RESUMO
STUDY OBJECTIVE: To evaluate the influence of oral anabolic steroids on body mass index (BMI), lean body mass, anthropometric measures, respiratory muscle strength, and functional exercise capacity among subjects with COPD. DESIGN: Prospective, randomized, controlled, double-blind study. SETTING: Pulmonary rehabilitation program. PARTICIPANTS: Twenty-three undernourished male COPD patients in whom BMI was below 20 kg/m2 and the maximal inspiratory pressure (PImax) was below 60% of the predicted value. INTERVENTION: The study group received 250 mg of testosterone i.m. at baseline and 12 mg of oral stanozolol a day for 27 weeks, during which time the control group received placebo. Both groups participated in inspiratory muscle exercises during weeks 9 to 27 and cycle ergometer exercises during weeks 18 to 27. MEASUREMENTS AND RESULTS: Seventeen of 23 subjects completed the study. Weight increased in nine of 10 subjects who received anabolic steroids (mean, +1.8+/-0.5 kg; p<0.05), whereas the control group lost weight (-0.4+/-0.2 kg). The study group's increase in BMI differed significantly from that of the control group from weeks 3 to 27 (p<0.05). Lean body mass increased in the study group at weeks 9 and 18 (p<0.05). Arm muscle circumference and thigh circumference also differed between groups (p<0.05). Changes in PImax (study group, 41%; control group, 20%) were not statistically significant. No changes in the 6-min walk distance or in maximal exercise capacity were identified in either group. CONCLUSION: The administration of oral anabolic steroids for 27 weeks to malnourished male subjects with COPD was free of clinical or biochemical side effects. It was associated with increases in BMI, lean body mass, and anthropometric measures of arm and thigh circumference, with no significant changes in endurance exercise capacity.
Assuntos
Anabolizantes/uso terapêutico , Índice de Massa Corporal , Pneumopatias Obstrutivas/tratamento farmacológico , Distúrbios Nutricionais/fisiopatologia , Músculos Respiratórios/efeitos dos fármacos , Administração Oral , Idoso , Anabolizantes/administração & dosagem , Antropometria , Braço/anatomia & histologia , Constituição Corporal , Método Duplo-Cego , Teste de Esforço , Terapia por Exercício , Tolerância ao Exercício/efeitos dos fármacos , Humanos , Inalação/fisiologia , Pneumopatias Obstrutivas/fisiopatologia , Pneumopatias Obstrutivas/reabilitação , Masculino , Contração Muscular/efeitos dos fármacos , Músculo Esquelético/anatomia & histologia , Músculo Esquelético/efeitos dos fármacos , Estudos Prospectivos , Músculos Respiratórios/fisiopatologia , Estanozolol/administração & dosagem , Estanozolol/uso terapêutico , Testosterona/administração & dosagem , Testosterona/uso terapêutico , Coxa da Perna/anatomia & histologia , Fatores de Tempo , Aumento de PesoRESUMO
Acetaminophen (APAP)-induced nephrotoxicity is age-dependent in male Sprague-Dawley (SD) rats: middle-aged (9-12 months old) rats exhibit nephrotoxicity at lower dosages of APAP than do young adults (2-3 months old). The present study was designed to test the hypothesis that the intrinsic susceptibility of renal tissue to APAP toxicity is increased in middle-aged rats. APAP toxicity was evaluated in renal slices from naive 3- and 12-month-old male SD rats incubated with 0-50 mM APAP for 2-8 h. Renal slice glutathione (GSH) and APAP concentrations were determined; renal function was assessed by organic anion (para-aminohippurate, PAH) and cation (tetraethylammonium, TEA) accumulation; and cell viability was assessed by lactate dehydrogenase (LDH) leakage. At each concentration of APAP tested, accumulation of APAP by renal slices was similar in 3- and 12-month-olds. APAP toxicity in renal slices from both 3- and 12-month-old rats was characterized by concentration-dependent increases in LDH leakage. In contrast to APAP nephrotoxicity in vivo, APAP toxicity in renal slices was accompanied by decreased accumulation of PAH and TEA. Additionally, APAP produced marked reductions in renal slice GSH content in a concentration-dependent manner: however, in contrast to APAP nephrotoxicity in vivo, APAP-induced GSH depletion in vitro did not precede cytotoxicity. No consistent age-dependent differences in the time- and concentration-response curves for APAP nephrotoxicity were observed. These data suggest that APAP cytotoxicity in vitro is not increased in 12-month-old rats. However, since the pattern (and mechanisms) of APAP cytotoxicity in vitro appears to be different from that observed in vivo, extrapolation of in vitro cytotoxicity to in vivo nephrotoxicity is limited. Therefore, age differences in intrinsic susceptibility of the intact kidney cannot be excluded as a mechanism contributing to enhanced APAP nephrotoxicity in middle-aged rats.