A low-carbohydrate diet may prevent end-stage renal failure in type 2 diabetes. A case report

An obese patient with type 2 diabetes whose diet was changed from the recommended high-carbohydrate, low-fat type to a low-carbohydrate diet showed a significant reduction in bodyweight, improved glycemic control and a reversal of a six year long decline of renal function. The reversal of the renal function was likely caused by both improved glycemic control and elimination of the patient's obesity. Insulin treatment in type 2 diabetes patients usually leads to weight increase which may cause further injury to the kidney. Although other unknown metabolic mechanisms cannot be excluded, it is likely that the obesity caused by the combination of high-carbohydrate diet and insulin in this case contributed to the patient's deteriorating kidney function. In such patients, where control of bodyweight and hyperglycemia is vital, a trial with a low-carbohydrate diet may be appropriate to avoid the risk of adding obesity-associated renal failure to already failing kidneys

A chimeric EBV gp350/220-based VLP replicates the virion B-cell attachment mechanism and elicits long-lasting neutralizing antibodies in mice

Epstein-Barr virus (EBV), an oncogenic gammaherpesvirus, causes acute infectious mononucleosis (AIM) and is linked to the development of several human malignancies. There is an urgent need for a vaccine that is safe, prevents infection and/or limits disease. Unique among human herpesviruses, glycoprotein (gp)350/220, which initiates EBV attachment to susceptible host cells, is the major ligand on the EBV envelope and is highly conserved. Interaction between gp350/220 and complement receptor type 2 (CR2)/CD21 and/or (CR1)/CD35 on B-cells is required for infection. Potent antibody responses to gp350/220 occur in animal models and humans. Thus, gp350/220 provides an attractive candidate for prophylactic subunit vaccine development. However, in a recent Phase II clinical trial immunization with soluble recombinant gp350 reduced the incidence of AIM, but did not prevent infection. Despite various attempts to produce an EBV vaccine, no vaccine is licensed. Herein we describe a sub-unit vaccine against EBV based on a novel Newcastle disease virus (NDV)-virus-like particle (VLP) platform consisting of EBVgp350/220 ectodomain fused to NDV-fusion (F) protein. The chimeric protein EBVgp350/220-F is incorporated into the membrane of a VLP composed of the NDV matrix and nucleoprotein. The particles resemble native EBV in diameter and shape and bind CD21 and CD35. Immunization of BALB/c mice with EBVgp350/220-F VLPs elicited strong, long-lasting neutralizing antibody responses when assessed in vitro. This chimeric VLP is predicted to provide a superior safety profile as it is efficiently produced in Chinese hamster ovary (CHO) cells using a platform devoid of human nucleic acid and EBV-transforming genes

Fitting the Elementary Rate Constants of the P-gp Transporter Network in the hMDR1-MDCK Confluent Cell Monolayer Using a Particle Swarm Algorithm

P-glycoprotein, a human multidrug resistance transporter, has been extensively studied due to its importance to human health and disease. In order to understand transport kinetics via P-gp, confluent cell monolayers overexpressing P-gp are widely used. The purpose of this study is to obtain the mass action elementary rate constants for P-gp's transport and to functionally characterize members of P-gp's network, i.e., other transporters that transport P-gp substrates in hMDR1-MDCKII confluent cell monolayers and are essential to the net substrate flux. Transport of a range of concentrations of amprenavir, loperamide, quinidine and digoxin across the confluent monolayer of cells was measured in both directions, apical to basolateral and basolateral to apical. We developed a global optimization algorithm using the Particle Swarm method that can simultaneously fit all datasets to yield accurate and exhaustive fits of these elementary rate constants. The statistical sensitivity of the fitted values was determined by using 24 identical replicate fits, yielding simple averages and standard deviations for all of the kinetic parameters, including the efflux active P-gp surface density. Digoxin required additional basolateral and apical transporters, while loperamide required just a basolateral tranporter. The data were better fit by assuming bidirectional transporters, rather than active importers, suggesting that they are not MRP or active OATP transporters. The P-gp efflux rate constants for quinidine and digoxin were about 3-fold smaller than reported ATP hydrolysis rate constants from P-gp proteoliposomes. This suggests a roughly 3∶1 stoichiometry between ATP hydrolysis and P-gp transport for these two drugs. The fitted values of the elementary rate constants for these P-gp substrates support the hypotheses that the selective pressures on P-gp are to maintain a broad substrate range and to keep xenobiotics out of the cytosol, but not out of the apical membrane

Decholesterolization of milk fat diets improve plasma and liver long-chain-omega3 profile (EPA,DHA) in hamsters

International audienc

Epithelial Cell Surface Sites Involved in the Polyvalent Adherence of Porphyromonas gingivalis: a Convincing Role for Neuraminic Acid and Glucuronic Acid

We investigated the target structures of the epithelial cells responsible for the attachment of Porphyromonas gingivalis by immunocytofluorimetry, enzyme-linked immunosorbent assay, and confocal microscopy. Integrins (β1, β3, and αV) and E-cadherin played no significant role. Carbohydrates (such as α-d-methylglucoside, l-fucose, d- and l-mannose, N-acetylglucosamine, and N-acetylgalactosamine) had little inhibitory effect on bacterial binding. Enzymatic treatments of the epithelial membranes and sugar competition studies showed that N-acetylneuraminic acid and glucuronic acid were involved in binding

A dairy fat matrix providing alpha-linolenic acid (ALA) is better than a vegetable fat mixture to increase brain DHA accretion in young rats

International audienceAchieving an appropriate DHA status in the neonatal brain is an important goal of neonatal nutrition. We evaluated how alpha-linolenic acid (ALA), provided for six weeks after weaning by different dietary fat matrix, improved brain DHA content of young male rats born from deficient-dams. The level of ALA achieved was based on the fat composition of usual infant vegetable formula. A palm oil-blend diet thus providing 1.5%ALA was compared to dairy fat-blend-based diets that provided either 1.5%ALA or 2.3%ALA, or a rapeseed oil diet providing 8.3%ALA (n - 6/n - 3 ratio were, respectively 10,10,5,2.5). The 1.5%ALA-dairy-fat-blend was superior to 1.5%ALA-palm-oil-blend to restore values of brain DHA, while the 2.3%ALA-dairy-fat-blend exhibited a further increase and reached the values obtained with pure rapeseed diet (8.3%ALA). Dairy-fat-blends enriched with ALA appear to be an interesting strategy for achieving optimal DHA levels in the brain of post-weaning rats. Providing dairy fat as well as a reduction of the LA/ALA ratio should be reconsidered to design infant formula. Published by Elsevier Ltd