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The effect of nicardipine, a calcium entry blocker, on paracetamol induced hepatic injury in mice
THE EFFECT OF NICARDIPINE, A CALCIUM ENTRY BLOCKER, INDUCED HEPATIC INJURY IN MICE.
67
ON PARACETAMOL
A Chitranukroh, P Cook and I James, Academic Department of Medicine, Royal Free Hospital, London, UK
Current treatment of paracetamol overdose is only effective when given before maximal hepatic gluthathione depletion occurs. We have investigated the use of nicardipine, a calcium entry blocker, in the late treatment of paracetamol overdose. METHOD: Female TO mice were injected i.p. with 500 mg/kg paracetamol. It was estimated that this dose would produce hepatic gluthathione depletion by lh after dosing. Nicardipine was given i.p. at I, 2, 3, or 4h post paracetamol. Plasma samples were obtained 8h post paracetamol and GPT concentrations determined. RESULTS: A single bolus of 50 mg/kg nicadipine at lh post paracetamol effectively reduced GPT concentrations, 1590+903'U/I as compared to 4185~1297 U/I for.controls. This dose of nicardipine was toxic when given at 2h post paracetamol. At a dose of 25 mg/kg, nicardipine was not toxic but it had no effect on GPT concentrations. A significant reduction was observed when nicardipine was given as a priming dose of 25 mg/kg at 2h post paracetamol followed by a booster dose of 5 mg/kg two hours later; 1415+483 U/I in tests and 3304+1299 in controls. When the booster dose was increased to 15 mg/kg,--nicardipine was effective--in reducing plasma concentrations even when the priming dose was given 4h post paracetamol} 1777+607 U/I in tests and 3910+1123 in controls. CONCLUSION: These results suggest the administration of nicardipine may be--an effective late treatment of paracetamol overdose.
68
OF ALL HBV MARKERS HBc Ag IN LIVER CORRELATES BEST WITH HISTOLOLOGICAL AGRESSIVITY : A PROSPECTIVE STUDY OF 899 CONSECUTIVE PATIENTS WITH CHRONIC LIVER DISEASE P. CHOSSEGROS, P. CHEVALLIER, P. ADELENE, M. SEPETJAN, R. BRETTE, C. TREPO, Laboratoire d'Hygi~ne Facult~ de M~decine Rockefeller 69008 LYON, Laboratoire d'Informatique M~dicale Avenue Lacassagne 69008 LYON, HOTEL DIEU 69002 LYON, Unit~ d'H~patologie HSpital des Charpennes 69603 VILLEURBANNE et Unit~ d'H~patologie INSERM U. 271 U.E.R. Alexis Carrel 69372 LYON
899 patients with chronic liver diseases have been hospitalized in our unit from 1980 to 1983 for liver biopsies. They have been tested for HBV serological markers (HBs and HBe Ags, anti HBs, anti HBc and anti HBe by RIA, Abbott) and HBc Ag in the liver (direct IF) : 109 were HBs and HBe Ags +, 9 1 H B s AE and anti HBe +, 155 anti HBs and anti HBc, 63 anti HBc, 481 without any HBV markers. Follow up biopsies were performed in 142 cases with a mean follow up of 22 months. Dependance of HBc Ag to HBV serologic markers and liver histological agressivity have been studied by regression analysis. i. HBc AE was highly correlated(p < 0,OO1) to HBV serological markers (in decreasing order : HBs and HBe Ag, HBs and anti HBe, anti HBs and anti HBc, anti HBc, no marker) and within each group to agressivity, 2. In most patients HBc AE persisted after HBe antigen~antibody seroconversion, 3. There was a global trend to clear HBc AE with time and HBe and HBs seroconversion, 4. In HBs Ag negative patients parallel fluctuations of anti HBs and anti HBc and HBc Ag were observed. This may suggest transient recurrence bouts of HBV replication in these cases.
$212
67
ON PARACETAMOL
A Chitranukroh, P Cook and I James, Academic Department of Medicine, Royal Free Hospital, London, UK
Current treatment of paracetamol overdose is only effective when given before maximal hepatic gluthathione depletion occurs. We have investigated the use of nicardipine, a calcium entry blocker, in the late treatment of paracetamol overdose. METHOD: Female TO mice were injected i.p. with 500 mg/kg paracetamol. It was estimated that this dose would produce hepatic gluthathione depletion by lh after dosing. Nicardipine was given i.p. at I, 2, 3, or 4h post paracetamol. Plasma samples were obtained 8h post paracetamol and GPT concentrations determined. RESULTS: A single bolus of 50 mg/kg nicadipine at lh post paracetamol effectively reduced GPT concentrations, 1590+903'U/I as compared to 4185~1297 U/I for.controls. This dose of nicardipine was toxic when given at 2h post paracetamol. At a dose of 25 mg/kg, nicardipine was not toxic but it had no effect on GPT concentrations. A significant reduction was observed when nicardipine was given as a priming dose of 25 mg/kg at 2h post paracetamol followed by a booster dose of 5 mg/kg two hours later; 1415+483 U/I in tests and 3304+1299 in controls. When the booster dose was increased to 15 mg/kg,--nicardipine was effective--in reducing plasma concentrations even when the priming dose was given 4h post paracetamol} 1777+607 U/I in tests and 3910+1123 in controls. CONCLUSION: These results suggest the administration of nicardipine may be--an effective late treatment of paracetamol overdose.
68
OF ALL HBV MARKERS HBc Ag IN LIVER CORRELATES BEST WITH HISTOLOLOGICAL AGRESSIVITY : A PROSPECTIVE STUDY OF 899 CONSECUTIVE PATIENTS WITH CHRONIC LIVER DISEASE P. CHOSSEGROS, P. CHEVALLIER, P. ADELENE, M. SEPETJAN, R. BRETTE, C. TREPO, Laboratoire d'Hygi~ne Facult~ de M~decine Rockefeller 69008 LYON, Laboratoire d'Informatique M~dicale Avenue Lacassagne 69008 LYON, HOTEL DIEU 69002 LYON, Unit~ d'H~patologie HSpital des Charpennes 69603 VILLEURBANNE et Unit~ d'H~patologie INSERM U. 271 U.E.R. Alexis Carrel 69372 LYON
899 patients with chronic liver diseases have been hospitalized in our unit from 1980 to 1983 for liver biopsies. They have been tested for HBV serological markers (HBs and HBe Ags, anti HBs, anti HBc and anti HBe by RIA, Abbott) and HBc Ag in the liver (direct IF) : 109 were HBs and HBe Ags +, 9 1 H B s AE and anti HBe +, 155 anti HBs and anti HBc, 63 anti HBc, 481 without any HBV markers. Follow up biopsies were performed in 142 cases with a mean follow up of 22 months. Dependance of HBc Ag to HBV serologic markers and liver histological agressivity have been studied by regression analysis. i. HBc AE was highly correlated(p < 0,OO1) to HBV serological markers (in decreasing order : HBs and HBe Ag, HBs and anti HBe, anti HBs and anti HBc, anti HBc, no marker) and within each group to agressivity, 2. In most patients HBc AE persisted after HBe antigen~antibody seroconversion, 3. There was a global trend to clear HBc AE with time and HBe and HBs seroconversion, 4. In HBs Ag negative patients parallel fluctuations of anti HBs and anti HBc and HBc Ag were observed. This may suggest transient recurrence bouts of HBV replication in these cases.
$212