RESUMEN
The effect of treatment with the alpha 1-specific adrenoceptor blocker, Doxazosin, on lipid parameters was studied in male Golden hamsters fed a cholesterol-enriched diet. Within 1 week the Doxazosin-treated animals had a lower plasma (-12%) and hepatic (-30%) cholesterol content than the cholesterol-fed controls. De novo cholesterol synthesis in the liver was lowered by 39% in the Doxazosin-treated animals. These data indicate that the reported beneficial effect of alpha 1-blockade on plasma cholesterol levels may be due to lowering of the hepatic cholesterol synthesis.
Asunto(s)
Antagonistas Adrenérgicos alfa/farmacología , Colesterol/biosíntesis , Hipercolesterolemia/metabolismo , Hígado/metabolismo , Prazosina/análogos & derivados , Acetatos/metabolismo , Animales , Colesterol/sangre , Colesterol en la Dieta , Cricetinae , Doxazosina , Lipoproteínas/sangre , Hígado/efectos de los fármacos , Masculino , Mesocricetus , Prazosina/farmacología , Valores de Referencia , Triglicéridos/sangreRESUMEN
The superoxide (O2-) production of stimulated polymorphonuclear leucocytes is increased in patients with rheumatoid arthritis and osteoarthritis compared with controls. Treatment of these different groups with pharmacological amounts of the non-steroidal anti-inflammatory drug piroxicam in vivo resulted in a decrease of about 25% in O2- secretion by isolated granulocytes. In vitro experiments showed that piroxicam inhibits O2- production of granulocytes by interference with the stimulation of the NADPH-oxidase. Piroxicam caused diminished O2- production of membrane fragments if it was present during the stimulation of the NADPH-oxidase of the intact cells. During the actual O2- production of the stimulated membrane fragments piroxicam had no effect. It is concluded that piroxicam is able to inhibit granulocyte O2- production by blocking the activation of NADPH-oxidase, which results in diminished tissue destruction by oxygen free radicals in inflammatory diseases.
Asunto(s)
Artritis/sangre , NADH NADPH Oxidorreductasas/sangre , Neutrófilos/metabolismo , Superóxidos/metabolismo , Tiazinas/farmacología , Artritis Reumatoide/sangre , Humanos , NADPH Oxidasas , Neutrófilos/efectos de los fármacos , Osteoartritis/sangre , Piroxicam , Superóxidos/antagonistas & inhibidores , Acetato de Tetradecanoilforbol/farmacologíaRESUMEN
T-lymphocytes are involved in the inflammatory response that occurs in affected joints of patients with rheumatoid arthritis (RA). Some second-line disease modifying anti-rheumatic drugs used in the treatment of patients with RA are known to block T-cell activation. The present study assessed whether tenidap, an investigational anti-rheumatic drug, affects in vitro T-cell responses such as proliferation and cytokine production. It was found that tenidap, in contrast to several nonsteroidal anti-inflammatory drugs, inhibits anti-CD3 or IL-2 driven proliferative responses of cloned human T-cells. Furthermore, tenidap was found to inhibit IFN-gamma production as well as the induction of mRNA encoding IFN-gamma or TNF-alpha. The results indicate that tenidap may exert at least part of its anti-inflammatory activity via inhibition of T-cell function and cytokine production.