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Increased Clearance (increased + clearance)
Selected AbstractsProduction and clearance of plasma triacylglycerols in ponies fed diets containing either medium-chain triacylglycerols or soya bean oilJOURNAL OF ANIMAL PHYSIOLOGY AND NUTRITION, Issue 5-6 2003J. M. Hallebeek Summary The hypothesis was tested that feeding ponies a diet containing medium-chain triacylglcyerols (MCT) instead of soya bean oil causes an increase in the production of plasma triacylglycerols, which, under steady-state conditions, is associated with an increased clearance of triacylglycerols. Six ponies were fed rations containing either MCT or an isoenergetic amount of soya bean oil according to a cross-over design. The concentration of MCT in the total dietary dry matter was about 13%. When the ponies were fed the diets for 3 weeks, plasma triacylglycerol concentrations were 0.42 ± 0.09 and 0.17 ± 0.03 mmol/l (mean ± SE, n = 6; p < 0.05) for the MCT and soya bean-oil treatment, respectively. Plasma triacylglycerol production was assessed using the Triton method and clearance with the use of Intralipid® infusion. Plasma triacylglycerol production was 2.91 ± 0.88 and 0.50 ± 0.14 ,mol/l·min (means ± SE, n = 4; p < 0.05) for the diets containing MCT and soya bean oil, respectively. It is suggested that the calculated rates of triacylglycerol production are underestimated, the deviation being greatest when the ponies were fed the ration of soya bean oil. Triacylglycerol clearance rates were calculated on the basis of group mean values for both the fractional clearance rate and the baseline levels of plasma triacylglycerols; the values were 4.28 and 3.52 ,mol/l·min for MCT and soya bean oil feeding, respectively. The mean, absolute clearance rates as based on those found in individual ponies did not show an increase when the diet with MCT was fed. Nevertheless, it is concluded that the data obtained support our hypothesis. [source] Cysteine-mutations in von Willebrand factor associated with increased clearanceJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 10 2005C. J. VAN SCHOOTEN Summary.,Background:,von Willebrand disease (VWD) is a bleeding disorder caused by the decrease of functional von Willebrand factor (VWF). Low levels of VWF can result from decreased synthesis, impaired secretion, increased clearance or combinations thereof. Several mutations lead to impaired synthesis or secretion of VWF, however, little is known about the survival of VWF in the circulation. Objectives:,To evaluate the effect of several VWF mutations on VWF clearance. Patients/methods:,The effect of three cysteine-mutations (C1130F, C1149R or C2671Y) on the in vivo survival of VWF was studied in patients carrying these mutations and in a VWF-deficient mice model. Results:,In patients carrying these mutations, we observed increased propeptide/mature VWF ratios and rapid disappearance of VWF from the circulation after desmopressin treatment. Detailed analysis of in vivo clearance of recombinant VWF in a VWF-deficient mice model revealed a fourfold increased clearance rate of the mutants. The mutations C1130F, C1149R and C2671Y are each associated with reduced survival of VWF in the circulation. Detailed analysis of the recombinant mutant VWF demonstrated that increased clearance was not due to increased proteolysis by ADAMTS-13. We did not identify functional or structural characteristics that the mutant proteins have in common and could be associated with the phenomenon of increased clearance. Conclusions:,Cysteine-mutations in VWF may result in reduced in vivo survival. The observation that various mutations are associated with increased in vivo clearance may have major implications for the therapeutic strategies that rely on the rise of endogenous VWF after desmopressin administration. [source] Unravelling a histone code for malaria virulenceMOLECULAR MICROBIOLOGY, Issue 6 2007Christy A. Comeaux Summary Epigenetic phenomena have been shown to play a role in the regulated expression of virulence genes in several pathogenic organisms, including the var gene family in Plasmodium falciparum. A better understanding of how P. falciparum can both maintain a single active var gene locus through many erythrocytic cycles and also achieve successive switching to different loci in order to evade the host immune system is greatly needed. Disruption of this tightly co-ordinated expression system presents an opportunity for increased clearance of the parasites by the immune system and, in turn, reduced mortality and morbidity. In the current issue of Molecular Microbiology, Lopez-Rubio and colleagues investigate the correlation of specific post-translational histone modifications with different transcriptional states of a single var gene, var2csa. Quantitative chromatin immunoprecipitation is used to demonstrate that different histone methylation marks are enriched at the 5, flanking and coding regions of active, poised or silenced var genes. They identify an increase of H3K4me2 and H3K4me3 in the 5, flanking region of an active var locus and expand on an earlier finding that H3K9me3 is enriched in the coding regions of silenced var genes. The authors also present evidence that H3K4me2 bookmarks the active var gene locus during later developmental stages for expression in the subsequent asexual cycle, hinting at a potential mechanism for transcriptional ,memory'. The stage is now set for work generating a complete catalogue of all histone modifications associated with var gene regulation as well as functional studies striving to uncover the precise mechanisms underlying these observations. [source] Inactivation of the rhlA gene in Pseudomonas aeruginosa prevents rhamnolipid production, disabling the protection against polymorphonuclear leukocytesAPMIS, Issue 7 2009MARIA VAN GENNIP Many of the virulence factors produced by the opportunistic human pathogen Pseudomonas aeruginosa are quorum-sensing (QS) regulated. Among these are rhamnolipids, which have been shown to cause lysis of several cellular components of the human immune system, e.g. monocyte-derived macrophages and polymorphonuclear leukocytes (PMNs). We have previously shown that rhamnolipids produced by P. aeruginosa cause necrotic death of PMNs in vitro. This raises the possibility that rhamnolipids may function as a ,biofilm shield'in vivo, which contributes significantly to the increased tolerance of P. aeruginosa biofilms to PMNs. In the present study, we demonstrate the importance of the production of rhamnolipids in the establishment and persistence of P. aeruginosa infections, using an in vitro biofilm system, an intraperitoneal foreign-body model and a pulmonary model of P. aeruginosa infections in mice. Our experimental data showed that a P. aeruginosa strain, unable to produce any detectable rhamnolipids due to an inactivating mutation in the single QS-controlled rhlA gene, did not induce necrosis of PMNs in vitro and exhibited increased clearance compared with its wild-type counterpart in vivo. Conclusively, the results support our model that rhamnolipids are key protective agents of P. aeruginosa against PMNs. [source] Long-chain fatty acyl-coenzyme A-induced inhibition of glucokinase in pancreatic islets from rats depleted in long-chain polyunsaturated ,3 fatty acidsCELL BIOCHEMISTRY AND FUNCTION, Issue 2 2008Ying Zhang Abstract The metabolism of D -glucose was recently reported to be impaired in pancreatic islets from second generation rats depleted in long-chain polyunsaturated ,3 fatty acids. Considering the increased clearance of circulating non-esterified fatty acids prevailing in these rats, a possible inhibition of glucokinase in insulin-producing cells by endogenous long-chain fatty acyl-CoA was considered. The present study was mainly aimed at assessing the validity of the latter proposal. The activity of glucokinase in islet homogenates, as judged from the increase in D -glucose phosphorylation rate in response to a rise in the concentration of the hexose represented, in the ,3-depleted rats, was only 81.8,±,4.8% (n,=,11; p,<,0.005) of the paired value recorded in control animals. This coincided with the fact that the inclusion of D -glucose 6-phosphate (3.0,mM) and D -fructose 1-phosphate (1.0,mM) in the assay medium resulted in a lesser fractional decrease of D -glucose phosphorylation in ,3-depleted rats than in control animals. Moreover, whereas palmitoyl-CoA (50,µM) decreased the activity of glucokinase by 38.0,±,6.0% (n,=,4; p,<,0.01) in islet homogenates from normal rats, the CoA ester failed to affect significantly the activity of glucokinase in islet homogenates from ,3-depleted rats. These findings afford direct support for the view that glucokinase is indeed inhibited by endogenous long-chain fatty acyl-CoA in islets from ,3-depleted rats, such an inhibition probably participating to the alteration of D -glucose catabolism prevailing in these islets. Copyright © 2007 John Wiley & Sons, Ltd. [source] | |||||||||||||