Evidence for a deficiency of interferon response in mononuclear cells from hepatitis C viremic patients.

Background/aims: The pathophysiology of chronic hepatitis C and the mechanisms of resistance to interferon alpha are poorly understood. The aim of this work was to assess the influence of HCV infection and the viral genotype on lymphocyte production of 2',5' oligo-adenylate synthetase activity and monocyte production of TNF alpha and IL1 beta.

Methods: Mononuclear cells from 50 consecutive patients were studied after 6 months of interferon treatment.

Bile acid inhibition of interferon activity in human lymphocytes: no evidence of oxidative stress.

Cholestasis and bile acids are two factors involved in resistance to interferon therapy in patients with chronic hepatitis C. As bile acids inhibit the biological activity of this cytokine in vitro and are capable of generating oxidative stress in hepatocytes, we investigated the potential involvement of such a mechanism in human lymphocytes. Thus, we evaluated (a) the effects of bile acids (0-200 mumol L-1) on lymphocyte reduced glutathione content and malondialdehyde production and (b) the ability of antioxidants to prevent the inhibitory effect of chenodeoxycholic acid on interferon-induced lymphocyte 2',5'-oligoadenylate synthetase activity, an index of the biological activity of interferon.

Effect of cholestasis and bile acids on interferon-induced 2',5'-adenylate synthetase and NK cell activities.

Background/aims: The mechanisms involved in resistance to interferon alfa in patients with chronic hepatitis C are unclear. Both cirrhosis and cholestasis have been shown to be predictive of resistance. The aim of this study was to evaluate the influence of cholestasis and bile acids on 2',5'-oligoadenylate synthetase and natural killer activities, which are both involved in the antiviral activity of interferon.

Choledocho-ureteral anastomosis in the rat. A new experimental model of long-term, total, internal bile diversion.

Choledocho-ureteral anastomosis is a new experimental model of total bile diversion in the rat. The anastomosis is carried out using a polyethylene tutor drain and requires neither an external drain nor restraint of the animal. After 14 days of diversion, bile flow fell by 53% and there were no biological signs of cholestasis.

Differential effects of chenodeoxycholic and ursodeoxycholic acids on interleukin 1, interleukin 6 and tumor necrosis factor-alpha production by monocytes.

Cell-mediated immunity and macrophage activity, especially that of Kupffer cells, are impaired during cholestasis. Some evidence exists that bile acids play a role in these immune defects. The purpose of this study was to evaluate the effects of individual bile acids on immunity and to determine whether monocytes could be a target.

Effect of bile acids on ischemia-reperfusion liver injury.

We investigated whether stimulation of bile flow by taurocholic acid (TCA), ursodeoxycholic acid (UDCA) or its taurine conjugate (TUDCA) could protect the liver from ischemia-reperfusion injury. The isolated perfused rat liver model was used. In livers perfused without bile acids (n = 8), 60 min of ischemia induced a significant reduction in bile flow and in portal flow, together with a marked increase in LDH, AST and uric acid release in the perfusate.

Lipid and lipoprotein synthesis in isolated and cultured hepatocytes from lean and obese Zucker rats.

Hepatocytes were isolated by EDTA perfusion of livers from lean (Fa/-) and obese (fa/fa) Zucker rats. Triacylglycerol (TG) and sn-glycerol 3-phosphate were increased in fa/fa hepatocytes, but free fatty acids, cholesterol and phospholipid concentrations were similar in both groups. In spite of an identical fatty acid uptake rate, glycerolipid synthesis was higher in obese compared to lean rat hepatocytes, and this difference remained for at least 2-3 days of culture.

Effects of ciprofibrate and fenofibrate on liver lipids and lipoprotein synthesis in normo- and hyperlipidemic rats.

The plasma lipoprotein and liver lipid composition, and the lipid, cholesterol and apolipoprotein synthesis have been studied in normal and diet-induced hyperlipidemic rats, receiving ciprofibrate (2.5 mg/kg body weight) or fenofibrate (50 mg/kg b.w.

Fecal bile acid excretion and liver cholesterol synthesis after sucralfate and cholestyramine administration in the rat.

The relative ability of the resin cholestyramine and sucralfate (disucrose octasulfate) to bind bile acids in the gastro intestinal tract and increase fecal bile acid excretion has been studied in normal rats under standard diet. Plasma and liver cholesterol concentrations and in vitro cholesterol synthesis from 14C-acetate by liver slices, have been determined before and after one and three weeks of drug administration (0.5 or 1.

Evidence for the lack of classical secretory phospholipase A2 in guinea-pig pancreas.

Several lipolytic enzymes from guinea-pig pancreas have been determined in a soluble extract and in a purified zymogen granule fractions. The positional specificity of phospholipolytic enzymes was detected using phospholipids bearing various radioactive labels. It is shown that guinea-pig pancreatic extracts are able to release both fatty acids from phosphatidylcholine, but with more efficiency towards the fatty acid occupying the 1-position of sn-glycerol.

Purification of two lipases with high phospholipase A1 activity from guinea-pig pancreas.

1. Two cationic lipases (Ia and Ib) were purified from homogenates of fresh guinea-pig pancreas by ion-exchange chromatography on DEAE-Sepharose and CM-Sepharose (twice for the latter) followed by gel filtration on Sephadex G-100. 2.

[Contribution to the definition of reference values in the hare: hematology -- blood biochemistry (author's transl)].

The following hematological and biochemical reference values were determined in 150 hares: hematocrit, blood count and leucocytic formula, Na, K, Cl, P, Ca, Mg, Cu, Zn, glucose, urea, creatinine, uric acid, cholesterol, bilirubin, triglycerides, proteins and fractions, PAL, PAC, TGO, TGP, amylase, GGT, LDH. Once the effects of sex and age have been established, the references defined here will be used as a base for interpreting disturbances linked either to pathology or nutrition.

Tissue and blood distribution of gamma-glutamyl transferase in the lamb and in the ewe.

Gamma-glutamyl transferase distribution was studied in 10 ewes and 10 lambs; in both groups kidney was the most active organ, followed by pancreas, liver and lungs. In kidney and liver, GGT was bound mainly to cellular structures. Blood GGT activity of 48 lambs was 44 +/- 11 iu/litre and 33 +/- 7 iu/litre of 45 ewes.

Blood and tissue distribution of gamma glutamyl transferase in calves.

In five male and five female calves, we studied the tissue distribution of gamma-glutamyl transferase. The enzyme was mainly in kidney, pancreas, and liver; there was no sex-related difference. The relative hepatic and pancreatic specificity of the enzyme indicated that the measure of its activity in serum could be a test of hepatic or pancreatic damage in the calf.

[Phospholipase of rat intestine: mode of action].

Phospholipase activities of rat intestinal mucosa homogenate have been determined from lysophosphatidylcholines [14C] and phosphatidylcholines [-3H-14C]. In the presence of phosphatidylcholines, at pH 6.5, the homogenate has a phospholipase B activity.

[Specificity of action of phospholipases of rat intestinal mucosa].

The total homogenate of rat intestine is devoid of C or D phospholipase activity. At pH 6,5 in the presence of phosphatidylcholines, it exhibits a B phospholipase activity and in the presence of exogen lysophosphatidylcholines an A1 lysophospholipase activity. At pH 8,5 the intestinal mucous membrane of a rat shows an isolated A2 phospholipase activity.