RESUMEN
Interactions of 27 steroids, among them 17 derivatives such as ethers, sulfates and amidosulfonates derived from 17 beta- and 17 alpha-estradiol, from testosterone and alpha- and beta-dihydrotesosterone and from dehydroepiandrosterone with rat liver microsomal cytochromes P450 (P450) were investigated in vitro by assessing binding to P450 and effects on P450 mediated monooxygenase functions as measured by different model reactions: ethoxyresorufin O-deethylation (EROD), ethoxycoumarin O-deethylation (ECOD) and ethylmorphine N-demethylation (EMND). With the exception of 17 alpha-estradiol-3-dimethylamidosulfonate, estrone, its -3-methylether and -3-amidosulfonate and testosterone, all other steroids displayed type I or reverse type I binding to P450. All steroids inhibited EROD activity in micromolar concentrations. An additional strong inhibition of ECOD and EMND activities was only demonstrated for the androgens and progestins. Estriol, estrone and mestranol displayed less inhibitory actions on the model reactions than estradiol. No major differences in comparison to the parent compounds were noted with the other derivatives. The only exceptions were 17 beta-(8,9-dehydro-14 alpha,15 alpha-methylene)estradiol, which displayed stronger effects than estradiol, and dehydroepiandrosterone-3-sulfate, which was less effective than dehydroepiandrosterone. Possible antioxidant properties of the steroids were examined by the stimulated lipid peroxidation (LPO), H2O2 production, and lucigenin (LC) and luminol (LM) amplified chemiluminescence (CL) using rat liver microsomes. Additionally, the influence on rat whole blood chemiluminescence (WB-CL) was assessed. All the estrogens, but not their methylethers and amidosulfonates inhibited LPO in micromolar concentrations. The effects on the other oxidase model reactions or on WB-CL were less distinct. Only ethinylestradiol and 17 beta-(8,9-dehydro-14 alpha,15 alpha-methylene)estradiol displayed a strong inhibitory action on all model reactions. With the exception of dehydroepiandrosterone-3-sulfate, which in general had only weak effects, the androgen and progestin derivatives, in contrast, strongly decreased H2O2 formation and LM- and LC-CL, but were mostly ineffective on LPO and WB-CL.
Asunto(s)
Androstenodiona/análogos & derivados , Sistema Enzimático del Citocromo P-450/metabolismo , Deshidroepiandrosterona/análogos & derivados , Estradiol/análogos & derivados , Microsomas Hepáticos/efectos de los fármacos , 7-Alcoxicumarina O-Dealquilasa/metabolismo , Androstenodiona/metabolismo , Androstenodiona/farmacología , Animales , Citocromo P-450 CYP1A1/metabolismo , Deshidroepiandrosterona/metabolismo , Deshidroepiandrosterona/farmacología , Estradiol/metabolismo , Estradiol/farmacología , Etilmorfina-N-Demetilasa/metabolismo , Hígado/metabolismo , Mediciones Luminiscentes , Masculino , Microsomas Hepáticos/enzimología , Microsomas Hepáticos/metabolismo , Ratas , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismo , Testosterona/análogos & derivados , Testosterona/metabolismo , Testosterona/farmacologíaRESUMEN
OBJECTIVE: To report our incidence of local and systemic complications after needle-catheter jejunostomy. DESIGN: Retrospective analysis. SETTING: University hospital, Switzerland. RESULTS: 100 patients (70 men and 30 women; mean age 65 years, range 42-90) had needle-catheter jejunostomy for postoperative enteral feeding. 26 developed catheter-related and 18 nutrition-related complications. Most of the complications were minor (lumenal obstruction of the catheter or local cellulitis) and only 3 patients needed reoperation, 2 because the catheter broke with extravasation of the nutrition formula into the subcutaneous tissue, and the other because of a small bowel obstruction. There was no small bowel necrosis and no patient died as a direct result of the jejunostomy. Overall, 92 patients were fed enterally according to the protocol, and 8 required removal of the catheter. CONCLUSION: Needle-catheter jejunostomy gives a safe and effective access for postoperative enteral feeding. Minor technical complications are common and can be reduced by a meticulous insertion technique and careful postoperative management. Regular clinical surveillance may reduce the incidence of nutrition-related complications.
Asunto(s)
Nutrición Enteral/métodos , Yeyunostomía , Procedimientos Quirúrgicos Operativos , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Cuidados Posoperatorios , Estudios RetrospectivosRESUMEN
Nine natural and synthetic estrogens all derived from endogenous 17 beta-estradiol, were tested for their affinity to cytochrome P-450 (P450). Binding spectra of the estrogens with rat liver microsomal P450 and inhibition kinetics with characteristic monooxygenase model reactions (ethylmorphine N-demethylation, EN, and ethoxycoumarin O-deethylation, EO) were determined. In addition, uncoupling effects and/or free radical scavenger functions were analysed by NADPH/Fe2+ stimulated microsomal luminol- and lucigenin-amplified chemiluminescense (CL). 17 beta-Estradiol, 17 alpha-ethynylestradiol, and D-estradiol 3-methyl ether inhibited both monooxygenase reactions of cytochrome P-450, whereas L-estradiol 3-methyl ether inhibited EO only. 17 beta-Estradiol, 17 alpha-ethynylestradiol, and D-estradiol 3-methyl ether seem to act as free radical scavengers. From the results both structure activity relationships could be established and data on possible interferences with drug metabolism obtained. The enantiomers D- and L-estradiol 3-methyl ether differ in their effects on these systems.