Evaluation of smooth muscle relaxant potential of Bismarckia nobilis (Hildebr. & Wendl.) in diarrhea, hypertension and asthma by ex-vivo and in-vivo method / Evaluación del potencial relajante en músculo liso de Bismarckia nobilis (Hildebr. & Wendl.) en diarrea, hipertensión y asma por métodos ex vivo e in vivo

To explore the mechanistic basis behind smooth muscle relaxant prospective of Bismarckia nobilis in gastrointestinal, respiratory and cardiovascular ailments. The methanolic extract of B. nobilis and sub-fractions have been evaluated in vitro rabbit isolated tissues, in vivo castor oil-induced diarrhea in rats and charcoal meal activity in mice. The B. nobilis extract relaxed spontaneous and K+(80 mM)- induced contractions in rabbit isolated jejunum preparations, CCh (1 µM) and K+ (80 mM)-induced contractions in tracheal and bladder preparations, PE (1 µM) and K+ (80 mM)-induced concentrations in aorta preparations, likewise verapamil. Spasmolytic activity of dichloromethane fraction is stronger as compared to aqueous fraction. In vivo castor oil-induced diarrhea in rats and charcoal meal activity in mice further supported spasmolytic activity. B. nobilis extract possess anti-spasmodic, anti-diarrheal, airway relaxant and vasodilator activities possible mediated through calcium channel blocking mechanism, justifying therapeutic utility of B. nobilis in diarrhea, asthma and hypertension.

El objetivo de trabajo fue explorar el mecanismo de acción relacionado con el efecto relajante del músculo liso inducido por Bismarckia nobilis (B. nobilis) en enfermedades gastrointestinales, respiratorias y cardiovasculares. El extracto metanólico de B. nobilis y subfracciones fue evaluado in vitro en tejidos aislados de conejos. Además se evaluó diarrea in vivo inducida con aceite de ricino en ratas y la actividad de harina de carbón vegetal en ratones. El extracto de B. nobilis relajó tanto las contracciones espontáneas como las inducidas por K+(80 mM) en preparaciones de yeyuno aisladas de conejos, las contracciones inducidas por PE (1 µM) y K+(80 mM) inducidas en preparaciones de aorta; de manera similar a verapamilo. La actividad espasmolítica de la fracción de diclorometano es más potente en comparación con la fracción acuosa. La diarrea inducida in vivo por el aceite de ricino en ratas y la actividad de la harina de carbón vegetal en ratones apoyaron aún más la actividad espasmolítica. El extracto de B. nobilis posee actividades antiespasmódicas, antidiarreicas, relajantes de las vías respiratorias y vasodilatadoras, posibles a través del mecanismo de bloqueo de los canales de calcio, lo que justifica la utilidad terapéutica de B. nobilis en la diarrea, el asma y la hipertensión.

Anti-inflammatory effects of Salvia plebeia R. Br extract in vitro and in ovalbumin-induced mouse model

BACKGROUND: Asthma is an increasing global health problem, and novel strategies to prevent or ameliorate the condition are needed. Here, the effects of 80 % ethanol extracts of Salvia plebeia R. Br. (SE) on an induced inflammatory response were investigated RESULTS: Salvia plebeia R. Br. inhibited production of pro-inflammatory cytokines, such as TNF-α and IL-6, as well as nitric oxide (NO) in LPS-stimulated RAW 264.7 cells. NO and pro-inflammatory cytokine production was suppressed more effectively by SE of the aerial parts (SE-A) than of the roots (SE-R) of S. plebeia. In BEAS-2B cells, both SE-A and SE-R inhibited the increase in production of the inflammatory cytokines IL-6 and IL-8. We also investigated the antiasthmatic effects of SE in an ovalbumin (OVA)-induced BALB/c mouse model. SE-A treatment significantly reduced the number of airway eosinophils, IL-4 and IL-13 levels, mucus production, and inflammatory infiltration, as compared with the corresponding levels in the untreated, OVA-induced mice, and had similar effects to dexamethasone CONCLUSIONS: Salvia plebeia ethanol extract ameliorated the induced inflammatory response in RAW 264.7 and BEAS-2B cells, with more effective inhibition noted for SE-A than for SE-R. SE-A treatment was effective in improving the histopathological changes in the lungs of asthma model mice via modulation of eosinophils and Th2 cytokines. These results suggest that SE-A can be considered as a therapeutic agent that can potentially relieve asthma

Pharmacologic bronchodilation response to salbutamol in COPD patients.

Background: Airway hyperresponsiveness (AHR) is the most characteristic feature of asthma, which is reported in COPD patients and smokers. Increased airway responsiveness to ί-agonists is also demonstrated in asthmatics as well as smokers. However, there is no report regarding AHR to ί-agonist drugs in COPD patients. Therefore, in this study pharmacologic bronchodilation response to salbutamol in COPD patients was examined. Materials and Methods: The threshold concentrations of inhaled salbutamol required for a 20% change in forced expiratory flow in 1 sec (FEV 1 ) as PC 20 , or a 35% change in specific airway conductance (sGaw) as PC 35 was measured in 14 COPD patients and 14 normal subjects. Results: Airway responsiveness to salbutamol in COPD patients (PC 20 = 14.14 ± 1.62 and PC 35 = 9.70 ± 1.48 mg/l) was significantly lower than normal subjects (PC 20 = 224.57 ± 16.62 and PC 35 = 81.87 ± 8.16 mg/l, P < 0.001 for both cases). The values of FEV 1 and sGaw in COPD patients (56.43 ± 14.45 and 0.081 ± 0.120 respectively) were significantly lower than those of normal subjects (104.07 ± 5.72 and 0.194 ± 0.041 respectively), (P < 0.001 for FEV 1 and P < 0.005 for sGaw). There was a significant correlation between FEV 1 with PC 20 salbutamol (r = 0.862, P < 0.001). The correlations between PC 20 and PC 35 was also statistically significant (r = 0.862, P < 0.001). Conclusion: These results showed increased airway responsiveness of most COPD patients to salbutamol which was highly correlated to airway caliber.

Beta 2 agonistas de acción prolongada en el tratamiento del asma en niños / Long acting beta 2 agonists in the treatment in children with asthma

A pesar del uso de corticoides inhalados en el tratamiento del asma bronquial existe un número variable de pacientes que no logran el control de su enfermedad. En estos casos, una de las alternativas terapéuticas propuesta por diversas guías clínicas es la adición de beta 2 agonistas de acción prolongada. Este articulo, revisa las características farmacológicas, posibles efectos adversos y las indicaciones en niños.

Nuevos corticoides inhalados / New inhaled corticosteroids

El asma es la enfermedad inflamatoria crónicas más frecuente en niños. Diversas guías clínicas nacionales y extranjeras recomiendan a los corticoides inhalados (CI) como el tratamiento de elección, de manera independiente de la severidad de la enfermedad. Nuevos CI han ingresado al mercado nacional, con características particulares que ameritan una revisión apropiada para su empleo. Este trabajo resume algunos aspectos farmacológicos básicos del uso de CI en niños así como su mecanismo de acción en sujetos con asma.

Anti-IgE monoclonal antibody for treatment of asthma and other manifestations related to allergic diseases

OBJETIVO: Descrever as características farmacológicas, a eficácia e a segurança do omalizumabe, o primeiro anticorpo monoclonal anti-IgE aprovado para uso clínico, uma nova opção de tratamento da asma e das doenças alérgicas. FONTES DE DADOS: Pesquisa não sistemática na MEDLINE. Os principais artigos de revisão ou ensaios clínicos foram escolhidos com base em sua relevância segundo a opinião dos autores. SíNTESE DOS DADOS: O artigo destaca o importante papel da IgE na patogênese da doença alérgica, a lógica biológica para o uso da anti-IgE, as evidências que definiram a sua indicação atual na asma não controlada e possíveis indicações futuras, bem como as recomendações para uso clínico com doses ajustadas pelo peso e níveis séricos de IgE. O omalizumabe foi aprovado para uso em pacientes com asma grave não controlada que apresentem teste cutâneo positivo a pelo menos um aeroalérgeno relevante ou que apresentem IgE sérica alérgeno-específica para alérgenos relevantes, e cujo nível de IgE total esteja entre 30 e 700 UI/mL. Por enquanto, o uso deve ser restrito a pacientes maiores de 12 anos, mas é possível que a droga seja aprovada para uso a partir dos 6 anos de idade. CONCLUSÕES: Em alguns pacientes, a asma grave não é controlada com as opções de tratamento disponíveis para prevenção de sintomas e exacerbações, exigindo o uso freqüente ou prolongado de corticosteróides sistêmicos. Esses pacientes poderiam se beneficiar de tratamento com anti-IgE depois de reavaliação meticulosa das possíveis razões para a falta de controle da sua asma.

OBJECTIVES: To report on the pharmacology, efficacy and safety of omalizumab , a new option for the treatment of asthma and allergic diseases and the first monoclonal anti-IgE antibody approved for clinical use. SOURCES: MEDLINE, a non-systematic search including reviews and original papers, chosen according to their relevance in the authors' opinion. SUMMARY OF THE FINDINGS: The paper emphasizes the central role IgE plays in allergic diseases and the biological rationale for its use, the evidence upon which the current recommendations for the use of anti-IgE in uncontrolled asthma are based and its possible future applications, in addition to the recommendation that in clinical practice doses must be adjusted for weight and serum IgE levels. Omalizumab was approved in Brazil for patients with severe uncontrolled asthma presenting with a positive skin prick test for one or more relevant aeroallergen, or IgE specific to a relevant allergen detected in serum, having a total IgE level of between 30 and 700 UI/mL. For the time being its use should be restricted to patients aged 12 years or more, but there are prospects that it will be licensed for use with children over 6 years old. CONCLUSIONS: Some severe asthma cases cannot be controlled with the regular treatment options aimed at preventing symptoms and exacerbations, and so require frequent or prolonged use of systemic corticosteroids. These patients may benefit from treatment with anti-IgE, after a meticulous reevaluation of possible reasons for the failure to control asthma.

Antileukotrienes in the treatment of asthma and allergic rhinitis

OBJETIVO: Comparar os antagonistas de leucotrienos (ARLT) aos outros grupos de medicamentos utilizados para tratar a asma e a rinite alérgica. FONTES DOS DADOS: MEDLINE, LILACS e Biblioteca Cochrane. Palavras chaves: leucotrienos, antileucotrienos, tratamento da asma, tratamento da rinite alérgica, asma e rinite alérgica. Procurou-se agrupar os principais trabalhos e revisões sobre o assunto. SíNTESE DOS DADOS: Os ARLT são mais eficazes do que placebo e potencializam os efeitos dos corticosteróides inalados. A associação de corticosteróides inalados com agentes beta2 agonistas de longa duração (LABA) é mais eficaz do que a associação de cortiscoteróides inalados + ARLT. Embora pareça racional o uso de ARLT na crise aguda de asma e rinite alérgica, mais estudos são necessários para comprovar esse benefício. Os ARLT promovem redução no tempo de hospitalização e no número de crises de sibilância em lactentes com bronquiolite viral aguda pelo vírus respiratório sincicial e na sibilância recorrente após bronquiolite viral aguda. Os ARLT são menos eficazes que os corticosteróides intranasais no manejo da rinite alérgica. Os ARLT são eficazes na asma induzida por exercício (AIE), embora não constituam a primeira linha de tratamento. CONCLUSÃO: Estudos controlados e randomizados mostram que os corticosteróides inalados são as drogas de escolha para o tratamento da asma persistente e rinite alérgica. :Não existem evidências suficientes para recomendar o uso de ARLT como medicamento de primeira linha (monoterapia) em crianças com asma (nível I). Nas crianças que não podem usar corticosteróides inalados, os ARLT podem ser uma alternativa (nível II).

OBJECTIVE: To compare leukotriene antagonists (LTA) to other groups of drugs used in asthma and allergic rhinitis treatment. SOURCES: MEDLINE, LILACS and Cochrane Library. Keywords: leukotrienes, antileukotrienes, asthma treatment, allergic rhinitis treatment, asthma and allergic rhinitis. An attempt was made to group the main studies and reviews about this topic. SUMMARY OF THE FINDINGS: LTA are more efficient than placebo and enhance the effects of inhaled corticosteroids. The association of inhaled corticosteroids with long-acting beta2-agonists is more efficient than the association of inhaled corticosteroids + LTA. Although use of LTA in acute asthma attacks and allergic rhinitis seems reasonable, more studies are needed to confirm this benefit. LTA reduce hospitalization time and the number of wheezing attacks in infants with acute viral bronchiolitis caused by respiratory syncytial virus, as well as recurrent wheezing after acute viral bronchiolitis. LTA are less efficient than intranasal corticosteroids for allergic rhinitis management. LTA are efficient in exercise-induced asthma, although they are not the first-line treatment. CONCLUSIONS: Controlled and randomized studies show that inhaled corticosteroids are the drugs of choice to treat persistent asthma and allergic rhinitis. There is not enough evidence to recommend the use of LTA as first-line drug (monotherapy) in children with asthma (level I). For children who cannot use inhaled corticosteroids, LTA may be a good alternative (level II).

Effect of inhalation of salbutamol, beclomethasone dipropionate & ipratropium bromide on mucociliary clearance in some patients with chronic stable bronchial asthma.

BACKGROUND & OBJECTIVES: Asthma is now regarded as an inflammatory disease and bronchial inflammation may disrupt mucociliary function. Inhaled drugs may act by improving mucociliary function. The aim of the study was to investigate the effect of salbutamol, ipratropium bromide and beclomethasone on mucociliary clearance in patients with chronic stable asthma and to compare the efficacy of these drugs on mucociliary clearance. METHODS: Ten patients with chronic stable asthma were enrolled in the study, but two patients did not complete the study. Patients with bronchial asthma were chosen on clinical grounds. (99m)Tc phytate radioaerosol generated through a nebulizer, was given to each patient on four days. After each administration the radioactivity over the thorax was constantly measured in sequential frame mode for 120 min. Radioactivity in the thorax was also measured after 24 h. A base-line pulmonary function test with reversibility was obtained. Salbutamol, ipratropium bromide, beclomethasone dipropionate and placebo inhalation were given randomly to each patient on four days. RESULTS: The mean age of patients (n = 8) was 36 +/- 9.3 yr and mean duration of symptoms was 5 +/- 6.6 yr. There was no visual impression that mucociliary clearance was enhanced with any of the drugs. The time activity curves did not show any visually recognisable change in slope. In only one patient the curve tended to show a steeper slope with ipratropium inhalation. In the rest of the patients the curves showed no difference at all with medication when compared with placebo. All the quantitative indices analyzed by two-way ANOVA at the end of one and two hours were comparable for the three test drugs and placebo. None of the three test drugs demonstrated statistically significant mucociliary clearance effect compared with placebo. However, the temporal difference in airways clearance efficiency (ACE) was significant with beclomethasone and ipratropium bromide. INTERPRETATION & CONCLUSION: Inhalation of any of the three drugs tested did not produce any immediate improvement in mucociliary clearance as compared to placebo in patients with stable bronchial asthma suggesting the need for further studies using higher doses of drugs for longer duration in a large sample.

Controvérsias no manejo farmacológico da asma aguda infantil / controversies in the pharmacological management of acute asthma in children

Objetivo: apresentar uma revisão acerca de questões controversas, relativas ao manejo farmacológico utilizado nos pacientes pediátricos portadores de asma aguda.Fontes dos dados: foram utilizadas informações de artigospublicados em revistas científicas nacionais e internacionais, selecionadas das bases de dados Lilacs e Medline. Síntese dos dados: o artigo foi estruturado em tópicos, apresentando aspectos consensuais no tratamento farmacológico da asma infantil. Questões relacionadas à utilização de inaladores dosimetrados versus nebulizadores, o papel das drogas ß2-adrenérgicas utili-zadas pela via endovenosa, bem como das metilxantinas e do sulfato de magnésio, são abordados de maneira crítica.Conclusões: os ß2-agonistas administrados pela via inalatória, associados aos coricosteróides, permanecem o tratamento de eleição para episódios agudos de asma na população pediátrica. Tanto os nebulizadores quanto os inaladores dosimetrados, acoplados a espaçadores, são efetivos para alívio dos sintomas agudos. Pacientes refratários ao tratamento convencional, que evoluem para quadros de asma aguda grave, devem ter considerada a utilização de drogas ß2-agonistas pela via endovenosa, desde que adequadamente monitorizados. Quanto às metilxantinas e ao sulfato de magnésio, devem ser considerados alternativas secundárias para pacientes selecionados(AU);#S#as#BR3.1-

Drug therapy of childhood asthma.

Drug therapy is used to prevent and control asthma, and also to reduce the frequency and severity of its exacerbations, and reverse airflow obstruction. Asthma medications are thus categorized into two general classes--bronchodilators (relievers) and anti-inflammatory drugs (preventers). Short acting beta2-agonists is the therapy of choice for relief of acute symptoms and prevention of exercise induced bronchospasm (EIB). Corticosteroids are the most potent and effective anti-inflammatory medication currently available. Inhaled form is used in the long-term control of asthma. Systemic corticosteroids are used to gain prompt control of the disease when initiating long-term therapy. Long acting bronchodilator used concomitantly with anti-inflammatory medications for long-term control of symptoms, especially nocturnal symptoms. Ipratropium bromide may provide some additive benefit to inhaled beta2-agonists in severe exacerbations. Sustained release theophylline is a mild to moderate bronchodilator used principally as adjuvant to inhaled corticosteroids for prevention of nocturnal asthma. Leukotriene modifiers may be considered as an alternative therapy to inhaled corticosteroids or cromolyn or nedocromil.

Antiallergic/antiasthmatic effect of novel antiallergic hexapeptide-95/220 in various experimental models.

The effects of newly synthesized antiallergic hexapeptide 95/220 was investigated on various allergic and asthmatic test models. This newly developed peptide was found to be more potent than clinically used drug disodium cromoglycate (DSCG). Hexapeptide 95/220 inhibited immediate hypersensitivity reactions such as passive cutaneous anaphylaxis (PCA) and mast cell degranulation in rats, antigen-induced bronchoconstriction in actively sensitized guinea pigs in dose dependent manner like DSCG. Antigen-induced contraction of guinea pig ileum was also markedly inhibited by this newly developed hexapeptide in the same fashion as ketotifen and DSCG did but at comparatively lower dose. Egg albumin-induced histamine release was also blocked by this hexapeptide from chopped lung tissues of sensitized guinea pigs. These results suggest that hexapeptide' 95/220 has potent inhibitory effect on immediate hypersensitivity reactions thereby inhibiting mediator release from mast cell. Moreover, this newly synthesized peptide is orally active and effective at lower doses as compared to standard drugs.

Nebulized saline solution of dry powder formoterol is useful for acute bronchospasm

Dos nuevos beta agonistas de efecto prolongado son actualmente usados clínicamente: salmeterol y formoterol. El primero no ha demostado efectividad en los casos de asma aguda mientras que el segundo, formoterol, comparable en su período de latencia al albuterol, no ha sido empleado en el manejo de las crisis de asma. En este estudio utilizamos mediciones de flujo espiratorio pico antes y después de la administración de 12 microgramos de fumarato de formoterol (ForadilR) en polvo seco vía nebulización, inmediatamente después de su dilución en solución salina estéril, a treinta pacientes con crisis de asma y grados variables de obstrucción bronquial. Los resultados muestran mejoría significativa a los 5 y 30 minutos después de su administración, sugiriendo estabilidad de este producto así como un novedoso enfoque costo efectivo por su menor dosificación y posible impacto sobre la frecuencia de readmisiones debido a una broncodilatación prolongada

Conjutivite alérgica perene estudo aberto com cromoglicato dissódico a 2 por cento / Perennial allergic conjunctivitis an open study with 2 percent sodium cromoglycate

Objetivo: Estudo aberto para avaliar a eficácia do cromoglicato dissódio a 2 por cento em gotas oculares, no tratamento da conjuntivite alérgica perene, durante o período de seis semanas. Métodos: Um grupo de 27 pacientes com conjuntivite alérgica perene foi selecionado no Serviço de Alergia do Hospital do Servidor Estadual em Säo Paulo. Eles foram orientados a usar colírio de cromoglicato de sódio a 2 por cento durante um período de seis semanas, para investigar a eficácia da droga, a adesäo ao tratamento e os efeitos adversos. Resultados: Todos os sintomas considerados apresentaram melhora estatisticamente significativa, com exceçäo da fotofobia. Onze efeitos adversos foram relatados, sete destes por pacientes com queixa de queimaçäo ou irritaçäo ocular. De modo geral a aceitaçäo foi considerada satisfatória ( 85 por cento aceitaram completamente na primeira reavaliaçäo) assim como a obediência na prescriçäo, especialmente levando-se em consideraçäo que a falta do uso ocorreu principalmente devido ao esquecimento. Conclusäo: Sessenta por cento dos pacientes consideraram o cromoglicato dissódico a 2 por cento bastante ou moderadamente eficaz no tratamento da conjuntivite alérgica perene, avaliaçäo esta coincidente com a do médico investigador em 65 por cento dos casos.

Botanical, chemical and pharmacological investigation on Cissampelos species from Paraíba (Brazil)

In our continuing search for biologically active compounds of local medicinal flora, we have investigated the genus Cissampelos (Meninspermaceae) whose species are used in ethnomedicine mainly for treatment of the diseases of the respiratory system. From the three species found in Paraiba: C. sympodialis, C. glaberrima and C. ovalifolia, only the first one was analyzed more extensively due to its greater availability and the high yield of warifteine, a bisbenzyltetrahydroisoquinoline alkaloid isolated from it. The water soluble fractions of the ethanolic extracts of the root, leaf and warifteine obtained from either of the fractions caused nonspecific smooth muscle relaxation in tissues such as the guinea pig trachea. The leaf fraction also showed bronchodilatory activity in whole animal experiments and inhibited human neutrophil degranulation induced by the peptide formyl-methionine-leucine-proline. The mechanism of action of the fraction involves on increase in intracellular cyclic adenosine monophosphate levels possibly as a result of the inhibition of nucleotide phosphodiesterase enzymes. The antiasthmatic use of the plant Cissampelos sympodialis may have scientific justification.

Estudo de parâmetros salivares em crianças asmáticas usuárias de antiinflamatórios / Study of salivary parameters in asthmatic children using anti-inflammatory agents

Este estudo longitudinal compreendeu um período de 210 dias, durante os quais os parâmetros salivares pH, capacidade tampäo (CTS), velocidade do fluxo salivar (VFS) e o percentual do cálcio foram analisados mensalmente, em 14 crianças asmáticas, entre 7-13 anos de idade, usuárias de aerossol de dipropionato de beclometasona (DPB) e de cromoglicato de sódio (CGD) por igual período de 90 dias, e um grupo-controle de 35 crianças clinicamente saudáveis, näo-usuárias de medicaçäo, com a mesma faixa etária. No tratamento estatístico, utilizou-se o teste T para amostras independentes, a fim de verificar se o uso das medicaçöes por 30 dias afetaria alguns fatores de proteçäo salivar do grupo experimental em relaçäo ao grupo-controle e comparar longitudinalmente os efeitos das medicaçöes na saliva das crianças asmáticas. Concluiu-se que as alteraçöes desses fatores observadas durante o uso do DPB e CGD reforçam a necessidade de lavagem da cavidade oral após o uso dessas medicaçöes e a preconizaçäo de medidas odontológicas preventivas durante o tratamento da asma brônquica com aerossol por tempo prolongado.