Comparative study of protective effects of salbutamol and beclomethasone against insulin induced airway hyper-reactivity on isolated tracheal smooth muscle of guinea pig

Inhalational insulin was withdrawn from the market due to its potential to produce airway hyper-reactivity and bronchoconstriction. So the present study was designed to explore the acute effects of insulin on airway reactivity of guinea pigs and protective effects of salbutamol and beclomethasone against insulin induced airway hyper-responsiveness on isolated tracheal smooth muscle of guinea pig. Effects of varying concentrations of insulin [10[-7] to 10[-3] M], insulin pretreated with fixed concentration of salbutamol [10[-7] M] and beclomethasone [10[-6] M] were studied on isolated tracheal tissue of guinea pig by constructing cumulative concentration response curves. Changes in tracheal smooth muscle contractions were recorded on four channel oscillograph. The mean +/- SEM of maximum amplitudes of contraction with increasing concentrations of insulin, insulin pretreated with fixed concentration of salbutamol and beclomethasone were 35 +/- 1.13 mm, 14.55 +/- 0.62 mm and 22 +/- 1.154 mm respectively. Although salbutamol and beclomethasone both had a profound inhibitory effect on insulin induced airway hyper-reactivity, yet salbutamol is more efficacious than beclomethasone. So we suggest that pretreatment of inhaled insulin with salbutamol may be preferred over beclomethasone in amelioration of its potential respiratory adverse effects such as bronchoconstriction

Microbial biotransformation of beclomethasone dipropionate by Aspergillus niger

In the present research, the steroidal anti-asthmatic drug beclomethasone dipropionate was subjected to microbial biotransformation by Aspergillus niger. Beclomethasone dipropionate was transformed into various metabolites first time from microbial transformation. New drug metabolites produced can act as new potential drug molecules and can replace the old drugs in terms of safety, efficacy, and least resistance. They were purified by preparative thin layer chromatography technique, and their structures were elucidated using modern spectroscopic techniques, such as 13C NMR, 1H NMR, HMQC, HMQC, COSY, and NOESY, and mass spectrometry, such as EI-MS. Four metabolites were purified: (i) beclomethasone 17-monopropionate, (ii) beclomethasone 21-monopropionate, (iii) beclomethasone, and (iv) 9beta,11beta-epoxy-17,21-dihydroxy-16beta-methylpregna-1,4-diene-3,20-dione 21-propionate.

Na pesquisa presente o fármaco esteróide antiasmático dipropionato de beclometasona foi submetido à biotransformação microbiana pelo Aspergillus niger. O dipropionato de beclometasona foi transformado, pela primeira vez, em metabólitos variados por biotransformação microbiana. Novos metabólitos do fármaco produzidos podem agir como novas moléculas potenciais e podem substituir os fármacos antigos em questão de segurança, eficácia e mínima resistência. Eles foram purificados por cromatografia em camada delgada preparativa e as suas estruturas foram elucidadas usando técnicas espectroscópicas modernas, como 13C NMR, 1H NMR; HMQC; HMQC; COSY, NOESY e espectrometria de massas, por exemplo, EI-MS. Purificaram-se quatro metabólitos, denominados (i) 17-monopropionato de beclometasona; (ii) 21-monopropionato de beclometasona: (iii) beclometasona e (iv) 21-propionato de 9beta,11beta-epoxi-17,21-diidroxi-16beta-metilpregna-1,4-dieno-3,20-diona.

Efeitos da inalação de beclometasona e furosemida sobre a função pulmonar e índice de oxigenação de recém-nascidos prematuros / Inhalation effects of beclomethasone and furosemide on pulmonary function and oxygenation index of preterm newborns / Efectos de la inhalación de beclometasona y furosemida sobre la función pulmonar e índice de oxigenación de recién nacidos prematuros

O objetivo deste estudo foi avaliar a função pulmonar e o índice de oxigenação de recém-nascidos pré-termo submetidos à inalação endotraqueal de beclometasona e furosemida. Foram avaliados 30 recém-nascidos pré-termo com idade gestacional <36 semanas, sob ventilação mecânica convencional por pelo menos 12 horas. Três inalações sequenciais com as respectivas medicações foram realizadas, com intervalo de três horas entre as mesmas. Foram coletadas amostras de sangue arterial para análise dos gases sanguíneos; após aspiração endotraqueal, a mensuração das variáveis respiratórias foi realizada em dois momentos, antes e após duas horas da última inalação. A complacência dinâmica, assim como o índice de oxigenação, não apresentou diferença estatística significativa entre os momentos antes e após as medicações; no entanto, a resistência de vias aéreas demonstrou redução no grupo beclometasona entre os momentos antes e após a intervenção (p=0,03). Diante desses resultados, não podemos afirmar que a beclometasona e a furosemida inalatória exercem influência significativa na função pulmonar e oxigenação dos recém-nascidos estudados.

The objective of this study was to evaluate lung function and oxygenation index of preterm infants undergoing endotracheal inhaling of beclomethasone and furosemide. We studied 30 newborn preterms with gestational age <36 weeks, undergoing conventional mechanical ventilation for at least 12 hours. Three sequential inhalations with their medications were executed with an interval of three hours between each. We collected samples of arterial blood for gas analysis, and after endotracheal aspiration, the measurement of respiratory variables was performed in two stages, two hours before and after the last inhalation. Dynamic compliance and the oxygenation index showed no statistically significant difference between before and after the medication, however, the airway resistance group demonstrated a reduction in beclomethasone between the moments before and after the intervention (p=0.03). These results cannot imply that inhaled beclomethasone and furosemide exerted significant influence on lung function and oxygenation in the newborn infants studied.

El objetivo de este estudio fue evaluar la función pulmonar e índice de oxigenación de recién nacidos de pre-término sometidos a la inhalación endotraqueal de beclometasona y furosemida. Fueron evaluados 30 recién nacidos de pre-término con edad gestacional <36 semanas, bajo ventilación mecánica convencional por lo menos 12 horas. Tres inhalaciones secuenciales con las respectivas medicaciones fueron realizadas, con intervalo de tres horas entre las mismas. Fueron tomadas muestras de sangre arterial para el análisis de los gases sanguíneos y después de la aspiración endotraqueal, la medición de las vías respiratorias fue realizada en dos momentos, antes y después de dos horas de la última inhalación. La compliance dinámica así como el índice de oxigenación, no presentaron diferencia estadísticamente significativa entre los momentos antes y después de las mediciones, sin embargo, la resistencia de las vías aéreas demostró reducción en el grupo beclometasona entre los momentos antes y después de la intervención (p=0,03). Mediante estos resultados no podemos afirmar que la beclometasona y la furosemida inhalatoria ejercen influencia significativa en la función pulmonar y oxigenación de los recién nacidos estudiados.

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.

Anti-inflammatory effects of salmeterol, compared to beclomethasone, and sustained-release theophylline measured by serum levels of tumor necrosis factor-alpha, and eosinophilic cationic protein in asthmatic children

Inhaled steroids are increasingly used in the management of asthma and although effective, they may cause systemic side effects. Theophylline is among the least expensive drugs used to treat asthma and consequently it remains a commonly used drug for this indication in many countries. In industrialized countries, the advent of inhaled corticosteroids, beta-2 agonists, and leukotriene modifying drugs has significantly diminished the extent to which theophylline is used. In addition to their bronchodilating effects, long acting inhaled beta2 agonists have recently been shown to have some anti-inflammatory properties. This work was designed to study the anti inflammatory effects of salmeterol compared to beclomethasone and theophylline by measuring of serum levels of tumor necrosis factor-alpha [TNF-alpha] and eosinophilic cationic protein [ECP] in children with mild and moderate to severe asthma. The study was carried out in The Chest and Allergy Unit, Pediatric Department, Tanta University Hospital, from October 2000 to January 2003. It comprised ninety asthmatic children who were presented by mild, and moderate to severe attack of asthma exacerbations, their ages ranged from 6-15 years. The asthmatic children were classified into 2 groups: Group I: Included thirty children with mild asthmatic attack with FEV1 of 70-80% of the expected normal value for age and sex at the time of presentation. These patients were subdivided into three sub-groups to receive one of the following drugs for eight weeks: Inhaled beclomethasone dipropionate by metered dose inhaler [MDI] in a dose of 200 microgram / 8 hours [Steroid subgroup-I], oral sustained-release theophylline in a dose of 15 mg / kg / day [12 Hourly] [Theophylline subgroup-I], and Inhaled long acting beta 2 agonist [Salmeterol] by MDI in a dose of 50 microgram [2 buffs] / 12 hours [Salmetemi subgroup-I]. Group II: Included sixty children with moderate to severe asthma exacerbation with FEV1 less than 70% of the expected values for the age and sex. Conventional therapy was given as required to these patients to control the exacerbations of the asthmatic attack, and to achieve FEV1 of 70-80% of the expected normal values of their age and sex. Then the patients were subdivided to three sub-groups [Steroid subgroup-Il, Theophylline subgroup-Il, and Salmeterol subgroup-Il] to receive either one of the three drug modalities by the same dose and for the same duration as mentioned before in children with mild asthma [group I]. Absolute eosinophilic count [AEC], serum levels of eosinophilic cationic protein [ECP] and tumor ncrosis factor-alpha [TNF-alpha] were measured at presentation during the acute exacerbation and 8 weeks after beginning of the different treatment modalities. We concluded that beclomethasone dipropionate had effectively diminished serum levels of TNF-alpha and ECP to a greater extent than the Ophylline and salmeterol in children with bronchial asthma. Long acting theophylline also diminished significantly serum levels of TNF-alpha and ECP at a lower than customarily recommended blood theophylline level after 8 weeks of regular treatment. On the other hand, salmeterol decreased serum levels of TNF-alpha and ECP in asthmatic children but this reduction was not significant after 8 weeks of regular administration in cases of mild and moderately severe asthma

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.

Nedocromil sódico y cromoglicato de sodio en la prevención del asma inducida por ejercicio / Sodium nedocromil and sodium cromoglycate in the prevention of exercise induced asthma

Se comparó la efectividad de nedocromil sódico, cromoglicato de sodio y placebo (beclometasona) en la prevención de la broncoconstricción provocada por ejercicio en 22 niños con asma leve o moderado de 6 a 14 años de edad, mediante el registro de la caída del flujo espiratorio máximo después de una carrera libre de 6 minutos de duración en espacio abierto. Para estos efectos todos los pacientes fueron sometidos a una serie de 4 ejercicios (basal, después de inhalación de beclometasona, cromoglicato y nedocromil, estos dos últimos fueron suministrados bajo un régimen de doble ciego). El índice de caída promedio basal (sin medicamentos) fue 33 por ciento, ante 28,9 por ciento (NS) después de inhalar placebo y 15 por ciento después de inhalar cromoglicato y nedocromil

Acciones de diversos fármacos sobre la hiperreactividad bronquial y el asma: consideraciones fisiopatogénicas y terapéuticas / Actions of different drugs on the bronchial hyperreactivity and the asthma: considerations physiopathogenic and therapy

En 48 pacientes asmáticos atópicos leves o moderados se investigó la respuesta a diversos fármacos. Luego de una semana de tratamiento con dipropionato de beclometasona (BECLO) o terfenadina (TER) o cetirizina (CET) o cromoglicato disódico (CGDS) o nedocromil sódico (NED), se evaluó: a)la evolución espirográfica tomando como parámetros VEF y FM antes y después de cada uno de los tratamientos. En el cotejo de los resultados obtenidos con cada fármaco se encontró que, tomando los promedios de ambos parámetros, el CGDDS, con el 50 por ciento, es el fármaco que mejor actua; luego siguen en orden decreciente, TER 38 por ciento, BECLO 35 por ciento, CET 29 por ciento y NED 7 por ciento. Las diferencias son estadísticamente significativas entre CGDS vs. NED, p<0,05. b) La capacidad de protección de cada uno de esos fármacos sobre la hiperreactividad bronquial con aire frío (HRB). Aquí el orden de protección para la broncoobstrucción, si se toman ambos parámetros(VEF y FM) es para la CET, del 65 por ciento, BECLO 50 por ciento, CGDS 46 por ciento y TER 8 por ciento. Si en lugar de considerar los promedios para ambos parámetros, se toma el número de evaluaciones espirográficas que son protegidas más del 10 por ciento ante la estimulación con aire frío, se observa que a la CET le corresponde el 90 por ciento de protección, al CGDS al 61,5 por ciento, a la BECLO el 60 por ciento a la TER el 28,6 por ciento y al NED el 12.5 por ciento. Estadísdicamente la CET es superior a TER y NED (P<0,02) y CGDS también vs. TER y NED p<0,02. Se concluye que si bien la HRB es una expresión del asma, en ésta se suma a la inflamación basal y broncoobstrucción, donde la histamina tiene un papel más importante que en las respuestas de HRB. Y que en la HRB por aire frío la acción antiinflamatoria de los fármacos u otras acciones, como anti PAF, puedan ofrecer mejores resultados, por lo que habría que elaborar criterios terapéuticos individuales de acuerdo con la mejor acción preventiva para cada una de las situaciones

Tratamento da alopécia areata: Revisäo bibliográfica de 10 anos / Treatment of alopecia areata: review bibliografic of 10 years

Os autores fazem uma revisäo do tratamento da alopécia areata durante um período de 10 anos e concluem pela näo existência ainda de um medicamento eficaz para curar esta afecçäo

Tratamiento del asma bronquial del niño: Parte II / Treatment of the bronchial asthma in children: Part II

El tratamiento del asma bronquial del niño persigue que el paciente y su familia tengan una vida normal o, al menos, lo más posible. Su manejo comprende el tratamiento farmacológico y específico, sin olvidar aspectos psicológicos y educativos. En esta segunda parte se revisa el tratamiento de los tipos de asma según su gravedad o edad, y también el tratamiento de la crisis de asma y del mal asmático