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Rapid Elimination (rapid + elimination)
Selected AbstractsBioaccumulation and biotransformation of polycyclic aromatic hydrocarbons during sediment tests with oligochaetes (Lumbriculus variegatus)ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 12 2007Merja Lyytikäinen Abstract In some kinetic studies with aquatic invertebrates, the bioaccumulation of polyaromatic hydrocarbons (PAHs) has been observed to peak at the beginning of the test. This has been explained by the depletion of PAHs from pore water due to limited desorption during the bioaccumulation test or, alternatively, by the activation of biotransformation mechanisms in the organisms. In the present study, we exposed the aquatic oligochaetes, Lumbriculus variegatus, to creosote oil,contaminated sediments to examine the bioaccumulation of PAHs and to clarify the importance of contaminant depletion and biotransformation for it. The contaminant depletion was studied by replanting test organisms into fresh, nondepleted test sediments at 3-d intervals over 12 d and by comparing the resulting body burdens to those of the organisms that were not replanted. The biotransformation capability of L. variegatus was assessed by following the concentration of 1-hydroxypyrene (1-HP), a phase I metabolite of pyrene, in oligochaete tissue during a 15-d test. We observed that the bioaccumulation of most PAHs indeed peaked at the beginning of the test. The concentrations in the replanted organisms were only 1.5 to 2 times higher than in nonreplanted organisms during the first 9 d of the test and, by day 12, no differences were detected. 1-Hydroxypyrene was detected in oligochaete tissue throughout the exposures, and concentrations decreased over time. However, the proportion of 1-HP to pyrene increased linearly during the test. These results indicated that the depletion of contaminants has only a minor effect on their bioaccumulation in oligochaetes and that the cause for the observed bioaccumulation curve shape is rapid elimination of the contaminants and, possibly to some degree, their metabolites. [source] The Pharmacokinetics of Antiepileptic Drugs in Rats: Consequences for Maintaining Effective Drug Levels during Prolonged Drug Administration in Rat Models of EpilepsyEPILEPSIA, Issue 7 2007Wolfgang Löscher Summary:, Rodent models of chronic epilepsy with spontaneous recurrent seizures likely represent the closest parallel to the human condition. Such models may be best suited for therapy discovery for pharmacoresistant epilepsy and for antiepileptogenic or disease-modifying therapeutics. However, the use of such rodent models for therapy discovery creates problems with regard to maintaining effective drug levels throughout a prolonged testing period. This is particularly due to the fact that rodents such as rats and mice eliminate most drugs much more rapidly than humans. Thus, knowledge about elimination rate of a test drug in a laboratory species is essential for development of a treatment paradigm that allows maintaining adequate drug levels in the system over the period of treatment. Currently, the most popular models of epilepsy with spontaneous seizures are poststatus epilepticus models of temporal lobe epilepsy in rats. Such models are both used for studies on antiepileptogenesis and drug resistance. For validation of these models, current antiepileptic drugs (AEDs) have to be used. In this article, the elimination rates of these AEDs and their effective plasma levels in rats are reviewed as a guide for developing treatment protocols for chronic drug testing. The advantages and disadvantages of several technologies for drug delivery are discussed, and some examples for calculation of adequate treatment protocols are given. As shown in this review, because of the rapid elimination of most AEDs in rats, it is no trivial task to maintain effective steady-state AED levels in the plasma throughout the day over multiple days to ensure that there will be adequate levels in the system for the purpose of the experiment. However, the use of an adequate dosing regimen that is based on elimination rate is an absolute prerequisite when using rat models for discovery of new antiepileptogenic therapies or therapies for pharmacoresistant epilepsy, because otherwise such models may lead to erroneous conclusions about drug efficacy. [source] The relevance of the bleeding severity in the treatment of acquired haemophilia , an update of a single-centre experience with 67 patientsHAEMOPHILIA, Issue 102 2010H. ZEITLER Summary., Acquired haemophilia (AH), an autoimmune disorder with clinical features ranging from harmless haematomas to life-threatening bleedings, still has a mortality rate of up to 25%. Owing to its low frequency (1,4 × 106), standardized treatment protocols for its variable manifestations are not available. In case of prominent severe bleedings, the treatment should aim at rapid elimination of the antibody to protect patients from bleedings and on reinduction of long-term immune tolerance. Clinical data, short- and long-term treatment results of 67 patients diagnosed by our centre are presented. Patients were treated depending on their bleeding severity either by an immunosuppressive treatment alone, or in case of life-threatening bleedings, by a combined protocol (modified Bonn,Malmö protocol, MBMP) consisting of antibody depletion through immunoadsorption, intravenous immunoglobulin treatment, immunosuppression and high-dose factor VIII (FVIII) substitution. Mild bleedings occurred in two patients who were treated successfully alone by immunosuppression. Complete remission (CR) was achieved in 90% of the patients treated with MBMP (60). Of the six patients (10%) who achieved a partial remission (PR), four suffered from cancer. Mortality under MBMP was not seen. In contrast, five patients, in whom diagnosis of AH was delayed, experienced fatal outcome during surgical interventions before initiation of MBMP treatment. Prognosis in AH depends mainly on its prompt diagnosis. Treatment procedures should be adapted to bleeding severity and inhibitor titres. Under these conditions, AH is a potentially curable autoimmune disorder with an excellent prognosis. [source] Kinetics of HBV DNA and HBsAg in acute hepatitis B patients with and without coinfection by other hepatitis virusesJOURNAL OF MEDICAL VIROLOGY, Issue 3 2003Vladimir P. Chulanov Abstract The kinetics of hepatitis B virus (HBV) and its surface antigen (HBsAg) during acute hepatitis has not yet been studied accurately in a representative number of patients. The influence of coinfecting hepatitis viruses during the acute phase of infection is not known. Three to four serum samples from 21 patients with acute HBV monoinfection and 27 with coinfection were taken at intervals of 6,10 days and analyzed for the number of HBV genome equivalents (ge) by real time polymerase chain reaction (PCR) and for HBsAg quantity using Laurell electrophoresis. Log HBV ge/ml decreased during the follow-up from 6.8,±,1.1 to 5.1,±,1.0 to 4.2,±,0.8 to 3.3,±,1.1 (mean,±,SD). The half-life times of HBV ge increased from 1.6 days at the beginning to 4 days at the end. HBsAg decreased much slower: from 38 to 23 to 12 to3.8 ,g/ml. Half-life time was around 8 days at the beginning and 5.7 days at the end, but 11 patients showed a rapid elimination of HBsAg and HBV DNA. Hepatitis C virus (HCV) coinfection did not change the kinetics of HBV ge and HBsAg significantly. A moderate but significant suppression of HBV ge levels was observed in hepatitis D virus (HDV) coinfected patients. HBsAg levels were, however, enhanced in this cohort. In conclusion, the data suggest that expression and elimination of HBV is in most patients with acute hepatitis B not altered by coinfecting hepatitis viruses. The initial decrease of HBV ge and HBsAg in serum appears to be caused by decay or non-specific removal in the absence of replacement. J. Med. Virol. 69:313,323, 2003. © 2003 Wiley-Liss, Inc. [source] The initiation and development of metamorphic foliation in the Otago Schist, Part 1: competitive oriented growth of white micaJOURNAL OF METAMORPHIC GEOLOGY, Issue 6 2005A. STALLARD Abstract The 3D shape, size and orientation data for white mica grains sampled along two transects of increasing metamorphic grade in the Otago Schist, New Zealand, reveal that metamorphic foliation, as defined by mica shape-preferred orientation (SPO), developed rapidly at sub-greenschist facies conditions early in the deformation history. The onset of penetrative strain metamorphism is marked by the rapid elimination of poorly oriented large clastic mica in favour of numerous new smaller grains of contrasting composition, higher aspect ratios and a strong preferred orientation. The metamorphic mica is blade shaped with long axes defining the linear aspect of the foliation and intermediate axes a partial girdle about the lineation. Once initiated, foliation progressively intensified by an increase in the aspect ratio, size and alignment of grains, although highest grade samples within the chlorite zone record a decrease in aspect ratio and reduction in SPO strength despite continued increase in grain size. These trends are interpreted in terms of progressive competitive anisotropic growth of blade-shaped grains so that the fastest growth directions and blade lengths tend to parallel the extension direction during deformation. The competitive nature of mica growth is indicated by the progressive increase in size and resultant decrease in number of metamorphic mica with increasing grade, from c. 1000 relatively small mica grains per square millimetre of thin section at lower grades, to c. 100 relatively large grains per square millimetre in higher grade samples. Reversal of SPO intensity and grain aspect ratio trends in higher grade samples may reflect a reduction in the strain rate or reduction in the deviatoric component of the stress field. [source] Addition, elimination, exchange, and epimerization in nitro sulfonesJOURNAL OF PHYSICAL ORGANIC CHEMISTRY, Issue 3 2007Charles A. Kingsbury Abstract Three reactions were studied in the diastereomers of 1-(benzenesulfonyl)-2-nitro-1-phenylpropane (1A and 1B) and briefly in related compounds: elimination of the benzenesulfonyl group, epimerization of one diastereomer to the other, and deuterium/hydrogen exchange at the methine group next to nitro in starting material. The two diastereomers showed quite different reactivity. The high melting diasteromer showed rapid elimination and some exchange. The low melting diastereomer (at approximately a half-life) showed extensive epimerization, and elimination to the alkene, but little exchange. There is little effect of aromatic substituents on reaction course. The situation is complicated by re-addition of benzenesulfinate to the alkene. The addition reaction was similar to elimination in agreement with the Principle of Microscopic Reversibility expectations. An electron transfer mechanism for addition is calculated to be comparatively favorable. Copyright © 2007 John Wiley & Sons, Ltd. [source] The mechanisms used by enteropathogenic Escherichia coli to control filopodia dynamicsCELLULAR MICROBIOLOGY, Issue 2 2009Cedric N. Berger Summary Enteropathogenic Escherichia coli (EPEC) subverts actin dynamics in eukaryotic cells by injecting effector proteins via a type III secretion system. First, WxxxE effector Map triggers transient formation of filopodia. Then, following recovery from the filopodial signals, EPEC triggers robust actin polymerization via a signalling complex comprising Tir and the adaptor proteins Nck. In this paper we show that Map triggers filopodia formation by activating Cdc42; expression of dominant-negative Cdc42 or knock-down of Cdc42 by siRNA impaired filopodia formation. In addition, Map binds PDZ1 of NHERF1. We show that Map,NHERF1 interaction is needed for filopodia stabilization in a process involving ezrin and the RhoA/ROCK cascade; expression of dominant-negative ezrin and RhoA or siRNA knock-down of RhoA lead to rapid elimination of filopodia. Moreover, we show that formation of the Tir-Nck signalling complex leads to filopodia withdrawal. Recovery from the filopodial signals requires phosphorylation of a Tir tyrosine (Y474) residue and actin polymerization pathway as both infection of cells with EPEC expressing TirY474S or infection of Nck knockout cells with wild-type EPEC resulted in persistence of filopodia. These results show that EPEC effectors modulate actin dynamics by temporal subverting the Rho GTPases and other actin polymerization pathways for the benefit of the adherent pathogen. [source] | |||||||||||||