(LSaO2) between the two groups before treatment(all P>0.05). After treatment, the symptom scores and LSaO2 of the control group were (1.90±0.53)points and (94.74±1.54)%, respectively, which of the observation group were (4.00±1.50)points and (85.34±10.57)%, respectively, the differences between the two groups were statistically significant(t=-7.416, 4.972, all P<0.05). There were statistically significant differences in the apnea hypopnea index(AHI) and obstructive apnea index(OAI) between the two groups(all P<0.05). After treatment, the A/N of the adenoids in the observation group was significantly decreased, and the difference in the tonsil classification was statistically significant(Z=-2.602, P<0.05). The effective rate of the observation group was 56.25%(18/32), which was significantly lower than that of the control group [100.00%(32/32)], the difference was statistically significant(χ2=17.920, P<0.05).@*Conclusion@#In summary, non-surgical treatment can alleviate OSAHS-related symptoms, reduce the size of tonsils and adenoids, and achieve the purpose of remission or cure.Non-surgical treatment can be selected when patients' families are reluctant to choose surgical treatment.

Position statement of the Brazilian Academy of Rhinology on the use of antihistamines, antileukotrienes, and oral corticosteroids in the treatment of inflammatory sinonasal diseases / Posicionamento da Academia Brasileira de Rinologia sobre o uso de anti-histamínicos, antileucotrienos e corticosteroides orais no tratamento de doenças inflamatórias nasossinusais

Abstract Introduction: Inflammatory conditions of the nose and paranasal sinuses are very prevalent in the general population, resulting in marked loss of quality of life in affected patients, as well as significant work, leisure, and social activity losses. These patients require specific and specialized treatment. A wide range of oral medications are available. Objective: The present document is aimed to clarify, for professionals treating patients with inflammatory sinonasal diseases, both specialists and general practitioners, specific oral therapies in noninfectious nasal inflammatory conditions. Methods: The methodology used to create this article included the search for the key words: oral corticosteroids, antihistamines, antileukotrienes, rhinitis, rhinosinusitis in the MEDLINE and EMBASE databases in the last 5 years. Since no relevant article was found for the text on the subject of interest in the last 5 years, the search was extended for another 5 years, and so on, according to the authors’ needs. Results: Relevant literature was found regarding the use of antihistamines, antileukotrienes and oral corticosteroids in these conditions. The Brazilian Academy of Rhinology emphasizes, after extensive discussion by the collegiate, key points in the treatment with these drugs. Conclusion: There is support in the literature for the use of these drugs; however, final considerations about the role of each of them have been made.

Resumo Introdução: As afecções inflamatórias do nariz e dos seios paranasais são muito prevalentes na população geral, causam acentuada perda de qualidade de vida dos pacientes afetados, geram perdas significativas das atividades de trabalho, lazer e sociais. Esses pacientes necessitam de tratamento específico e especializado e uma ampla gama de medicações orais está disponível. Objetivo: O presente documento tem por objetivo esclarecer àqueles que tratam das doenças nasossinusais inflamatórias, tanto especialistas quanto generalistas, sobre as terapêuticas orais nas afecções inflamatórias nasais não infecciosas. Método: A metodologia usada para elaboração deste artigo incluiu a busca das palavras chave: corticosteroides orais, anti-histamínicos, antileucotrienos, rinite, rinossinusite nos bancos de dados Medline e Embase nos últimos 5 anos. Como não foi achado artigo relevante para o texto sobre o assunto de interesse nos últimos 5 anos, a busca foi estendida por mais 5 anos, e assim por diante, de acordo com a necessidade dos autores. Resultados: Literatura relevante foi encontrada com relação ao uso dos anti-histamínicos, antileucotrienos e corticosteroides orais nessas afecções. A Academia Brasileira de Rinologia ressalta, após amplo debate do colegiado, pontos-chave no tratamento com esses medicamentos. Conclusão: Há respaldo na literatura para o uso desses medicamentos, entretanto considerações finais acerca do papel de cada deles foram feitas.

Asthma Severity and the Controller Prescription in Children at 12 Tertiary Hospitals

PURPOSE: Guidelines need to be tailored to where they are applied. We aimed to describe the distinctive asthma severity profile and the pattern of controller prescription in Korean children. METHODS: Twelve pediatric allergists from tertiary medical centers reviewed medical records of all asthmatic children who visited their clinics between September 1 and November 30 of 2013. Controller prescriptions were re-classified into 4 categories, then the prevalence of each asthma severity category and the controller prescription patterns according to asthma severity assessed by a Western (Global Initiative for Asthma, GINA) and an Asia-Pacific (Japanese Pediatric GuideLine, JPGL) guideline were evaluated. RESULTS: A total of 840 cases were reviewed. Both GINA and JPGL revealed that 328 (39.0%) and 249 (29.6%) subjects had intermittent asthma whereas 24 (2.9%) and 21 (2.5%) subjects had severe persistent asthma, respectively. Although higher category controllers tended to be prescribed to those who had more severe asthma, there was much overlap in categories of prescribed controllers between groups with regard to asthma severities. Leukotriene receptor antagonists (LTRA) was the most frequently prescribed as a single controller (40%) or as an add-on medication (19%) in the group of asthmatic children <6 years. CONCLUSIONS: Korean children have distinctive patterns of asthma severity and management strategies with a lower prevalence of severe asthma and a preference toward LTRA rather than low dose inhaled corticosteroids (ICS) alone or add-on long-acting beta-agonist (LABA) in the group of <6 year-old asthmatics that has not been predicted in Western countries. Thus, strategies tailored to regional situations need to be developed and recommended.

The beneficial effects of Montelukast against 2 3 7 8 tetrachlorodibenzo dioxin toxicity in female reproductive system in rats

ABSTRACT PURPOSE: To determine the toxic effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on reproductive system and the beneficial effects of Montelukast (ML) with histological and biochemical analysis. METHODS: Rats were randomly divided into four equal groups (control, TCDD, ML and TCDD+ML). Tissue samples were collected on day 60 and oxidative status and histological alterations were analyzed. RESULTS: The results showed a significant increase in oxidative and histological damage on uterine and ovarian tissues. Otherwise, the oxidative and histological damages caused by TCDD were prevented with ML treatment. CONCLUSION: The toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on female reproductive system were reversed with Montelukast treatment. Therefore, we claimed that ML treatment might be useful for TCDD toxicity.

A Case of Pranlukast-Induced Anaphylactic Shock

Leukotriene receptor antagonists, which are generally considered safe with a few adverse drug reactions, are increasingly used in the treatment of various allergic diseases, including asthma and allergic rhinitis. Although a few anaphylactic reactions to montelukast have been reported worldwide, there is still a lack of reports about severe adverse drug reactions associated with pranlukast. Here, we report a case of severe hypersensitivity reaction associated with pranlukast. A 65-year-old woman developed anaphylactic shock that presented as generalized urticaria, angioedema, collapse, and loss of consciousness after receiving pranlukast. A positive response to oral challenge and skin prick testing with pranlukast was observed in the patient. In this case, it was demonstrated that pranlukast can induce anaphylaxis, possibly mediated by the IgE-dependent pathway.

The efficacy and safety of Montelukast sodium in the prevention of bronchopulmonary dysplasia / 소아과

PURPOSE: The purpose of this study was to evaluate the efficacy and safety of Montelukast sodium in the prevention of bronchopulmonarydysplasia (BPD). METHODS: The Interventional study was designed as a multicenter, prospective, and randomized trial, with open labeled and parallel-experimental groups, 66 infants were enrolled and allocated to either the case group (n=30) or the control group (n=36) based on gestational age (GA). Infants in the case group were given Montelukast sodium (Singulair) based on their body weight (BW). Zero week was defined as the start time of the study. RESULTS: The incidence of moderate to severe BPD was not different between the groups (case group: 13 of 30 [43.3%] vs. control group: 19 of 36 [52.8%], P=0.912). Additionally, secondary outcomes such as ventilation index, mean airway pressure and resort to systemic steroids were not significantly different. There were no serious adverse drug reactions in either group, and furthermore the rate of occurrence of mild drug related-events were not significantly different (case group: 10 of 42 [23.8%] vs. control group: 6 of 48 (15.8%), P=0.414). CONCLUSION: Montelukast was not effective in reducing moderate or severe BPD. There were no significant adverse drug events associated with Montelukast treatment.

Effects of U75302, blocker of leukotriene B4 receptor 1, on cellular immunity and inflammation in septic mice / 第二军医大学学报

Objective To observe the influence of U75302, blocker of leukotriene B4 receptor 1, on immune function in septic mice, so as to explore the implication of blocking leukotriene B4 receptor 1 for treatment of sepsis. Methods Experimental sepsis model was induced by cecal ligation and puncture (CLP). A total of 18 male C57BL/6 mice were randomly divided into sham group (n=6), CLP group (n=6) and CLP + U75302 intraperitoneal injection group (n = 6). The peripheral blood cytokine tumor necrosis factor- α (TNF-α) and interleukin-10 (IL-10) levels, peritoneal lavage fluid Gr-1+ cell count and thymus T lymphocytes apoptosiswere detected in mice of three groups 24 h after surgery. Results Compared with the CLP group, CLP + U75302 intraperitoneal injection group had significantly reduced blood TNF-α level (by 43%, P< 0. 05), significantly increased IL-10 levll (by 88%, P<0. 05), signficantly decreased Gr-1+ cell counts in peritoneal lavage fluid (P<0. 05), and significantly decreased apoptosis of thymus T lymphocytes (P<0. 01). Conclusion Blocking leukotriene B4 receptor 1 with U75302 may decrease peripheral TNF-α level, increase IL-10 level, and improve cellular immunity, which may be involved in inflammation of sepsis.

Effects of and Smeton on inflammatory mediator levels and therapeutic outcomes in elderly patients with chronic obstructive pulmonary disease / 中华老年医学杂志

Objective To compare the effects of and Smeton on inflammatory mediator levels and therapeutic outcomes in elderly patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD).Methods Ninety AECOPD patients hospitalized at our department from June 2012 to June 2013 were selected and randomly divided into the group and the Smeton group.In addition to routine therapy,such as anti-infection medication and water & electrolyte balance maintenance,for both groups,patients in the group were given a single 10 mg oral dose of,taken at night before bedtime,while patients in the Smeton group were given 2 pills of a compounding formulation containing,three times a day,for two months.Changes in plasma inflammatory mediator levels before and after treatment and therapeutic outcomes were monitored.Results Highsensitivity C-reactive protein (hs-CRP) levels decreased and interleukin-10 (IL-10) levels increased two months after treatment,compared with pretreatment levels [hs-CRP,(4.01±0.69) mg/L vs.(15.23±4.39) mg/L,and IL-10,(19.44±6.35) g/L vs.(7.86±3.24) g/L,for the group; hsCRP,(7.09±1.70) mg/L vs.(7.86±3.24) g/L,andIL-10,(11.6±3.2 g/L vs.6.7±2.8 g/L),for the Smeton group; P＜0.05 or 0.01].The magnitude of increases or decreases in inflammatory mediator levels was greater in the group than in the Smeton group (P＜0.05 for both),and the overall effectiveness rate was higher in the Smeton group than in the group (95.6％ vs.82.2％,x2 =4.05,P ＜0.05).Conclusions When used for treatment of patients with AECOPD,ontelukast has more beneficial effects on inflammatory mediator levels,whereas is more effective in clinical symptom improvement.

Omalizumab: opción terapéutica para la urticaria crónica espontánea de difícil control con vasculitis asociada, reporte de tres casos / Omalizumab: therapeutic option in chronic spontaneous urticaria difficult to control with associated vasculitis, report of three cases

Introducción. Aproximadamente el 50 % de los casos de urticaria crónica no mejoran adecuadamente con las dosis convencionales de antihistamínicos, por lo cual se han planteado múltiples opciones terapéuticas, entre las cuales el omalizumab es una herramienta novedosa que ahora cuenta con evidencia de alta calidad que soporta su uso en los casos difíciles, que mejora rápidamente el índice sintomático y el uso de medicamentos, y cuenta con un buen perfil de seguridad. Objetivo. Presentar tres casos de mujeres adultas con urticaria crónica espontánea de más de ocho años de evolución, que no mejoraron con el tratamiento con altas dosis de antihistamínicos, asociados a antileucotrienos e inmunomoduladores y en quienes se combinaban varios mecanismos fisiopatológicos: urticaria crónica espontánea con componente de autoinmunidad, componente de presión y urticaria vasculítica. Materiales y métodos. Se reportan los casos con sus respectivas evaluaciones clínicas y de laboratorio, los medicamentos usados y la respuesta después del inicio de omalizumab y se hace una revisión de la literatura científica sobre uso de este medicamento en la urticaria crónica. Resultados. En los tres casos presentados se obtuvo una mejoría completa de los síntomas tras el inicio del omalizumab. Conclusión. El omalizumab es una opción terapéutica exitosa en casos de urticaria crónica de difícil control con vasculitis asociada, cuando se han agotado las opciones propuestas por las guías internacionales.

Introduction: Approximately 50% of chronic urticaria cases do not respond adequately to conventional doses of antihistamines, so a number of other therapeutic options have been suggested. Among these, omalizumab is an innovative tool, which now has high-quality evidence that supports its use in difficult cases, rapidly improving the symptom index and the use of medications with a good safety profile. Objective: To report three cases of adult women with spontaneous chronic urticaria with an evolution of more than eight years, which did not improve with high doses of antihistamines and leukotriene receptor blockers, associated with immunomodulatory therapy in which several etiologic mechanisms were combined: chronic spontaneous urticaria with autoimmune and pressure components, and vasculitis. Materials and methods: We report the cases with their clinical and laboratory evaluations, used medication, the response after the start of omalizumab and we performed a review of the literature on the use of this drug in chronic urticaria. Results: In all the presented cases, we obtained complete improvement of symptoms after starting omalizumab. Conclusion: Omalizumab is a successful treatment option in cases of difficult to control chronic urticaria with associated vasculitis in which the options proposed by international guidelines have been exhausted.

Effect of zafirlukast on capsular contracture around silicone implants in rats / Efeito do zafirlukast na contratura capsular ao redor de implantes de silicone em ratos

PURPOSE: To evaluate the effect of zafirlukast on capsular contracture around silicone implants by measuring the pressure within the implant, using a rat experimental model. METHODS: Forty adult female Wistar rats were used. Each one received two silicone implants, one with smooth-surface and the other with textured-surface. They were randomly divided into four groups (n=10). The rats of control group I were sacrificed after the implants. The remaining animals were subjected to a daily regimen of intra-peritoneal injection for a period of 90 days and they were distributed as follows: control group II received 0.9 percent physiological saline solution; experimental group I received zafirlukast 1.25 mg/kg; and experimental group II received zafirlukast 5 mg/kg. The measurement of intra-implant pressure of control group I was determined on the surgery day and in other groups on the ninetieth day, after being sacrificed. RESULTS: In the evaluation of textured implants there was an increase of internal pressure in the control group II, and there was no increase in the experimental groups. Compared to the controls there were not significant differences in smooth implants. CONCLUSION: Zafirlukast reduced the risk of developing capsular contracture around silicone implants with textured surface.

OBJETIVO: Avaliar o efeito do zafirlukast na contratura capsular ao redor de implantes de silicone, através da aferição da pressão intra-implante, utilizando-se um modelo experimental de ratos. MÉTODOS: Quarenta ratos fêmeas Wistar foram utilizados. Cada um recebeu dois implantes de silicone, sendo um com superfície lisa e outro texturizada. Foram divididos aleatoriamente em quatro grupos (n=10). Os ratos do grupo controle I foram sacrificados após o implante. O restante dos animais foi submetido a um regime diário de injeção intraperitoneal por um período de 90 dias e foram distribuídos: grupo controle II recebeu solução salina fisiológica 0,9 por cento, grupo experimental I recebeu zafirlukast 1,25 mg/kg, e grupo experimental II recebeu zafirlukast 5 mg/kg. O grupo controle II recebeu solução salina; grupo experimental I, 1,25 mg/kg/dia de zafirlukast; grupo experimental II, 5mg/kg/dia de zafirlukast. A aferição da pressão intra-implante do grupo controle I foi averiguada no dia do ato operatório, e nos outros grupos no nonagésimo dia, após serem sacrificados. RESULTADOS: Na avaliação dos implantes texturizados houve aumento da pressão interna no grupo controle II e, não se observou aumento nos grupos experimentais. Na comparação com os controles não foram observadas diferenças significativas nos implantes lisos. CONCLUSÃO: O Zafirlukast reduziu o risco de desenvolver contratura capsular em torno de implantes de silicone com superfície texturizada.

Combined therapeutic effects of Huaiqihuang and Montelukast sodium on airway inflammation and expression of IL-17 in asthmatic rat / 中国医师杂志

ObjectiveTo explore the mechanism of Montelukast combined with Huang Qi Huai in the treatment of asthma.MethodsForty male Sprague-Dawley (SD) rats were chosen and randomly divided into five groups:control group (Control),model group (Model),Montelukast group (MK),Huang Qi Huai group (H),Montelukast + Huang Qi Huai group (MK + H),each group has 8 rats.The other four groups except the control group were built to chronic rat asthma model.The treatment groups were administered intragastrically with Montelukast,Huang Qi Huai and Montelukast + Huang Qi Huai respectively.All animals were sacrificod; plasma and bronchoalveolar lavage fluid (BALF) and superior lobe of right lung tissues were collected.Superior lobes of right lung tissues were used to measure the expression of IL-17 in lung tissue by immunohistochemistry.The airway inflammation was analyzed by histochemistry staining with H.E.Total cells score and differential score in BALF were counted.The levels of IL-17 in the plasma and BALF were measured by Enzyme-linked immunosorbent assay (ELISA).ResultsCompared with the control group,the degree of inflammatory cell around the airway in the model group were significantly higher (P ＜ 0.05).Compared with group model,the degree of inflammatory cell around the airway in the Group MK,group H and group MK + H were significantly ameliorated ( P ＜0.05).Compared with Group MK,the degree of inflammatory cell around the airway in group MK + H was significantly ameliorated ( P ＜O.05),the expression of IL-17 in lung tissues was significantly lower ( P ＜0.05),the numbers of total cells and the concentration of IL-17 in plasma and BALF were decreased too ( P ＜0.05).Correlation analysis showed that the level of IL-17 in the plasma and BALF was positively correlated with the level of IL-17 in the lung tissue( P ＜ 0.05 ).ConclusionsCombined Huang Qi Huai adjuvant Montelukast treatment of asthmatic rat further reduced the concentration of IL-17 in the plasma and BALF,reduced the expression of IL-17 in lung tissue,improved the airway inflammation.Down regulation the expression of IL-17 was probably one of the mechanisms of anti-inflammatory.

Protection of leukotriene receptor antagonist against aspirin-induced bronchospasm in asthmatics

PURPOSE: Leukotriene receptor antagonists (LTRAs) are used to treat aspirin-intolerant asthma (AIA); however, the protective effects of long-term LTRA administration against aspirin-induced bronchospasm have not been evaluated. OBJECTIVES: We investigated the efficacy of a 12-week treatment with a LTRA in protecting against aspirin-induced asthma in AIA patients. METHODS: Fifty-two adult patients with AIA underwent an aspirin challenge test just before administration of montelukast (10 mg/day) and just after 12 weeks of treatment. The protective effect was assessed as the disappearance of aspirin-induced bronchospasm after 12 weeks of treatment. The results were compared according to the patients' clinical and physiological parameters. RESULTS: The decline in FEV1 following aspirin challenge was significantly reduced from 28.6+/-1.9% to 10.2+/-1.7% (P=0.0001) after 12 weeks of montelukast treatment. However, 14 subjects (30%) still showed a positive response (>15% decline in FEV1) to aspirin challenge. Grouping the subjects into good and poor responders according to post-treatment responses revealed that the pretreatment aspirin-induced FEV1 decline was significantly greater in the poor responders and that the triggering dose of aspirin and the induction time for a positive response were lower and shorter, respectively, in the poor responders. Histories of aspirin hypersensitivity and sinusitis were more prevalent among the poor responders than among the good responders. CONCLUSIONS: Twelve weeks of treatment with montelukast protected against aspirin-induced bronchospasm in 70% of the AIA cases. A poor response was associated with more severe aspirin-induced bronchospasms before treatment and a history of aspirin hypersensitivity or sinusitis. CLINICAL IMPLICATIONS: A severe response to aspirin challenge may be a predictor of poor responsiveness to leukotriene antagonist treatment.

Expression and function of cysteinyl leukotriene receptors on human keratinocytes / 中华皮肤科杂志

Objective To detect the expression and function of cysteinyl leukotriene receptors (CysLTRs)in keratinocytes.Methods Human keratinocytes were isolated from the tissue of foreskin by digestion with dispase Ⅱ and trypsin,and subjected to primary culture.By using confocal laser scanning microscopy and reverse transcriptase PCR,the localization and expression of CysLTRs were studied in kemtinocytes.respectively.Some primarily cultured keratinocytes were pretreated with leukotriene D4 (30 nmoi/L),MK571(300 nmol/L),and BAYu9773 for 5 minutes followed by the detection of intmcellular calcium level using the Ca2+ indicator dye Fura-2/AM as well as cell proliferation bv MTT assay.Results The expressions of CysLTR1 and CysLTR2 were observed in cultured keratinocytes,and they were mainly located on cell membrane,partly in cytoplasm and nuclei.Compared with non.stimulated cells,a significant increase Was noted in the expression of CysLTRs,especially in the nuclei of keratinocytes stimulated by LTD4(P＜0.05),together with an elevation in intracellular calcium level(42.27±3.00 mmol/L,P＜0.01)and acceleration in cell proliferation (P＜0.01).However,both MK571 and BAYu9773 could completely block the effect of LTD4 on intmcellular calcium level and cell proliferation.and there was no significant difference in the blocking effect between MK571 and BAYu9773.Conclusions Functional CysLTRs are expressed in human keratinocytes.and they carl increase the intracellular calcium level in,and cell proliferation of,keratinocytes.

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.

Effect of Inhibitor of TNF-alpha and Oxatomide on Experimental Immune Mediated Otitis Media with Effusion / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Local immune response, one of the pathogenesis of middle ear effusion (MEE) is associated with the development and persistence of effusion in the middle ear cavity and inflammatory mediators play a major role in the production of MEE. The purpose of this study was to determine the effects of TNF-alpha antagonist and oxatomide on the outcome of immune mediated otitis media with effusion (OME) in rats. MATERIALS AND METHOD: Otitis media was induced by injecting KLH (Keyhole lympet hemocyanin) transtympanically 7 days after systemic immunization. Phosphate-buffered saline solution was used as control. Other groups were pretreated with TNF-alpha antagonist (soluble TNF receptor type I, sTNF RI) or oxatomide respectively before transtympanic injection of KLH. Seventy-two hours after the transtympanic injection, temporal bones in each group were examined histopathologically and vascular permeability of the middle ear mucosa was measured by the Evans blue vital dye technique. RESULTS: In the KLH, sTNF RI and oxatomide groups, MEE was developed in 83%, 0%, 66% of the ears, respectively. The oxatomide group and sTNF RI group showed significant decrease in inflammation, mucosal thickening and vascular permeability as compared with KLH group and those parameters of sTNF RI group showed lower values than those of oxatomide group. CONCLUSION: Transtympanic administration of sTNF RI and oxatomide appears to suppress the development of immune mediated OME. In terms of inhibiting MEE, sTNF RI was more effective than oxatomide. This study suggests that TNF-alpha antagonist and oxatomide may have a adjunctive role in the treatment and prevention of otitis media with effusion.

The Effects of Leukotriene Receptor Antagonist on Nasal Mucous Membrane in Allergic Model of Guinea Pigs / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: The leukotriene (LT) receptor antagonist is subject to an on-going study of allergic rhinitis, nasal polyposis and chronic paranasal sinusitis. This study was designed to evaluate the change of nasal patency and morphological changes by assessing the role of 4-oxo-8-benzopyren-hemihydrate (ONO-1078, BH), a cysLT1 receptor antagonist to treatment of allergic rhinitis. MATERIALS AND METHOD: Sixty-five guinea pigs (GPs) were divided into 3 groups: 15 for the control group, 25 for sensitized GPs group and 25 for nonsensitized GPs group. Sensitized GPs were actively sensitized by intraperitoneal injection of 10 mug DNP-As containing 1 mL Al (OH)3 and booster injections were given intraperitoneally 2, 4 and 6 weeks after the initial immunization. Measurements of nasal volume were made by acoustic rhinometry. Also transmission electron microscopy was performed to investigate ultrastructural changes of the nasal mucosal membrane in the LTD4 administrated GPs and the BH treated GPs. RESULTS: Acoustic rhinometry revealed that the changes of nasal volume showed significant reduction at 30 minutes and 6 hours after instillation of LTD4 in nonsensitized guinea pigs (GPs). However, neither nonsensitized nor sensitized GPs with systemic administration of BH showed any changes in nasal patency. Many neutrophils and eosinophils were seen in perivascular space after local administration of LTD4 in control GPs. However there are no eosinophil infiltration into the subepithelial space in BH treated GPs in both nonsensitized and sensitized group. CONCLUSION: The results suggest that BH might be a potent LT receptor antagonist in the allergic model of GPs, which reduces nasal blockage and block chemotaxis of eosinophils to the mucous membrane of the nose.