1,720,966 research outputs found
Review article: cardiac adverse effects of gastrointestinal prokinetics
No full textGastrointestinal prokinetics, such as metoclopramide, cisapride and levosulpiride, are widely used for the management of functional gut disorders. Recently, several studies have shown that cisapride (a partial 5-HT4 receptor agonist) can induce dose-dependent cardiac adverse effects, including lengthening of the electrocardiographic QT interval, syncopal episodes and ventricular dysrhythmias. Until recently, it was not clear whether these effects were dependent on 5-HT4 receptor activation or related to peculiar characteristics in the molecular structure of single agents within the benzamide class. Experimental evidence now favours the second hypothesis: cisapride possesses Class III antiarrhythmic properties and prolongs the action potential duration through blockade of distinct voltage-dependent K+ channels, thus delaying cardiac repolarization and prolonging the QT interval. Patients at risk of cardiac adverse effects are children, subjects with idiopathic, congenital or acquired long QT syndrome and, in particular, those receiving concomitant medication with Class III antiarrhythmic agents, some H1-receptor antagonists (e.g. terfenadine), or drugs such as azole antifungals (e.g. ketoconazole, itraconazole, miconazole and fluconazole) and macrolide antibacterials (e.g. erythromycin, clarithrod-mycin and troleandomycin), which can inhibit cisapride metabolism by interfering with the CYP3A4 isoenzym
Neurotrasmettitori nelle vie aeree: caratterizzazione farmacologica del sistema non adrenergico non colinergico inibitorio nella trachea di cavia
No full textIn order to characterize the role of nitric oxide (NO), vasoactive intestinal peptide (VIP), ATP and carbon monoxide (CO) in the neurally mediated EFS-induced relaxation of isolated guinea-pig trachea, we evaluated the relaxing responses before and after treatment with known blockers of either synthesis or action of each mediator. The role of NO and ATP was shown to be both significant and similar. Peptide mediators did not show a significant role. The role of CO was shown only incases of blockage of the other mediators. In conclusion, apart from the most well-known mediators, at least two other mediators, i.e. ATP, or a related purine, and CO, are involved in the NANC relaxation of guinea-pig trachea
Nandrolone and bone regeneration
No full textAim of this study is to achieve better bone quality using steroids since many attempts to find factors useful in boosting bone regeneration has failed. In a preliminary study performed in a mini-pig model we analyzed the effect of stanazolol. Greater amount of newly formed bone surrounding the implants and active osteoblasts covering bone surfaces were found in mini-pig treated with stanazolol. The effect of nandrolone, given parenterally to adult male rabbits, was analyzed after insertion of titanium dental fixtures in the tibias of treated and control animals. Samples of blood were collected before surgery. Treatment groups, each of 4, underwent injection of nandrolone after the fixture insertion and 7 days later. Control groups (of 2 rabbits) were saline injected. Bone labelling was performed by Tetracycline injection 7 days before sacrifice. Rabbits were sacrificed after 2, 3 and 4 weeks. The organs of the animals underwent histological analysis to verify damages due to the drug administration. The undecalcified tibia specimens analyzed on microradiographs and fluorescence microscope showed an increased amount of newly formed tissue and a substantial absence of injures to organs in nandrolone-treated rabbits. The results of this research seem to confirm the capability of nandrolone on boosting bone processes
Materiali osteoconduttori: sperimentazione animale e osservazioni microscopiche (nota 1)
No full textEffects of thallium on primary cultures of testicular cells
No full textThe objective of this in vitro study was to examine the response of mixed cultures of Sertoli and germ cells to treatment with thallium (TI) at the range of concentrations that, in previous studies, was shown in vivo to affect reproduction. Cultures were prepared from the testis of Sprague-Dawley rats. Cultures containing approximately3.75 à 106cells/ml were treated with Tl concentrations corresponding to 35, 7, and 1.4 Î1⁄4g Tl/g testis, estimated from protein content of cultures. Observations at 24, 48, and 72 h after treatment showed a significant release of germ cells into the culture medium that was both concentration and time dependent. Cultures treated with 35 Î1⁄4g Tl/g testis showed a threefold increase in germ-cell detachment compared with controls after only 24 h of exposure. As the treatment time increased to 48 h of exposure, even cultures exposed at the lowest Tl concentration (1.4 Î1⁄4g Tl/g testis) showed significant loss of germ cells. After 48 h, cultures exposed to 7 Î1⁄4g Tl/g testis exhibited a 2.5- fold increase in germ-cell detachment, and those exposed to 35 Î1⁄4g Tl/g testis exhibited a 10-fold increase over controls. Morphological investigations of cell cultures showed evident loss of germ cells with significant reduction in prepachytene and pachytene spermatocytes and changes in the shape of Sertoli cells. These results are in agreement with in vivo studies, in which thallium treatment at comparable exposure levels manifested its earliest toxic testicular effects in Sertoli and germ cells. They also demonstrate the usefulness of this in vitro culture technique to assess toxic testicular damage rapidly. © 1988 by Hemisphere Publishing Corporation
Fluoroquinolone-induced motor changes in the guinea-pig isolated ileum
No full textThe effects of norfloxacin and enoxacin were examined on spontaneous motor activity in the guinea-pig isolated ileum. Micromolar concentrations of both compounds caused a biphasic response consisting of relaxation followed by transient contraction. Relaxation to norfloxacin, which was unaffected by phentolamine, propranolol and hyoscine (each at 1 microM), was partially sensitive to tetrodotoxin (1 microM). This indicates that the response is partly mediated by non-adrenergic non-cholinergic (NANC) inhibitory nerves, and partly related to a direct action on the smooth muscle. Apamin (0.1 microM) and suramin (300 microM) inhibited norfloxacin-induced relaxations to an extent similar to that of tetrodotoxin. Conversely, NG-nitro-L-arginine (300 microM) was ineffective. In the presence of theophylline (100 microM) and 3-isobutyl-1-methylxanthine (10 microM), norfloxacin caused relaxation less effective than when added alone. Based on this observation, the NANC component of the relaxation apparently depends on ATP release, whereas the direct component might be due, at least in part, to phosphodiesterase inhibition. Norfloxacin-induced contractions were neurogenic and cholinergic in nature. They were reduced by indomethacin or S-ketoprofen (both at 0.01-1 microM) and suramin (300 microM), suggesting involvement of local prostaglandin production probably induced by ATP release. Previous findings revealed that norfloxacin acted as a non-competitive antagonist at enteric GABAA receptors. In this study the same property was shared by enoxacin against the contractile response to 3-aminopropane sulphonic acid (3-APS), a GABAA receptor agonist. In conclusion, fluoroquinolones exert inhibitory and excitatory effects in the guinea-pig ileum. These are mediated by ATP, prostaglandin and acetylcholine release that might underlie, at least in part, the alterations of gastrointestinal motility observed after fluoroquinolone administration. Furthermore, isolated intestinal preparations might be useful to predict the GABAA-antagonist potential of this class of compounds
Review of the implications of dietary tryptophan intake in patients with irritable bowel syndrome and psychiatric disorders
No full textIn this review, we address the possible role of the essential amino acid L-tryptophan or its metabolic derivative 5-hydroxytryptophan in the modulation of serotonin (5-hydroxytryptamine) synthesis and thereby in affecting the pathophysiology of central and peripheral nervous system disorders, including depression and irritable bowel syndrome. L-Tryptophan may represent a link between apparently disparate functional disorders and is of interest for general gastroenterologists, neurogastroenterologists, and neurologists. On the basis of estimates showing that approximately 20% of patients with functional bowel disorders seeking care in referral centres have psychiatric comorbidity, we attempt to provide a conceptual framework for defining the possible role of L-tryptophan in this population
5-HT4 receptors contribute to the motor stimulating effect of levosulpiride in the guinea-pig gastrointestinal tract
No full textEndothelin and nitric oxide-synthase in lymphatic endothelial cells: immunolocalization in vivo and in vitro.
No full textA re-appraisal of the nature of the atropine-resistant contraction to electrical field stimulation in the human isolated detrusor muscle
No full textWe investigated whether in human isolated detrusor strips the atropine-resistant contractile response to electrical field stimulation was mediated by ATP (or a related purine), as previously shown in the urinary bladder of other mammalian species. Electrical stimulation (1-50 Hz for 5 s at 1 min intervals, 0.1 ms pulse width, 60 V) elicited reproducible, frequency-dependent twitch contractions, which were markedly reduced by atropine (10 microM). Tetrodotoxin (TTX: 1 microM) inhibited contractile responses to a similar degree. When applied together, atropine and TTX caused an inhibition which was superimposable to that caused by either drug alone. The TTX-resistant contractions were totally unaffected by omega-conotoxin GVIA (omega-CTX: 0.1 microM). The atropine-resistant contractions were unaffected by the P2-purinoceptor antagonists suramin (300 microM) and PPADS (30 microM), at concentrations which virtually suppressed the contractile response induced by applied ATP (10 microM(-1) mM). As previously described, antagonism of the ATP-induced contractions by suramin (30, 100, 300 microM) and PPADS (3, 10, 30 microM) was insurmountable, with apparent 'pA2' values (calculated at the lowest antagonist concentrations) of 4.9 and 5.2, respectively. It is concluded that, under our experimental conditions, the non-cholinergic (atropine-resistant) component of the excitatory transmission in the human detrusor is not mediated by neural release of ATP, in spite of the presence of excitatory P2-purinoceptors on the effector cells. The TTX- and omega-CTX-resistant, non-cholinergic component might be related to the release of unknown transmitter(s) through a mechanism independent of both Na+- and N-type Ca2+-channels. More likely, the atropine-resistant component may reflect direct smooth muscle excitation since the human detrusor has a very short chronaxie
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