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Biomedical subjects

M Mestre

Publications and source records attributed to M Mestre.

At least 55 records · Page 3Linked to original sources
PubMed1987

Cellular immunity abnormalities in patients with recurrent Bell's palsy.

Recurrent Bell's palsy is a rare form of facial paralysis. To investigate the role which cellular immunity plays in the aetiology of recurrent Bell's palsy, we evaluated a series of such patients using a laboratory test specially formulated to test the cellular immune system. We measured T-lymphocyte and T-lymphocyte subsets in the peripheral blood of 10 recurrent Bell's palsy patients and in 30 healthy volunteers. T-lymphocytes and T-lymphocyte subsets were reduced significantly in the patients, but the T-helper: T-cytotoxic ratio was normal. Cellular immunity abnormalities were therefore found in the peripheral blood of patients with recurrent Bell's palsy, supporting the concept that this is an immunomediated demyelinating disease.

Adolescent↗
PubMed1986

PK 11195, an antagonist of peripheral type benzodiazepine receptors, modulates Bay K8644 sensitive but not beta- or H2-receptor sensitive voltage operated calcium channels in the guinea pig heart.

In a partially depolarized guinea pig papillary muscle preparation, BAY K8644 stimulated voltage-operated calcium channels, promoting slow action potentials; this effect was dose-dependent over a concentration range of 3 X 10(-7) M to 3 X 10(-6) M. Isoproterenol and histamine also induced slow action potentials by stimulating beta or H2 receptors, respectively. PK 11195, the antagonist of peripheral type benzodiazepine receptors, inhibited the effect of BAY K8644, but not those of histamine or isoproterenol. Moreover, PK 11195 "dose-dependently" antagonized the ability of RO5-4864 to inhibit the slow action potentials elicited by barium chloride. Thus, in the heart, PK 11195, an antagonist of peripheral type benzodiazepine receptors, can modulate voltage-operated calcium channels when they are activated directly, but not when they are activated by stimulation of neurotransmitter receptors.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1985

PK 11195, an antagonist of peripheral benzodiazepine receptors, reduces ventricular arrhythmias during myocardial ischemia and reperfusion in the dog.

PK 11195, an antagonist of peripheral type benzodiazepine receptors, in doses from 5 to 25 mg/kg i.d. protected in a dose-dependent manner dogs against both early and delayed ventricular arrhythmias induced by 20 min ischemia and against ventricular fibrillation following reperfusion. Thus, peripheral-type benzodiazepine receptors might represent a novel target in the treatment of angina and cardiac ischemia.

Animals↗
PubMed1985

Comparative effects of heparin and PK 10169, a low molecular weight fraction, in a canine model of arterial thrombosis.

The comparative properties of heparin and PK 10169, a low molecular weight fraction, were studied using an antithrombotic test in anaesthetized dogs. The antithrombotic properties of the two compounds were evaluated by measuring inhibition of thrombus formation following transluminar stimulation of coronary artery with anodal current and by measuring anticoagulant properties, anti Xa and anti IIa activities. The results show that PK 10169 displayed significant antithrombotic activities above 0.625 mg/kg and was equipotent at 2.5 mg/kg s.c. with heparin 10 mg/kg s.c. No correlation could be observed between antithrombotic/anti Xa ratio of both compounds. Moreover it was shown that, unlike heparin, PK 10169 s.c. was devoid of obvious anticoagulant properties and induced a negligible anti IIa activity contrasting with a high anti Xa level. A similar dissociation between anti Xa and anti IIa activities was observed following i.v. administration of 2.5 mg/kg of PK 10169 but not with heparin. This low molecular weight heparin fraction might thus be regarded as a potential arterial antithrombotic agent devoid of appreciable anticoagulant effect.

Animals↗
PubMed1985

Electrophysiological and pharmacological evidence that peripheral type benzodiazepine receptors are coupled to calcium channels in the heart.

PK 11195, an antagonist of the peripheral type benzodiazepine receptor, does not affect either the duration of the action potential or the tension of the guinea pig papillary muscle. However, it antagonized the effects of the calcium channel blockers, nitrendipine, verapamil, diltiazem, and of BAY K8644, a calcium channel agonist in this heart preparation. On the other hand, PK 11195 does not change the increase in the action potential duration provoked by the potassium channel blocker tetraethylammonium. RO5-4864, an agonist of the peripheral type benzodiazepine receptor, decreased the tension of the guinea pig papillary muscle. The effect was reversed by increasing extracellular Ca2+ concentrations up to 4 mM. These results suggest that in the heart the peripheral type benzodiazepine receptors are coupled to calcium channels.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1985

Pharmacology of peripheral type benzodiazepine receptors in the heart.

RO5-4864 decreased in a dose-dependent manner the duration of intra cellular action potential and the contractility in the guinea pig papillary muscle. Diazepam was less active and clonazepam inactive. The effects of RO5-4864 were blocked by PK 11195 but not by RO15-1788. These results indicate that peripheral type benzodiazepine binding sites are pharmacological receptors. PK 11195 antagonized the increase and the decrease in the duration of intracellular action potential induced by BAY K-8644 and calcium channel blockers (nitrendipine, diltiazem, verapamil) respectively but not the increase induced by tetraethylammonium which blocks potassium channel. Moreover the decrease in contractility provoked by RO5-4864 was antagonized by 4 mM Ca2+. Thus peripheral type BZ receptors are coupled with Ca2+ channels in the heart.

Action Potentials↗
PubMed1985

Humoral and cellular immunological abnormalities in hypertensive patients.

A high frequency of immunological disturbances were recorded in 19 mild and 23 malignant hypertensive patients. IgG levels were raised in patients who survived a malignant phase of hypertension. We also found increased frequency of autoantibodies (26% vs. 9% in controls), increased T-lymphocyte reactivity against arterial-wall antigens (p = 0.001), a significant frequency of low responders to PHA (p = 0.003), and a statistically significant correlation (p = 0.031) between the presence of autoantibodies and T-cell hyper-reactivity against arterial antigens in mild hypertensive patients. We suggest that these abnormalities might be relevant in the pathogenesis of some hypertensive conditions. Autoantibody production is likely to be correlated with a predisposition to hypertension through some autoimmune mechanisms.

Adult↗
PubMed1984

Electrophysiological and pharmacological characterization of peripheral benzodiazepine receptors in a guinea pig heart preparation.

RO5-4864 decreased in a dose-dependent manner, from 3 X 10(-9) M to 3 X 10(-6) M, the duration of intracellular action potential and the contractility in a guinea pig preparation. Diazepam was less effective and clonazepam inactive. The effects of RO5-4864 were GABA-independent and antagonized by PK 11195 but not by the selective antagonist of the brain type benzodiazepine receptors RO15-1788. These results show the pharmacological relevance of peripheral type benzodiazepine binding sites at the cardiac level.

Action Potentials↗
PubMed1983

1-[4-(2-ter-butyl-quinolyl)]-3-(4-piperidyl)propanol (PK 10139): a new potent and long-acting antiarrhythmic agent.

PK 10139 is a new synthetic quinoline antiarrhythmic agent 10 times more potent and at least 2 to 3 times longer acting than quinidine sulfate. In the dog, the near 100% active dose (1.5 mg/kg i.v.) completely converted to sinus rhythm ouabain-induced ventricular tachycardia for over 30 min. The efficacy of this compound against multifocal beats induced by two-stage ligation of the left coronary artery (Harris) in the conscious dog was demonstrated after i.v. and oral administration with no peripheral and central nervous system side effects after the higher effective dose contrary to quinidine. In the anesthetized dog, PK 10139 like quinidine, increased atrial, atrioventricular nodal and ventricular refractory periods as determined with the programmed extrastimulus technique. PK 10139 also increased electrical stimulus threshold and intracardiac conduction times evaluated by measurement of A-H nodal conduction time, H-V conduction time and QRS interval as seen with all the class I antiarrhythmic agents. Thus, PK 10139 is a much more potent and long-acting agent than quinidine, with better tolerance.

Animals↗
PubMed1982

Complement-fixing antibody to Epstein-Barr virus soluble antigen in populations at high and low risk for nasopharyngeal carcinoma.

Greenland Eskimos comprise an ethnic group with one of the highest recorded incidence rates for nasopharyngeal carcinoma in the world. Sera from 625 Eskimos and 73 Danes (Caucasians) living in Greenland, as well as from 62 Danes living in Denmark, were tested for complement-fixing antibody to Epstein-Barr virus (EBV) soluble antigen and, from this study group, 129 donors were matched by age and sex for a study comparing antibody to viral capsid antigen, early antigen, and soluble antigen. Both Eskimos and Danes living in Greenland had significantly higher titers of EBV antibodies than Danes living in Denmark, suggesting that environment was more important than genetics or socio-economic factors in determining the antibody response to EBV. Age and sex were also factors, higher titers occurring in females and young Eskimos.

Adolescent↗