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Biomedical subjects

G Pinardi

Publications and source records attributed to G Pinardi.

At least 37 records · Page 2Linked to original sources
PubMed1995

Muscarinic receptor subtypes in the bisected vas deferens of the rat.

1. The nature of muscarinic receptor subtypes in the isolated prostatic and epididymal segments of the vas deferens of the rat were studied. 2. Presynaptic receptors were characterized in segments under neurogenic transmural stimulation; postsynaptic receptors in segments without stimulation. 3. The present work suggests that the potency of ACh required to activate muscarinic receptors is higher in the prostatic than in the epididymal segment. 4. McN-A-343 was only able to induce dose-dependent contractions in the prostatic segment. 5. The pA2 value for 4-DAMP suggests that in the prostatic segment the postsynaptical ACh receptors seem to be pharmacologically similar to the ACh-M3 subtype. 6. Antagonism of the presynaptic ACh receptor subtype by pirenzepine supports the evidence that these receptors belong to the ACh-M1 subtype.

(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethy↗
PubMed1995

Effect of p-chlorophenylalanine and alpha-methyltyrosine on the antinociceptive effect of antidepressant drugs.

The role of para-chlorophenylalanine and alpha-methyl-DL-p-tyrosine in the antinociceptive effects of the intracerebroventricular administration of the antidepressant drugs clomipramine, zimelidine, imipramine and maprotiline was studied using the acetic acid writhing test in mice. The results demonstrated an antinociceptive effect for all these antidepressants. Pretreatment with para-chlorophenylalanine significantly reduced the antinociception induced by the ED50's of imipramine and maprotiline, and did not modify the effects of zimelidine and clomipramine, pretreatment with alpha-methyl-tyrosine did not modify the antinociception induced by these drugs except maprotiline. Pretreatment with para-chlorophenylalanine plus alpha-methyltyrosine significantly reduced the antinociceptive effect of all the antidepressants tested. The main finding of the present study is that the association of para-chlorophenylalanine plus alpha-methyltyrosine reduced the antinociceptive action of all the antidepressants. This means that critical levels of both 5-HT and NA are responsible for mediating the antinociceptive effects of antidepressants on the writhing test in mice.

Acetates↗
PubMed1994

Effects of CDP-choline on acetylcholine-induced relaxation of the perfused carotid vascular beds of the rat.

1. The effects of an infusion of cytidine-5'-diphosphocholine (CDP-choline) on the relaxation induced by exogenous acetylcholine (ACh) was studied in the isolated and perfused external (ECB) and internal (ICB) carotid vascular beds of the rat. Changes in perfusion pressure were recorded during a dose-response curve to ACh and after a 30 min perfusion with CDP-choline (1 mg/min). 2. ACh induced a dose-dependent relaxation in both vascular beds, indicating the presence of muscarinic receptors. The affinity of the receptors for ACh in the ICB was significantly lower than in the ECB (ED50: 120 +/- 21.4 ng and 69 +/- 10.3 ng, respectively). 3. In the ICB the infusion of CDP-choline for 30 min significantly shifted the dose-response curve to ACh to the left, potentiating the relaxation. This effect was not seen in the ECB. 4. The infusion of hemicholinium (4 microM) for 30 min together with CDP-choline completely prevented the potentiation of exogenous ACh-induced relaxation in the ICB. 5. The results of the present work suggest that CDP-choline is acting by increasing choline levels in the cholinergic nerve terminals of the ICB, increasing the synthesis and/or release of ACh.

Acetylcholine↗
PubMed1994

Pre- and postjunctional muscarinic receptor subtypes in the vas deferens of rat.

1. A pharmacological study of the pre- and postjunctional muscarinic receptors of the isolated rat vas deferens was carried out using more selective agonists and antagonists. 2. The prejunctional receptor was characterized on electrically stimulated preparations, while the postjunctional receptor was studied on vasa deferentia without stimulation. 3. The results indicate that atropine exhibited a similar affinity for the two populations of muscarinic receptor subtypes of this tissue. 4. 4-DAMP was able to differentiate with high affinity a subtype located at postjunctional level which had pharmacological similarities with the M3-ACh subtype and with low affinity a subtype located at prejunctional level. 5. The selective M1-ACh agonist McN-A-343 was not able to activate the postjunctional receptor, but showed a similar affinity to ACh for the prejunctional one. 6. At present, the prejunctional receptor can be considered as an atypical M1-ACh subtype based on the results obtained with the selective drugs available.

Animals↗
PubMed1994

Gender differences in diazepam withdrawal syndrome in mice.

The present work was designed to study the influence of testosterone and oestrogens on the benzodiazepine withdrawal syndrome in mice. Several withdrawal signs were induced by 15 mg/kg intraperitoneally of flumazenil in diazepam-treated mice. The most noticeable were jerks, usually accompanied by tail lifts, and seizures. The intensity of the diazepam withdrawal syndrome was significantly lower in male than in female mice, especially in relation to the incidence of seizures. Castrated male mice showed a significant increase in the intensity of withdrawal syndrome. In addition, diazepam produced a significant increase of body weight in males but not in females. The principal finding of the present work is that the incidence of seizures produced by the administration of flumazenil was significantly lower in male than in female diazepam-treated mice. This fact suggests that the mechanism of action of benzodiazepines is modulated by the action of sexual hormones, and that testosterone plays a relevant role.

Animals↗
PubMed1993

Previous administration of indomethacin or naloxone did not influence ketorolac antinociception in mice.

We studied the effects of the inhibition of prostaglandin biosynthesis and opioid antagonism in the antinociceptive action of ketorolac using the mouse acetic acid writhing test. Ketorolac was administered via the intraperitoneal, intrathecal, or intracerebroventricular routes. Although the ketorolac induced a significant dose-dependent antinociceptive effect, the intracerebroventricular administration was the most effective route. Indomethacin and naloxone pretreatments did not change the ketorolac-induced antinociception. The present findings suggest that this antinociceptive action of ketorolac is not mediated by the inhibition of prostaglandin biosynthesis nor by activation of opioid receptors.

Animals↗
PubMed1992

Antinociceptive effects of Ca2+ channel blockers.

The antinociceptive action of four Ca2+ channel blockers, nifedipine, nimodipine, verapamil and diltiazem, was evaluated and compared to that of morphine using three algesiometric tests in mice and rats, namely, formalin, writhing and modified hot-plate test. Dose-response curves for all the drugs tested were similar and a significant dose-dependent antinociceptive action was evident in the formalin and writhing tests. However, in the hot-plate test, only nimodipine exhibited a significant analgesic effect, confirming the misleading results previously reported for this test. The findings suggest a pharmacological role of Ca2+ channel blockers in the modulation of antinociception under acute conditions. The analgesic action of Ca2+ channel blockers could be mediated by an increase in the nociceptive threshold resulting from interference with Ca2+ influx at opioid receptors, because Ca2+ influx is critical for the release of neurotransmitters and other substances implicated in nociception and inflammation. It is suggested that if a substance has a Ca2+ channel blocking effect, it should probably have some antinociceptive properties.

Analgesics↗
PubMed1992

Effects of chronic ethanol consumption on alpha-adrenergic-induced contractions in rat thoracic aorta.

1. The effects of chronic oral administration of ethanol (EtOH, 80 mM daily during 15-18 days) on the modulation exerted by the endothelium on the contractions induced by phenylephrine (Ph) and clonidine (C) were studied in rat aortic rings with and without endothelium. 2. The maximal contraction induced by a 70 mM KCl depolarizing solution was similar in control and EtOH treated-rings. 3. EtOH pretreatment significantly enhanced the contractile response to Ph in vessels with intact endothelium, but did not significantly affect the response of endothelium-denuded rings. 4. This effect reflects a reduction of the modulation exerted by the endothelial cells on alpha 1-adrenergic vasoconstriction. 5. C did not contract control aortic rings with endothelium, but after EtOH treatment, the response reached about 20% of the maximal KCl-induced contraction. 6. EtOH pretreatment significantly enhanced the contractile response to C both in endothelium-denuded and intact aortic rings. 7. The results indicate that chronic EtOH consumption significantly potentiates alpha-adrenergic-induced contractions in rat aortic rings, probably through interference with the production and/or the release of EDRF.

Animals↗
PubMed1992

Vasomotor responses in the isolated perfused external and internal carotid vascular beds of the rat.

1. The external (ECB) or the internal (ICB) carotid vascular beds of the rat were isolated and perfused with Krebs-Henseleit solution at constant flow (1 ml/min). Changes in perfusion pressure (PP) were recorded after cervical sympathetic stimulation and after the administration of norepinephrine (NE) and serotonin (5-HT). 2. Sympathetic stimulation induced an increase in PP (vasoconstriction) in both vascular beds, however, this effect was significantly higher in the ECB than in the ICB. 3. Exogenous NE also induced a significantly higher contractile response in the ECB. 4. Prazosin (10(-8) M) significantly inhibited the response to sympathetic stimulation and to NE both in the ECB and in the ICB, but yohimbine (10(-7) M) had no effect, suggesting that the vasoconstriction was mainly due to the activation of alpha 1-adrenoceptors. 5. 5-HT induced a contractile response both in the ECB and the ICB. In contrast with the response to NE, the contraction induced by 5-HT in the ICB was significantly higher than in the ECB. 6. Ketanserine (10(-8) M) antagonised both responses, indicating the involvement of 5-HT2 receptors. 7. The contractile effect of 5-HT in the ECB was significantly enhanced by a subthreshold sympathetic stimulation that did not modify the PP by itself. This effect was not seen in the ICB. 8. The differential perfusions of the ECB or the ICB demonstrated a different reactivity of ECB and ICB, both to sympathetic stimulation and to the administration of exogenous NE or 5-HT. 9. Furthermore, the response to 5-HT in the ECB was modulated by a subthreshold sympathetic stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Removal of the endothelial layer in perfused mesenteric vascular bed of the rat.

The endothelial layer was removed from the isolated mesenteric vascular bed of the rat by perfusion with hypotonic Tyrode solution for 12.5 min. This procedure damaged more than 95% of the endothelial cells. After endothelial removal, the response to norepinephrine was significantly enhanced, whereas the relaxation induced by acetylcholine (ACh) was completely abolished. The results of this work show that perfusion with hypotonic solutions provides a reliable method of endothelial removal in isolated perfused vascular beds, allowing the study of endothelial-dependent vascular responses.

Acetylcholine↗
PubMed1992

Cholinergic receptors in the human vas deferens.

This study represents the first investigation demonstrating the contractile response to exogenous acetylcholine (ACh) in the isolated human vas deferens. Pharmacological characterization of cholinergic receptors was achieved using selective antagonists to define receptor subtypes. In the HVD the effect of exogenous ACh is revealed as a dose-dependent sudden increase in the basal tension of the vasa. The ACh receptors of the HVD were competitively antagonized by atropine (ATR) with a high pA2 value (8.78). The main finding of this study is the presence of cholinergic receptors of the pharmacologically defined M1-ACh subtype in the isolated HVD, according to the pA2 values obtained with pirenzepine (PRZ) 7.39, AF-DX 116 (AF) 5.92 and 4-DAMP 5.65, M1-ACh, M2-ACh and M3-ACh selective antagonists, respectively. Prazosin (PZ), a selective alpha 1-adrenergic antagonist, displayed a similar competitive antagonism for the contractile response evoked both by ACh (pA2 = 8.69) and NE (pA2 = 8.58) in the HVD. The antagonism exerted by PZ on the ACh-induced contractile response of the HVD, suggests that ACh probably acts at a presynaptic level stimulating the release of NE from an adrenergic neuron. According to these findings, the receptor involved in this action, located in the proximity of the nerve terminals, seems to be of the M1-ACh subtype.

Acetylcholine↗
PubMed1991

Modulation of alpha-adrenergic-induced contractions by endothelium-derived relaxing factor in rat aorta.

1. In rat thoracic aorta, endothelium removal produced a significant increase of the maximal contraction (Emax) and of the pD2 value (-log ED50) induced by norepinephrine, phenylephrine and clonidine, and did not affect the maximal contractile response to 70 mM KCl. 2. Clonidine did not induce a contraction in aorta with intact endothelium, but after endothelium removal, the contractile response was 94.8% of the Emax produced by norepinephrine in aorta with endothelium. 3. Pre-incubation with methylene blue (10(-5) M) and hemoglobin (0.02%), which inhibit EDRF effects, produced the same effects as the mechanical removal of endothelium on the contractile responses to alpha-adrenergic agonists. 4. These results suggest that EDRF formation and release is an important factor in the modulation of alpha-adrenergic-induced vasoconstriction.

Adrenergic alpha-Agonists↗
PubMed1991

Influence of extracellular Ca2+ on the modulation of alpha-adrenergic-induced contractions in rat aorta.

1. Rat thoracic aortic rings with and without endothelium incubated in a Ca2(+)-free solution showed a significant reduction of the maximal contraction (E max) induced by norepinephrine (NE) and phenylephrine (Ph), while the contraction induced by a 70 mM KCl depolarizing solution was completely abolished. 2. After Ca2+ removal, pD2 values (-log ED50) for NE and Ph were significantly reduced only in vessels without endothelium. 3. Under control conditions, clonidine (C) induced a contraction only in vessels without endothelium; this response was completely abolished by Ca2+ removal and by nifedipine (10(-8) M). 4. Pre-incubation with nifedipine (10(-8) M) produced an effect similar, although less pronounced, than the removal of Ca2+ in vessels with and without endothelium. 5. Nevertheless, aortic rings with intact endothelium showed a greater reduction of E max than rings without endothelium, suggesting that the endothelial layer may act in synergism with calcium channel blockers to inhibit the contractions induced by alpha-adrenergic agonists. 6. The modulation exerted by the endothelium on alpha 1- and alpha 2-adrenergic-induced contractions in rat aortic rings seems to depend both on extracellular Ca2+ concentration and on the release and action of endothelial relaxing factor(s).

Animals↗
PubMed1991

Mortality in acute stroke with atrial fibrillation. The Italian Acute Stroke Study Group.

We compared 211 consecutive patients who had acute ischemic hemispheric stroke and atrial fibrillation with 837 consecutive patients who had stroke without atrial fibrillation. The atrial fibrillation group included a higher frequency of women, older subjects, and those with a severe neurologic deficit, abnormal computed tomogram, and elevated heart rate. The 1-month case-fatality rate in the atrial fibrillation group was 27% while that in the group without atrial fibrillation was 14%. The 6-month case-fatality rates in the two groups were 40% and 20%, respectively. The risk of death attributable to atrial fibrillation, adjusted for the effect of other prognostic factors, was significant at 1 month (relative risk = 1.55) and at 6 months (relative risk = 1.74). The causes of death were equally distributed in the two groups during both the acute and subacute phases. We conclude that atrial fibrillation is a negative prognostic factor in patients hospitalized for acute stroke. Nevertheless, cerebral embolism alone does not completely explain the increase in mortality for stroke patients with atrial fibrillation. Other associated pathogenetic mechanisms must also be taken into account.

Acute Disease↗
PubMed1990

[The chronic fatigue syndrome. A multifactorial approach and the treatment possibilities].

The chronic fatigue syndrome is a poorly defined symptoms complex characterized primarily by chronic or recurrent debilitating fatigue and various combinations of other symptoms, including psychological symptoms, sore throat, lymph node pain, headache, myalgia, arthralgias. Psychological disturbances, ranging from mild depression or anxiety to severe behavioral abnormalities, are always present. Chronic fatigue syndrome is the name that more accurately describes this symptom complex of unknown cause. A viral aetiology has long been hypothesized: many viruses are potential candidates, including any of the 23 Coxsackie A or 6 Coxsackie B viruses, herpes viruses, particularly Epstein-Barr virus and varicella. These studies, though interesting, remain unconvincing because of methodological flaws such as a poor case definition and inadequate control groups. This syndrome may represent an infection by a yet unidentified virus. It is more likely due to an abnormal immune response toward different intracellular pathogens. There is no treatment to ameliorate the chronic fatigue syndrome. Epidemiological studies are essential with explicit operational case definition before progress can be made in the management of this distressing disorder.

Diagnosis, Differential↗
PubMed1989

Intracerebral stimulation of the seventh cranial nerve in the rat. Effects on cerebrospinal fluid pressure.

The effect of the intracerebral stimulation of the seventh cranial nerve was studied in anesthetized, artificially ventilated rats. The stimulation was carried out at the genu level by inserting a micropipette according to known stereotaxic coordinates. In 9 experiments, the cerebrospinal fluids pressure increased significantly 0.92 to 1.05 cm H2O above basal level after the stimulation of the same point on the left and right sides of the brain, without changes in mean arterial blood pressure. This response was interpreted as a sudden increase in cerebral blood volume produced by the dilatation of cerebral blood vessels. The section of the right greater superficial petrosal nerve abolished the increase in cerebrospinal fluid pressure after stimulation of the right side, while the response to stimulation of the left side was similar to the one observed in control animals. Consequently, the neurogenic vasodilation produced by intracerebral stimulation of the seventh cranial nerve in the rat seems to be mediated by a functional Chorobski-Penfield pathway running with the greater superficial petrosal nerve.

Animals↗