1,720,991 research outputs found
Biological markers of neurotoxic diseases
No full textThe paper describes relevant examples of biomarkers of neurotoxicity (biomarkers of exposure, effect, and susceptibility) that can be applied in cinical studies of neurotoxic disease
Neurotoxicity and molecular effects of methylmercury
No full textThe paper reviews molecular effects of methylmercury that can be seen at low doses/concentrations. Examples of relevant molecular changes that can impact on developmental neurotoxicity of methylmercury in humans are presented
Ethanol selectively interferes with the trophic action of NMDA and carbachol on cultured cerebellar granule neurons undergoing apoptosis
No full textExposure of mature rat cerebellar granule neurons to non-depolarizing conditions (5 mM K+) for 24 h resulted in the onset of apoptosis. NMDA, forskolin, carbachol and GABA attenuated low K+-induced toxicity, although to a different extent, with NMDA and GABA being the most effective agents. When cells were co-exposed for 24 h to ethanol, the survival promoting action of NMDA and carbachol, but not that of forskolin and GABA, was attenuated. By contrast, a 24 h cell pre-treatment with ethanol, followed by its removal prior to K+ deprivation, was ineffective towards the neurotrophic action of NMDA and carbachol. The concomitant presence of alcohol and neurotrophic factors was not required for the pro-apoptotic effect of ethanol to be manifest after a long-term alcohol exposure: inhibition of NMDA- and carbachol-mediated neurotrophism was still observed when cells were pre-exposed for 72 h to alcohol in depolarizing conditions, prior to the challenge with 5 mM K+-containing medium and the test compounds in the absence of ethanol. The present study shows that ethanol promotes apoptotic cell death of cultured cerebellar neurons by selectively inhibiting the neurotrophic effect of NMDA and carbachol, and suggests that alcohol may cause permanent changes in the control mechanisms of apoptosis: this finding may have significant implications for the in vivo toxicity of prenatal ethanol exposure on the developing cerebellum
Cyclic GMP formation induced by muscarinic receptors is mediated by nitric oxide synthesis in rat cortical primary cultures
No full textIn rat primary cortical cultures, carbachol caused a time- and concentration-dependent increase in guanosine cyclic 3',5'-monophosphate (cGMP) levels, which was antagonized by the muscarinic antagonist atropine. Glutamate and sodium nitroprusside also caused large increases in cGMP levels, as previously reported. Two nitric oxide (NO) synthase inhibitors, L-NG-nitroarginine and L-NG-monomethylarginine, were tested for their ability to inhibit the carbachol- and the glutamate-induced cGMP formation. The cGMP response to carbachol was decreased by both compounds in a dose-dependent fashion. The effect of L-NG-nitroarginine was competitively reversed by addition of an excess of L-arginine. Similarly, the stimulatory effect of glutamate on cGMP levels was antagonized by L-NG-nitroarginine and L-NG-monomethylarginine. Hemoglobin, a scavenger of NO, also blocked the carbachol-stimulated cGMP production. These results indicate that muscarinic receptor-stimulated cGMP formation in rat cerebral cortex is mediated by NO
[Oncogenes as indicators of occupational exposure to carcinogenic agents]
No full textOncogenes are a class of genes capable of inducing neoplastic alterations of the cell. Recently, oncogenes have received greater attention in environmental medicine, since they may be useful tools for monitoring individuals exposed to carcinogenic chemicals. Their potential use as biomarkers is supported by studies indicating changes in the expression of growth factors and oncoproteins in chemically induced cancer. These alterations may even take place prior to clinical diagnosis. In addition, availability of new immunoblotting techniques, which allow the detection of oncoproteins and growth factors in easily accessible tissues, such as serum and urine, has provided promising preliminary results in humans. In this paper, mechanisms of oncogene activation and their role in occupational carcinogenesis are briefly discussed. Recent human studies suggesting a link between occupational toxicants and oncogenes, as well as a potential use of oncogenes as biomarkers, are also reported. Finally, advantages and limits of oncogenes over more traditional biomarkers are discussed
Effects of the muscarinic agonist oxotremorine on membrane fluidity in rat lymphocytes
No full textThe muscarinic agonist oxotremorine produced a concentration-dependent increase in membrane fluidity in intact viable rat splenic lymphocytes in vitro. This effect was antagonized by atropine, but only at high concentrations (1 mM), while scopolamine was ineffective. Two other muscarinic agonists, carbachol and pilocarpine, did not affect membrane fluidity in lymphocytes. The fluidizing effect of oxotremorine occurred at both 10 and 37 degrees C with a similar time-course. Oxotremorine also increased membrane fluidity in liposomes of DMPC in gel phase, although its effect was less pronounced than in lymphocytes. The data suggest that the fluidization caused by oxotremorine is primarily nonreceptor-mediated and associated with a nonspecific physicochemical effect
Interaction of aluminum ions with phosphoinositide metabolism in rat cerebral cortical membranes
No full textAluminum (Al) is believed to exert a primary role in the neurotoxicity associated with dialysis encephalopathy and has been suggested to be involved in a number of other neurological disorders, including Alzheimer's disease. Al, complexed with fluoride to form fluoroaluminate (AlF4-), can activate the GTP-binding (G) proteins of the adenylate cyclase and retinal cyclic GMP phosphodiesterase systems. Since an involvement of G-proteins with cerebral phosphoinositide (PtdIns) metabolism has also been suggested, in this study we investigated the interaction of the stable GTP analogue GTP(S), Al salts and NaF with this system. In rat cerebral cortical membranes, GTP(S) dose-dependently stimulated [3H]inositol phosphates ([3H]InsPs) accumulation. This effect was potentiated by carbachol and was partially prevented by the GTP-binding antagonist GDP(S), indicating that CNS muscarinic receptor activation is coupled to PtdIns hydrolysis via putative G-protein(s). GTP(S) stimulation was also inhibited by phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C, which is known to exert a negative feedback control on agonist-stimulated PtdIns metabolism. Both Al salts and NaF mimicked the action of GTP(S) in stimulating PtdIns turnover. Their actions were highly synergistic, suggesting that AlF4- could be the active stimulatory species. However, the stimulatory effects of AlCl3 and/or NaF were not potentiated by carbachol and were not inhibited by GDP(S) and PMA, suggesting that separate sites of action might exist for GTP(S) and AlF4-. In the nervous tissue, activation of PtdIns hydrolysis by Al (probably as AlF4-) may be mediated by activating a regulatory G-protein at a location distinct from the GTP-binding site or by a direct stimulation of phospholipase C
Metabolism and toxicity of occupational neurotoxicants: genetic, physiological and environmental determinants
No full text
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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