Search results for "TOXICITY"
showing 10 items of 2261 documents
Reduction in the Motoneuron Inhibitory/Excitatory Synaptic Ratio in an Early-Symptomatic Mouse Model of Amyotrophic Lateral Sclerosis
2010
Excitotoxicity is a widely studied mechanism underlying motoneuron degeneration in amyotrophic lateral sclerosis (ALS). Synaptic alterations that produce an imbalance in the ratio of inhibitory/excitatory synapses are expected to promote or protect against motoneuron excitotoxicity. In ALS patients, motoneurons suffer a reduction in their synaptic coverage, as in the transition from the presymptomatic (2-month-old) to early-symptomatic (3-month-old) stage of the hSOD1(G93A) mouse model of familial ALS. Net synapse loss resulted from inhibitory bouton loss and excitatory synapse gain. Furthermore, in 3-month-old transgenic mice, remaining inhibitory but not excitatory boutons attached to mot…
Demographic parameters of Brachionus calyciflorus Pallas (Rotifers) exposed to sublethal endosulfan concentrations
1991
The effects of sublethal levels of endosulfan (0, 1, 1.5, 2.5 and 3.3 mg 1−1) on the demography of the rotifer Brachionus calyciorus were studied. Life expectancy at birth (e o), net reproductive rate (Ro), generation time (T) and intrinsic rate of natural increase (r) were significant differentes between blank controls and controls with acetone. The effective endosulfan concentration at which a given parameter value was reduced to 50% of the controls (EC50) was calculated for life expectancy.
Identification of sequences in the human peptide transporter subunit TAP1 required for transporter associated with antigen processing (TAP) function
2001
The heterodimeric peptide transporter associated with antigen processing (TAP) consisting of the subunits TAP1 and TAP2 mediates the transport of cytosolic peptides into the lumen of the endoplasmic reticulum (ER). In order to accurately define domains required for peptide transporter function, a molecular approach based on the construction of a panel of human TAP1 mutants and their expression in TAP1(-/-) cells was employed. The characteristics and biological activity of the various TAP1 mutants were determined, and compared to that of wild-type TAP1 and TAP1(-/-) control cells. All mutant TAP1 proteins were localized in the ER and were capable of forming complexes with the TAP2 subunit. H…
Mildronate improves cognition and reduces amyloid-β pathology in transgenic Alzheimer's disease mice
2013
Mildronate, a carnitine congener drug, previously has been shown to provide neuroprotection in an azidothymidine-induced mouse model of neurotoxicity and in a Parkinson's disease rat model. The aim of this study was to investigate the effects of mildronate treatment on cognition and pathology in Alzheimer's disease (AD) model mice (APP(SweDI)). Mildronate was administered i.p. daily at 50 or 100 mg/kg for 28 days. At the end of treatment, the animals were behaviorally and cognitively tested, and brains were assessed for AD-related pathology, inflammation, synaptic markers, and acetylcholinesterase (AChE). The data show that mildronate treatment significantly improved animal performance in w…
The role of plasma lipid transfer proteins in lipoprotein metabolism and atherogenesis.
2008
The plasma lipid transfer proteins promote the exchange of neutral lipids and phospholipids between the plasma lipoproteins. Cholesteryl ester transfer protein (CETP) facilitates the removal of cholesteryl esters from HDL and thus reduces HDL levels, while phospholipid transfer protein (PLTP) promotes the transfer of phospholipids from triglyceride-rich lipoproteins into HDL and increases HDL levels. Studies in transgenic mouse models and in humans with rare genetic deficiencies (CETP) or common genetic variants (CETP and PLTP) highlight the central role of these molecules in regulating HDL levels. Human CETP deficiency is associated with dramatic elevations of HDL cholesterol and apolipopr…
Effects of neuron-specific ADAM10 modulation in an in vivo model of acute excitotoxic stress.
2008
A disintegrin and metalloprotease (ADAM) 10 is the main candidate enzyme for the alpha-secretase processing of the amyloid precursor protein (APP). Neuron-specific ADAM10 overexpression proved beneficial in the APP[V717I] mutant Alzheimer mouse model [Postina R, Schroeder A, Dewachter I, Bohl J, Schmitt U, Kojro E, Prinzen C, Endres K, Hiemke C, Blessing M, Flamez P, Dequenne A, Godaux E, van Leuven F, Fahrenholz F (2004) A disintegrin-metalloproteinase prevents amyloid plaque formation and hippocampal defects in an Alzheimer disease mouse model. J Clin Invest 113:1456-1464]. Since Alzheimer patients have a high prevalence for epileptic seizures, we investigated the effects of ADAM10 modula…
Naturally occurring autoantibodies interfere with β-amyloid metabolism and improve cognition in a transgenic mouse model of Alzheimer's disease 24 h …
2013
There is evidence that naturally occurring antibodies directed against Aβ (nAbs-Aβ) have a role in Aβ-metabolism and Aβ-clearance. The presence of nAbs-Aβ leads to a reduction in amyloid fibrillation and thus a reduction in their toxicity. We investigated the effects of nAbs-Aβ in respect to oligomerization and used the Tg2576 transgenic mouse model in order to investigate the rapid effect with a single-dose (24 h) on oligomer breakdown and cytokine secretion along with immunohistochemical characterization of synaptic plasticity. nAbs-Aβ were able to reduce toxic oligomer concentration with an increase in Aβ-monomers. Cytokine secretion was significantly reduced. Synaptic plasticity was als…
Detection of mammalian carcinogens with an immunological DNA synthesis-inhibition test.
1992
There is a close relationship between genotoxicity, mutagenicity and carcinogenicity. But the controversy of which short-term test system best recognizes human carcinogens is still going on. Currently, the Salmonella gene mutation assay ('Ames test') is the most widely used test for the screening of mutagens. However, many in vitro tests hold unsatisfactory validity data, presumably because of the inability of present short-term tests to detect non-genotoxic carcinogens, which are increasingly being brought into focus in the discussions of genesis of cancer. One principle often neglected in this context is the property of genotoxic agents to inhibit replicative DNA synthesis in (proliferati…
Photochemical genotoxicity: principles and test methods
2004
In recent years, assessing the photogenotoxic potential of a compound became an issue for certain drugs and cosmetical products. Therefore, existing methods performed according to international guidelines (e.g. OECD guidelines) were adapted to the use of concurrent UV-visible (UV-Vis) light irradiation for the assessment of photomutagenicity/photogenotoxicity. In this review, photobiological bases of the processes occurring in the cell after irradiation with UV- and/or visible (vis)-light as well as a compilation of testing methods is presented. Methods comprise cell free investigations on naked DNA and in vitro methods, such as the photo-Ames test, the photo-HPRT/photo-mouse lymphoma assay…
Estrogenic effects of food wrap packaging xenoestrogens and flavonoids in female Wistar rats : a comparative study
2003
International audience; The objective of this study was to compare the estrogenicity of xenoestrogens found in food wrap packaging and phytoestrogen flavonoids. Uterotrophic and vaginal cornification assays were performed on immature and ovariectomized rats. Genistein, bisphenol F, and octylphenol were identified as estrogenic only in immature rats. Using vaginal cornification as a more specific estrogenic parameter, all tested compounds except tangeretin were active in immature rats. While apigenin and kaempferol appeared to have low estrogenic activity, they potentialized the uterotrophic effect of 17β-estradiol in immature rats. These data showed that (i) phytoestrogens like genistein ca…