RESUMEN
In rats, erythromycin has been shown to induce microsomal enzymes and to promote its own transformation into a metabolite which forms an inactive complex with reduced cytochrome P-450. To determine whether similar effects also occur in humans, we studied hepatic microsomal enzymes from six untreated patients and six patients treated with erythromycin propionate, 2 g per os daily for 7 days. In the treated patients, NADPH-cytochrome c reductase activity was increased; the total cytochrome P-450 concn was also increased but part of the total cytochrome P-450 was complexed by an erythromycin metabolite. The concn of uncomplexed (active) cytochrome P-450 was not significantly modified and the activity of hexobarbital hydroxylase remained unchanged. We also measured the clearance of antipyrine in six other patients; this clearance was not significantly decreased when measured again on the seventh day of the erythromycin propionate treatment. We conclude that the administration of erythromycin propionate induces microsomal enzymes and results in the formation of an inactive cytochrome P-450-metabolite complex in humans. However, the concn of uncomplexed (active) cytochrome P-450 and tests for in vitro and in vivo drug metabolism were not significantly modified.
Asunto(s)
Eritromicina/farmacología , Microsomas Hepáticos/enzimología , Adulto , Anciano , Antipirina/metabolismo , Sistema Enzimático del Citocromo P-450/metabolismo , Femenino , Humanos , Masculino , Tasa de Depuración Metabólica/efectos de los fármacos , Microsomas Hepáticos/efectos de los fármacos , Persona de Mediana EdadRESUMEN
In rats, it has been shown that troleandomycin induces its own transformation into a metabolite forming an inactive complex with reduced cytochrome P-450. To determine whether similar effects occur in humans, we studied hepatic microsomes from 6 untreated patients and 6 patients treated with troleandomycin, 2 g per os daily for 7 days. In the treated patients, NADPH-cytochrome c reductase activity was increased by 48%; total cytochrome P-450 concentration was also increased, but 33% of total cytochrome P-450 was complexed by a troleandomycin metabolite. The cytochrome P-450 Fe(II)-metabolite complex exhibited properties identical to those of the inactive complex formed in rats: it exhibited a Soret peak at 456 nm, was unable to bind CO, and was destroyed by addition of 50 microM potassium ferricyanide. We also measured the clearance of antipyrine in 6 other subjects. This clearance was decreased by 45% when measured again on te seventh day of the troleandomycin treatment. We conclude that repeated administration of troleandomycin induces microsomal enzymes, produces an inactive cytochrome P-450 Fe(II)-metabolite complex, and decreases the clearance of antipyrine in humans.
Asunto(s)
Sistema Enzimático del Citocromo P-450/metabolismo , Compuestos Ferrosos/metabolismo , Hierro/metabolismo , Troleandomicina/farmacología , Adulto , Anciano , Antipirina/metabolismo , Inducción Enzimática , Femenino , Humanos , Hígado/metabolismo , Masculino , Tasa de Depuración Metabólica/efectos de los fármacos , Persona de Mediana Edad , Troleandomicina/metabolismoRESUMEN
Exsudative enteropathy was suspected in a 27-year-old man with lower limb edema, hypoprotidemia and hypoalbuminemia. Gastrointestinal mucosa, kidney, liver, and heart were normal. Laparoscopy showed diffuse small intestine lymphangiectasia. This diagnosis was confirmed by the microscopic examination of several biopsies obtained at laparotomy. Pathological examination of peritoneal, lymph nodes, and liver biopsies showed fibrous thickening of the peritoneum and fibrosis of the lymph nodes. Our patient has been followed for 16 years. Substantial improvement of clinical symptoms was obtained by following a special salt-free diet containing short-chain triglycerides. However biochemical abnormalities have persisted. Exsudative enteropathy due to intestinal lymphangiectasia may be observed in heart and liver diseases as well as in malignant affections of mesenteric lymph nodes. If these conditions are excluded, intestinal lymphangiectasia may be considered as a primitive lymph vessel malformation. The discovery of primitive intestinal lymphangiectasia in an adult cannot be attributed to congenital abnormalities alone. Fibrosis encountered in some cases suggests that an inflammatory process of unknown origin may trigger the onset of intestinal lymphangiectasia.
Asunto(s)
Cicatriz , Linfangiectasia Intestinal/complicaciones , Enteropatías Perdedoras de Proteínas/etiología , Adulto , Biopsia , Fibrosis , Humanos , Linfangiectasia Intestinal/diagnóstico , Linfangiectasia Intestinal/patología , Masculino , Enteropatías Perdedoras de Proteínas/diagnóstico , Enteropatías Perdedoras de Proteínas/patología , SíndromeAsunto(s)
Abdomen/efectos de la radiación , Absorción Intestinal/efectos de la radiación , Enfermedades Intestinales/etiología , Intestino Delgado/efectos de la radiación , Traumatismos por Radiación , Radioterapia/efectos adversos , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana EdadAsunto(s)
Amiloidosis/patología , Enfermedades del Yeyuno/patología , Adulto , Biopsia/métodos , Endoscopía , Humanos , Masculino , Persona de Mediana EdadAsunto(s)
Cirrosis Hepática Alcohólica/complicaciones , Neoplasias/etiología , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana EdadAsunto(s)
Catárticos/efectos adversos , Enfermedades del Colon/inducido químicamente , Colonoscopía , Hiperpigmentación/inducido químicamente , Enfermedades del Colon/diagnóstico , Femenino , Humanos , Hiperpigmentación/diagnóstico , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/patología , Persona de Mediana Edad , Remisión EspontáneaAsunto(s)
Proctitis/diagnóstico , Traumatismos por Radiación/diagnóstico , Radioterapia/efectos adversos , Corticoesteroides/uso terapéutico , Anciano , Endoscopía , Humanos , Coagulación con Láser , Fotocoagulación , Masculino , Mesalamina/uso terapéutico , Proctitis/etiología , Proctitis/terapia , Neoplasias de la Próstata/radioterapia , Traumatismos por Radiación/etiología , Traumatismos por Radiación/terapia , Sucralfato/uso terapéuticoAsunto(s)
Anemia/etiología , Úlcera Gástrica/complicaciones , Anciano , Femenino , Hemorragia Gastrointestinal/complicaciones , Hemorragia Gastrointestinal/tratamiento farmacológico , Hemorragia Gastrointestinal/etiología , Gastroscopía , Humanos , Omeprazol/uso terapéutico , Radiografía , Úlcera Gástrica/diagnóstico por imagen , Úlcera Gástrica/tratamiento farmacológicoAsunto(s)
Enfermedades Gastrointestinales , Antibacterianos/efectos adversos , Endoscopía , Enfermedades Gastrointestinales/diagnóstico , Enfermedades Gastrointestinales/fisiopatología , Enfermedades Gastrointestinales/terapia , Hormonas Gastrointestinales/fisiología , Humanos , Radioterapia/efectos adversosRESUMEN
Three hundred and eighty three patients with epigastric pain underwent radiological and endoscopic examination of the bulb of the duodenum. Clinical, radiological and endoscopic characteristics were compared in the 79 patients with a duodenal ulcer and in the 68 with duodenitis only. Pain and a past history of ulcer disease were of no use in differentiating duodenal ulcer from duodenitis only. Radiological deformity of the bulb appeared to be a sign of duodenitis and not of duodenal ulcer, in contrast to a crater and convergence of the folds. No endoscopic sign was of value in differentiating duodenitis only from duodenitis associated with an ulcer. Active duodenal ulcers could be differentiated from scarred duodenal ulcers only on the basis of endoscopic findings. Endoscope is the best means for the study and diagnosis of duodenal disease. On the basis of these results and data already published, an analysis was undertaken of the relationship between duodenal ulcer and duodenitis only, and it is felt that many arguments are in favour of a unitary hypothesis, duodenal ulcer and duodenitis possibly being two forms of duodenal ulcer disease.