Effect of neurotensin on pancreatic function in man

The effect of neurotensin on submaximally-stimulated hepatobiliary and pancreatic secretion was studied in 6 healthy subjects. An intravenous infusion of neurotensin 1.4 ± 0.3 pmol/kg/min, designed to reproduce plasma neurotensin immunoreactivity levels within the physiological range, produced a significant increase in pancreatic bicarbonate output. Plasma concentrations of pancreatic polypeptide rose by 83 ± 16 pmol/l and were associated with a small reduction in trypsin, but no significant change in bilirubin outputs.     

Aging of mesenchymal stem cell in vitro

Background  

A hot new topic in medical treatment is the use of mesenchymal stem cells (MSC) in therapy. The low frequency of this subpopulation of stem cells in bone marrow (BM) necessitates their in vitro expansion prior to clinical use. We evaluated the effect of long term culture on the senescence of these cells.     

Age-associated decline in effective immune synapse formation of CD4(+) T cells is reversed by vitamin E supplementation

Aging is associated with reduced IL-2 production and T cell proliferation. Vitamin E supplementation, in aged animals and humans, increases cell division and IL-2 production by naive T cells. The immune synapse forms at the site of contact between a T cell and an APC and participates in T cell activation. We evaluated whether vitamin E affects the redistribution of signaling proteins to the immune synapse. Purified CD4(+) T cells, from the spleens of young and old mice, were treated with vitamin E before stimulation with a surrogate APC expressing anti-CD3. Using confocal fluorescent microscopy, we observed that CD4(+) T cells from old mice were significantly less likely to recruit signaling proteins to the immune synapse than cells from young mice. Vitamin E increased the percentage of old CD4(+) T cells capable of forming an effective immune synapse. Similar results were found following in vivo supplementation with vitamin E. When compared with memory cells, naive T cells from aged mice were more defective in immune synapse formation and were more responsive to vitamin E supplementation. These data show, for the first time, that vitamin E significantly improves age-related early T cell signaling events in naive CD4(+) T cells.     

Age-Dependent Changes in the Sphingolipid Composition of Mouse CD4+ T Cell Membranes and Immune Synapses Implicate Glucosylceramides in Age-Related T Cell Dysfunction

To determine whether changes in sphingolipid composition are associated with age-related immune dysfunction, we analyzed the core sphingolipidome (i.e., all of the metabolites through the first headgroup additions) of young and aged CD4⁺ T cells. Since sphingolipids influence the biophysical properties of membranes, we evaluated the compositions of immune synapse (IS) and non-IS fractions prepared by magnetic immuno-isolation. Broadly, increased amounts of sphingomyelins, dihydrosphingomyelins and ceramides were found in aged CD4⁺ T cells. After normalizing for total sphingolipid content, a statistically significant decrease in the molar fraction of glucosylceramides was evident in both the non-IS and IS fractions of aged T cells. This change was balanced by less dramatic increases in the molar fractions of sphingomyelins and dihydrosphingomyelins in aged CD4⁺ T cells. In vitro, the direct or enzymatic enhancement of ceramide levels decreased CD4⁺ T cell proliferation without regard for the age of the responding T cells. In contrast, the in vitro inhibition of glucosylceramidase preferentially increased the proliferation of aged CD4⁺ T cells. These results suggest that reductions in glucosylceramide abundance contribute to age-related impairments in CD4⁺ T cell function.     

Age-associated increase in PGE2 synthesis and COX activity in murine macrophages is reversed by vitamin E

We previouslyshowed that increased macrophage andPGE₂ production with age is due toenhanced cyclooxygenase (COX) activity and COX-2 expression. This studydetermined the effect of vitamin E supplementation on macrophagePGE₂ synthesis in young and old mice and its underlying mechanism. Mice were fed 30 or 500 parts permillion vitamin E for 30 days. Lipopolysaccharide (LPS)-stimulated macrophages from old mice produced significantly morePGE₂ than those from young mice.Vitamin E supplementation reversed the increasedPGE₂ production in old mice buthad no effect on macrophage PGE₂production in young mice. In both LPS-stimulated and unstimulated macrophages, COX activity was significantly higher in old than in youngmice at all intervals. Vitamin E supplementation completely reversedthe increased COX activity in old mice to levels comparable to those ofyoung mice but had no effect on macrophage COX activity of young miceor on COX-1 and COX-2 protein or COX-2 mRNA expression in young or oldmice. Thus vitamin E reverses the age-associated increase in macrophagePGE₂ production and COX activity.Vitamin E exerts its effect posttranslationally, by inhibiting COXactivity.

     

Peripartum Cardiomyopathy Presenting With Ventricular Tachycardia: A Rare Presentation

A 25-year-old previously asymptomatic pregnant woman at 36 weeks'' gestation was noticed to have repetitive monomorphic ventricular tachycardia. A dilated left ventricle with moderately reduced systolic function was found on echocardiographic examination. This is a very rare presentation of peripartum cardiomyopathy (PPCMP) presenting with repetitive monomorphic ventricular tachycardia.     

A recently silenced, duplicate PgiC locus in Clarkia

Previous electrophoretic analysis showed that 17 diploid species of the wildflower Clarkia (Onagraceae) have two cytosolic isozymes of phosphoglucose isomerase (PGIC; EC 5.3.1.9), whereas 15 other diploid species have a single PGIC. Molecular studies revealed that the two isozymes in the former species are encoded by duplicate genes, PgiC1 and PgiC2, whereas the single isozyme in the latter is always encoded by PgiC1. Phylogenetic analysis of the nucleotide sequences implied that PgiC2 was silenced four times independently in the genus. Here we describe a psi PgiC2 from C. mildrediae, a species in which only PgiC1 is expressed. The discovery of the psi PgiC2 is significant because it confirms a formal prediction of the phylogenetic analysis. The psi PgiC2 includes 5,039 nucleotides corresponding to 18 of the 23 exons of PgiC, as well as the intervening introns and 3' nontranslated region. The absence of an increase of nucleotide substitutions in its "exons" suggests that the gene was silenced recently. The present study appears to be the first to establish that a specific duplicate gene locus regularly expressed in a group of related plant species has been silenced in one of them. The multiple independent silencings of PgiC2 suggest that it remained functional but inessential in ancestral lineages. We discuss the possibility that PgiC2 may have been preserved in these lineages by selection against mutants causing defective PGIC1- PGIC2 heterodimers.      

Dietary supplementation with high dose of epigallocatechin-3-gallate promotes inflammatory response in mice

Epigallocatechin-3-gallate (EGCG) from green tea has been indicated to have anti-inflammatory activity. However, most of the evidence is in vitro studies in which EGCG is often added at levels unachievable by oral intake. With few exceptions, in vivo studies along this line have been conducted in animal models of diseases, and the results are inconclusive. In this study, we fed C57BL/6 mice a diet containing 0%, 0.15%, 0.3% or 1% (w/w) EGCG for 6 weeks. Contrary to the assumption that EGCG would reduce inflammatory response, mice fed 0.15% and 0.3% EGCG diet exhibited no change while those fed 1% EGCG diet produced more proinflammatory cytokines tumor necrosis factor-α, interleukin (IL)-6, and IL-1β and lipid inflammatory mediator prostaglandin E(2) in their splenocytes and macrophages (MΦ) and less IL-4 in splenocytes. Spleens from the mice fed 1% EGCG diet also had higher proportions of regulatory T cells, MΦ, natural killer (NK) cells and NKT cells compared to those from mice fed the other diets. These results suggest that high intake of EGCG may induce a proinflammatory response, and this change may be associated with a disturbed homeostasis of immune cells involving changes in both function and number of specific immune cell populations. While the mechanisms and clinical significance for this effect of EGCG remain to be investigated further, these data suggest the need for defining accurate EGCG dose limits to induce an anti-inflammatory effect since current data indicate that higher doses would produce an inflammatory response.