Liver fluke (Fasciola hepatica)-derived peptides activate rat peritoneal mast cells

Short peptides with sequences derived from those found in the tegumental antigen of Fasciola hepatica have been synthesised. Incubation of some of these peptides with rat peritoneal mast cells resulted in the degranulation of the cells as measured by a histamine release assay. This activity was shown to be associated with the proline-lysine-proline motif, which is responsible for the induction of mast cell degranulation by the mammalian bioactive peptide substance P. Studies on the mode of action of the fluke-derived peptide indicated that it was operating through the same biochemical pathways as substance P. The implications of these findings for the development of immune responses during parasite infections are discussed. (C) 2003 Elsevier Science B.V. All rights reserved.

Determination of the molecular weight distribution of non-enzymatic browning products formed by roasting of glucose and glycine and studies on their effects on NADPH-cytochrome c-reductase and glutathione-S-transferase in Caco-2 cells

After thermal treatment of a mixture of glucose and glycine for 2 h at 125 degreesC, about 60% of the starting material was converted into nonsoluble, black pigments, whereas 40% of the mixture was still water-soluble. Dialysis of the latter fraction revealed 30.4% of low molecular weight compounds (LMWs; MW <10 000 De) and 10.0% high-molecular weight products [HMWs; MW greater than or equal to 10000 Dal. The water-soluble Maillard reaction products (MRPs) were separated by gel permeation chromatography and ultrafiltration, revealing that 60% of the water-soluble products of the total carbohydrate/amino acid mixture had MWs <1 000 Da and consisted mainly of non-coloured reaction products. MRPs with MWs between 1000 and 30000 Da were Found in comparatively low yields (about 1.3%). In contrast, about 31.1% of the MRPs exhibited MWs > 30000 Da, amongst which 14.5% showed MWs > 100000 Da, thus indicating an oligomerisation of LMWs to melanoidins under roasting conditions. To investigate the physiological effects of these MRPs, xenobiotic enzyme activities were analysed in intestinal Caco-2 cells. For Phase-I NADPH-cytochrome c-reductase, the activity in the presence of the LMW and HMW fraction was decreased by 13% and 22%: respectively. Phase-II glutathione-S-transferase activity decreased by 15% and 18%, respectively, after incubation with the LMW and the HMW fractions. Considering the different yields, 30% and 10%, respectively, of the LMW and the HMW fractions, the total amount of the LMW fraction present in the glucose-glycine mixture is more active in modulating three enzyme activities than that of the HMW fraction.

Understanding genetic diversity of the liver fluke Fasciola hepatica

Economical breeding is important to obtain maximum gain from the breeding in the animal sector. The economic loss has to be eliminated or should be minimized. The liver fluke, Fasciola hepatica, present mostly in sheep and dairy cattle affect the yield of animals and even cause their death. To eliminate or minimize the impact of these parasites on the animals, it is important to understand the genetic diversity of the liver fluke populations and the relationship between parasite and host at regional bases. This research was carried out to determine diversity by sequence analysis of the mitochondrial ND1 gene and ribosomal ITS1 region.

Relative activity of triclabendazole metabolites against the liver fluke, Fasciola hepatica

A study has been carried Out to determine the relative activity Of triclabendazole (TCBZ) and its sulphoxide (TCBZ(center dot)SO) and sulphone (TCBZ(center dot)SO(2)) metabolites against the adult stage of the liver fluke, Fasciola hepatica. Flukes were incubated for 24 h in vitro in 15 mu g/ml of each of the compounds and prepared for scanning and transmission electron microscopy.

Influence of ABCB1 polymorphisms and haplotypes on tacrolimus nephrotoxicity and dosage requirements in children with liver transplant

AIMS
The aim of this study was to investigate the in?uence of genetic polymorphisms in ABCB1 on the incidence of nephrotoxicity and tacrolimus dosage-requirements in paediatric patients following liver transplantation.
METHODS
Fifty-one paediatric liver transplant recipients receiving tacrolimus were genotyped for ABCB1 C1236>T, G2677>T and C3435>T polymorphisms. Dose-adjusted tacrolimus trough concentrations and estimated glomerular ?ltration rates (EGFR) indicative of renal toxicity were determined and correlated with the corresponding genotypes.
RESULTS
The present study revealed a higher incidence of the ABCB1 variant-alleles examined among patients with renal dysfunction (30% reduction in EGFR) at 6 months post-transplantation (1236T allele: 63.3% vs 37.5% in controls,P = 0.019; 2677T allele: 63.3% vs. 35.9%, p = 0.012; 3435T allele: 60% vs. 39.1%,P = 0.057). Carriers of the G2677->T variant allele also had a signi?cant reduction (%) in EGFR at 12 months post-transplant (mean difference = 22.6%; P = 0.031). Haplotype analysis showed a signi?cant association between T-T-T haplotypes and an increased incidence of nephrotoxicity at 6 months post-transplantation (haplotype-frequency = 52.9% in nephrotoxic patients vs 29.4% in controls; P = 0.029). Furthermore, G2677->T and C3435->T polymorphisms and T-T-T haplotypes were signi?cantly correlated with higher tacrolimus dose-adjusted pre-dose concentrations at various time points examined long after drug initiation.
CONCLUSIONS
These ?ndings suggest that ABCB1 polymorphisms in the native intestine signi?cantly in?uence tacrolimus dosage-requirement in the stable phase after transplantation. In addition, ABCB1 polymorphisms in paediatric liver transplant recipients may predispose them to nephrotoxicity over the ?rst year posttransplantation. Genotyping future transplant recipients for ABCB1 polymorphisms, therefore, could have the potential to individualize better tacrolimus immunosuppressive therapy and enhance drug safety

A low molecular weight hydro and organogelator derived from an isohexide and sol-gel transcription of the alcogel

Heating 2,5-di-O-methanesulfonyl-1,4:3,6-dianhydro-D-sorbitol (1) in a range of solvents led to the formation of a gel state at low concentrations. 1 was found to gel aromatics, alcohols and water. The structure of 1 in the solid state was solved by single crystal X-ray crystallography; no strong hydrogen bonds or associated solvents were found in the crystal. Electron micrographs revealed the morphology of the gels to be predominantly rod-like. The ethanol alcogel was used to template silica by sol-gel transcription.

Low-fat versus low-carbohydrate weight reduction diets:Effects on weight loss, insulin resistance, and cardiovascular risk: a randomized control trial

OBJECTIVE Low-fat hypocaloric diets reduce insulin resistance and prevent type 2 diabetes in those at risk. Low-carbohydrate, high-fat diets are advocated as an alternative, but reciprocal increases in dietary fat may have detrimental effects on insulin resistance and offset the benefits of weight reduction.

RESEARCH DESIGN AND METHODS We investigated a low-fat (20% fat, 60% carbohydrate) versus a low-carbohydrate (60% fat, 20% carbohydrate) weight reduction diet in 24 overweight/obese subjects ([mean ± SD] BMI 33.6 ± 3.7 kg/m2, aged 39 ± 10 years) in an 8-week randomized controlled trial. All food was weighed and distributed, and intake was calculated to produce a 500 kcal/day energy deficit. Insulin action was assessed by the euglycemic clamp and insulin secretion by meal tolerance test. Body composition, adipokine levels, and vascular compliance by pulse-wave analysis were also measured.

RESULTS Significant weight loss occurred in both groups (P < 0.01), with no difference between groups (P = 0.40). Peripheral glucose uptake increased, but there was no difference between groups (P = 0.28), and suppression of endogenous glucose production was also similar between groups. Meal tolerance–related insulin secretion decreased with weight loss with no difference between groups (P = 0.71). The change in overall systemic arterial stiffness was, however, significantly different between diets (P = 0.04); this reflected a significant decrease in augmentation index following the low-fat diet, compared with a nonsignificant increase within the low-carbohydrate group.

CONCLUSIONS This study demonstrates comparable effects on insulin resistance of low-fat and low-carbohydrate diets independent of macronutrient content. The difference in augmentation index may imply a negative effect of low-carbohydrate diets on vascular risk.