G. Schäfer

Impact of fish oil enriched total parenteral nutrition on DNA synthesis, cytokine release and receptor expression by lymphocytes in the postoperative period

A prospective randomized study on sixty patients was conducted to investigate the effects of a fish oil containing total parenteral nutrition (TPN) regimen in the postoperative period on lymphocyte subset distribution, proliferation, cytokine production and interleukin-2 receptor (IL-2R) expression. Patients who underwent large bowel surgery were divided into three groups. Nineteen patients received TPN with fish oil (0.2 g/kg body weight per day) plus soybean oil (1.0 g/kg per day), twenty patients received soybean oil (1.2 g/kg per day), and twenty-one patients who were on a fat-free regimen served as the control group. Natural killer (NK) cells, total, B-, T-, T4-, T8-lymphocytes, proliferation of lymphocytes, in vitro production of IL-2, IFN-gamma, TNF-alpha, and IL-2R expression were measured. Fish oil administration did not affect subset distribution and proliferation of lymphocytes. Production of interleukin-2 (IL-2), interferon gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) was augmented, and IL-2R expression less enhanced compared with the controls. It is concluded that administration of 0.2 g/kg per day fish oil after a moderate surgical stress is not immunosuppressive, but enhances the production of IFN-gamma, TNF-alpha and possibly IL-2.

Simvastatin in primary biliary cirrhosis: effects on serum lipids and distinct disease markers

BACKGROUND/AIMS Primary biliary cirrhosis (PBC) is an autoimmune disease of the liver with inflammation of small and middle-sized bile ducts. Serum lipids are frequently elevated, but the use of a lipid lowering drug therapy in PBC is still a matter of debate. Application of an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase in hypercholesterolemic PBC patients was therefore the subject of the present study. METHODS Six female patients (aged 46.5 (32-61) years; median (range)) were treated with the HMG-CoA reductase inhibitor simvastatin (5 or 20 mg/day). Levels of serum total cholesterol, low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol were determined prior to and after 2 months of treatment. Concentrations of serum markers of cholestasis, antimitochondrial antibodies (AMA), and immunoglobulins A, G and M were also assessed. RESULTS Simvastatin significantly (P<0.05) reduced serum levels of total cholesterol, LDL cholesterol, alkaline phosphatase, -glutamyltransferase, and immunoglobulin M (by 19, 26, 12, 37 and 14%, respectively). CONCLUSIONS The lipid lowering potency of the HMG-CoA reductase inhibitor simvastatin was confirmed in hypercholesterolemic patients with PBC. The drug might also prove useful as modulator of cholestasis and of immune response in this disease.

Conversion of somatostatin-28 to somatostatin-14 during maturation of epithelial cells in the porcine jejunum

Fractions of isolated epithelial cells were harvested from a segment of porcine jejunum by ten successive incubations with a chelating buffer. The cell fractions showed a progressive decrease in the activity of the brush-border enzymes, alkaline phosphatase and sucrase, with increasing incubation number but a progressive increase in the ability to incorporate labelled thymidine into DNA. Fractions enriched in cells from the crypt region (fractions 9 and 10) contained higher concentrations per mg protein of somatostatin-like immunoreactivity (1.8-fold), glucagon-like immunoreactivity (5.3-fold) and serotonin (3.0-fold) than fractions enriched in cells from the villus tip (fractions 1 and 2). Analysis of extracts of the fractions by gel filtration/radioimmunoassay showed that somatostatin-28 represented the predominant molecular form of somatostatin-like immunoreactivity in all cell fractions but the relative proportion of somatostatin-14 (and related metabolites) to somatostatin-28 was significantly higher (P less than 0.05) in fractions enriched in villus cells (fraction 1 and 2) than in fractions enriched in crypt cells (fractions 5-10). This result suggests that metabolism of somatostatin-28 to somatostatin-14 takes place during migration of the D cell from the crypt base to the villus tip. Heterogeneity in the somatostatin-14 region of the chromatograms indicates that the peptide may be further metabolized by the action of aminopeptidases.

Einbau von15N-Glyzin in VLDL und LDL: In-vivo-Synthese von Apolipoprotein B beim Menschen postabsorptiv und im Fastenzustand

SummaryIn vivo synthesis of apolipoprotein B 100 (ApoB) was recently determined in man using stable isotopes. With this procedure we analyzed (1) the effect of fasting on synthesis of ApoB from very low density lipoprotein (VLDL) and (2) tracer enrichment in low density lipoprotein (LDL).After a 36-hour fasting period and in the post-absorptive state 4 healthy subjects were given a priming dose (8.7 µmol/kg) of15N glycine followed by a constant infusion (10 µmol/kg/h for 8 h) to achieve 5% tracer enrichment in the plasma pool of glycine. The K-values, i.e. fractional synthetic rates/hr of ApoB from VLDL were 0.53±0.26 vs. 0.43±0.16 (p>0.05). Tracer enrichment in ApoB from LDL at the end of the infusions was 0.19% vs. 1.46% in ApoB from VLDL.The results indicate that (1) in young healthy postabsorptive individuals about 40% of ApoB from VLDL in plasma is synthesized per hour, (2) fasting does not materially affect fractional ApoB synthesis and (3) at 5%15N enrichment in plasma glycine, tracer enrichment in ApoB from LDL is at the lower limit of detection for the procedure employed.In vivo synthesis of apolipoprotein B 100 (ApoB) was recently determined in man using stable isotopes. With this procedure we analyzed (1) the effect of fasting on synthesis of ApoB from very low density lipoprotein (VLDL) and (2) tracer enrichment in low density lipoprotein (LDL). After a 36-hour fasting period and in the post-absorptive state 4 healthy subjects were given a priming dose (8.7 mumol/kg) of 15N glycine followed by a constant infusion (10 mumol/kg/h for 8 h) to achieve 5% tracer enrichment in the plasma pool of glycine. The K-values, i.e. fractional synthetic rates/hr of ApoB from VLDL were 0.53 +/- 0.26 vs. 0.43 +/- 0.16 (p greater than 0.05). Tracer enrichment in ApoB from LDL at the end of the infusions was 0.19% vs. 1.46% in ApoB from VLDL. The results indicate that (1) in young healthy postabsorptive individuals about 40% of ApoB from VLDL in plasma is synthesized per hour, (2) fasting does not materially affect fractional ApoB synthesis and (3) at 5% 15N enrichment in plasma glycine, tracer enrichment in ApoB from LDL is at the lower limit of detection for the procedure employed.

Relationship between amino-acid metabolism and immune functions in human lymphocytes

Amino-acid degradation, interleukin-2 (IL-2) production, and DNA synthesis were analysed in concanavalin A (ConA)-treated peripheral venous lymphocytes from healthy blood donors and in lymphocytes from patients after uneventful abdominal surgery. ConA augmented (14)CO(2) production from (U-(14)C) glutamine (492 +/- 44 vs. 2274 +/- 174 pmol/10(6) cells x 40 min(-1)) while it had little effect on (14)CO(2) production from (1-(14)C) leucine (132 +/- 8 vs. 161 +/- 17 pmol/10(6) cells x 40 min(-1)) compared with the respective controls. Similar effects on amino-acid degradation were observed in response to surgery. Glutamine but not leucine amplified IL-2 production from ConA-treated cells, and it was a prerequisite for DNA synthesis. In lymphocytes from operated patients, spontaneous incorporation of ((3)H) thymidine was higher on day 3 and day 6 (310 and 2660 cpm/10(6) cells) after surgery, compared with the pre-operative day (68 cpm/10(6) cells; median values). These results indicate 1) that glutamine is more critical than leucine for the immune function of T-lymphocytes, and 2) that lymphocytes from patients undergoing uneventful abdomional surgery have become stimulated in vivo. It is suggested that these cells may qualify as a suitable experimental model to study the metabolic basis for immunologic functions after antigenic stimulation in vivo.

Regulation of leucine transport and oxidation in peripheral human lymphocytes by glutamine

In this study we investigated the influence of physiological levels of glutamine, isoleucine, and valine on leucine oxidation and transport by peripheral lymphocytes in an in vitro system. The presence of glutamine in the incubation mixture inhibited leucine oxidation by 61%. This effect was not significantly augmented by addition of isoleucine and valine. Leucine transport revealed a Km of 124 mumol/L and a Vmax of 24 pmol/10(6) cells/30 sec. Glutamine inhibited leucine transport by 63%. The capacity of lymphocytes for leucine transport exceeded the capacity for leucine oxidation by a factor of 7.8 (13.6 +/- 0.6 v 1.74 +/- 0.1 pmol/10(6) cells/30 sec). It is concluded that glutamine is a regulator of leucine transport and oxidation in human peripheral lymphocytes, and the inhibition of leucine oxidation by glutamine is not due to an alteration of leucine transport but reflects an intracellular event.