Carvedilol as primary prophylaxis for gastric variceal bleeding in portal hypertension model in rats / Carvedilol como profilaxia de sangramento em varizes gástricas em modelo de hipertensão portal em ratos

ABSTRACT Background: Portal hypertension (PH) can be measured indirectly through a hepatic vein pressure gradient greater than 5 mmHg. Cirrhosis is the leading cause for PH and can present as complications ascites, hepatic dysfunction, renal dysfunction, and esophagogastric varices, characterizing gastropathy. Aim: To evaluate the use of carvedilol as primary prophylaxis in the development of collateral circulation in rats submitted to the partial portal vein ligament (PPVL) model. Method: This is a combined qualitative and quantitative experimental study in which 32 Wistar rats were divided into four groups (8 animals in each): group I - cirrhosis + carvedilol (PPVL + C); group II - cirrhosis + vehicle (PPVL); group III - control + carvedilol (SO-sham-operated + C); group IV - control + vehicle (SO-sham-operated). After seven days of the surgical procedure (PPVL or sham), carvedilol (10 mg/kg) or vehicle (1 mL normal saline) were administered to the respective groups daily for seven days. Results: The histological analysis showed no hepatic alteration in any group and a decrease in edema and vasodilatation in the PPVL + C group. The laboratory evaluation of liver function did not show a statistically significant change between the groups. Conclusion: Carvedilol was shown to have a positive effect on gastric varices without significant adverse effects.

RESUMO Racional: A hipertensão portal (HP), medida indiretamente através do gradiente pressórico da veia hepática >5 mmHg, tem como principal causa etiológica a cirrose. Possui como complicações a ascite, disfunção hepática, disfunção renal e varizes esofagogástricas, que caracterizam o quadro de gastropatia. Objetivo: Avaliar o uso do carvedilol como profilaxia primária no desenvolvimento da circulação colateral em ratos submetidos ao modelo de ligadura parcial de veia porta (LPVP). Método: Estudo experimental qualitativo e quantitativo no qual foram utilizados 32 ratos Wistar, divididos em quatro grupos (n=8): grupo I - cirrose + carvedilol (LPVP+C); grupo II - cirrose + veículo (LPVP); grupo III - controle + carvedilol (SO - sham-operated+C); grupo IV - controle + veículo (SO - sham-operated). Após transcorridos sete dias do procedimento cirúrgico, foi administrado carvedilol (10 mg/kg) e veículo (1mL) para os respectivos grupos por sete dias consecutivos. Resultados: A análise histológica não mostrou alteração hepática em nenhum grupo e diminuição de edema e vasodilatação no grupo LPVP+C. A avaliação laboratorial da função hepática não mostrou alteração com significância estatística entre os grupos. Conclusão: Carvedilol mostrou ser fármaco com efeito positivo no sangramento das varizes gástricas e sem efeitos adversos significantes.

Bronchodilator test in extreme old age: Adverse effects of short-acting beta-2 adrenergic agonists with clinical repercussion and bronchodilator response

SUMMARY OBJECTIVE: To evaluate chronological age as a limiting factor to perform the bronchodilator test, determine significant adverse effects of short-acting beta 2 agonists with clinical repercussions, and assess bronchodilator response in extreme-old-age patients who undergo the spirometry test. METHODS: This is a cross-sectional and retrospective study. The sample was extracted from the database (spirometer and respiratory questionnaire) of a pulmonary function service. Patients over 90 years old were included in the research, and we evaluated their bronchodilator response and its significant adverse effects that may have clinical repercussions related to the bronchodilator. RESULTS: A sample of 25 patients aged 92.12 ± 2.22 years (95% CI, 91.20 - 93.04), with a minimum age of 90 years and a maximum of 97 years and a predominance of females with 72% (18/25). The bronchodilator test was performed in 84% (21/25) of the patients. The bronchodilator response was evaluated in 19 of the 21 patients (90.47%) who underwent the bronchodilator test. Two tests did not meet the criteria of acceptability and reproducibility. No clinical adverse effects were observed with the bronchodilator medication (salbutamol) during or after the exam. CONCLUSIONS: Chronological age is not a limiting factor for the bronchodilator test, short-acting beta-2 agonists did not present adverse effects with significant clinical repercussion and were useful in the diagnosis and therapeutic guidance of extreme-old-age patients.

RESUMO OBJETIVOS: Avaliar se idade cronológica é um fator limitante para realizar prova broncodilatadora, determinar efeitos adversos significativos com repercussão clínica dos beta-2 agonistas de curta ação e avaliar a resposta broncodilatadora na espirometria, na velhice extrema. MÉTODOS: Estudo transversal, retrospectivo. Amostra extraída do banco de dados (espirômetro e questionário respiratório) de um serviço de função pulmonar. Incluídos na pesquisa pacientes com ≥90 anos, sendo avaliados a resposta broncodilatadora e efeitos adversos significativos com repercussão clínica ao broncodilatador. RESULTADOS: Amostra de 25 pacientes com idade de 92,12 ± 2,22 anos (IC 95%; 91,20 - 93,04), idade mínima de 90 anos e máxima de 97 anos, predominando o sexo feminino, com 72% (18/25). A prova broncodilatadora foi realizada em 84% (21/25) dos pacientes. A avaliação da resposta ao broncodilatador foi feita em 19 dos 21 pacientes (90,47%) que realizaram a prova broncodilatadora, uma vez que dois desses exames não preencheram os critérios de aceitabilidade e reprodutibilidade. A resposta broncodilatadora foi significativa em 10,52% (2/19) dos pacientes, ambos portadores de pneumopatia obstrutiva. Não foram observados efeitos adversos com repercussão clínica da medicação broncodilatadora (salbutamol) durante ou após sua realização. CONCLUSÕES: A idade cronológica não é um fator limitante para a realização da prova broncodilatadora, os beta-2 agonistas de curta ação não apresentaram efeitos adversos com repercussão clínica significativa e foram bastante úteis para auxiliar no diagnóstico e orientação terapêutica na velhice extrema.

Propranolol inhibits myocardial infarction-induced brown adipose tissue D2 activation and maintains a low thyroid hormone state in rats

Considering the recognized role of thyroid hormones on the cardiovascular system during health and disease, we hypothesized that type 2 deiodinase (D2) activity, the main activation pathway of thyroxine (T4)-to-triiodothyronine (T3), could be an important site to modulate thyroid hormone status, which would then constitute a possible target for β-adrenergic blocking agents in a myocardial infarction (MI) model induced by left coronary occlusion in rats. Despite a sustained and dramatic fall in serum T4 concentrations (60-70%), the serum T3 concentration fell only transiently in the first week post-infarction (53%) and returned to control levels at 8 and 12 weeks after surgery compared to the Sham group (P<0.05). Brown adipose tissue (BAT) D2 activity (fmol T4·min-1·mg ptn-1) was significantly increased by approximately 77% in the 8th week and approximately 100% in the 12th week in the MI group compared to that of the Sham group (P<0.05). Beta-blocker treatment (0.5 g/L propranolol given in the drinking water) maintained a low T3 state in MI animals, dampening both BAT D2 activity (44% reduction) and serum T3 (66% reduction in serum T3) compared to that of the non-treated MI group 12 weeks after surgery (P<0.05). Propranolol improved cardiac function (assessed by echocardiogram) in the MI group compared to the non-treated MI group by 40 and 57%, 1 and 12 weeks after treatment, respectively (P<0.05). Our data suggested that the beta-adrenergic pathway may contribute to BAT D2 hyperactivity and T3 normalization after MI in rats. Propranolol treatment maintained low T3 state and improved cardiac function additionally.

CANG and preoperative use of beta-blockers in patients with stable angina are associated with better cardiovascular survival

Abstract Objective: In contrast to unstable angina, optimal therapy in patients with stable angina is debated. Our aim was to evaluate the outcomes of patients with stable angina scheduled for isolated coronary artery bypass grafts and the effect of preoperative use of beta-blockers. Overall and cardiovascular survivals were our primary outcome. Operative mortality and postoperative complications along with subgroup analysis of diabetic patients were our secondary outcomes. Methods: Retrospective evaluation of patients with stable angina scheduled for isolated coronary artery bypass grafts was included. Pre- and postoperative variables were extracted from the institution database. Survival was obtained from the National Registry. Results: We included 282 patients with stable angina, with a mean age of 65.6±9.5 years. 26.6% were female and 38.7% had diabetes. Three-vessel disease was present in 76.6% of patients. Previous beta-blocker treatment was evident in 69.9% of patients. 10-year overall survival in the whole population was 60.5% (95% confidence interval [CI]: 50.3-70.7%). Operative mortality during the study period was 3.5%. Patients with preoperative use of beta-blocker therapy had better overall survival (9.0 years, 95%CI: 8.6-9.5) than those without treatment (7.9 years, 95%CI: 7.1-8.8 years; P=0.048). Predictors for overall survival were: hypertension, diabetes, and age. Predictors for cardiovascular survival in diabetic patients were: beta-blocker use, gender, and age. Conclusion: Coronary artery bypass grafts surgery in patients with stable angina carries low operative mortality, postoperative complications, and excellent long-term cardiovascular survival. The preoperative use of beta-blockers in diabetic patients is associated with better cardiovascular survival after coronary artery bypass grafts.

Comparison of botulinum toxin and propranolol for essential and dystonic vocal tremors

OBJECTIVES: Vocal tremors, which cause social difficulties for patients, may be classified as resting or action tremors. Of the vocal action tremors, essential and dystonic tremors are the most common. Botulinum toxin and oral medications have been used to treat vocal tremors, but no comparative clinical trials have been performed. The aim of this study was to compare the effects of botulinum toxin injection and the oral administration of propranolol in the treatment of essential and dystonic vocal tremors. METHODS: This clinical trial recruited 15 patients, divided into essential and dystonic vocal tremor groups. Patients in both groups received successive treatment with botulinum toxin and propranolol. The treatments were administered at different times; the order of treatment was randomly selected. Patients were assessed with flexible nasofibrolaryngoscopy and with perceptual and acoustic voice evaluations. A statistical significance level of 0.05 (5%) was used. RESULTS: Botulinum toxin produced statistically significant improvements in perceptual measures of vocal instability in patients with dystonic vocal tremors compared with baseline values and treatment with propranolol. The acoustic measure of variability in the fundamental frequency was significantly lower in patients with dystonic vocal tremors after treatment with botulinum toxin. CONCLUSION: Essential and dystonic vocal tremors responded differently to treatment. Dystonic vocal tremors responded significantly to treatment with botulinum toxin but not oral propranolol. Essential vocal tremors did not respond significantly to either treatment, perhaps due to the small number of patients, which is a limitation of this research.

A study on reducing the absorption of lidocaine from the airway in cats

Abstract Purpose: To determine if the combination of lidocaine with epinephrine or gamma globulin would decrease the rate or reduce the amount of local absorption of lidocaine through the airway. Methods: Twenty adult male cats were randomly and evenly distributed into four groups: 1) Group LG: lidocaine administered with gamma globulin; 2) Group LS: lidocaine administered with physiological saline); 3) Group LE: lidocaine administered with epinephrine; 4) Group C: control group. Invasive blood pressure, heart rate, and concentration of lidocaine were recorded before and after administration. Results: The peak of plasma concentrations appeared difference (Group LG: 1.39 ± 0.23 mg/L; Group LS: 1.47 ± 0.29 mg/L and Group LE: 0.99 ± 0.08 mg/L). Compared to Group C, there were significant differences in the average heart rate of Groups LG, LS, and LE (P < 0.05). The average systolic blood pressures were significantly different when each group was compared to Group C (P < 0.05). The biological half-life, AUC0-120, peak time, and half-life of absorption among the three groups have not presented statistically significant differences (P > 0.05). Conclusion: Administering lidocaine in combination with gamma globulin through airway causes significant decrease the rate and reduce the amount of local absorption of lidocaine in cats.

Noradrenaline and dobutamine effects on the volume expansion with normal saline in rabbits subjected to hemorrhage

ABSTRACT PURPOSE: To evaluate the effects of dobutamine (DB), noradrenaline (NA), and their combination (NADB), on volume retention in rabbits submitted to hemorrhage. METHODS: Thirty six rabbits were randomly divided into 6 groups: SHAM, Control, Saline, DB, NA, DB+NA. All the animals, except for SHAM, were subjected to hemorrhage of 25% of the calculated blood volume. Control animals were replaced with their own blood. The other groups received NSS 3 times the volume withdrawn. The intravascular retention, hematocrit, diuresis, central venous pressure, mean arterial pressure, NGAL, dry-to-wet lung weight ratio (DTWR) and the lung and kidney histology were analyzed. RESULTS: Replacement with NSS and NA, DB or NA+DB did not produce differences in the intravascular retention. After hemorrhage, the animals presented a significant decrease in the MAP and CVP, which were maintained until volume replacement. Regarding NGAL, dry-to-wet-lung-weight ratio, lung and kidney histology, there were no statistical differences between the groups. CONCLUSION: The use of noradrenaline, dobutamine or their combination did not increase the intravascular retention of volume after normal saline infusion.

Clorhidrato de isoxuprina endovenoso o progesterona vaginal en la amenaza de parto pretérmino / Intravenous isoxuprin clorhidrate or vaginal progesterone in treathened preterm labor

El objetivo fue comparar la eficacia del clorhidrato de isoxuprina endovenoso o la progesterona vaginal en la amenaza de parto pretérmino en la Maternidad “Dr. Nerio Belloso”. Hospital Central “Dr. Urquinaona”, Maracaibo, Estado Zulia. Se Seleccionaron 82 embarazadas con edad gestacional entre 24 y 34 semanas y diagnóstico de amenaza de parto pretérmino para recibir progesterona vaginal (grupo A; n=41) o clorhidrato de isoxuprina endovenoso (grupo B; n=41). Se evaluaron tiempo de cese de las contracciones y los efectos adversos maternos. El promedio de edad gestacional de las pacientes al momento del inicio del tratamiento fue de 31.7 ± 2.1 semanas en el grupo A y 32.4 ± 2.4 semanas en el grupo B (P=ns). En las primeras 24 horas de tratamiento clorhidrato de isoxuprina fue más efectivo que la progesterona vaginal con una tocólisis efectiva (26,8% en el grupo A y en 61.0% en el grupo B, p<0.05). Sin embargo, después de 7 días de tratamiento, 73.2% de las pacientes del grupo A y 36.6% de las pacientes en el grupo B aún permanecían sin contracciones (P<0.05). El retraso del parto más allá de las 34 semanas se logro en 80.5% de las pacientes en el grupo A y 26.8% de las pacientes grupo B (P<0.05). La cefalea fue el efecto adverso más frecuente en el grupo de pacientes del grupo A. La progesterona vaginal es más efectiva que el clorhidrato de isoxuprina endovenoso en el tratamiento de la amenaza de parto pretérmino.

The objetive was to compare the efficacy of endovenous isoxuprine clorhidrate of vaginal progesterone in treathened preterm labor in the Maternidad “Dr. Nerio Belloso”. Hospital Central “Dr. Urquinaona”, Maracaibo. Estado Zulia. Eighty two patients with a gestational age between 24 and 34 weeks and treathened preterm labor were selected to receive vaginal progesterone (group A; n= 41) or endovenous isoxuprine clorhidrate (group B; n=41). Time of ceasing of uterine contractions and maternal adverse effects were evaluated. Mean gestational age of patients at beginning of treatment was 31.7 ± 2.1 weeks in group A and 32.4 ± 2.4 weeks in group B(P=ns). At the first 24 hours of treatment, isoxuprine clorhidrate was more effective than vaginal progesterone for effective tocolysis (26.8% in group A and 61.0% in group B, P<0.05). However, after 7 days of treatment, 73.2% of patients in group A and 36.6% of patients in group B still were without contractions (P<0.05). Delay of delivery beyond 34 weeks was achieved in 80.5% of patients in group A and 26.8% of patients in group B (P<0.05). Headache was the most frequent adverse effects in patients of group A. Vaginal progesterone is more effective than endovenous isoxuprine clorhidrate in the treatment of treathened preterm labor.

Efeitos macrovasculares, microvasculares e interação leucócito-endotélio, na endotoxemia experimental após o uso de Dobutamina com e sem ressuscitação volêmica / Macrovascular and microvascular effects and leukocyte-endothelial interaction in experimental endotoxemia after use of dobutamine with and without volume ressuscitation

Na sepse, o mecanismo desencadeador de morte é a disfunção múltipla de órgãos e sistemas. Com isso a microcirculação é considerada o motor na patogênese da sepse. A perfusão microcirculatória representa um dos principais objetivos para melhorar as taxas de sobrevida. Uma vez reconhecida a síndrome séptica, o protocolo clínico estabelece o uso de fluidoterapia com salina, de forma vigorosa na primeira hora e seguida de suporte inotrópico com Dobutamina. A partir daí foi levantada a hipótese das drogas β-agonistas serem relevantes na recuperação da microcirculação, antes mesmo de seu conhecido papel na recuperação do choque cardiogênico. Assim, estudar o papel da Dobutamina, um β-agonista, na resposta adrenérgica em situação de sepse se faz necessário e urgente e o entendimento de sua ação, associada à reposição volêmica, foi objeto deste estudo. Foram usados no presente estudo, 78 hamsters, induzida a endotoxemia com LPS (2mg/kg/de massa de peso corporal) e divididos em 9 grupos: controle (n=10), endotóxico(n=10), endotóxico tratados com Dobutamina na dose de 5 e 15 μg /kg/min (n=10), Isoproterenol(n=10), ressuscitação volêmica (n=10) e ressuscitação volêmica associada à Dobutamina 5 (n=10) e 15 μg/kg/min (n=4) e Isoproterenol (n=4). Foram comparados os resultados de recuperação da densidade capilar funcional ao longo do tempo entre os grupos, e obteve-se resultado estatisticamente significativo no grupo em que se usa Dobutamina de 5μg/kg/min associada à ressuscitação volêmica p< 0,05. Em conclusão este estudo mostra que o papel da ressuscitação volêmica é crucial na resposta da microcirculação para melhorar a densidade capilar funcional, que a velocidade da hemácia capilar tem relação direta com a melhora na perfusão tecidual e que a associação de recuperação volêmica com solução salina e Dobutamina na dose de 5 μg /kg /min melhora significativamente sua resposta e melhora a perfusão.

uring sepsis the mechanism responsible for death is multiple dysfunctions of organs and systems and therefore the microcirculation is considered the motor in the pathogenesis of sepsis and microcirculatory perfusion represents one of the main objectives to improve survival rate. Once one recognizes the septic syndrome, the clinical protocol establishes the use of fluid therapy with physiological saline, in a vigorous way, in the first hour followed by inotropic support with dobutamine. With these facts in mind, our hypothesis is that β-agonist drugs are relevant for microcirculatory recuperation, even before their role was known in the recuperation of cardiogenic shock. In this way, to study the role of dobutamine, a β-agonist, in the adrenergic response in sepsis is needed and urgent. The understanding of its action associated to volume resuscitation was the aim of our study. Seventy-eight male hamsters were used in our study, endotoxemia being induced with LPS (2 mg/kg body weight), divided in 9 groups: control (n=10), endotoxic (n=10), endotoxic treated with dobutamine in the concentrations of 5 and 15 μg/kg/min (n=10, each), isoproterenol (n=10), volume resuscitation associated to dobutamine 5 μg/kg/min (n=10), 15 μg/kg/min (n=4), isoproterenol (n=4) or not (n=10). The microcirculation was observed in the dorsal window chamber and the results compared the recuperation of function capillary density with time and the group treated with dobutamine 5 μg/kg/min associated to volume resuscitation showed a statistically significant improvement (p<0.05) of it. In conclusion, this study has shown that volume resuscitation plays a crucial role in the microcirculatory response in terms of improvement of functional capillary density, the velocity of red blood cells in the capillary has a direct relationship with the improvement of tissue perfusion and the association of volume resuscitation with physiological saline and dobutamine 5 μg/kg/min elicits ...

Acute hemodynamic effects of inhaled nitroglycerine, intravenous nitroglycerine, and their combination with intravenous dobutamine in patients with secondary pulmonary hypertension.

Objectives: The presence of pulmonary artery hypertension (PAH) affects the prognosis of patients; therefore, it is important to treat it. The aim of this study is to compare the acute hemodynamic effects of inhaled nitroglycerine (iNTG), intravenous nitroglycerine (IV NTG) alone and their combination with intravenous dobutamine (IV DOB) during the early postoperative period, in patients with PAH undergoing mitral valve or double valve replacement surgery. Materials and Methods: In the study, 40 patients with secondary PAH were administered iNTG 2.5 μg/kg/min, IV NTG 2.5 μg/kg/min, a combination of iNTG 2.5 μg/kg/min + IV DOB 10 μg/kg/min, and IV NTG 2.5 μg/kg/min + IV DOB 10 μg/kg/min for 10 minutes each following valve replacement surgery, in random order. The hemodynamic parameters were recorded before (T0) and immediately after the intervention. (T1). Results: iNTG effectively decreased mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance index (PVRI), and the PVR / SVR ratio, without affecting arterial pressures, systemic vascular resistance or mixed venous oxygen saturation (SvO 2 ). IV NTG produced both systemic and pulmonary vasodilation along with a significant fall in SvO 2 . The combination of iNTG and IV DOB caused a significant decrease in mPAP and PVRI, with no significant change in SVRI, PVR / SVR ratio, and SvO 2 . A combination of IV NTG + IV DOB caused both pulmonary and systemic vasodilatation with a significant decrease in SvO 2 . None of the drugs caused any significant change in the cardiac index. Conclusion: All drugs were of similar efficacy in reducing the pulmonary vascular resistance index. Only iNTG produced selective pulmonary vasodilatation, while IV NTG and its combination with IV dobutamine had a significant concomitant systemic vasodilatory effect.

Simulação técnico-econômica da inclusão de ractopamina em dietas de suínos em terminação / Technical-economic simulation of ractopamine inclusion in diets for finishing pigs

Foi realizada simulação técnico-econômica a partir de resultados de publicações para avaliar a inclusão de ractopamina em dietas de suínos em terminação. Foram utilizados 18 artigos, que avaliaram níveis de 0, 5, 10 e/ou 20ppm de ractopamina na dieta, totalizando 2.991 animais. A partir dos resultados técnicos das publicações avaliadas, foram geradas equações que foram utilizadas na simulação do desempenho técnico-econômico. Verificou-se que os custos independem do sistema de receitas do produtor e oscilam de 3 a 6ppm de ractopamina adicionada à dieta. O lucro máximo foi obtido com os níveis de 10 e 12ppm de ractopamina, respectivamente, para os sistemas de receita por peso vivo e por bonificação. Os resultados evidenciam melhor desempenho econômico da utilização de ractopamina, na dieta dos suínos em terminação, pelo sistema de receita por bonificação. As análises de sensibilidade para a variação na receita dos produtores apresentam valores ótimos de 9 a 12ppm de ractopamina, com oscilação de até R$ 49,00/cabeça entre os cenários testados.

A technical-economic simulation was performed based on results from publications for assessing the inclusion of ractopamine in the diet of finishing pigs. Eighteen articles were used, which assessed levels of 0, 5, 10, and/or 20ppm of ractopamine in the diet, totalizing 2,991 animals. Based on the results obtained in these technical publications, equations were used for the simulation of the technical-economic performance. From this study, it was established that the costs are independent of the system of revenue of the producer and range from 3 to 6ppm of ractopamine added in the diet. The maximum profit was obtained with the levels of 10 and 12ppm of ractopamine, respectively, for the systems of revenue per body weight and per bonus. The results show a better economic performance with the use of ractopamine in the diet of finishing pigs, by the system of revenue per bonus. Analyses of sensitivity of changes in the revenue of producers presented optimal values of 9 to 12ppm of ractopamine, with a range of up to R$ 49.00 per capita between the tested scenarios.

Factores determinantes del éxito de la terapia con inhaladores de dosis medida en niños / Therapy with metered-dose inhalers in children

Este artículo revisa los factores que influyen en el éxito de terapias con inhaladores de dosis medida en niños las que comprenden desde características farmacocinéticas de las drogas hasta la adherencia al tratamiento.

Effect of beta2-Adrenergic Receptor Polymorphism in Asthma Control of Patients Receiving Combination Treatment

PURPOSE: Combination treatment of inhaled corticosteroid (ICS) plus long-acting beta2-agonist (LABA) is widely used as a maintenance regimen for the management of asthma. This study evaluated the effect of the beta2-adrenergic receptor (ADRB2) polymorphism on lung function and asthma control with regular use of combination treatment of an inhaled ICS plus LABA. MATERIALS AND METHODS: 43 Korean asthmatics who were symptomatic despite regular ICS use for at least 3 months were enrolled. For a 2-week run-in period, they received ICS (budesonide 800 microgram/day) plus terbutaline (5 microgram prn). as needed. During the 24-week active treatment period, they received budesonide 160 microgram and formoterol 4.5 microgram b.i.d. as maintenance and rescue medication. Pulmonary function and quality of life scores were monitored every 8 weeks; morning/evening peak expiratory flow meter (PEFR) was recorded daily. Patients were genotyped for ADRB2 Arg16Gly using single base extension methodology. RESULTS: During the run-in period, there were no significant between-group differences in lung function; after 8 weeks of active treatment, Arg/Arg patients had significantly higher forced expiratory volume in 1 secord (FEV1) and maximal mid-expiratory flow (MMEF) (p = 0.023 and p = 0.021, respectively), and better asthma control and quality of life after 24 weeks (p = 0.016 and p = 0.028, respectively). During treatment, there was a greater improvement in morning/evening PEFR in Arg/Arg patients. CONCLUSION: Asthmatic patients with the Arg/Arg genotype at codon 16 of ADRB2 achieve better asthma control with long-term regular use of combined budesonide and formoterol treatment, suggesting that the ADRB2 genotype may dictate choice of treatment strategy.

The effect of a low dose of clenbuterol on rat soleus muscle submitted to joint immobilization

The aim of the present study was to evaluate the effect of joint immobilization on morphometric parameters and glycogen content of soleus muscle treated with clenbuterol. Male Wistar (3-4 months old) rats were divided into 4 groups (N = 6 for each group): control, clenbuterol, immobilized, and immobilized treated with clenbuterol. Immobilization was performed with acrylic resin orthoses and 10 µg/kg body weight clenbuterol was administered subcutaneously for 7 days. The following parameters were measured the next day on soleus muscle: weight, glycogen content, cross-sectional area, and connective tissue content. The clenbuterol group showed an increase in glycogen (81.6 percent, 0.38 ± 0.09 vs 0.69 ± 0.06 mg/100 g; P < 0.05) without alteration in weight, cross-sectional area or connective tissue compared with the control group. The immobilized group showed a reduction in muscle weight (34.2 percent, 123.5 ± 5.3 vs 81.3 ± 4.6 mg; P < 0.05), glycogen content (31.6 percent, 0.38 ± 0.09 vs 0.26 ± 0.05 mg/100 mg; P < 0.05) and cross-sectional area (44.1 percent, 2574.9 ± 560.2 vs 1438.1 ± 352.2 µm²; P < 0.05) and an increase in connective tissue (216.5 percent, 8.82 ± 3.55 vs 27.92 ± 5.36 percent; P < 0.05). However, the immobilized + clenbuterol group showed an increase in weight (15.9 percent; 81.3 ± 4.6 vs 94.2 ± 4.3 mg; P < 0.05), glycogen content (92.3 percent, 0.26 ± 0.05 vs 0.50 ± 0.17 mg/100 mg; P < 0.05), and cross-sectional area (19.9 percent, 1438.1 ± 352.2 vs 1724.8 ± 365.5 µm²; P < 0.05) and a reduction in connective tissue (52.2 percent, 27.92 ± 5.36 vs 13.34 ± 6.86 percent; P < 0.05). Statistical analysis was performed using Kolmogorov-Smirnov and homoscedasticity tests. For the muscle weight and muscle glycogen content, two-way ANOVA and the Tukey test were used. For the cross-sectional area and connective tissue content, Kruskal-Wallis and Tukey tests were used. This study emphasizes the importance of anabolic pharmacological...

Uso de dexametasona y salbutamol nebulizados en bronquiolitis aguda: estudio clínico comparativo / Comparative clinical study of dexamethasone vs. nebulized salbutamol in acute bronchiolitis

Objetivo: Evaluar la eficacia de salbutamol y dexametasona nebulizados comparados con salbutamol solo en pacientes con bronquiolitis aguda. Material y métodos: Estudio clínico controlado, aleatorizado, en pacientes de 1 a 18 meses de edad con diagnóstico de bronquiolitis aguda y evolución menor de tres días. Se asignaron dos grupos: 1) salbutamol (n = 24) o 2) salbutamol más dexametasona (n = 25) administrado por micronebulizaciones cada cuatro horas por 24 horas. Se midieron las frecuencias cardiaca y respiratoria, la gravedad del cuadro mediante el Respiratory Distress Assigment Index, el Silvermann-Andersen, saturación de O2 y tiempo de desaparición de la dificultad respiratoria y frecuencia de altas en 24 horas. Resultados: No se encontraron diferencias significativas entre los grupos de estudio, excepto en la frecuencia de altas hospitalarias en las primeras 24 horas, 75 vs 96 % p < 0.04 respectivamente. Conclusiones: La aplicación de salbutamol más dexametasona es más rápida para controlar la dificultad respiratoria en niños con bronquiolitis aguda en comparación con la aplicación de salbutamol solo.

OBJECTIVE: Asess the efficacy of nebulized salbutamol and dexamethasone compared with nebulized salbutamol, in patients with bronchiolitis. MATERIAL AND METHODS: A blinded clinical trial was performed with 49 patients between 1-18 months diagnosed with bronchiolitis with three days or less of disease evolution. Participant's parents signed an informed consent and patients did not receive prior medication. Patients were randomly assigned to two groups: nebulized salbutamol or salbutamol plus dexamethasone, which they received every four hours during twenty-four hours. We measured heart and respiratory rate; respiratory distress index, oxygen saturation, and Silverman Andersen scores. RESULTS: No significant differences were found between groups for treatment response; but the frequency of hospital release at 24 hrs was significant among groups; 75 vs 96 % respectively (p = 0.04). CONCLUSIONS: The administration of salbutamol plus dexamethasone is more effective in the control of respiratory distress in children with bronchiolitis compared with the use of salbutamol alone.

Evidence based review on levosalbutamol.

Salbutamol, the most commonly used bronchodilator, is a chiral drug with R (levosalbutamol) and S-isomers (also known as enantiomer). The commonly used formulation is a racemic mixture that contains equal amounts of both R and S isomers. Levosalbutamol is the therapeutically active isomer and has all the beta 2 agonist activity. Until recently S-salbutamol was considered inert filler in the racemic mixture but animal as well as human studies have shown that S-salbutamol is not inert rather it may have some deleterious effects. Enantioselective metabolism of salbutamol leads to higher and sustained plasma levels of S-salbutamol with repeated dosing. There has been concern that chronic use of racemic salbutamol may lead to loss of effectiveness and clinical deterioration. Formulation of salbutamol containing only R- isomer (levosalbutamol) has been available in international market since last few years. Clinical trials in acute as well as chronic asthma in adults as well as children have shown that it has therapeutic advantage over racemic salbutamol and also is more cost effective. But, large multicenter trials are needed to prove its therapeutic superiority and cost-effectiveness in long term.

Status of inhalation therapy in bronchial asthma in adults above twelve years of age in armed forces.

OBJECTIVE: The aim of this study was to evaluate the status of inhalation therapy in bronchial asthma in terms of frequency of its use, role of general physicians and general practitioners in prescribing inhalation therapy, role of inhaled steroids and B2 agonists, concurrent use of oral drugs, technique of using inhaler devices, use of spacer devices and peak flow monitoring. MATERIAL AND METHODS: 150 patients (76 males, 74 females) of bronchial asthma over 12 years of age referred to chest clinic of a tertiary care hospital for inadequate control were interviewed on the basis of a questionnaire and screening of prescription and case records wherever available. RESULTS: 127 (84.6%) patients were on inhalation therapy and maximum number of prescriptions was by general physicians (81%). The dosages of inhaled steroids were less than 400 mg in 60 (83.3%) cases and 26 (36%) patients discontinued it after some time. All patients were on beta-2 agonist inhalers and 74 (58.3%) patients were using these on regular basis. The concurrent use of oral short acting B2 agonist and oral steroids was seen in 107 (84%) and 41 (32.2%) patients respectively. Metered dose inhalers (MDIs) were most frequently used inhaler devices in 100 (78.7%) cases followed by rotahalers in 27 (21%) cases. The technique of using MDI and rotahalers was incorrect in 64 (64%) and 7 (25.9%) cases respectively. Spacer devices were used rarely and none of the patients were monitored by peak flow rates. CONCLUSIONS: Although inhalation therapy was being prescribed in large number of patients, more so by general physicians, yet the therapy was not being effective considering the fact that the referral to chest clinic in all the cases was for uncontrolled asthma. The main reasons for ineffective inhalation therapy were, underuse of inhaled steroids, overuse of B2 agonists and incorrect use of inhaler devices. There is an urgent need to educate general physicians especially in regards to usefulness of inhaled steroids, as on demand use of B2 agonists, demonstration of correct inhalation technique to patients, use of spaces devices and peak flow monitoring.

Effect of salbutamol on pulmonary responsiveness in chronic pulmonary allergic inflammation in guinea pigs

Beta-2-agonists have been widely used by asthmatic subjects to relieve their obstructive symptoms. However, there are reports that continuous use could lead to loss of bronchial protection and exacerbation of asthma symptoms. We evaluated the effect of two regimens of salbutamol administration (twice and five times a week) in a model of chronic airway inflammation in male Hartley guinea pigs (protocol starting weight: 286 ± 30 g) induced by repeated exposures to aerosols of ovalbumin (OVA). After sensitization, guinea pigs were exposed to aerosols of 0.1 mg/ml salbutamol solution twice a week (OVA + S2x, N = 7) or five times a week (OVA + S5x, N = 8). We studied allergen-specific (OVA inhalation time) and -nonspecific (response to methacholine) respiratory system responsiveness. Seventy-two hours after the last OVA challenge, guinea pigs were anesthetized and tracheostomized, respiratory system resistance and elastance were measured and a dose-response curve to inhaled methacholine chloride was obtained. Specific IgG1 was also quantified by the passive cutaneous anaphylactic technique. OVA-sensitized guinea pigs (N = 8) showed reduction of the time of OVA exposure before the onset of respiratory distress, at the 5th, 6th and 7th exposures (P < 0.001). The OVA + S2x group (but not the OVA + S5x group) showed a significant increase in OVA inhalation time. There were no significant differences in pulmonary responsiveness to methacholine among the experimental groups. OVA + S2x (but not OVA + S5x) animals showed a decrease in the levels of IgG1-specific anaphylactic antibodies compared to the OVA group (P < 0.05). Our results suggest that, in this experimental model, frequent administration of ß2-agonists results in a loss of some of their protective effects against the allergen.

Transient lactic acidosis as a side effect of inhaled salbutamol therapy in asthmatic children

In spite of the effectiveness of inhaled beta-2 agonists as bronchodilator therapy in bronchial asthma management in children; they produce a number of biochemical changes. The clinical relevance of these biochemical changes is not clearly defined. One of these observed changes is the transient lactatemia. The aim of this study is to evaluate the presence of lactic acidosis as a transient side effect of inhaled salbutamol therapy during the management of asthmatic attacks. Thirty-six asthmatic children presenting in acute asthma, 20 males and 16 females with age range between 6 and 10 years [mean +/- SD: 7.47 +/- 1.13 years], were included in this study. All of them were subjected to full history taking, thorough clinical examination and lab evaluation including: Serum lactate levels before salbutamol inhalation therapy, one hour after start of inhalation therapy and 24 hours later. Blood gas analysis before and after inhalation therapy were also done. Salbutamol inhalation therapy was given to all patients in the form of 3-successive doses, 20 minutes apart, in a dose of 0.15 mg/kg/dose, thereafter intensive management was continued. A statistically highly significant increase in the early post treatment serum lactate level was found in comparison to both pre treatment and 24 hours post treatment levels. In spite of the return of serum lactate levels to normal limits, the difference between the 24-hour post treatment and pre treatment levels was also statistically highly significant. The results of this study confirm that transient lactic acidosis occurs as a side effect of inhaled salbutamol. Physicians should be aware of this side effect of bronchodilators, which might prove of clinical significance in the more severe cases where other causes of metabolic acidosis coexist. Abbreviation: S.I.T. = salbutamol inhalation therapy

Efeito do salbutamol liberado através de inalador de pó seco sobre o broncoespasmo induzido por metacolina / Effects of salbutamol delivered by dry-powder inhaler on methacholine-induced bronchoconstriction

INTRODUÇAO: Os beta2-agonistas de curta duração sob a forma de nebulímetro pressurizado são os fármacos utilizados rotineiramente na reversão do broncoespasmo induzido pela metacolina. A administração desses fármacos na forma de pó seco, liberados por inaladores de pó seco pode ser uma alternativa eficaz. OBJETIVO: Avaliar a efetividade e rapidez de ação do salbutamol liberado através de inalador de pó seco pulvinal (Butovent®) na reversão do broncoespasmo induzido por metacolina, comparando-o com o salbutamol liberado por nebulímetro pressurizado. MÉTODO: Foram avaliados prospectivamente 60 pacientes sucessivos com broncoespasmo induzido por metacolina, cuja queda do volume expiratório forçado no primeiro segundo (VEF1) foi de, no mínimo, 20 por cento. Foram randomizados 30 pacientes para receber 200 mcg de salbutamol liberado por nebulímetro pressurizado e 30 pacientes para receber 200 mcg de salbutamol através de inalador de pó seco (pulvinal), na etapa final do teste de broncoprovocação, com o objetivo de reverter o broncoespasmo induzido pela metacolina. Foram avaliados os VEF1 obtidos 1 minuto e 5 minutos após a administração do broncodilatador. RESULTADOS: Os grupos foram pareados por sexo, idade, peso, altura, dose provocativa causadora de queda de 20 por cento no VEF1 (primeiro grupo: 1,3 mg ; segundo grupo: 1,19 mg; p = 0,79) e VEF1 pós-metacolina (primeiro grupo: 2,03 l; segundo grupo: 1,99 l; p = 0,87), sem diferença significativa entre eles. O incremento médio do VEF1 foi de 16,2 por cento (1 minuto) e 22,2 por cento (5 minutos) no primeiro grupo e de 17 por cento (1 minuto) e 23,6 por cento (5 minutos) no segundo grupo, não havendo diferença estatística entre eles (p = 0,8). CONCLUSÕES: Os beta2-agonistas administrados através de inalador de pó seco (pulvinal) apresentam a mesma eficácia broncodilatadora e rapidez de ação que no tradicional método por nebulímetro pressurizado.