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| Id: | 18936
| | Autor: | Vescovo, Giorgio; Ravara, Barbara; Angelini, Annalisa; Sandri, Marco; Carraro, Ugo; Ceconi, Claudio; Dalla Libera, Luciano
| | Título: | Effect of thalidomide on the skeletal muscle in experimental heart failure
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| | Fonte: | s.l; s.n; 2002. 6 p. ilus, tab.
| | Resumo: | BACKGROUND: Tumour Necrosis Factor alpha (TNFalpha) has been shown to contribute to heart failure (CHF) progression. AIMS: We have tried to antagonise the detrimental effects of TNFalpha on skeletal muscle apoptosis, by using thalidomide, a drug that inhibits its biosynthesis. METHODS: CHF was induced in 20 rats by injecting monocrotaline, which determines right ventricle (RV) failure. After 2 weeks, when CHF developed, 12 rats were treated with thalidomide 3.5.mg/kg per day for 2 weeks. Eight had saline and served as CHF controls. RESULTS: Thalidomide failed to decrease TNFalpha and its second messenger sphingosine (SPH), but was able to prevent the shift toward the fast myosin heavy chains. In the Tibialis Anterior muscle of the thalidomide group, the degree of atrophy, the number of apoptotic nuclei and the levels of caspases, were similar to those of the CHF controls. CONCLUSIONS: Thalidomide, at the doses used in this study, which are the same employed for the treatment of tubercolosis, leprosy, AIDS and cancer in humans, did not lower either TNFalpha or SPH and only marginally influenced the apoptosis-induced muscle atrophy. Since other TNFalpha blockers are under investigation for improving the clinical status of patients with CHF, the present data could be relevant in the design of randomised clinical trials in humans. (AU).
| | Descritores: | APOPTOSE/ef drogas
INSUFICIÊNCIA CARDIACA CONGESTIVA/ind quim
INSUFICIÊNCIA CARDIACA CONGESTIVA/patol
MONOCROTALINA/tox
MUSCULO ESQUELETICO/ef drogas
MUSCULO ESQUELETICO/patol
ATROFIA MUSCULAR/ind quim
ATROFIA MUSCULAR/patol
CADEIAS PESADAS DE MIOSINA/metab
RATOS SPRAGUE-DAWLEY
ESFINGOSINA/antag
ESFINGOSINA/metab
TALIDOMIDA/farmacol
FATOR DE NECROSE TUMORAL/antag
FATOR DE NECROSE TUMORAL/metab
DISFUNCAO VENTRICULAR DIREITA/ind quim
DISFUNCAO VENTRICULAR DIREITA/patol
| | Limites: | ANIMAL
RATOS
| | Meio Eletrônico: | - .
| | Localização: | BR191.1; 09104/s |
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