1,721,033 research outputs found
Farmacovigilanza e fitovigilanza
No full textLa Farmacovigilanza, secondo l'Organizzazione Mondiale della Sanità (OMS), è "l'insieme delle attività correlate all’identificazione, comprensione e prevenzione degli effetti avversi o di ogni altro possibile problema legato all'uso di farmaci" o, secondo l'Agenzia Italiana del Farmaco (AIFA), " il complesso di attività finalizzate a valutare in maniera continuativa tutte le informazioni relative alla sicurezza dei farmaci e ad assicurare, per tutti i medicinali in commercio, un rapporto beneficio/rischio favorevole per la popolazione". La fitovigilanza, o fitosorveglianza invece si occupa del monitoraggio e della sicurezza di impiego di prodotti a base di piante officinali e integratori alimentari. La necessità di un sistema di fitovigilanza deriva dall’uso sempre più diffuso e indiscriminato dei prodotti contenenti piante officinali, spesso di scarsa qualità, condotto sulla base dell’automedicazione, e sempre più spesso utilizzati da fasce di popolazione particolarmente sensibili (e.g. pazienti anziani in politerapia, donne in gravidanza o allattamento)
Simvastatin acutely reduces hypoxia-ischemia induced brain damage in the immature rat via Akt activation and reduction of inflammatory cell recruitment
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Characterization of ouabain-induced phosphoinositide hydrolysis in brain slices of the neonatal rat
No full textThe effect of the Na/K-ATPase inhibitor ouabain on phosphoinositide (Ptdlns) hydrolysis was studied in rat brain cortical slices. Ouabain induced a dose-dependent accumulation of inositol phosphates (InsPs) which was much higher in neonatal rats (1570 +/- 40% of basal) than in adult animals (287 +/- 18% of basal). For this reason, all experiments were conducted with 7 day-old rats. Strophantidin caused a similar stimulation of Ptdlns hydrolysis, although it was less potent than ouabain. The order of potency for ouabain-stimulated InsPs accumulation in brain areas was hippocampus greater than cortex greater than brainstem greater than cerebellum. The effect of ouabain was not blocked by antagonists for the muscarinic, alpha1 -adrenergic and glutamate receptors. Also ineffective were the K+ channel blockers 4-aminopyridine and tetraethylammonium, the sodium channel blocker tetrodotoxin, and the calcium channel blocker verapamil, whereas the Na/Ca exchanger blocker amiloride partially antagonized the effect of ouabain. The accumulation of InsPs induced by ouabain was additive to that of carbachol and norepinephrine, as well as to that induced by high K+ and veratrine, but not to that of glutamate. Removal of Na+ ions from the incubation buffer completely prevented the accumulation of InsPs induced by ouabain. The effect of ouabain was also dependent upon extracellular calcium and was under negative feedback control of protein kinase C. Despite the higher effect of ouabain on Ptdlns hydrolysis of immature rats, the density of [3H]ouabain binding sites, as well as the activity of Na/K-ATPase were higher in adult animals. Furthermore, a poor correlation was found between ouabain-stimulated Ptdlns hydrolysis and [3H]ouabain binding in brain regions.(ABSTRACT TRUNCATED AT 250 WORDS
Interaction of ethanol and anoxia with muscarinic receptor--stimulated phosphoinositide metabolism during brain development
No full textThe mechanism(s) by which ethanol induces alterations in brain development may involve direct actions (e.g. changes in specific biochemical pathways), or indirect effects, such as cerebral hypoxia resulting from ethanol - induced circulatory changes. Since both ethanol and hypoxia are known to affect the metabolism of phosphoinositides, which has been suggested as a possible target for ethanol's developmental neurotoxicity, in the present study we have investigated the in vitro effects of both severe hypoxia (anoxia) and ethanol (alone or in combination) on muscarinic receptor-stimulated phosphoinositide metabolism in cerebral cortex slices from neonatal rats. Anoxia markedly inhibited carbachol - stimulated phosphoinositide metabolism in adult rats (67%), but only slightly (10%) in neonatal animals. Reoxygenation reversed the effect of anoxia at both ages. On the other hand, ethanol's inhibitory effect was pronounced in neonatal rats only, and was additive to that of anoxia. The presence of ethanol did not affect the recovery of carbachol - stimulated phosphoinositide metabolism following anoxia and reoxygenation. These results indicate that ethanol and anoxia differently and independently affect muscarinic receptor - stimulated phosphoinositide metabolism and may mutually contribute to the CNS effects observed following developmental ethanol exposure
EFFECTS OF ETHANOL ON MUSCARINIC RECEPTOR-STIMULATED PHOSPHOINOSITIDE METABOLISM DURING BRAIN DEVELOPMENT
No full textThe pattern of muscarinic receptor-stimulated inositol metabolism during postnatal development has a striking resemblance with the curve of rat brain growth spurt. Therefore, the enhanced hydrolysis of membrane inositol lipids by cholinergic agonists during this period may have a relevant role in cell proliferation and differentiation. In this study we have investigated whether exposure to EtOH to rat pups during the brain growth spurt, known to cause a permanent microencephaly, would alter muscarinic receptor-stimulated inositol metabolism in cerebral cortex. Female Long-Evans rats were administered 4 g/kg of EtOH, in two doses of 2 g/kg, by gastric intubation from postnatal day 4 to day 10. This treatment did not have any effect on the pups' body weight as compared to an equally handled, sucrose-fed group of animals. Blood EtOH concentration in the pups during exposure ranged between 237 and 283 mg/dl. Muscarinic receptor-stimulated inositol metabolism was measured in cerebral cortex slices of control and EtOH-treated rats at days 4, 7, 10, 12, 20 and 45 of age. Carbachol-induced accumulation of [3H] inositol phosphates was reduced significantly in EtOH-exposed animals on day 7 and 10, but not at other ages. This decrease was not due to an alteration of muscarinic receptor density or affinity. Exposure to EtOH had no effect on phosphoinositide metabolism stimulated by norepinephrine, serotonin or histamine in cerebral cortex, whereas the effect of glutamate was increased. Similar results were observed in the hippocampus. An identical treatment with EtOH in adult rats did not cause alteration in any of the biochemical parameters of the cholinergic system measured.(ABSTRACT TRUNCATED AT 250 WORDS
MUSCARINIC RECEPTOR STIMULATION OF PHOSPHOLIPASE-D ACTIVITY IN THE DEVELOPING RAT-BRAIN
No full textIn addition to stimulating the metabolism of phosphoinositides, cholinergic muscarinic agonists have also been shown to activate hydrolysis of phosphatidylcholine by phospholipase D. This reaction, which yields phosphatidic acid (PA) and choline, has been identified in a number of in vitro cell preparation; however, several investigators failed to observe stimulation of phospholipase D activity by carbachol in hippocampal or cortical slices from adult rats. Here we report that carbachol causes activation of phospholipase D, measured by the formation of phosphatidylethanol (PEtOH) in the presence of ethanol, and of PA, in cortical slices from 7 day-old rats. The effect of carbachol was blocked by the muscarinic antagonist atropine but not by H7, an inhibitor of PKC, and was mimicked by glutamate and the phorbol ester TPA. Activation of phospholipase D by carbachol was also observed in rat cortical astrocytes in primary cultures. Differently from brain slices, PA formation in astrocytes appeared to totally derive from hydrolysis of phosphatidylcholine. Activation of phospholipase D by muscarinic agonists in brain from immature rats may play a relevant role in some developmental actions of acetylcholine such as, for example, its mitogenic effect in astrocytes
Administration of ethanol during brain growth spurt causes dose-dependent microencephaly and inhibition of muscarinic receptor-stimulated phosphoinositide metabolism in the rat
No full textDifferent dose levels of ethanol (2,3,4,5 g/kg) were administered to rat pups between postnatal days 4 and 10. Ethanol caused a dose-dependent decrease in brain weight (measured on postnatal day 12) and inhibition of carbachol-stimulated phosphoinositide metabolism (measured in cerebral cortex slices on postnatal day 7). The 2 g/kg dose, which gave blood alcohol levels of 128 mg/dl, was a no-effect-level for both endpoints. Ethanol administration did not alter the relative distribution of phosphoinositides in the cerebral cortex from 7 day-old rats. These results show a dose-dependent correlation between ethanol-induced microencephaly and inhibition of muscarinic receptor-stimulated phosphoinositide metabolism and add support to the hypothesis that this second messenger system may be involved in the developmental neurotoxicity of ethanol
The muscarinic receptor-coupled phosphoinositide metabolism as a potential target for the developmental neurotoxicity of aliphatic alcohols
No full textSimvastatin acutely reduces ischemic brain damage in the immature rat via Akt and CREB activation
No full textWe have previously shown that simvastatin (Sim) has long-lasting neuroprotective effects in a neonatal model of hypoxia-ischemia. Herein we evaluated the neuroprotective effect of different doses and duration of Sim treatment and further addressed its mechanism of action. Neonatal rats were subjected to occlusion of the right carotid artery followed by 2.5 h hypoxia (hypoxia-ischemia, HI). Sim was given at the dose of 10 or 5 mg/kg, s.c. from postnatal day 1 (PN1) to PN7, or at 20 mg/kg from PN4 to PN7, or at 20 mg/kg in a single administration 18 h before the onset of the ischemic procedure. Low-dose treatments or a single administration of the drug were effective in reducing HI-induced brain damage and its behavioural outcomes. Sim increased both Akt and CREB phosphorylation in neuronal cells and treatment with wortmannin completely blocked neuroprotection and p-Akt. These data demonstrate that even a single prophylactic Sim administration protects from hypoxic ischemic brain damage and that neuroprotection is in part obtained by preserving Akt and stimulating CREB phosphorylation in neuronal cells. Prophylactic Sim administration set in motion biochemical events that are known to increase brain tolerance to harmful factors, suggesting that the drug may exert neuroprotection by inducing pharmacological preconditioning
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