Search PubMed⌕ Search

Biomedical subjects

M Mestre

Publications and source records attributed to M Mestre.

At least 37 records · Page 2Linked to original sources
PubMed1993

Is the sigma 2 receptor in rat brain related to the K+ channel of class III antiarrhythmic drugs?

The sigma 2 receptor subtype was studied in rat cerebral cortex and in C6 glioma cells homogenates using various compounds including class III antiarrhythmic drugs. The characteristics of (+)-[3H]-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine ((+)-[3H]-3-PPP) binding were assessed in competition experiments with different displacers which revealed the presence of sigma 2 receptors. Various class III antiarrhythmic drugs inhibited (+)-[3H]-3-PPP binding with high affinity and their binding affinity was found to correlate with the potency of these compounds to increase the duration of action potentials measured in Purkinje fibers in electrophysiological studies. Since class III antiarrhythmic drugs are known to interact with voltage-dependent K+ channels, the present results provide evidence that the (+)-[3H]-3-PPP binding sites in rat brain possess the characteristics of K+ channels of class III antiarrhythmic drugs.

Action Potentials↗
PubMed1993

CD23 expression on B-lymphocytes and its modulation by cytokines in allergic patients.

The aim of this study was to assess the expression of CD23 on peripheral blood B-cells, and its in vitro modulation by recombinant human interferon-gamma (IFN-gamma) in phytohaemagglutinin-(PHA) or recombinant human interleukin-4 (IL-4)-stimulated cultures in atopic patients with Dermatophagoides pteronyssinus hypersensitivity and in healthy non-atopic subjects. Atopic patients with asthma not receiving allergen-specific immunotherapy (n = 21) were studied and further compared with a group of atopic subjects with asthma under allergen-specific immunotherapy (n = 21). They were age-(+/- 5 yr) and sex-matched. The results were also compared with those obtained in the non-atopic group (n = 11). CD23 expression on B-lymphocytes and its modulation were analyzed by flow cytometry using conjugated monoclonal antibodies with a double immunofluorescence method. Atopic patients had an increase in the percentage of B-cells expressing CD23 in peripheral blood. Phytohaemagglutinin and IL-4 induced a rise in the percentage of CD23-positive B-cells in both atopic groups and non-atopic subjects. Phytohaemagglutinin provoked an increase in the intensity of CD23 expression on B-cells from stimulated cultures in all groups, while IL-4 only produced a significant increase in atopic patients. The presence of IFN-gamma decreased the CD23 expression on B-cells in PHA-stimulated culture of atopic patients, whereas it caused an increase in CD23 expression in the non-atopic group. Furthermore, the presence of IFN-gamma in IL-4-stimulated cultures induced a decrease in CD23 expression on B-cells in all cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

IgE antibodies against bovine serum albumin in a case of eosinophilic gastroenteritis.

Eosinophilic gastroenteritis is a disease characterized histologically by an eosinophilic infiltration of the gut. The cause of this disease remains unclear, although both food allergy and food intolerance have been implicated in its pathogenesis. We report the case of a 22-year-old man in whom gastrointestinal symptoms first appeared in childhood, with involvement of mucosa and muscularis layers of stomach and bowel. He presented high IgE blood levels, and his prick test was positive to bovine, pig, and lamb sera. Immunoblots from calf, pig, and lamb sera, incubated with the patient's serum and revealed by autoradiography, demonstrated the presence of a 65-kDa protein band that was recognized by IgE antibodies but not by IgG. This band corresponded to bovine serum albumin, while IgE did not show reactivity with human albumin. These data suggest a possible role for IgE-mediated hypersensitivity mechanisms in the pathogenesis of eosinophilic gastroenteritis.

Adult↗
PubMed1992

Lymphocyte immunophenotyping by flow cytometry in normal adults. Comparison of fresh whole blood lysis technique, Ficoll-Paque separation and cryopreservation.

In the present report we have assessed the extent to which Ficoll-Paque separation and cryopreservation of mononuclear cells alter the measurement of lymphocyte subsets by flow cytometry. Standard Ficoll-Paque separation increased the percentage of CD4+, CD19+ and CD4+CD45RA+ cells, as well as decreasing that of CD8+, and CD4+CD29+ cells, compared to the fresh whole blood lysis technique. Moreover, cryopreservation caused a depletion of CD4+ p80+ cells, but normal whole blood values were restored following a short incubation.

Adult↗
PubMed1992

Enoxaparin (Clexane, Lovenox), a low molecular weight heparin, enhances t-PA-induced coronary thrombus lysis in anesthetized dogs without inducing hypocoagulability.

An occlusive coronary thrombus was obtained in barbiturate anesthetized dogs within 60 min following the angiographic placement of a copper coil into the left descending coronary artery. This thrombus persisted for the 60 min experimental period, within which the effects of i.v. t-PA (10 micrograms/kg/min for 30 min) alone or combined with i.v. heparin (0.63 mg/kg twice) or enoxaparin (1.5 mg/kg twice) were evaluated. t-PA alone achieved recanalization for 20 min in only 2 out of the 5 dogs studied. Combination of t-PA with either heparin or enoxaparin produced this effect in all the 5 dogs studied. In dogs treated with t-PA associated to either heparin or enoxaparin, the thrombus weight was smaller (decreases of 34% and 44% respectively) than in animals given t-PA alone. The plasma amidolytic activity, expressed as t-PA activity, was greater 15 min after the beginning of t-PA infusion, in dogs pretreated with either heparin or enoxaparin than in animals given t-PA alone. Conversely, during t-PA infusion, the apparent t-PA inhibitor and antiplasmin activities were no longer measurable in the plasma, but reappeared 10 min after the end of t-PA infusion. Plasma coagulation time was not modified by t-PA, but was slightly prolonged (2-fold) by enoxaparin and markedly (7-fold) by heparin on initiation of t-PA infusion. Plasma anti-IIa activity was 3-fold higher in dogs pretreated with heparin as opposed to enoxaparin. On the contrary, both compounds increased similarly plasma anti-Xa activity. In conclusion, these results indicate that enoxaparin, like heparin, enhances the thrombolytic effects of t-PA. This favourable effect occurs independently of a plasma hypocoagulable state, which was clearly produced by heparin but not enoxaparin. Its mechanism may be the significant elevation of plasma t-PA activity produced by both heparin and enoxaparin during t-PA infusion.

Amino Acid Sequence↗
PubMed1992

Antilymphocyte globulin versus OKT3 induction therapy in cadaveric kidney transplantation: a prospective randomized study.

Different induction therapies have been used in renal transplantation to avoid cyclosporine (CsA) nephrotoxicity and early acute graft rejection. This study compares the efficacy of a short course of prophylactic OKT3 to that of antilymphocyte globulin (ALG) in preventing acute renal allograft rejection when administered concomitantly with CsA and steroids. Between March 1988 and December 1990, 140 first-cadaver renal transplant recipients were randomly allocated to two immunosuppression groups--ALG group (n = 68): ALG 15 mg/kg just before transplant surgery, ALG 12 mg/kg the first day after transplant, followed by four doses of 10 mg/kg on alternate days; and OKT3 group (n = 72): OKT3 5 mg just before transplant, followed by four doses of 5 mg/d. Both groups included low-dose CsA and steroids. The incidence of rejection during the first 3 months after transplantation was 15% in the ALG group and 19% in the OKT3 group (NS). Kaplan-Meier estimates of patients free of rejection at 2 years was 85% in the ALG group and 77% in the OKT3 group (NS). The 3-year actuarial graft survival was 82% and 85% (NS), and 3-year patient survival was 97% and 98% (NS), in the ALG and OKT3 groups, respectively. These results indicate that the concomitant association of CsA and ALG or OKT3 constitutes a safe and effective therapeutic strategy that provides a low incidence of rejection and gives good results for patient and graft survival.

Adolescent↗
PubMed1992

RP 58866 and its active enantiomer RP 62719 (terikalant): blockers of the inward rectifier K+ current acting as pure class III antiarrhythmic agents.

The present article presents an overview of the pharmacologic profile of the benzopyran derivative RP 58866, a racemic mixture, and of RP 62719 (terikalant), its active enantiomer. In normal cardiac tissues studied in vitro, both drugs dose-dependently prolonged the atrial and ventricular action potential but affected neither the upstroke of the action potential nor the diastolic potential. Patch-clamp experiments demonstrated that the prolongation of the action potential induced by the drugs is due to a specific blockade of the inward rectifier K+ current. In vivo, intravenous administration to anesthetized dogs of low doses of RP 62719 consistently induced bradycardia and prolonged the atrial, nodal, and ventricular refractory periods, but did not affect the conduction velocity. Because of these properties, RP 58866 and RP 62719 exert potent antiarrhythmic and antifibrillatory actions both at the atrial and ventricular levels in various experimental models of arrhythmia. Our results demonstrate that RP 58866 and RP 62719 are K(+)-channel blockers acting as pure class III antiarrhythmic drugs.

Action Potentials↗
PubMed1992

Positive inotropic effects of RP 62719, a new pure class III antiarrhythmic agent, on guinea pig myocardium.

The mechanical effects of RP 62719 [(-)1-[-2-(3,4-dihydro-2H-1- benzopyran-4-yl)ethyl]-4-(3,4-dimethoxyphenyl)-piperidine] were tested in vitro on guinea pig left ventricular papillary muscle. RP 62719 is a novel pure class III antiarrhythmic agent known to prolong the cardiac action potential duration by selectively blocking the inward rectifying K+ current. Mechanical parameters were determined from contraction and relaxation phases under isotonic and isometric conditions. At a concentration of 0.02 microM, RP 62719 did not produce significant effects on inotropy or lusitropy. At 0.2 and 2 microM, the drug improved contraction under both heavy and low loading conditions, as evidenced by a 30% increase in maximum unloaded shortening velocity (Vmax, P < .001), peak amplitude of shortening (delta L, P < .001), peak isometric active force normalized per cross-sectional area (AF/s, P < .001) and positive peak of the force derivative per mm2 (+dF/s, P < .001). At the same concentrations, positive lusitropic effects were evidenced by an increase in maximum lengthening velocity (maxVr) and negative peak of force derivative per mm2 (-dF/s, P < .001). At a higher concentration (20 microM), effects of RP 62719 on inotropy and lusitropy were less marked, thus accounting for the bell-shaped form of the dose-response curve. An increase in the extracellular Ca++ concentration from 2.5 to 3.75 mM improved inotropy to a similar extent (+30-50%) as did 2 microM RP 62719. However, lusitropy and mechanical coupling between contraction and relaxation were not modified in the same proportion under RP 62719 and under 3.75 mM Ca++.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

[Antilymphocyte serum, cyclosporine and corticoids, versus OKT3, cyclosporine, and corticoids in kidney transplantation].

UNLABELLED: The use of the antilymphoblast globulin (ALG) or OKT3 associated with cyclosporine (CyA) and steroids has been useful in kidney cadaveric transplantation. 101 patients who received their first cadaveric renal transplant were randomized according to the immunosuppression used. Group A (n = 53): horse ALG 15 mg/kg just before transplant surgery; ALG 12 mg/kg on the first day after transplant followed by 4 doses of 10 mg/kg on alternate days; Cya p.o 8 mg/kg/d; prednisone 0.25 mg/kg/d. Group B (n = 48): OKT3 5 mg just before transplant followed by 4 doses of 5 mg/d.; CyA and prednisone were administered using the same schedule as group A. RESULTS: the incidence of rejection during the first 3 months was: group A: 13 percent, group B: 17 percent (NS). The probability of being free of acute rejection (Kaplan-Meier) 24 months after transplant was 89 percent in group A and 79 percent in group B (NS). The day of onset of the first acute rejection episode was 25 +/- 20 days after transplant in group A, and 17 +/- 10 day in group B (NS). Incidence of tubular necrosis: group A 21 percent, group B 19 percent (NS).

Adrenal Cortex Hormones↗
PubMed1991

Nicorandil: differential contribution of K+ channel opening and guanylate cyclase stimulation to its vasorelaxant effects on various endothelin-1-contracted arterial preparations. Comparison to aprikalim (RP 52891) and nitroglycerin.

In endothelium-denuded rat aortic rings, the sustained contractile effects produced by endothelin-1 (ET-1; 3.2 nM) were concentration-dependently overcome by nicorandil, aprikalim (RP 52891), a specific K+ channel opener, and nitroglycerin, a stimulant of guanylate cyclase (EC50: 2.55 +/- 0.06, 0.37 +/- 0.05 and 0.3 +/- 0.008 microM respectively, n = 13-16/group). The decontractant activity of aprikalim was not affected by the guanylate cyclase inhibitor methylene blue (10 microM), whereas it was markedly antagonized by glibenclamide (1 microM) (pKB: 7.19 +/- 0.15), an antagonist of ATP-gated K+ channels in pancreatic beta cells. This sulfonylurea failed to modify nitroglycerin-induced effects, but slightly reduced (10-15%) those produced by high concentrations of nicorandil. By contrast, methylene blue significantly displaced (4-fold) the control concentration-vasorelaxant response curves obtained with nitroglycerin and nicorandil. Zaprinast (20 microM), an inhibitor of soluble low Km cyclic GMP phosphodiesterase, enhanced the effects of nitroglycerin and nicorandil but did not alter those of aprikalim. Nicorandil relaxed ET-1-contracted rings from micropig left circumflex coronary artery with an EC50 of 24 +/- 2.8 microM (n = 7); this effect was antagonized by methylene blue (10 microM) and glibenclamide (3 microM) (2- and 4-fold dextral shift of the control concentration-response curve, respectively). In rat Langendorff-perfused heart with base-line coronary flow reduced by the addition of ET-1 to the perfusion medium, nicorandil and aprikalim increased coronary flow, while nitroglycerin did not. The vasodilator effects of the two compounds were also inhibited by glibenclamide (pKB congruent to 7).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Antilymphoblast globulin, cyclosporine, and steroids in cadaveric renal transplantation.

In order to avoid cyclosporine (CsA) nephrotoxicity and rejection, especially during the early posttransplant periods, different immunosuppression regimens have been adopted. A prospective trial was conducted to evaluate the benefits of initially low CsA doses associated with antilymphoblast globulin and steroids in the first days after transplant, in comparison with higher doses of CsA and steroids. Between 1/86 and 1/88, two groups of first-cadaver renal transplant recipients were documented based on the immunosuppression regimen used. In group A (n = 50), oral CsA was started at 8 mg/kg/day and subsequent doses adjusted to maintain CsA whole-blood levels between 300 and 600 ng/ml. Horse ALG at 10 mg/kg was given the day after transplant and on alternate days to a maximum of 6 doses. After 3 doses, ALG was stopped if CsA blood levels were equal to or greater than 400 ng/ml. ALG dosage modifications were made in order to maintain peripheral CD3+ cells between 10 and 20%. Prednisone was given at 0.25 mg/kg/day. In group B (n = 50), oral CsA was started at 15 mg/kg/day. The CsA whole-blood levels were maintained between 300 and 800 ng/ml. Prednisone was administered at 0.5 mg/kg/day. The incidence of postransplant renal failure was the same in both groups (16%), but the duration of oliguria was lower in group A than in group B (3.3 +/- 2 vs. 16.2 +/- 10.7 days, P less than 0.05), as well as the incidence of acute rejection during the first 3 months (18% vs. 40%, P = 0.01. The cumulative doses of CsA and steroids were significantly lower in group A than in group B. Mean serum creatinine at 6 and 12 months remained similar in both groups. There was no difference between the 2 groups in the incidence of infection. There was no mortality in either group. The actuarial graft survival was significantly higher in group A than in group B at one (100% vs. 94%), two (97% vs. 87%), and three years (89% vs. 73%), respectively (P = 0.041). In summary, the triple regimen using simultaneously low-dose CsA, ALG, and steroids minimizes early graft dysfunction, provides efficient immunosuppression without severe infections, and gives good long-term patient and graft survival.

Adult↗
PubMed1990

Potassium accumulation in the globally ischemic mammalian heart. A role for the ATP-sensitive potassium channel.

We investigated the contribution of opening of the ATP-sensitive K+ channel to extracellular accumulation of K+ during ischemia with the use of glibenclamide, a specific blocker of this K+ channel. To characterize the electrophysiological effects of glibenclamide during metabolic inhibition (by either application of dinitrophenol or hypoxia) we performed patch-clamp studies in isolated membrane patches of guinea pig myocytes and in intact guinea pig myocytes and studied action potential parameters in isolated superfused guinea pig papillary muscle. We studied the effect of glibenclamide on extracellular accumulation of K+ and H+ in isolated retrogradely perfused globally ischemic hearts of rat, guinea pig, and rabbit. Experimental evidence is presented that supports the conclusions that glibenclamide 1) effectively blocks open K+ATP channels, 2) reverses the dinitrophenol-induced increase of the outward current and prevents the hypoxia-induced shortening of the action potential, 3) decreases the rate of K+ accumulation during the first minutes of ischemia in stimulated hearts, an effect which was entirely absent in quiescent hearts, and 4) does not influence the rate and extent of ischemia-induced extracellular acidification.

Action Potentials↗
PubMed1989

[Sarcoidosis in Catalonia: analysis of 425 cases].

In a retrospective cooperative study carried out in three Barcelona hospitals, 425 patients in whom a diagnosis of sarcoidosis had been made during a 15-year period were evaluated. Several parameters were evaluated and compared with those from the longest series in the literature. Remarkable epidemiological and clinical features included the female predominance, explained by the high frequency of clinical presentations with erythema nodosum; the high incidence of other skin lesions, and, by contrast, the low frequency of eye involvement. It was also remarkable that in a few cases the diagnosis was made in a routine chest radiogram. In diagnostic procedures there was a good diagnostic yield from mediastinoscopy and muscle and pre-scalene fat biopsies The results of Kveim's test, functional respiratory testing and such current activity markers as 67-gallium pulmonary scintigraphy, serum levels of angiotensin converting enzyme and bronchoalveolar lavage were analyzed, and no differences with other series from the literature were found. The presence of the B8 allele and the A1 B8 haplotype was highly significant in subacute sarcoidosis. It is concluded that sarcoidosis is not an uncommonly found condition in this country if the suspicion index is high and an appropriate diagnostic workup is carried out. Its features are not different, as a rule, from those in other European series.

Adolescent↗
PubMed1989

Vasorelaxant effects of cromakalim in rats are mediated by glibenclamide-sensitive potassium channels.

Cromakalim (BRL 34915), a K+ channel activator, and diltiazem relaxed isolated rat aortic rings contracted with a low KCl concentration (25 mM). Gilbenclamide (0.1-3 microM) did not modify base-line resting tension or responses to KCl but prevented the vasorelaxant effects of cromakalim without affecting those of diltiazem or nitrendipine. Cromakalim, in contrast to the latter compounds, did not relax aortic rings contracted with 55 mM KCl. In pentobarbital-anesthetized rats prepared for hemodynamic measurements with Doppler flow probes, a 20-min i.v. infusion of cromakalim (5.0 micrograms/kg/min) lowered mean carotid artery blood pressure. This effect reached maximum after administration and was accompanied by decreases in systemic (35%), hindquarter (45%), mesenteric (27%), and renal (19%) vascular resistances. The blood pressure effects of cromakalim were not modified by BW 755C (lipo and cyclooxygenase inhibitor), idazoxan, methylatropine, methysergide, promethazine, propranolol, SCH 23390 (DA-1 receptor antagonist), S-sulpiride, RP 59227 (antagonist of platelet activating factor receptors) or by bilateral vagotomy associated with ligation of carotid arteries. However, in rats pretreated with the hypoglycemic sulfonylureas glibenclamide or glipizide (20 mg/kg i.v.), cromakalim, in contrast to diltiazem or dihydralazine, failed to produce hypotension. In rats deprived of sympathetic drive by pithing, cromakalim produced only a minor fall in blood pressure; however, this effect became pronounced when the low base-line blood pressure of this preparation was elevated by an i.v. infusion of vasopressin and could be prevented by glibenclamide. In conclusion, cromakalim posseses a novel mechanism of vasorelaxation that is consistent with the activation of a cellular outward K+ current.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗