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Biomedical subjects

S Lecchini

Publications and source records attributed to S Lecchini.

At least 73 records · Page 4Linked to original sources
PubMed1987

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↗
PubMed1986

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↗
PubMed1985

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↗
PubMed1985

Effects of carbamazepine on prolactin secretion in normal subjects and in epileptic subjects.

The effects of carbamazepine (CBZ) on spontaneous secretion of prolactin (PRL) and after stimulation with thyrotropin releasing hormone (TRH) were evaluated. Volunteer subjects after acute CBZ administration, and epileptic subjects with complex partial seizures chronically treated with CBZ, were examined. In an epileptic group, CBZ did not change TRH stimulatory effect on PRL secretion. No appreciable changes of PRL spontaneous secretion were observed, and only a small increase of sleep-entrained values with preservation of the normal secretory circadian rhythm was noted, both in normal subjects and in epileptic subjects. This result could be explained by a serotoninergic activity of PRL changes produced by CBZ in these various conditions agrees with the absence of published reports of CBZ side effects associated with hyperprolactinemia.

Adult↗
PubMed1985

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↗
PubMed1984

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↗
PubMed1984

Pharmacokinetic and pharmacodynamic studies with a new controlled-release formulation of propranolol in normal volunteers: a comparison with other commercially available formulations.

The kinetics and dynamics (inhibition of exercise tachycardia) of two controlled-release preparations of propranolol (Elanolol and Inderal LA) were examined in six normal volunteers. Conventional propranolol (Inderal) was also studied for comparison purposes. As compared to conventional propranolol (120 mg), single doses of Elanol (120 mg) and Inderal LA (160 mg) produced a smoother serum level profile, with lower and delayed peak times. Dose-corrected AUC0-24 values were greater after Elanol than after Inderal LA (651 +/- 147 vs 402 +/- 159 ng ml-1 h, means +/- s.e. mean, P greater than 0.05). The profile of inhibition of exercise tachycardia mirrored closely that of the serum levels. At steady state, all regimens studied (Inderal 40 mg three times daily; Elanol 120 mg once daily; Inderal LA 160 mg once daily) ensured relatively sustained serum levels and a stable degree of pharmacological effect. Dose-corrected AUC0-24 values were 797 +/- 148 ng ml-1 h after Inderal, 908 +/- 113 ng ml-1 h after Elanol and 602 +/- 122 ng ml-1 after Inderal LA. The bioavailability of Inderal LA was significantly lower than that of the other preparations. These results demonstrate that long-acting formulations of propranolol can be developed which are not necessarily associated with reduced bioavailability secondary to enhanced first-pass metabolism.

Adult↗
PubMed1984

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↗
PubMed1983

5-HT mediated GABA excitatory responses in the guinea-pig proximal ileum.

GABA (3--100 microM) and 5-HT (0.03--30 microM) caused concentration-dependent transient contractions of the longitudinal muscle of the guinea-pig ileum. The contractile response to GABA was antagonized by hyoscine (2.2 microM). TTX (0.7 microM), bicuculline (3 microM), furosemide (25 microM) and desensitization to GABA itself, while hexamethonium (20 microM) and methysergide (20 microM) were without effect. The contractile response to 5-HT was antagonized by hyoscine (2.2 microM), TTX (0.7 microM) and desensitization to 5-HT itself and was unaffected by bicuculline (10 microM), hexamethonium (20 microM), furosemide (25 microM) and methysergide (20 microM). A desensitization procedure that caused a 84.7-fold increase in the 5-HT EC50 also resulted in a 74.1-fold increase of the GABA EC50. Desensitization to GABA caused a reduction of 5-HT induced response but only in preparations desensitized by high (50 microM) concentrations of GABA. The results indicate that GABA-induced contractions in the guinea-pig ileum are mediated by activation of cholinergic motor neurones. This effect appears to be mediated by interneuronal release of 5-HT rather than by a direct stimulatory action of GABA on the effector neurones.

Animals↗
PubMed1983

Reduction of phenytoin clearance caused by cimetidine.

The effect of cimetidine on the disposition kinetics of phenytoin was investigated in 7 healthy volunteers. Each subject received a single intravenous dose of phenytoin on two occasions, in the control state, and during concurrent treatment with cimetidine 1 200 mg/day for 6 days. A slight but statistically significant decrease both in the rate of elimination and total body clearance of phenytoin was observed during the administration of cimetidine. The effect is probably due to inhibition of metabolism.

Adult↗
PubMed1983

Penicillin CSF levels following intravenous therapy in syphilitic patients.

Serum and CSF levels of penicillin have been determined in 13 syphilitic patients treated with relatively high doses of penicillin G by the intravenous route. Wide individual variability in the CSF/serum concentration ratio was observed. In all patients the concentration of the antibiotic in the CSF was equal to or greater than 0.03 IU/ml., which is considered to be the minimal therapeutic concentration. The potential clinical usefulness of different therapeutic regimens in the treatment of neurosyphilis is discussed.

Adult↗
PubMed1983

Purine receptors in the guinea-pig internal anal sphincter.

1 In the isolated internal anal sphincter of the guinea-pig, adenosine 5'-triphosphate (ATP) and adenosine induced a concentration-dependent and tetrodotoxin-insensitive relaxation. 2 Pretreatment with theophylline (25-50 microM) had no significant effect on the concentration-response curves obtained with either purine compound. 3 Reactive blue 2 (25-100 microM) shifted the curve to ATP to the right in a dose-dependent fashion leaving that to adenosine unaltered. The antagonism appeared to be non-competitive. 4 Neither reactive blue 2 nor purine receptor occupation by ATP or adenosine altered the electrically-induced non-adrenergic, non-cholinergic inhibitory response. 5 The actions of ATP and adenosine in the guinea-pig internal anal sphincter appear to be mediated by separate receptors. These receptors are not involved in the nerve-mediated relaxation.

Adenosine↗
PubMed1982

Mode of action of ATP on propulsive activity in rabbit colon.

ATP induced a concentration-dependent reduction of the velocity of propulsion in isolated segments of rabbit colon as assessed by the aboral displacement of an intraluminal rubber balloon, and delayed the onset of the propulsive wave. ATP depressed both the reflex contraction of the circular coat above the distended balloon and the response of the circular muscle to transmural (cholinergic) stimulation. On the contrary, ATP (up to 200 muM), while causing relaxation of the circular muscle, had no effect on either the muscular contractile response induced by carbachol and histamine or the non-adrenergic inhibitory responses elicited by electrical stimulation and by radial distension of the gut wall. Within the concentration range used (10-200 muM), ATP concentration-depression curves for propulsion and transmural excitatory stimulation were shifted to the right in the presence of theophylline (10 muM). Theophylline, however, had no influence on either the direct inhibitory action of ATP on circular smooth muscle or the non-adrenergic relaxation in response to electrical stimulation. These data are consistent with the concept that at least two populations of purinergic receptors are present in intestinal tissue. Those populations located presynaptically, unlike those located postsynaptically, are blocked by theophylline. Since the contractile machinery does not appear to be affected by ATP concentrations up to 200 muM, the mechanism by which ATP impairs propulsive activity is probably dependent on activation of presynaptic purinergic receptors located on the nervous pathways subserving the wave of contraction, without having any appreciable influence on descending inhibition.

Adenosine Triphosphate↗
PubMed1982

Effects of desensitization to adenosine 5'-triphosphate and adenosine on non-adrenergic inhibitory responses in the circular muscle of rabbit colon.

An approximate eight fold desensitization of the circular coat of the distal rabbit colon to adenosine 5'-triphosphate (ATP) and adenosine could be achieved by repeatedly exposing the organ to relatively low concentrations (10-100 microM) of these compounds. The desensitization was specific and reversible after prolonged washing. It could be overcome by increasing the concentrations of the purine agonists. Dipyridamole potentiated the non-adrenergic inhibition in response to transmural stimulation but failed to influence the caudad relaxation evoked by radial distension. Desensitization to ATP and adenosine (and to ATP + adenosine simultaneously) did not affect the non-adrenergic inhibition in response to radial distension or transmural stimulation. These results suggest that neither ATP nor adenosine are the final transmitters mediating the non-adrenergic inhibitory responses in the distal colon of the rabbit.

Adenosine↗
PubMed1982

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↗