RESUMO
To examine directly the hepatic and renal toxicity of 7-hydroxymethotrexate (7-OH-MTX) without interference of the parent compound methotrexate (MTX), we purified and gave 100 mg/kg 7-OH-MTX to rats, a dose resulting in serum levels of 7-OH-MTX comparable with those achieved in the clinic after the administration of high-dose MTX (HD-MTX). After only 5 h, the 7-OH-MTX-treated rats demonstrated 2.6-fold increases in serum creatinine values and 2-fold elevations in serum aspartate aminotransferase (ASAT) levels as compared with the controls. Morphologic evidence of toxicity, however, was apparent only in the kidneys. Intraluminal cellular debris containing membranous material and deteriorated organelles was seen, but no precipitate of the delivered drug. The peak serum concentration of 7-OH was up to 939 microM, and concentrations of 7-OH-MTX declined triphasically, showing a t1/2 alpha value of 2.45 min, a t1/2 beta value of 30.5 min, and a terminal half-life (t1/2 gamma) of 240 min. The total clearance value was 14.5 ml min-1 kg, and the postdistributional volume of distribution (V beta) was 5070 ml/kg. Our results may indicate a direct toxic effect of 7-OH-MTX on kidney and liver cells.
Assuntos
Antagonistas do Ácido Fólico/toxicidade , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Metotrexato/análogos & derivados , Animais , Cromatografia Líquida de Alta Pressão , Relação Dose-Resposta a Droga , Antagonistas do Ácido Fólico/administração & dosagem , Antagonistas do Ácido Fólico/análise , Antagonistas do Ácido Fólico/isolamento & purificação , Antagonistas do Ácido Fólico/farmacocinética , Humanos , Rim/metabolismo , Rim/patologia , Fígado/metabolismo , Fígado/patologia , Masculino , Metotrexato/administração & dosagem , Metotrexato/análise , Metotrexato/isolamento & purificação , Metotrexato/farmacocinética , Metotrexato/toxicidade , Ratos , Ratos Wistar , Fatores de Tempo , Distribuição TecidualRESUMO
Two patients with lipomatosis and two patients with true lipoma of the ileocecal valve are described. The symptomatology, radiological appearances, pathological findings and treatment are discussed. True lipomas of the ileocecal valve should be differentiated from the more commonly occurring lipomatosis or lipohyperplasia. The rare true lipomas have a demarcating capsule around the fatty tissue and are confined to only one of the ileocecal lips. The lipomatosis, on the other hand, is characterized by a diffus fatty deposition in the submucosa of the valve with no encapsulation. Lipomatosis as well as true lipomas may appear as rounded, smoothly outlined and sharply demarcated masses on barium enema examination. Occasionally, these filling defects may present problems of differential diagnosis with respect to malignant involvement of the ileocecal region. A correct preoperative diagnosis, however, is important to prevent unnecessary or too radical surgical treatment.