The influence of 12(S)-hydroxyicosatetraenoic acid (1 2-HETE), that we have previously shown to decrease the proliferative response of human lymphocytes to mitogens, on diacylglycerol and phosphatidic acid (PtdOH) formation was investigated in stimulated human peripheral blood mononuclear cells (PBMC). When human PBMC were first enriched with 12-HETE, then stimulated by the mitogenic lectin concanavalin A (Con A), the production of PtdOH normally associated with Con A stimulation was markedly increased as compared with non-enriched cells. The Con-A-induced rise in the PtdOH mass was markedly decreased by 1 % ethanol in 12-HETE-enriched cells, whereas it was unaffected in control cells stimulated by Con A alone. Furthermore, in ['Hlarachidonic-acid-labelled cells previously enriched with 12-HETE, the formation of [iH]arachidonic-acid-labelled phosphatidylalcohol was significantly increased upon Con A stimulation, no phosphatidylalcohol being synthesized in non-enriched cells. Collectively, these results suggest that, in the presence of 12-HETE, Con A stimulates a phospholipase D activity which was not triggered by Con A alone. These data are consistent with the lack of effect of suramin, reported as a phospholipase D inhibitor, which we observed in cells stimulated by Con A alone and with the suramin-induced decrease of PtdOH mass in 12-HETE-plus-Con-A-treated cells. Moreover, 12-['H]HETE-enriched PBMC produced a significant amount of 12-[3H]HETE-containing PtdOH (0.4 % of the total PtdOH) in resting conditions. Upon mitogenic Stimulation by Con A, the phorbol ester tetradecanoylphorbol acetate or the anti-CD3 mAb OKT3, this proportion was decreased to 0.1-0.2%, since the total PtdOH mass was more drastically increased than the 12-HETE-containing PtdOH species. Although present in relatively low amount in stimulated cells, 12-HETE-containing PtdOH species might have been generated in strategic compartments of the membrane bilayer so that the following events involved in the transduction of the mitogenic signal could be impaired. GC analyses have pointed out drastic variations in the fatty acid composition of PtdOH in non-enriched and in 12-HETE-enriched stimulated cells. Especially PtdOH synthesized in 12-HETE-enriched cells upon Con A stimulation contained a higher amount of saturated fatty acids and a lower amount of arachidonic acid than that formed in control cells stimulated with Con A alone. Such saturated PtdOH species with a low arachidonic acid content are very likely to have a low mitogenic potential.
β-Hydroxy-β-methylbutyrate (HMB) supplementation increases muscle and strength mass in some muscle-wasting disorders. Malnutrition and sarcopenia are often present in liver cirrhosis. We aimed to investigate the effects of oral HMB supplementation on changes in body composition and liver status in patients with cirrhosis and malnutrition. In a randomized, controlled, double-blind trial, 43 individuals were randomized to receive twice a day and for 12 weeks an oral nutritional supplement (ONS) enriched with 1.5 g of calcium HMB per bottle or another supplement with similar composition devoid of HMB. Inclusion criteria were liver cirrhosis with at least one previous decompensation and clinical malnutrition. Liver function, plasma biochemistry analyses, and physical condition assessment were carried out at baseline, then after six and 12 weeks of supplementation. A total of 34 patients completed the clinical trial. An improvement in liver function and an increase in fat mass index were observed in both groups. None of the two ONS changed the fat-free mass. However, we observed an upward trend in handgrip strength and a downward trend in minimal hepatic encephalopathy in the HMB group. At the end of the trial and regardless of the supplement administered, fat mass content increased with no change in fat-free mass, while liver function scores and nutritional analytic markers also improved.
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