0000000000088327
AUTHOR
Ramón Trullenque
Drug biotransformation by human hepatocytes. In vitro/in vivo metabolism by cells from the same donor.
Abstract Background/Aims : Cultured human hepatocytes are considered a close model to human liver. However, the fact that hepatocytes are placed in a microenvironment that differs from that of the cell in the liver raises the question: to what extent does drug metabolism in vitro reflect that of the liver in vivo? This issue was examined by investigating the in vitro and in vivo metabolism of aceclofenac, an analgesic/anti-inflammatory drug. Methods : Hepatocytes isolated from programmed liver biopsies were incubated with aceclofenac, and the metabolites formed were investigated by HPLC. During the course of clinical recovery, patients were given the drug, and the metabolites, largely prese…
Intracellular glutathione in human hepatocytes incubated with S-adenosyl-L-methionine and GSH-depleting drugs
Abstract The present study was undertaken to investigate (a) whether S- adenosyl- L -methionine (SAMe) added to culture medium can increase intracellular glutathione (GSH) levels in human hepatocytes and (b) whether SAMe can prevent the GSH depletion found in human hepatocytes incubated with GSH-depleting drugs (paracetamol, opiates, ethanol). Incubation of hepatocytes with increasing concentrations of SAMe resulted in a dose-dependent elevation of intracellular GSH content, which reached its maximum (35% increase) at 30 μM after 20 h. SAMe, as the only sulfur source in the medium, was efficient in repleting GSH-depleted hepatocytes following treatment with diethyl maleate. Incubation of hu…
Genetic alterations and oxidative metabolism in sporadic colorectal tumors from a Spanish community
Deletions of loci on chromosomes 5q, 17p, 18q, and 22q, together with the incidence of p53 mutations and amplification of the double minute-2 gene were investigated in the sporadic colorectal tumors of 44 patients from a Spanish community. Chromosome deletions were analyzed by means of loss of heterozygosity analysis using a restriction fragment length polymorphism assay. Allelic losses were also detected by polymerase chain reaction (PCR)-single-stranded conformation polymorphism (SSCP) analysis of a polymorphic site in intron 2 of the p53 gene. The percentages of genetic deletions on the screened chromosomes were 39.3% (5q), 58.3% (17p), 40.9% (18q), and 40% (22q). Mutations in p53 exons …
Influencia de la octreótida en la anastomosis tras obstrucción cólica experimental
Resumen Introduccion Se valora el efecto de la octreotida sobre la oclusion experimental del colon y posterior anastomosis. Material y metodo Se realiza una oclusion de colon en dos grupos de ratas Wistar, a uno de los cuales se le administra octreotida. A las 48 h se relaparotomizo a los animales, se valoraron el grado de oclusion y el contenido intestinal y se reseco un fragmento intestinal para estudio histologico, confeccionando una anastomosis termino-terminal. A los 7 dias se reintervino a los animales y se valoraron las complicaciones, determinando la presion de rotura de la anastomosis, la cantidad de colageno que contiene y su histologia. Resultados El grupo tratado con octreotida …