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Biomedical subjects

A Delgado

Publications and source records attributed to A Delgado.

At least 109 records · Page 6Linked to original sources

GABAB receptor activation inhibits Ca2+-activated potassium channels in synaptosomes: involvement of G-proteins.

86Rb-efflux assay from preloaded synaptosomes of rat cerebral cortex was developed to study the effect of GABAB receptor agonist baclofen on Ca2+-activated K+-channels. Depolarization (100 mM K) of 86Rb-loaded synaptosomes in physiological buffer increased Ca2+-activated 86Rb-efflux by 400%. The 86Rb-efflux was blocked by quinine sulphate, tetraethylammonium and La3+ indicating the involvement of Ca2+-activated K+-channels. (-)Baclofen inhibited Ca2+-activated 86Rb-efflux in a stereospecific manner. The inhibitory effect of (-)baclofen was mediated by GABAB receptor activation, since it was blocked by GABAB antagonist phaclofen, but not by bicuculline. Further, pertussis toxin also blocked the ability of baclofen or depolarizing action to affect Ca2+-activated K+-channels. These results suggest that baclofen inhibits Ca2+-activated K+-channels in synaptosomes and these channels are regulated by G-proteins. This assay may provide an ideal in vitro model to study GABAB receptor pharmacology.

Animals↗

New 1,4-dihydropyridine derivatives combining calcium antagonism and alpha-adrenolytic properties.

A series of twelve 1,4-dihydropyridine derivatives incorporating an alpha-adrenergic moiety in one of the ester chains was synthesized. The compounds were evaluated for their calcium antagonist activities by the inhibition of [3H]nitrendipine binding and, in vitro, on pig coronary artery. Their alpha 1- and alpha 2-adrenolytic effects were assessed from their inhibition of [3H]prazosin and [3H]yohimbine binding and, in vitro, on rat aorta and guinea pig vas deferens. Compounds 6 and 9-11 displayed strong calcium antagonist activities, identical with that of nicardipine. The moderate alpha-adrenolytic properties observed were attributed to the presence of alpha-adrenergic moieties. The four chiral derivatives 6a (R,R), 6b (S,S), 6c (S,R), and 6d (R,S) with an N-methyl-N-(benzodioxanylmethyl)amino group on the ester chain were prepared and tested as done previously. Some structure-activity relationships are discussed.

Animals↗

Effect of nicardipine on renal sodium handling in normotensive insulin-dependent diabetics and controls.

In 12 newly diagnosed normotensive insulin-dependent diabetics and eight controls, we compared the effects of acute nicardipine administration on renal haemodynamics and segmental tubular movement of sodium assessed as by lithium clearances. Both in the controls and the insulin-dependent diabetics, nicardipine induced similar haemodynamic changes, including a mild decrease in mean arterial pressure and renal vascular resistance, whereas the glomerular filtration, renal plasma flow and filtration fraction were unchanged. Despite a fall in blood pressure, nicardipine exerted a marked natriuretic effect in both groups, which appears to have been primarily due to a decrease in distal reabsorption and, to a lesser extent, in proximal reabsorption.

Adult↗

Influence of nicardipine on renal hemodynamics and segmental tubular reabsorption of sodium in humans.

Calcium antagonists induced natriuresis in humans as well as in experimental animals. However, the tubular sites involved have not been precisely evaluated in humans. Using both free-water and lithium clearance, the latter as a marker of absolute sodium distal delivery, we measured segmental tubular movement of sodium before and after acute intravenous (i.v.) nicardipine administration 2.5 mg as a single dose in eight healthy normotensive volunteers on normal sodium diet. Nicardipine decreased slightly but significantly the mean arterial pressure (MAP) (from 98.9 +/- 8.8 to 91.8 +/- 9.2 mm Hg; p less than 0.01) and the renal vascular resistance (from 6,142 +/- 1,082 to 5,578 +/- 893 dynes.s/cm5 . 1.73 m2; p less than 0.05), whereas the glomerular filtration rate (GFR), the renal plasma flow (RPF), and the filtration fraction (FF) were unchanged. Nicardipine acutely increased the absolute and the fractional excretion of sodium (from 282 +/- 60 to 427 +/- 152 mumol/min.1.73 m2; p less than 0.01 and from 0.015 +/- 0.004 to 0.023 +/- 0.013; p less than 0.01, respectively). When assessed by either lithium clearance or free-water clearance, both proximal and distal fractional reabsorption of sodium were decreased by nicardipine. These results indicate that the nicardipine-induced natriuretic effect is due to decreased sodium reabsorption in both proximal and distal sites of the nephron. Shifts in segmental tubular sodium reabsorption obtained from either free-water or lithium clearance were directionally similar but quantitatively different.

Adult↗

Influence of captopril on renal hemodynamics and segmental tubular reabsorption of sodium in humans.

Acute angiotensin-converting enzyme inhibitors (ACEIs) have been found to induce natriuresis in humans as well as in experimental animals. However, the tubular sites involved have not been precisely evaluated in humans. Using both free-water and lithium clearance, the latter as a marker of proximal tubular reabsorption, we measured segmental tubular movement of sodium before and after acute captopril administration in eight healthy normotensive volunteers on normal sodium diet. Captopril decreased slightly but significantly glomerular filtration rate (GFR), filtration fraction, and mean arterial pressure (MAP), whereas renal plasma flow (RPF) was unchanged. Captopril acutely increased excretion rate and fractional excretion of sodium. When assessed by lithium clearance, both absolute and fractional proximal reabsorption of sodium and fractional distal reabsorption of sodium were found to be decreased by captopril. When assessed by free-water clearance, both fractional proximal and distal reabsorption of sodium were found to be decreased by captopril but only the decrease in fractional proximal reabsorption was significant. These results indicate that captopril-induced natriuretic effect is due to decreased sodium reabsorption in both proximal and distal sites of the nephron. Shifts in segmental tubular sodium reabsorption obtained from either free-water or lithium clearance are directionally similar but quantitatively different. Results obtained from lithium clearance indicate that the rate of fluid delivery to the diluting segment is at least twice as great as that estimated from free-water calculations. Lithium clearance techniques therefore appear to be more sensitive in detecting subtle changes in segmental tubular reabsorption.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Characteristics of intrafamilial transmission of the hepatitis B virus: a case load contribution and review of the literature].

A total of 143 subjects have been investigated (83 adults and 60 children). All of them are relatives of 50 HBsAg carriers (26 females adults and 24 children). Relatives of these 26 females adults presents a intrafamilial prevalence of infection of 28.8% (40% in males partners). In the 24 paediatric cases, intrafamilial diffusion of HBV is more elevated 67% seropositives (72.4% of adults and 57.5% of children). Greater intrafamilial transmission of HBV are seen in chronic forms of disease. We do insist that is very necessary to investigate the immunity of HBV in relatives of HBsAg (+) subjects. Specific vaccination for those who will be seronegative should be indicated.

Adolescent↗

[Comparative study of the quality of prenatal care at health centers and hospitals].

The quality of prenatal care offered in health centers (HC) and in the hospital (H) have been compared. Two samples were evaluated. One consisted of 476 pregnant women seen in HC and another of 213 who were seen in H. Five out of the 22 selected markers did not show differences in both levels (date of delivery; weight gain in g/week; measurement of uterine weight and height; and hypertension detection). Ten markers were better fulfilled in H than in HC (obstetrical formula; gynecological examination, fetal heart beats and edema examination; detection of diabetes, urinary tract infection and anemia). By contrast, there were seven markers that were better fulfilled in HC (serological tests for syphilis and hepatitis B; treatment of urinary tract infection and anemia; and compliance with follow up). The better fulfillment of the markers in H might be due to the recent inclusion of prenatal care programs in HC. The fact that in the first level of care the controls are earlier and more frequent shows that this level facilitates the access of pregnant women to services and their follow up.

Ambulatory Care Facilities↗

[Effect of cyclosporin A on blood pressure and renal hemodynamics in insulin dependent diabetes].

In 13 patients with very recent onset insulin-dependent diabetes (IDD) (less than 3 months) we studied arterial pressure and renal hemodynamics before (M0) and after 3 months (M3) of treatment with cyclosporine A (5 mg/kg/d). Glomerular filtration rate (GFR) and effective renal plasma flow (RPF) were measured by inulin and PAH clearance respectively. Results, expressed as mean +/- SD were compared to those obtained in 8 healthy controls (C). At M0, GFR and filtration fraction were 143 +/- 21 ml/mn.1.73 m2 and 0.22 +/- 0.04 respectively and significantly increased as compared to control values. After 3 months of chronic cyclosporine administration, mean arterial pressure (MAP) significantly increased from 84.7 to 91.8 mmHg whereas GFR and FF significantly decreased to 114 +/- 23 ml/mn.1.73 m2 and 0.18 +/- 0.01 respectively. Renal vascular resistance (RVR) showed a trend toward increase from 658 +/- 161 to 728 +/- 225 MPa.s/L.1.73 m2 whereas natriuresis was unchanged. We concluded: 1) Cyclosporine A significantly increased MAP in patients with IDD; 2) Cyclosporine-induced increase in MAP may be in part related to rise in RVR; 3) In spite of the decrease in GFR, cyclosporine did not seem to induce persistent antinatriuretic effect.

Blood Pressure↗

[Hypokalemia, hypomagnesemia and ventricular arrhythmia during diuretic treatment of arterial hypertension].

Diuretics have been used for 25 years in the treatment of arterial hypertension, where they have proved effective and well tolerated. However, recent therapeutic trials have failed to demonstrate a significant reduction of coronary disease mortality in moderately hypertensive patients under antihypertensive therapy. These disappointing results have led to a reappraisal of the cardiovascular risk inherent in antihypertensive treatments and notably diuretics. Thiazides and the so-called heigh-ceiling diuretics increase urinary potassium excretion, thereby reducing serum potassium levels by 0.3 to 0.6 mmol/l on average. Kalaemia falls below 3.0 mmol/l in 1 to 7 percent of the patients. The long-term consequences of hypokalaemia are imperfectly known. Several authors have used continuous or exertion electrocardiographic recordings to evaluate the risk of ventricular arrhythmia induced by hypokalaemia, but their results are conflicting and inconclusive. The risk of ventricular arrhythmia is perhaps not negligible when hypokalaemia occurs in certain patients with coronary disease or left ventricular hypertrophy who are under digitalis therapy. Diuretics also reduce serum levels of magnesium. The consequences of isolated hypomagnesaemia are obscure. The risk of hyperexcitability seems to be increased when hypokalaemia is associated with digitalis toxicity. The fall in serum concentrations of potassium and magnesium is dose-dependent, and it occurs mainly with the excessive doses formerly prescribed. The dose-response curve of antihypertensive agents is relatively flat, which suggests that diuretics should be used in lower dosage.

Arrhythmias, Cardiac↗

[Gastroenteritis caused by Campylobacter jejuni in childhood. Study of 100 cases].

Authors report results of the study on a series of 100 pediatrics patients with Campylobacter gastroenteritis whose ages were between 1 month and 14 years. Incidence of Campylobacter jejuni isolation among 2,733 samples of diarrheal stools, examined during a period of 3 years, was 146 cases (5.03%). Several epidemiological, clinical and therapeutic aspects of the infection are analysed. Campylobacter jejuni is an important enteric pathogen in infancy, and clinical symptoms due to infection are diarrhea, fever, vomits and abdominal pain. Illness is frequently self-limited and resolution is favourable in most cases with symptomatic treatment.

Campylobacter Infections↗