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Biomedical subjects

B Lacour

Publications and source records attributed to B Lacour.

At least 163 records · Page 9Linked to original sources
PubMed1989

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↗
PubMed1989

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↗
PubMed1989

Calcium uptake by duodenal enterocytes isolated from young and mature SHR and WKY rats: influence of dietary calcium.

Intestinal calcium (Ca2+) transport was examined at the cellular level using duodenal enterocytes isolated from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). Compartmental analysis of 45Ca2+ uptake was performed on enterocytes isolated from young (12- to 14-wk-old) and mature animals (24- to 26-wk-old) fed either normal (1%) or high (2%) calcium diets. Intracellular Ca2+ flux (Jc) was reduced in SHR compared with WKY for both young (0.67 +/- 0.05 vs. 1.08 +/- 0.08 nmol Ca2+.mg protein-1.min-1 P less than 0.01) and mature (0.39 +/- 0.03 vs. 0.71 +/- 0.05 nmol Ca2+.mg protein-1.min-1; P less than 0.001) animals on a normal calcium diet. On a high-calcium diet, this strain difference of Jc disappeared in the young rats (0.87 +/- 0.09 vs. 1.06 +/- 0.06 nmol Ca2+.mg protein-1.min-1, NS). In mature SHR, the high-calcium diet stimulated Jc, whereas it lowered it in mature WKY resulting in a similar flux for both strains (0.56 +/- 0.05 vs. 0.49 +/- 0.05 nmol Ca2+.mg protein-1.min-1, NS). Young SHR had a lower intracellular Ca2+ pool compared with WKY. This defect was corrected by a high-calcium diet. The membrane Ca2+ flux (Jm) was lower in mature SHR than WKY fed a normal calcium diet (P less than 0.02); Jm increased to the control value (P less than 0.05) in the SHR on a high-calcium diet. Diet-induced changes of plasma 1,25(OH)2 vitamin D levels in the SHR did not parallel the observed changes of intestinal Ca2+ fluxes. Thus duodenal enterocytes from SHR appear to have an intrinsic alteration of Ca2+ transport that can be corrected in part by a higher calcium diet.

Aging↗
PubMed1989

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↗
PubMed1989

Influence of end-stage renal failure on concentrations of free apolipoprotein A-1 in serum.

We determined, immunoturbidimetrically, the concentrations of apolipoprotein A-I (apo A-I) (a) in total serum, (b) in total lipoproteins, and (c) in the fraction of d greater than 1.21 kg/L (free apo A-I) in 31 uremic patients (16 on hemodialysis, HD, and 15 with end-stage renal failure, ESRF) and 14 control subjects. The concentration of free apo A-I in serum was significantly increased in both groups of uremic patients (0.27 +/- 0.07 g/L for HD and 0.22 +/- 0.08 g/L for ESRF, mean +/- SD), in comparison with the control group (0.14 +/- 0.04 g/L). The ratio of total apo A-I to high-density-lipoprotein cholesterol was significantly increased in sera from both uremic groups, whereas the apo A-I/HDL-chol ratio of total lipoproteins was similar in all three groups. No apo A-I could be detected in five ultrafiltrates of plasma, even after 100-fold concentration. Analysis of apo A-I isoforms by isoelectrofocusing revealed a significant relative increase in apo A-I3 and a decrease in apo A-I5 isoform in ESRF patients, but not in HD patients. Finally, we found no relationship between serum TG and free apo A-I concentration.

Adult↗
PubMed1989

Diet-induced hyperlipoproteinemia and lipid accumulation within spontaneous arterial lesions in the rat.

The extent of diet-induced lipid accumulation evaluated histologically within rat caudal artery lesions, which represent sites of spontaneous intimal injury, was studied in relation to plasma cholesterol and lipoprotein changes in two consecutive experiments: 1) Rats were fed diets enriched with various amounts of cholesterol and saturated lipids from 5 to 12 weeks of age. A large range of values of cholesterolemia was observed at the time of sacrifice, and the more the diet was enriched in cholesterol and saturated lipids, the more the mean of the arterial score, which expressed the extent of lipid deposits within caudal artery lesions, was elevated. Among the biochemical parameters studied, in decreasing order, total cholesterol, LDLchol and VLDLchol were determinant for the arterial score. 2) Rats were fed a diet containing a moderate amount of lipids and the cholesterol concentration in the 3 classical plasma lipoprotein fractions was determined at 1.5, 3 and 6.5 weeks after starting the diet. In this experiment, statistical analysis showed that the degree of lipid accumulation within caudal artery lesions correlated only with the values of VLDLchol determined early (1.5 week) after starting the diet and not with those at the time of sacrifice. However, VLDLchol values correlated with those of LDL and total plasma cholesterol. The data from these two series of experiments suggest that in diet-induced hypercholesterolemia, the intensity of lipid deposits within areas of the arterial wall where spontaneous injury had occurred was related to the values of total plasma cholesterol as reflected both by VLDLchol and LDLchol. An independant effect of one of these lipoproteins cannot be demonstrated since they are correlated with one another.

Animals↗
PubMed1989

Evaluation of mAST/tAST ratio as a marker of alcohol misuse in a non-selected population.

Serum mitochondrial aspartate aminotransferase (mAST) and gamma-glutamyl transpeptidase activities were measured in 303 outpatients upon visits to their general practitioner. Alcohol consumption was evaluated by interview, using a standard questionnaire. Thirty-four patients drank more than 80 g of alcohol per day but none complained of an alcohol-related disease. These 34 heavy drinkers presented a mean serum mAST value which was significantly higher than that of the 269 normal drinkers; however, only 14 out of the 34 (41%) exhibited an increased mAST value. The sensitivity, specificity and predictive positive value of the mAST/tAST ratio were 0.29, 0.77 and 0.13, respectively; the corresponding figures for GGT were 0.5, 0.81 and 0.23, respectively. These results are in sharp contrast with those obtained for mAST activity in a population of hospitalized alcoholics. The explanation may lie in differences in alcohol consumption, in nutritional status and in the frequency of alcohol-related diseases in inpatients as compared to outpatients.

Adult↗
PubMed1988

Anomalies in composition of uremic lipoproteins isolated by gradient ultracentrifugation: relative enrichment of HDL in apolipoprotein C-III at the expense of apolipoprotein A-I.

Using a discriminating gradient separation technique combined with careful analysis of lipid and apolipoprotein (apo) composition, serum lipoproteins of 20 chronically uremic patients have been compared with those of 19 normal controls matched for age and sex. In uremic subjects, serum VLDL concentration was markedly increased. These particles were enriched in protein and cholesterol and relatively poor in triglycerides (TG). They contained more frequently apo B-48, and a decreased proportion of apo E. Expressed in percent, total apo C was normal but the ratio of apo C-III2/apo C-III1 was elevated. Uremic IDL, whose serum concentration was markedly increased, were characterized by an increased proportion of protein. Total uremic LDL whose serum concentration was normal, contained less esterified cholesterol (EC) and more TG than normal LDL, their EC/TG ratio being very low. Moreover, the concentration of the mature subfraction of LDL having a mean density of 1.043 g/ml, was markedly decreased in uremic subjects. Taken together, these anomalies indicate a delayed transformation of VLDL into LDL in chronic renal failure. The decreased concentration of total HDL in uremic subjects was more marked in HDL2 (-46%) than HDL3 (-24%). Both uremic HDL2 and HDL3 were relatively enriched in TG, and uremic HDL3 were poorer in EC than normal HDL3.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Pathogenesis of abnormal acid-base balance in the young spontaneously hypertensive rat.

1. We have previously reported reduced blood pH and plasma bicarbonate in young Okamoto-Aoki spontaneously hypertensive rats (SHR) compared with normotensive Wistar-Kyoto rats (WKY). Acid loading with 1.5% (w/v) NH4Cl as the sole drinking fluid produced identical falls in blood pH, the difference remaining significant. 2. The ability of SHR to excrete acid and alkaline loads was compared with that of WKY under metabolic cage conditions. The effects of such manipulations on urinary sodium, potassium, calcium and phosphate excretion were also determined. 3. No difference was found in the ability to excrete an acid load or to reduce urine pH. Neither total urinary ammonium ion nor titratable acid differed significantly between the strains under either baseline or acid-loading conditions. 4. Baseline urinary bicarbonate excretion was not significantly different between strains but intraperitoneal administration of NaHCO3 at 2.0 mmol/kg body weight resulted in enhanced excretion in the SHR (SHR vs WKY: 625.2 +/- 71.5 vs 381.8 +/- 40.6 mumol 24 h-1 kg-1 body weight, P less than 0.01, mean +/- SEM). 5. No difference in urinary sodium or potassium excretion was observed between SHR and WKY, but basal calcium and phosphate excretion were reduced in SHR (P less than 0.05). 6. Increased urinary bicarbonate excretion in the presence of significantly reduced plasma bicarbonate suggests reduced tubular reabsorption of bicarbonate, which may contribute to the mild metabolic acidosis in young SHR.

Acidosis↗
PubMed1988

Influence of fast, body weight and diet on serum cholesterol, triglycerides, and phospholipids concentrations in the aging rat.

The present study was performed to document factors playing a role in the age-related increase of serum total cholesterol, triglycerides, and phospholipids in male WISTAR rats. In 59 and 122 week old rats, serum concentrations of all three parameters were significantly higher than those determined in younger rats (15-17 weeks of age). Serum triglycerides and cholesterol concentrations were higher in post absorptive than in fasting state. In mature rats of same age (59 weeks), mean concentrations of cholesterol, triglycerides, and phospholipids were significantly higher in the heavier animals than in the others. A strong correlation could be established between body weight and serum cholesterol or triglycerides of these animals. The composition of diet appears to play a role in serum cholesterol concentration but not in serum triglycerides concentration in old rats (59-65 weeks of age). This effect is demonstrated even if daily caloric intake and daily body weight gain of old rats (40-50 weeks of age) were not significantly different with both diets tested (2900 and 3250 cal/kg). In conclusion old Wistar rats develop increased concentrations of serum lipids parameters.

Aging↗
PubMed1988

Endogenous digitalislike circulating substances in spontaneously hypertensive rats.

Circulating digitalislike compounds have been proposed to be involved in some Na+-dependent types of experimental hypertension and in human essential hypertension. The level of circulating Na+-K+ pump inhibitor(s) was investigated in the spontaneously hypertensive rat of the Okamoto strain (SHR), its normotensive control, Wistar-Kyoto rat (WKY), and the regular Wistar rat using the following criteria: the ability of whole plasma to inhibit the total active Na+ efflux from Wistar rat erythrocytes and to cross-react with digoxin antibodies and the ability of plasma extracts to inhibit Na+,K+-adenosine triphosphatase (ATPase) activity of membranes from rat kidney. SHR plasma inhibited the net Na+ efflux from Wistar erythrocytes by up to 27% compared with WKY or Wistar plasma. For a given number of cells, the inhibition increased with the amount of available plasma. Cross-reactivity with digoxin antibodies was twice as high in SHR as in WKY or Wistar plasma. It was already enhanced in 3- to 4-week-old rats. Plasma extracts from SHR significantly inhibited Na+,K+-ATPase activity when compared with WKY extracts (75.6 +/- 2.6 vs 89.3 +/- 2.4 mumol Pi/mg/hr; p less than 0.01) but did not differ from Wistar plasma extracts. These results strongly suggest that circulating digitalislike compound(s) are present in elevated amounts in SHR as early as 3 to 4 weeks of age, but their exact participation in blood pressure elevation or maintenance remains to be clarified.

Animals↗
PubMed1988

[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↗
PubMed1988

Purification of anti-apolipoprotein CIII antibodies by exploiting their affinity for apolipoprotein CIII linked to polyacrylamide gel after isoelectric focusing.

A new immunoaffinity technique for purifying anti-apolipoprotein CIII antibodies has been developed by isolating bands of apo CIII2 from isoelectric focusing (IEF) gel. Total apo C was obtained from delipidated very-low-density lipoprotein by chromatography on Sephacryl S 200. Apo CIII2 was separated from the apo CII band by IEF on polyacrylamide gel with use of pH 4-6 ampholytes. After sonication of the band in distilled water and various different washes, we directly mixed with antiserum a suspension of apo CIII2 bound to IEF-polyacrylamide gel. After their elution, we tested the specificity of the antibodies by an enzyme immunoassay technique, using plates coated with apolipoprotein, 100 ng per well. No cross-contamination of eluted anti-apo CIII antibodies by anti-apo CII or anti-apo E antibodies was observed. This affinity technique is easy to use, rapid to perform, and no sophisticated apparatus is needed. The gels can be used repeatedly and yield reproducible results with a very good analytical recovery (94%). We anticipate that this technique will prove useful for purification of other antibodies, particularly antibodies to apolipoproteins such as anti-apo CII and anti-apo E.

Acrylic Resins↗
PubMed1987

Disturbance of acid-base balance in the young spontaneously hypertensive rat.

1. The acid-base status of young spontaneously hypertensive rats (SHR) was compared with that of Wistar-Kyoto rats (WKY) in the steady state, after acid loading and after blood pressure had been maintained at normal levels from weaning. Whole blood ionized calcium was measured simultaneously. 2. In the prehypertensive stage (4 weeks of age), plasma bicarbonate was significantly lower in SHR than in WKY, while blood pH did not differ significantly. 3. After 6 weeks of age, blood pH and plasma bicarbonate were significantly lower in both anaesthetized and conscious SHR than in corresponding WKY. After 7 days administration of NH4Cl in the drinking fluid, both parameters decreased significantly in both strains and the difference in pH remained constant (0.05 pH unit, P less than 0.01). 4. In none of the groups investigated did non-pH-adjusted ionized calcium differ significantly between the SHR and WKY. 5. Prevention of the development of hypertension in SHR by hydralazine treatment from weaning did not increase pH or bicarbonate compared with untreated SHR, indicating that the metabolic acidosis in the SHR was not a consequence of raised blood pressure. 6. Disturbance in acid-base balance may be involved in the pathogenesis of raised blood pressure in this animal model of genetic hypertension.

Acid-Base Imbalance↗
PubMed1987

Chronic triiodothyronine supplementation does not improve the lipoprotein disorders of mildly uremic rats.

The present study was performed to appreciate the potential role that thyroid deficiency could play in the energy homeostasis and lipid metabolism of experimental chronic renal failure. For this purpose, 12 uremic rats that were supplemented with T3 (0.4 microgram/100 g body weight/day) during 5 weeks by means of osmotically driven minipumps were compared to 12 unsupplemented uremic rats and 12 control rats. The chronic supplementation of uremic rats with T3 induced no significant change in body weight gain or in the serum concentration of insulin, glucose, glycerol, nonesterified fatty acids, total triglycerides (TG), total cholesterol, and total choline phospholipids. Similarly, the metabolism of TG-rich lipoproteins was not affected by the supplementation with T3 in these uremic rats as appreciated by TG production or TG degradation (adipose tissue lipoprotein lipase activity). T3 administration induced a significant decrease in serum beta-hydroxybutyrate concentration and an increase in serum lactate concentration. Furthermore, heparin-releasable hepatic TG lipase activity as expressed per total liver mass was decreased in uremic rats treated with T3. The latter changes were observed in the absence of modifications of serum glucose or TG concentration. We conclude from these observations that rats with a moderate degree of chronic uremia do not seem to have a cellular thyroid deficiency sufficient to disturb their energy or lipid metabolism.

Animals↗