[Liver urea and glucose production in patients with alcohol-induced cirrhosis]. / Harnstoff- und Glucoseproduktion der Leber bei Patienten mit alkoholinduzierter Zirrhose.

OBJECTIVE: To use stable isotopes for the analysis of hepatic metabolic pathways (urea synthesis, glucose production), comparing them in alcoholic and normal liver, in order to obtain specific and quantitative information on metabolic functions of the liver. PATIENTS AND METHODS: Urea and glucose production as well as alanine metabolism in the liver were studied by means of stable isotopes in 7 males with alcoholic liver cirrhosis (mean age 46 +/- 4 years; height 173 +/- 5 cm; weight 73 +/- 3 kg) and 7 healthy male volunteers as controls (age 26 +/- 3 years; height 180 +/- 5 cm; weight 75 +/- 6 kg). The plasma concentrations of adrenaline, noradrenaline, insulin, glucagon and amino-acids were also measured. RESULTS: Urea synthesis was lower in the cirrhosis patients than in the controls (3.3 +/- 2.2 mumol/kg.min vs 4.8 +/- 0.9 mumol/kg.min, P < 0.05). But there were no differences in glucose production, alanine metabolism and adrenaline concentrations. The concentrations of glutamine, phenylalanine, tyrosine, insulin, glucagon and noradrenaline were significantly raised in the cirrhotic patients, those of valine and leucine significantly lower. CONCLUSIONS: Contrary to hepatic glucose production, which was within normal limits, urea synthesis was reduced by 30% in the cirrhotic patients. The use of stable isotopes provided detailed information on specific metabolic processes in cirrhotic livers.

Glycerol metabolism in patients with alcohol-induced liver cirrhosis.

The clearance rate of glycerol has been found to be impaired in alcoholic liver disease. However it remains unclear, if this can be ascribed to a defect of hepatic gluconeogenesis. Thus, the purpose of this work was to investigate glycerol clearance and hepatic glucose production in patients with liver cirrhosis. 13 patients with alcohol-induced Child B cirrhosis and 8 healthy volunteers were studied. Rates of appearance (R(a)) of glycerol, glucose and alanine were determined using stable isotope techniques. In addition indocyanine green clearance (ICGC) and plasma substrate concentrations were measured. Clearance rates were calculated as R(a) divided by the corresponding substrate concentration. R(a) of glycerol in patients was not different from controls, but glycerol clearance was significantly reduced (29 +/- 3 vs. 41 +/- 4 ml/kg/min). No differences in R(a) of glucose and alanine and corresponding plasma concentrations were observed. ICGC in patients was about 35% lower than reference values. Diminished glycerol clearance in patients with liver cirrhosis was not due to impaired hepatic gluconeogenesis. Since glycerol is almost completely extracted by the liver decreased glycerol clearance possibly simply reflected compromised liver perfusion as seen by reduced ICGC.

Liposome mediated in vivo gene transfer into different tissues of the gastrointestinal tract.

The possibility to transfer and express genetic material in mammalian cells represents a new approach to the treatment of genetic and acquired disorders. So far, most studies use in vitro techniques to introduce foreign DNA into cultured cells, followed by reintroduction of these genetically altered cells into living organisms. In the present study we demonstrate that the LacZ marker gene can be selectively delivered, by in vivo techniques, to various locations of the gastrointestinal tract. Genetic material was targeted to the stomach, the colon, the liver and the pancreas using cationic liposomes. For transfer into the stomach and colon an intraluminal application, in the liver a portal access and in the pancreas an intraductal infusion was chosen. 48 hours after administration, the LacZ gene product beta-galactosidase could be localized in these tissues by cytochemistry. These experiments suggest a new approach to study gastrointestinal physiology and may offer novel aspects for the treatment of gastrointestinal diseases.

Correlation between density of beta 2-adrenergic receptors on peripheral blood mononuclear cells and serum levels of soluble interleukin-2 receptors in patients with chronic inflammatory diseases.

In order to study the influence of the autonomic nervous system on the immune response, we evaluated the density and the equilibrium dissociation constants (KD) of beta 2-adrenergic receptors (beta 2R) on peripheral blood mononuclear cells (PBMC) in patients with rheumatoid arthritis (RA), Crohn's disease (CD), and in controls. Results were correlated with the serum concentrations of soluble interleukin-2 receptors (sIL-2R) as a marker for T-cell activation in vivo. The density of beta 2R was significantly decreased in patients with RA (P < 0.05) and CD (P < 0.05) as compared with controls. The number of beta 2R in patients with RA was significantly lower than in CD patients (P < 0.05). KD values of beta 2R were markedly but not significantly decreased in both patient groups as compared with control values. Serum concentrations of sIL-2R were significantly elevated in RA patients as compared with those in CD patients (P < 0.05) and controls (P < 0.05), while there was no difference between the latter two groups. In patients with RA, a significant negative correlation between beta 2R density and serum IL-2R levels (r = -0.66, P < 0.02) was observed. These results demonstrate the close correlation between the modulation of beta 2R on PBMC and the activation of the immune response. However, the role of beta 2R stimulation in the pathogenesis of immunologically mediated diseases remains to be clarified.