1,721,036 research outputs found

    Spatiotemporal role of muscarinic signaling in early chick development: exposure to cholinomimetic agents by a mathematical model

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    Awareness is growing that, besides several neurotoxic effects, cholinomimetic drugs able to interfere the cholinergic neurotransmitter system may exert a teratogen effect in developing embryos of vertebrate and invertebrate organisms. Cholinomimetic substances exert their toxic activity on organisms as they inhibit the functionality of the cholinergic system by completely or partially replacing the ACh molecule both at the level of the AChE active site and at the level of acetylcholine receptors. In this work, we focused the attention on the effects of muscarinic antagonist (atropine) and agonist (carbachol) drugs during the early development and ontogenesis of chick embryos. An unsteady-state mathematical model of the drug release and fate was developed, to synchronize exposure to a gradient of drug concentrations with the different developmental events. Since concentration measures in time and space cannot be taken without damaging the embryo itself, the diffusion model was the only way to establish at each time-step the exact concentration of drug at the different points of the embryo body (considered two-dimensional up to the 50 h stage). This concentration depends on the distance and position of the embryo with respect to the releasing source. The exposure to carbachol generally enhanced dimensions and stages of the embryos, while atropine mainly caused delay in development and small size of the embryos. Both the drugs were able to cause developmental anomalies, depending on the moment of development, in a time- and dose-dependent way, regardless the expression of genes driving each event

    Cholinergic molecules and sperm functions

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    Molecules acting on neurotransmitter systems are known to be present in sperms of several species: their presence was correlated to the regulation of sperm propulsion. To understand their function, a study was carried out on sperm activation, in the presence of cholinergic drugs (acetylcholine and drugs competitive at cholinergic receptors, agonist and antagonist, both muscarinic and nicotinic ones). The in vivo effects were also studied by demonstrating membrane depolarization with merocyanine, a potentiometric dye. Concentrated acetylcholine, up to 100 muM, inhibited both activation and membrane depolarization, while diluted to 10 muM, ACh enhanced it. The competitive drugs exerted on activation more or less the same effects as those on movement, reported in literature. 100 muM atropine reversibly prevented activation, while, more diluted, only delayed it. 1 muM nicotine and carbachol enhanced, and curare delayed activation and merocyanine staining. The results show the possibility that both nicotinic and muscarinic AChRs are involved in the mechanism of sperm activation. Further, the possibility that an ACh-like substance concentrated in the sperm liquid may be involved in maintaining the sperms in the quiescent state is discussed

    Sea urchin coelomocytes cultured on nanoporous aluminium oxide as a potential tool for marine environmental monitoring

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    Oceans and seas are of paramount importance to the health of planet Earth and human kind. Marine ecosystems should be defended against attack of polluting agents by continuous monitoring; the means of such monitoring should be as green as possible, i.e. based on sensors manufactured by biocompatible and easily disposable raw materials. In this study, we lay the basis for the future development of biosensors of marine environment based on sea urchin cells cultured on nanoporous aluminium oxide. These cells are promising as in previous works they demonstrated high response to stressors, and the proposed substrates have low costs since fabricated by inexpensive anodization process from consumer quality aluminium foils. Coelomocytes of the Mediterranean sea urchin Paracentrotus lividus were cultured on the nanoporous alumina for up to 5days invitro. Then, a biochemical characterization was carried out, checking the cholinergic system pathway by means of serotonin autofluorescence induced by aldehyde exposure and by expression and functionality of neuroactive molecules, such as acetylcholinesterase and muscarinic acetylcholine receptors. Both living cell quality and system biochemistry were not affected after the culture, and both electrical modulation and non-self-reactivity were maintained. These findings sug- gest the possibility of using the sea urchin immune cells cultured on nanoporous alumina as tools for monitoring the marine water quality, based on their electrical response

    Effects of the neurotoxic thionophosphate pesticide chlorpyrifos on differentiating alternative models

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    Studies by researchers worldwide have revealed that, even in industrialised nations, people, infants and the aged in particular, are even more exposed to neurotoxic drugs as a consequence of the increased quantity of pesticide residues in food. This phenomenon, as underlined by The Worldwatch Institute (2006), is linked to the exponential increase in the use of these toxic compounds over the last 40. years, up from 0.49. kg per hectare in 1961 to 2. kg in 2004, with the result that these substances are found in the daily diet.Many studies have demonstrated how the assumption of pesticides in the neonatal period and early infancy can alter the development and function of the nervous, immune, endocrine and reproductive apparatuses. Moreover, the unequivocal relationship between brain tumours, infant leukemia and pesticides are well recognised.On the basis of the above information, the effects of the neurotoxic thionophosphate pesticide chlorpyrifos (CPF) have been tested, considering biomarkers of toxicity and toxicity endpoint, on the biological models Dictyostelium discoideum, Paracentrotus lividus, and NTera2 Cells, as they are compatible with the 3Rs strategy (Reduction, Replacement, and Refinement in animal experiments). Our results have revealed that developing organisms are particularly sensitive to the toxic effects of CPF. © 2012 Elsevier Ltd
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