RESUMO
Chronic interleukin (IL)-1 administration is associated with negative nitrogen balance and the loss of lean body mass. To elucidate the molecular mechanism(s) by which IL-1 modulates protein metabolism in muscle, we investigated the effects of chronic (6 day) IL-1alpha infusion on protein synthesis in Individual muscles (gastrocnemius, soleus, heart) compared with saline-infused control rats. IL-1 significantly decreased muscle weight, protein content, and the rate of protein synthesis in gastrocnemius (fast-twitch muscle). IL-1 had no effect on these parameters in the heart, whereas only the rate of protein synthesis was reduced in soleus (slow-twitch muscle). The reduction in gastrocnemius protein synthesis was not the result of a decrease in total RNA content, but was associated with a diminished translational efficiency. The diminished translational efficiency correlated with a 40% reduction in the epsilon-subunit of eukaryotic initiation factor 2B (elF2Bepsilon) in gastrocnemius from IL-1 -treated animals. However, the content of the alpha-subunit of elF2 (elF2alpha) was unaffected. In contrast, the elF2alpha content in heart was increased by IL-1, although elF2Bepsilon levels were unchanged. Reductions in skeletal muscle protein synthesis were not associated with a concomitant reduction in circulating or tissue content of insulin-like growth factor I. In summary, the IL-1-induced decrease in gastrocnemius protein synthesis appears to be regulated at the level of RNA translation via a reduction in elF2Bepsilon. These findings support a regulatory role for IL-1 as a mediator of muscle protein synthesis and the alterations in body composition observed in catabolic states where this cytokine is overexpressed.
Assuntos
Interleucina-1/metabolismo , Músculo Esquelético/metabolismo , Biossíntese de Proteínas , Animais , Corticosterona/metabolismo , Hormônio do Crescimento/sangue , Fatores de Troca do Nucleotídeo Guanina , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Proteína 2 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Interleucina-1/farmacologia , Masculino , Músculo Esquelético/efeitos dos fármacos , Miocárdio/metabolismo , Proteínas/efeitos dos fármacos , Proteínas/metabolismo , RNA/metabolismo , Ratos , Ratos Sprague-DawleyAssuntos
Medicina de Emergência , Medicina Baseada em Evidências , Ossos Pélvicos/diagnóstico por imagem , Ferimentos não Penetrantes/diagnóstico por imagem , Acidentes de Trânsito , Adulto , Humanos , MEDLINE , Masculino , Ossos Pélvicos/lesões , Exame Físico , Radiografia , Sensibilidade e Especificidade , Estados UnidosAssuntos
Aborto Legal , Atitude do Pessoal de Saúde , Feminino , Humanos , Legislação Médica , Gravidez , África do SulRESUMO
The prevalence of tuberculosis in the household contacts of 67 smear-positive patients was compared with that in a 'non-contact' population. The prevalence of smear-positive cases among adult contacts was 3.03% as opposed to 1.35% in non-contacts; 27.9% and 11.43% respectively of children in the two groups had positive tuberculin tests (Heaf grade III or IV). The differences in children are statistically significant and could be used to justify the contention that active case-finding in underdeveloped areas should be limited to intensive contact-tracing. It is argued, however, that this may be an inherently conservative response that will not meet the needs of tuberculosis control. A plea is therefore made for a redistribution of resources in order to meet these needs.
