ABSTRACT:Liver grafts discarded for transplantation because of macrosteatosis can constitute a valuable source of human hepatocytes for in vitro metabolic and pharmacotoxicological studies or for therapeutic applications. A condition for using hepatocyte suspensions for these purposes is the preservation of their metabolic competence and, particularly, drug-metabolizing enzymes. A reduction in microsomal cytochrome P450 (P450) activities was observed in fatty livers (>40% steatosis) with respect to normal tissue. Similarly, decreased levels of 7-ethoxycoumarin O-deethylation and testosterone metabolism were observed in human hepatocyte cultures prepared from steatotic liver tissue. To clarify the potential impact of lipid accumulation on human hepatic P450 enzymes, we have used an in vitro model of "cellular steatosis" by incubation of cultured hepatocytes with increasing concentrations (0.25-3 mM) of long-chain free fatty acids (FFA). A dose-dependent accumulation of lipids in the cytosol is induced by FFA mixture. Hepatocytes exposed to 1 mM FFA for 14 h showed lower activity values of CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2D6, CYP2E1, and CYP3A4 enzymes than nontreated hepatocytes (about 45-65% reduction). This treatment also produced significant decreases in CYP1A2, CYP2A6, CYP2C9, CYP2D6, CYP2E1, and CYP3A4 mRNA to about 55 to 75% of mRNA levels in control cells. Our results suggest that although human hepatocytes isolated from steatotic liver show reduced P450 activities, they are metabolically competent and can be used for drug metabolism studies.
Treatment of acute cholecystitis is still under debate. The aim of this study was to evaluate the efficacy of early laparoscopic cholecystectomy (ELC) in comparison with conservative treatment followed by delayed laparoscopic cholecystectomy (DLC) in the management of acute cholecystitis. This prospective comparative study involved two groups of patients presenting with acute cholecystitis within 72 hours of the onset of symptoms. ELC was performed in 82 consecutive patients, whereas DLC was performed in 87 patients who previously underwent medical treatment. Surgical variables, hospital stay, and postoperative morbidity were evaluated in both groups. Time of surgery and conversion rate were lower in the ELC group. Postoperative morbidity was similar in both groups. Overall hospital stay was shorter in the ELC group. ELC within 72 hours of the onset of acute cholecystitis is a safe procedure with better results than DLC in terms of surgical timing, conversion rate, and hospital stay.
The aim of this study was to compare the rate and characteristics of postoperative neuralgia after 2 methods of inguinal hernia repairs. Between July 1997 and December 2000, 400 inguinal hernia repairs were performed and followed up in a prospective trial about postoperative nerve irritations: 200 patients with laparoscopic transabdominal hernioplasty (TAPP group), and 200 patients with tension-free hernia repair using Lichtenstein's technique (LICH group). We applied a clinic protocol of data about pain location, neuralgia characteristics, and period of time until the patient was completely pain free. The global rate of nerve irritation in the study was 7.6% (30 cases); in the TAPP group, it was 5.5% (n = 11) and in the LICH group, it was 9.5% (n = 19) (P = .03). The genitofemoral nerve was affected with particularly high frequency (4.3% in the global series); although in laparoscopic repair, the lateral cutaneous nerve of the thigh (LFC) was most damaged (3.3% in TAPP group). We observed more persistent symptoms in LICH group, while in TAPP group the most of cases was transitory (P = .08). There were no significant differences in pain characteristics according to clinical type of hernia. The TAPP method causes less rate of postoperative inguinal neuralgia than Lichtenstein repair, emphasizing more persistent discomfort in anterior approach than laparoscopic repair.
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