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Biomedical subjects

M Cosentino

Publications and source records attributed to M Cosentino.

At least 55 records · Page 3Linked to original sources
PubMed1995

N-methyl-D-aspartate receptors modulate neurotransmitter release and peristalsis in the guinea pig isolated colon.

To assess the role of NMDA receptors in modulating neurotransmitter release in the myenteric plexus, we studied the effects of L-glutamic acid and NMDA on endogenous acetylcholine and noradrenaline overflow (assayed by HPLC) from the guinea pig isolated distal colon. L-Glutamic acid and NMDA enhanced electrically evoked acetylcholine and noradrenaline overflow and these effects were reversed by selective NMDA receptor antagonists. The possible functional significance of these findings was studied by measuring the efficiency of the colonic peristaltic reflex in the presence of NMDA receptor agonists. NMDA inhibited propulsion velocity at all concentrations tested, this effect being antagonized by (+/-)-2-amino-5-phosphonopentanoic acid and virtually abolished in sympathetically denervated animals. In conclusion, the inhibitory effect of NMDA on peristalsis, being almost entirely dependent on the integrity of sympathetic pathways, could be, at least in part, due to NMDA-induced noradrenaline release.

2-Amino-5-phosphonovalerate↗
PubMed1995

Inhibitory effects of SR 58611A on canine colonic motility: evidence for a role of beta 3-adrenoceptors.

1. In order to clarify whether atypical or beta 3-adrenoceptors can modulate canine colonic motility in vivo, we studied the effects of SR 58611A (a selective agonist for atypical beta-adrenoceptors) alone and after pretreatment with beta-adrenoceptor antagonists on colonic motility in the conscious dog. The gastrocolonic response (postprandial increase in motility) was monitored by means of electrodes and strain-gauge force transducers chronically implanted along the distal colon. In some experiments, heart rate was also measured. The possible role of beta 3-adrenoceptors in mediating the effects of SR 58611A was also tested in vitro in circular muscle strips taken from the canine distal colon. 2. Intravenous infusion of SR 58611A, ritodrine or isoprenaline at doses inducing the same degree of tachycardia inhibited the gastrocolonic response to a different extent, with SR 58611A and ritodrine being more effective than isoprenaline. 3. In a dose-response study, SR 58611A was more potent in inhibiting colonic motility than in inducing tachycardia: the ED35 values for inhibition of colonic motility and induction of tachycardia were 23 and 156 micrograms kg-1, i.v., respectively. 4. The inhibitory effect of SR 58611A 100 micrograms kg-1, i.v., on the gastrocolonic response was reversed by alprenolol (non-selective beta-adrenoceptor antagonist), but resistant to CGP 20712A (beta 1-adrenoceptor antagonist) or ICI 118551 (beta 2-adrenoceptor antagonist). 5. In vitro, SR 58611A concentration-dependently relaxed circular muscle strips, an effect that was competitively antagonized by alprenolol with a pA2 value of 7.1, but resistant to CGP 20712A (100 nM), ICI 118551 (100 nM) or tetrodotoxin (1 microM). 6. The present study provides strong functional evidence for a role of atypical or beta 3-adrenoceptors in the modulation of canine colonic motility both in vivo and in vitro by an inhibitory effect most likely at the smooth muscle level.

Adrenergic beta-Agonists↗
PubMed1994

Effect of desipramine-induced blockade of neuronal uptake mechanisms on adrenoceptor-mediated responses in the guinea-pig colon.

In order to clarify whether adrenoceptors in the guinea-pig distal colon are under sympathetic control, we assessed possible variations in the sensitivity to adrenoceptor agonists after blockade of neuronal catecholamine uptake mechanisms by desipramine (DMI). First, experiments were carried out to investigate the effects of DMI added in the organ bath on propulsion velocity, endogenous and [3H] prelabelled acetylcholine overflow, electrically evoked noradrenaline overflow and longitudinal smooth muscle tone. Secondly, we studied the effects of adrenoceptor agonists on the above parameters in untreated animals and in animals chronically treated with DMI. DMI added in the organ bath at concentrations equal to or higher than 30 nM inhibited all the parameters under study. Thus, when evaluating the effect of DMI on concentration-response curves to adrenoceptor agonists, concentrations which were per se inactive were used. DMI added in the organ bath at concentrations up to 30 nM potentiated the inhibitory effects of exogenous noradrenaline on propulsion velocity and acetylcholine overflow, but it did not affect the concentration-response curve to exogenous noradrenaline on longitudinal smooth muscle tone. Furthermore, 30 nM DMI inhibited propulsion velocity during sympathetic nerve stimulation. In preparations obtained from animals chronically treated with DMI, no significant change of propulsion velocity, endogenous and [3H] prelabelled acetylcholine overflow was found with respect to untreated animals. Nevertheless, in such preparations subsensitivity to isoprenaline (acting mainly on muscular beta-adrenoceptors) and clonidine (acting on neuronal alpha 2-adrenoceptors) and super-sensitivity to phenylephrine were observed. Electrically evoked noradrenaline overflow was enhanced, in a frequency-dependent way, by yohimbine and inhibited by clonidine.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1994

Suksdorfin: an anti-HIV principle from Lomatium suksdorfii, its structure-activity correlation with related coumarins, and synergistic effects with anti-AIDS nucleosides.

Suksdorfin (1), which is isolated from the fruit of Lomatium suksdorfii, was found to be able to inhibit HIV-1 replication in the T cell line, H9, with an average EC50 value of 2.6 +/- 2.1 microM. In addition, suksdorfin was also suppressive during acute HIV-1 infections of peripheral blood mononuclear cells, monocyte/macrophages and the promonocytic cell line, U937. Combinations of 1 and the anti-HIV nucleosides ddI and ddC demonstrated statistical synergy in inhibiting HIV-1 replication (ddC > ddI). However, the viral inhibition mediated by combining 1 with AZT was not statistically synergistic. Furthermore, the presence of suksdorfin did not antagonize the suppression mediated by the three nucleoside reverse transcriptase inhibitors. Comparison of the structure and activity of 1 with those of ten related compounds indicated that the dihydroseselin type of pyranocoumarin possessing a 4'-isovaleryl group is important to suksdorfin's enhanced anti-HIV activity.

Antiviral Agents↗
PubMed1994

[An evaluation of the pulmonary venous flow pattern by transesophageal and transthoracic Doppler echocardiography in a normal subject].

Transesophageal echocardiographic studies have permitted a pulmonary venous flow velocity pattern to be identified which is comparable to that recorder using invasive methods. The pattern consists of 4 stages: an anterograde systolic flow with an early (S1) and late (S2) peak velocity, a diastolic anterograde flow (D) and a retrograde flow liked to atrial contraction (Ar). The aim of this study was to evaluate the pattern of pulmonary venous flow velocity using transesophageal and transthoracic colour Doppler echocardiography in normal subjects in an attempt to: 1) determine normal values derived from the pulmonary venous flow pattern which may contribute to future studies; 2) find correlations between the pattern of pulmonary venous flow and a number of physiological, hemodynamic and echocardiographic parameters which take account of the morphological variations of this flow pattern within a normal range; 3) demonstrate the possibility of being able to carry out study using transthoracic colour Doppler echocardiography. The study was carried out in 38 normal subjects aged between 15 and 76 years old (mean 45 +/- 15) who underwent transthoracic and transesophageal colour-Doppler echocardiography. The following parameters were measured: left atrium diameter, diameters and telediastolic and telesystolic volumes of the left ventricle, ejection fraction and systolic percentage shortening of the left ventricle, peak velocity of the mitral flow pattern and the pulmonary venous flow pattern. The results obtained show that: 1) the pattern of pulmonary venous flow alters with ageing causing the prevalence of systolic over diastolic peak velocity; 2) the pulmonary venous flow parameters which appear to be most significant in hemodynamic terms are the peak velocities of the early systolic flow and anterograde diastolic flow and the ratios S1/S2 and S2/D; 3) the echocardiographic parameters most closely correlated with the peak velocity of pulmonary venous flow are the dimensions of the left atrium, telediastolic and telesystolic ventricular volumes, and the pattern of transmitral flow; 4) heart rate does not appear to influence the pulmonary venous flow pattern significantly (at least within the range of 50-100 b/min), except for retrograde flow. Similar results were obtained using transesophageal and transthoracic Doppler echocardiography and therefore if future studies succeed in obtaining useful information, of not only speculative but also practical interest, from the evaluation of pulmonary venous flow, these can be obtained using a simple, widespread and completely non-invasive method such as transthoracic Doppler echocardiography.

Adolescent↗
PubMed1993

Calcium-channel blockers and gastrointestinal motility: basic and clinical aspects.

Several calcium-channel blockers currently in use for the treatment of cardiovascular disorders have recently been tested for their effects on gastrointestinal motility. The rationale for this approach centers on the concept that calcium-channel blockers are at least as potent in inhibiting intestinal smooth muscle as in relaxing vascular smooth muscle. This review will give an outline of the most recent findings on the role of calcium and calcium channels in smooth muscle and neuronal function in the digestive system. It will also consider the mechanisms by which calcium-channel blockers may affect gastrointestinal motility and assess potential clinical applications in gastroenterology. The main goal for researchers in this field will be the development of gut-selective agents, with no cardiovascular side effects.

Animals↗
PubMed1993

Immunological adverse effects of anticonvulsants. What is their clinical relevance?

Long term administration of anticonvulsants is sometimes associated with impairment of the humoral and/or cellular immune response. Furthermore, certain well known adverse reactions to antiepileptics may have an immunotoxicological origin e.g. lymphadenopathy, pseudolymphoma and systemic lupus erythematosus. However, two important questions remain unresolved. First, the possibility that epilepsy per se might be primarily associated with immune alterations makes it difficult to assess the pathogenetic role of a specific drug, especially in a patient population usually on multiple drug therapy. Secondly, the clinical relevance of some of the observed immunological abnormalities is still highly controversial. This review is intended to give an outline of the present state of knowledge on the effects of anticonvulsants on humoral, cellular and nonspecific immunity, with particular regard to some of the major clinical conditions that have been ascribed to drug-induced immune dysregulation, such as pseudolymphoma and systemic autoimmune diseases. The immunotoxic potential of anticonvulsants appears to be low, and immunological monitoring is not usually required except in patients with known immune defects.

Antibody Formation↗
PubMed1993

Differential effects of antimuscarinic agents on intestinal motility in the conscious dog.

In this study we investigated the effects of antimuscarinics with different selectivity on the intestinal migrating myoelectric complex (MMC) in five fasting, conscious dogs, chronically fitted with electrodes along the small bowel. Furthermore, we evaluated the chronotropic and mydriatic effects to assess the in vivo selectivity of the agents tested. Dose-response studies were performed with the following drugs administered i.v.: atropine, telenzepine (M1 antagonist), AF-DX 116 [11,2-(diethylamino)methyl-1-piperidinyl-acetyl-5,11-dihydro-6H-pyrido-2 ,3b- 1,4-benzodiazepine-6-one (M2 antagonist)] and 4-diphenylacetoxy-N- methylpiperidine methiodide (4-DAMP) (M3 antagonist). All the antimuscarinics tested dose-dependently increased the duration of the MMC period and inhibited spike activity, except low-dose telenzepine (3-10 nmol/kg), which shortened the MMC period and stimulated spike activity. High-dose telenzepine (> 100 nmol/kg) mimicked the inhibitory effect of atropine on the intestine. ED50 values for delay of MMC onset were 87,232, > 10,000 and 129 nmol/kg for atropine, telenzepine, AF-DX 116 and 4-DAMP, respectively. At doses lengthening the MMC period, atropine and 4-DAMP also induced tachycardia and mydriasis. At doses shortening the MMC period, telenzepine had no effect on pupil diameter or heart rate, except at the dose of 10 nmol/kg, which reduced heart rate. Finally, AF-DX 116, at doses inducing marked tachycardia, had a minor intestinal effect and no mydriatic effect. The present data are consistent with the hypothesis that both M1 and M3 receptors are involved in the regulation of the MMC: M1 receptors are probably located on an inhibitory pathway, whereas M3 receptors mediate excitatory stimuli.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Motility of rabbit proximal colon. Relevance of cholinergic pathways and role of different muscarinic receptor subtypes.

To better define the physiologic relevance of the cholinergic muscarinic input to the rabbit colon and the role of different muscarinic receptor subtypes, we studied the effects of atropine, telenzepine (MI antagonist) and DF594 (M3 antagonist) on colonic motility in eight conscious rabbits fitted with bipolar electrodes and strain gauges along the proximal colon. In some experiments, the chronotropic and mydriatic effect of the pharmacological agents were also assessed. Two main patterns of spike activity were identified: short spike bursts (SSBs), which were usually stationary, and long spike bursts (LSBs), which were usually propagated. Both myoelectrical patterns were dose-dependently inhibited by atropine (0.06-4 mumol/kg). Atropine, at the doses of 2-4 mumol/kg, abolished both myoelectrical and mechanical activity. Telenzepine (0.008-0.125 mumol/kg) dose-dependently inhibited migrating LSBs without significant effect on SSBs. Higher doses (0.25-0.5 mumol/kg) inhibited both LSBs and SSBs. DF594 (0.06-2 mumol/kg) dose-dependently inhibited both migrating LSBs and SSBs. The three antimuscarinic agents, at doses that inhibited colonic spike activity by approximately 80% (equiactive doses), behaved as follows on heart rate and pupil diameter: atropine induced tachycardia and mydriasis, telenzepine had no effect, and DF594 induced slight mydriasis with no effect on heart rate. We conclude that spontaneous motility in the rabbit proximal colon depends on a muscarinic excitatory input. M3 receptors are involved in the control of both LSBs and SSBs, while M1 receptors play an important role in the regulation of LSBs. The development of selective antimuscarinic drugs, acting on a given motility pattern and with minimal side effects, may offer new perspectives in the treatment of functional bowel motor disorders.

Action Potentials↗
PubMed1992

Effect of calcium channel blockers on postprandial gastrointestinal motility in the dog.

We have compared the ability of nifedipine and lacidipine, a new 1,4-dihydropyridine, to interfere with postprandial gastrointestinal motility. Five conscious dogs, fitted with 8 bipolar electrodes along the gastrointestinal tract, were studied. Gastrointestinal spike activity was evaluated by means of a computer system. Lacidipine (8 micrograms kg-1) was administered as an i.v. bolus immediately followed by a 10 micrograms kg-1 h-1 i.v. infusion for 3 h, starting 30 min before a standard meal. This dose of lacidipine decreased systolic blood pressure by approximately 20%. Nifedipine was used at equihypotensive doses (30 micrograms kg-1 i.v. bolus followed by 300 micrograms kg-1 h-1 i.v. infusion). Lacidipine had no effect on either gastric or intestinal postprandial spike activity. Nifedipine significantly delayed the appearance of the fed pattern and reduced the number of spikes in the small bowel, while it had no effect on gastric spike activity. We conclude that equihypotensive doses of lacidipine and nifedipine differ in their effects on the gastrointestinal tract, lacidipine having a better cardiovascular selectivity profile than nifedipine, and that the sensitivity to nifedipine varies in different parts of the gut.

Animals↗
PubMed1992

Human immunodeficiency virus infection induces both polyclonal and virus-specific B cell activation.

Peripheral blood lymphocytes (PBL) were obtained from HIV-1-infected patients at different stages of disease. The absolute number of IgM-, IgG-, and IgA-producing lymphocytes per 10(6) PBL was increased 2.8-, 3.4-, and 1.9-fold, respectively, compared with normal controls. 2-17% of IgG-secreting patient cells reacted with the gp160 envelope glycoprotein of HIV-1 (a 737-fold increase over background), while 1-9% reacted with p24 (140-fold over background). In addition to this HIV-specific B cell activation, the number of lymphocytes reactive with nonviral antigens such as DNA, myosin, actin, trinitrophenylated keyhole limpet hemocyanin, and ovalbumin was increased by a mean of 17.9-fold. Evidence suggests that the latter changes reflect an HIV-induced polyclonal B cell activation unrelated to the production of anti-HIV antibodies. For example, the proportion of IgG anti-gp160- and anti-p24-secreting lymphocytes declined in patients with advanced disease, whereas the number of B cells producing antibodies to non-HIV antigens rose. Moreover, CD4 cell count and T4/T8 ratio showed a significant inverse correlation with the degree of polyclonal activation but not with anti-HIV responsiveness. These observations demonstrate that both quantitative and qualitative changes in B cell activation accompany (and may be predictive of) disease progression in HIV-infected individuals.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Personality and psychological distress in legal abortion, threatened miscarriage and normal pregnancy.

A sample of 208 pregnant women (78 before the voluntary termination of pregnancy, 63 admitted to hospital because of a threatened miscarriage, 67 at the outpatient clinic for a routine antenatal visit) performed a personality test (EPI) and two tests to evaluate psychological distress (SCL-90 and GHQ). The women who were about to abort exhibited a higher level of psychological distress which was also related to an underlying personality structure with neurotic traits. The group with a threatened miscarriage exhibited an intermediate level of psychological distress but a structure of personality similar to the antenatal group.

Abortion, Legal↗
PubMed1991

Physiopharmacology of the peristaltic reflex: an update.

The peristaltic reflex is one of the simplest models which can be used to study the function of enteric neurons by recording intestinal motor activity. Peristalsis consists of a coordinated, aborally propagating motor activity which requires the functional integrity of receptor pathways, excitatory and inhibitory neural pathways and neuromuscular junctions. Luminal distension elicits polarized responses: an ascending excitatory response (ascending contraction) and a descending inhibitory response (descending relaxation). The present paper reviews the most recent acquisitions on the neural pathways and neurotransmitters involved in the regulation of the peristaltic reflex.

Humans↗
PubMed1988

Variations in anxiety levels during pregnancy and psychosocial factors in relation to obstetric complications.

Patterns of variation of state and trait anxiety during pregnancy and after delivery were studied prospectively in relation to some obstetrical and neonatal disturbances. Specific pregnancy anxiety, social support, and coping style were also evaluated. State anxiety in the 3rd month was significantly higher among women with obstetric complications and oscillated during the course of pregnancy, with significantly higher levels in the 3rd and 9th months. No such variations were found in the women with uncomplicated pregnancies. None of the other psychosocial variables examined were related to complications.

Adaptation, Psychological↗
PubMed1985

Toxoplasmosis. Two observations and a specification.

On the basis of two interesting observations of toxoplasmic disease the Authors attempt to interpret the various pathological pictures, comparing two different formulations of toxoplasmic disease: that of Sabin and that of more modern AA.

Abortion, Habitual↗
PubMed1984

The role of computerized axial tomography in the follow-up of patients with carcinoma of the ovary.

In order to assess the accuracy of CAT in the follow-up of the patients affected by ovarian carcinoma, we compared the results of this method to those of second-look laparotomy in 19 patients. In 16 out of 19 patients the CAT showed the presence or absence of disease correctly. There were 3 false negatives, caused by small diffuse peritoneal metastases, and no false positives. The results of this study show that CAT, though useful in studying the evolution of abdominal and pelvic carcinomas, cannot replace the surgical second-look in cases of ovarian cancers, due to the high incidence of false negatives.

Carcinoma↗
PubMed1983

Computerized axial tomography in the evaluation of gynecologic pelvic masses.

The Authors retrospectively evaluate the advantages and limitations of CAT in 57 patients presenting suspected gynecologic pelvic masses. CAT showed great accuracy in identifying the presence or absence of the mass (only 3 false negatives and no false positive) whereas it diagnosed the nature of the lesion correctly only in 19 cases. In 41 cases the CAT provided clinically significant information adding to those of the gynecologic examination. Despite some limitations, CAT has proven to be a useful and accurate method to diagnose and evaluate suspected gynecologic masses before the surgical intervention.

Abdominal Neoplasms↗