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Biomedical subjects

M Marcoli

Publications and source records attributed to M Marcoli.

At least 37 records · Page 2Linked to original sources

Opioid-induced modification of granulocyte function.

Inhibition of human granulocyte chemotaxis towards casein was observed in the presence of both the mu and kappa opioid receptor agonists, which, per se, exhibited chemokinetic activity. Naloxone was found to prevent both the opioid-related and opioid-unrelated increase in granulocyte migration. Moreover, morphine inhibited the aggregation response of granulocytes in a naloxone-sensitive way, while the opioid peptides were ineffective. Although opioid agonists with different receptor specificity were capable of strongly modifying human granulocyte migration, no conclusion can be drawn on the role of opioid receptors in regulating migrating activity. On the other hand, opioid receptor activation by morphine is likely to be responsible for aggregation inhibition.

Adenosine Triphosphate↗

Assessment of lymphocyte and phagocytic cell function in healthy volunteers undergoing short-term phenytoin administration.

The effect of short-term (2 weeks) administration of the anticonvulsant drug phenytoin on humoral and cellular immune function and phagocytic cell system activity was tested in nine healthy volunteers. No change either in the absolute or relative counts of leukocytes was found after drug treatment. Moreover, immunoglobulin serum concentration and lymphocyte subsets positive for OKT3, OKT4, OKT8, OKDRIA, OKB2, Leu 7, Leu 11a, anti-beta 2-microglobulin and antitransferrin monoclonal antibodies were not affected by phenytoin administration. A significant impairment of both polymorphonuclear neutrophil migrating activity and stimulated metabolism as measured by nitro blue tetrazolium reduction and superoxide anion generation was found after drug treatment or when phenytoin was added in vitro to the cells at concentrations lying within the anticonvulsant therapeutic range. Monocyte function was unaffected both after phenytoin administration and after direct application to the cells. The phenytoin-induced changes of polymorphonuclear neutrophil function was completely reverted within 2 weeks after drug withdrawal. The phenytoin-induced alterations of the phagocytic cell system are discussed in relation not only to the possible implications in the pathogenesis of adverse effects of anticonvulsant therapy but also to the potential therapeutic exploitation in immunologically mediated disorders.

Adult↗

A facilitatory effect of bicuculline on the enteric neurones in the guinea-pig isolated colon.

Changes in the efficiency of the peristaltic reflex, acetylcholine (ACh) output and motor responses to transmural and periarterial nerve stimulation produced by bicuculline and gamma-aminobutyric acid (GABA) receptor desensitization were investigated in the guinea-pig isolated colon. Bicuculline, at concentrations unable to affect spontaneous colonic motility and lacking anticholinesterase activity, produced a dose-dependent increase of both the efficiency of the peristaltic reflex and the stimulated ACh output. Such effects could not be observed in GABA-desensitized preparations. A frequency-dependent potentiation of the cholinergic excitatory and non-adrenergic non-cholinergic (NANC) inhibitory responses to transmural stimulation was also observed in the presence of bicuculline. Conversely bicuculline exhibited an inhibitory effect on the relaxation induced by periarterial nerve stimulation. Acute GABA-desensitization was unable to affect the contractile responses to transmural stimulation, the ACh output and the efficiency of the peristaltic reflex. On the contrary, desensitization was able to mimic the effects of bicuculline on the inhibitory responses to both transmural and periarterial nerve stimulation. Our results are consistent with a significant role played by an intrinsic GABAergic pathway in the modulation of both cholinergic excitatory and NANC inhibitory neurones. The hypothesis is advanced that a feed-back modulation carried out through bicuculline-sensitive GABAergic synapses could operate during the propagation of peristaltic motor activity.

Acetylcholine↗

Assessment of polymorphonucleate leucocyte functions in adult epileptic patients undergoing long-term phenytoin treatment.

Twelve patients given more than 1 year phenytoin monotherapy and 12 healthy control subjects taking no drugs and matched for sex and age were examined for polymorphonucleate (PMN) functions. To assess PMN activity, cell locomotion and directed migration, phagocytosing ability and bactericidal activity were investigated. No change either in the absolute or relative counts of PMN leucocytes was found in the patients. However, a significant impairment of both PMN chemotaxis and stimulated Nitro Blue Tetrazolium reduction or superoxide anion generation was observed in the patients as compared with the control group of subjects.

Adult↗

Subsensitivity of enteric cholinergic neurones to alpha 2-adrenoceptor agonists after chronic sympathetic denervation.

The concentration-effect relationships of noradrenaline, dopamine and clonidine in inhibiting resting and stimulated acetylcholine output have been studied in intact and in sympathetically denervated preparations of guinea pig isolated distal colon. The order of potencies for the inhibition of resting acetylcholine release in intact preparations was clonidine greater than dopamine greater than noradrenaline while the order of intrinsic activities was noradrenaline greater than dopamine greater than clonidine. Sympathetic denervation was able to modify the potency of either clonidine, dopamine and noradrenaline. Noradrenaline was 6 times more potent in inhibiting resting acetylcholine release in denervated than in intact preparations, while clonidine and dopamine underwent a 18-fold and a 11-fold decrease in potency after denervation. The potency of clonidine relative to noradrenaline was 110 in intact preparations and only 1.2 in denervated organs. The intrinsic activities of noradrenaline, dopamine and clonidine were almost unchanged in denervated organs. A dose-dependent facilitatory effect of yohimbine on both the resting acetylcholine output and the peristaltic reflex could be observed in intact but not in sympathetically denervated preparations at concentrations ranging from 2.5 X 10(-8) M to 2.5 X 10(-7) M. Yohimbine was able to counteract the inhibitory effect of dopamine and to remove the inhibitory effect of periarterial nerve stimulation on both acetylcholine release and the peristaltic reflex. Our results are consistent with the existence of a tonic physiological modulation of enteric cholinergic neurones by postganglionic sympathetic fibres. The order of potencies of adrenoceptor agonists and the antagonism by yohimbine is consistent with such a modulation being entirely carried out through alpha 2-heteroceptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

The opioid receptors in the hamster vas deferens are of the delta-type.

The motor responses of the isolated vas deferens of the hamster were unaffected by opioid-receptor agonists which are selective for the mu- or kappa-receptor, while agonists which show degrees of selectivity for the delta-opioid receptor caused dose-related inhibition of the stimulation-evoked contractions. The agonist action of the enkephalins and their congeners was only apparent when various inhibitors of tissue peptidases were present. Responses to opioid agonists were antagonised in a competitive manner by naloxone and by the selective delta-receptor antagonist, ICI 174864. It is noteworthy that the benzomorphans bremazocine, ethylketocyclazocine and Mr 2034, which are agonists at kappa-receptors in other tissues, are antagonists at the delta-receptor of the hamster vas deferens. Thus, the vas deferens of the hamster contains opioid receptors only of the delta-type and may therefore provide a simple and specific test for the assay of activity at the delta-opioid receptor.

Animals↗

Effect of chronic anticonvulsant monotherapy on lymphocyte subpopulations in adult epileptic patients.

Sixty-five patients undergoing long-term monotherapy for at least 3 months with phenytoin, carbamazepine or phenobarbital were screened for lymphocyte and immunoglobulin abnormalities. In 57% of patients the duration of therapy was longer than 12 months. The control subjects were matched for sex and age and none of them was taking drugs. The average serum immunoglobulin (IgG, IgA, IgM) values did not differ in control and patient groups. A significant decrease of OKT4+ cells was seen with all drugs, while other lymphocyte subpopulations were differently affected depending on the drug used. It is concluded that long-term single-drug treatment with phenytoin, carbamazepine and phenobarbital exhibits immunosuppressant effects through a complex action which involves more than one lymphocyte subpopulation. Moreover, the possible interference of the disease state with the immune functions of epileptic patients is discussed.

Adolescent↗

Changes in sensitivity to the inhibitory effects of adrenergic agonists on intestinal motor activity after chronic sympathetic denervation.

The concentration-effect relationships of adrenergic agonists in inhibiting muscular tone, carbachol-induced contraction of circular muscle strips and nerve-mediated motor activity during the peristaltic reflex have been studied in intact and sympathetically denervated preparations of isolated guinea-pig colon. The order of potencies of adrenergic agonists was different for muscular and nerve-mediated effects, being clonidine greater than noradrenaline greater than methoxamine greater than isoprenaline for the inhibition of peristalsis and isoprenaline greater than noradrenaline greater than methoxamine greater than clonidine for the relaxation of circular muscle. Denervation supersensitivity was specific for the adrenergic agonists and developed both to the muscular and nerve-mediated effects, involving both alpha and beta receptors. The degree of potentiation was similar for noradrenaline and isoprenaline when measured for the muscular effects but was significantly higher for noradrenaline than for isoprenaline or methoxamine when measured for peristalsis inhibition. No potentiation could be observed for papaverine and for the muscular effects of methoxamine and phenylephrine. The increase in potency of noradrenaline ranged from a 26-fold increase for the inhibition of propulsion velocity to a 2.5-fold increase for the inhibition of carbachol-induced contraction. A much narrower range was observed for isoprenaline. Potentiation could also be observed for the inhibitory effect of noradrenaline on acetylcholine release. Clonidine was the most potent agonist against peristaltic reflex and the weakest agonist in relaxing circular muscle. Denervated preparations became subsensitive to the inhibitory effect of clonidine on peristaltic reflex. The potency of clonidine relative to noradrenaline was 488 in intact preparations and only 3.1 in denervated organs.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

Hamster vas deferens contains delta-opioid receptors.

Electrical field stimulation of the hamster, isolated vas deferens produces regular contractions that are unaffected by opioid-receptor agonists which are selective for the mu- or kappa-receptor types. However, agonists which show a selectivity for the delta-opioid receptor produce dose-related inhibitions of the stimulation-evoked contractions. Response of delta-opioid receptor agonists are antagonized in a competitive fashion by the selective delta-receptor antagonist ICI 174864, and also by naloxone. The "kappa-opioid-agonist" benzomorphans, bremazocine and ethylketocyclazocine are antagonists in the hamster vas deferens; bremazocine is particularly potent in this regard. In conclusion, the hamster, isolated vas deferens may contain only delta-opioid receptors and provides a simple and specific test for the assay of activity at the delta-opioid receptor.

Animals↗

5-hydroxytryptamine desensitization fails to modify GABA-induced inhibitory responses in the guinea-pig colon.

In segments of guinea-pig colon, treated with 1 microM hyoscine, a 5-HT desensitization procedure that decreased the potency of 5-HT 41-fold in relaxing the longitudinal musculature, failed to modify the non-adrenergic GABA-induced inhibitory responses, suggesting that the action of GABA in this preparation is not 5-HT-mediated. These results are at variance with those obtained in the guinea-pig ileum where 5-HT seems to play a role in GABA-induced cholinergic contractions.

Animals↗

Dilazep: an inhibitor of adenosine uptake with intrinsic calcium antagonistic properties.

Concentrations of dilazep which were ineffective in altering the muscular tone of the guinea-pig taenia caeci (0.03, 0.3 microM) or the phasic mechanical activity of the rabbit proximal ileum (0.03 microM) markedly potentiated the inhibitory action of adenosine on both these parameters. Dilazep, 0.3 microM or greater, dose-dependently inhibited the mechanical activity of the proximal ileum. This inhibitory action was probably mediated by more than one mechanism, as shown by the fact that theophylline (50, 100 microM) antagonized the effect at lower dilazep concentrations (up to 3 microM) leaving essentially unchanged the response to higher concentrations (6, 10 microM). Similarly, the responses to low doses of dilazep were reduced after desensitization of the organ to adenosine, whilst the responses to higher doses were unaffected by this procedure. In a Ca2+-free, high-K+ medium, dilazep (1-10 microM) caused a parallel shift to the right of the Ca2+-induced contractions of the guinea-pig taenia caeci. Adenosine showed only slight Ca2+-antagonistic properties within the mM range of concentrations. These findings suggest that, at the higher concentration tested, dilazep exhibits Ca2+-antagonistic properties unrelated to its adenosine-mediated mode of action.

Adenosine↗

Motor responses of rat stomach in vitro after subacute oral administration of trithiozine.

The effects of ten days' oral treatment with 200 mg/kg/d of 4-(3,4,5-trimethoxythiobenzoyl)tetrahydro-1,4-oxazine (trithiozine) on the mechanical responses of rat stomach in vitro have been studied. Gastric muscular excitation due to vagal stimulation was partially reduced in the trithiozine-pretreated animals, while the amount of acetylcholine (Ach) released both at rest conditions and in response to field stimulation was similar in both controls and drug-pretreated rats. Also muscular responses induced by dopamine (DA) and by serotonin (5-HT) were of similar degree in both groups of rats. On the contrary, the nonadrenergic and non-cholinergic inhibitory response evoked by vagal stimulation in the presence of muscarinic and alpha- and beta-adrenergic receptor blockade, respectively, was enhanced in the drug-pretreated animals. Moreover, trithiozine pretreatment caused an increase of spontaneous motor activity and a remarkable degree of potentiation of the contractile response to prostaglandins (PGs), both exogenously applied or endogenously released by ATP. Our results give further evidence that trithiozine has no anticholinergic activity and that some therapeutic properties of the molecule could be accounted for by an involvement of endogenous PGs.

Acetylcholine↗

Effects of metopimazine on gastro-intestinal and biliary tract smooth muscle in vitro.

The effects of the phenothiazine derivative metopimazine on the spontaneous or induced activities of guinea-pig isolated stomach and of the rabbit biliary and intestinal tracts were studied. A predominant inhibitory effect was observed except for the circular muscle layers of the duodenum and colon where activation appeared. Evidence from in vitro experiments suggest that metopimazine exerts an inhibitory action partly through a direct effect on smooth muscle cells and partly by reducing stimulated acetylcholine release (at least in the stomach). Finally the involvement of a non-adrenergic, non-cholinergic inhibitory system is postulated.

Acetylcholine↗

A double-blind, placebo-controlled clinical study on the effect of a standardized ginseng extract on psychomotor performance in healthy volunteers.

Various tests of psychomotor performance were carried out in a group of 16 healthy male volunteers given a standardized preparation of Korean ginseng (G 115; 100 mg twice a day for 12 weeks) and in a similar group given identical placebo capsules under double-blind conditions. A favourable effect of G 115 relative to baseline performance was observed in attention (cancellation test), processing (mental arithmetic, logical deduction), integrated sensory-motor function (choice reaction time) and auditory reaction time. However, end performance of the G 115 group was superior statistically to the placebo group only in mental arithmetic. No difference between G 115 and placebo was found in tests of pure motor function (tapping test), recognition (digit symbol substitution) and visual reaction time. No adverse effects were reported. It is concluded that G 115 may be superior to placebo in improving certain psychomotor functions in healthy subjects.

Adult↗

Presence and distribution of serotonin immunoreactivity in the cyprids of the barnacle Balanus amphitrite.

In this work, the presence and distribution of serotonin in the cyprid of the barnacle Balanus amphitrite were investigated by immunohistochemical methods. Serotonin-like immuno-reactive neuronal cell bodies were detected in the central nervous system only. Various clusters of immunoreactive neuronal cell bodies are distributed in the brain (protocerebrum, deutocerebrum, optical lobes), and at least, four pairs of neuronal cell bodies were detected in the centrally positioned neuropil of the posterior ganglion. Rich plexuses of immunoreactive nerve fibers in the neuropil area were also observed. Furthermore, bundles of strongly immunoreactive nerve fibers surrounding the gut wall were localized, and immunoreactive nerve terminals in the antennules and compound eyes were observed. These data demonstrate the presence of a serotonin-like immunoreactive substance in the barnacle cyprids; furthermore, its immunolocalization in the cephalic nerve terminals allows us to postulate the involvement of this bioactive molecule in substrate recognition during the settlement process.

Animals↗