Search PubMed⌕ Search

Biomedical subjects

B Lacour

Publications and source records attributed to B Lacour.

At least 109 records · Page 6Linked to original sources
PubMed1993

Molecular characteristics of uronic-acid-rich protein, a strong inhibitor of calcium oxalate crystallization in vitro.

Uronic-acid-rich protein (UAP) is a new urinary macromolecule which strongly inhibits calcium oxalate crystal formation. It is a glycoprotein with a molecular weight of about 35,000 Da, and its carbohydrate content is 8.5%. This inhibitor is composed of two polypeptidic chains crosslinked by chondroitin sulfate. It exhibits partial structural homology with alpha 1-microglobulin. The inhibitory activity seems to be supported by peptidic chains as determined by enzymatic assay.

Amino Acid Sequence↗
PubMed1993

Isolation and purification of a new glycoprotein from human urine inhibiting calcium oxalate crystallization.

A calcium oxalate crystal growth inhibitor was isolated from human urine using DEAE-Sephacel gel followed by Sephacryl S-300 chromatography and FPLC column. The isolated inhibitor was a uronic-acid-rich protein (UAP). It was found to be a glycoprotein with a molecular weight of 35,000 Da as determined by SDS-polyacrylamide gel electrophoresis. Inhibitory activity was demonstrated using a calcium oxalate crystallization system. In addition UAP, nephrocalcin (NC) or nephrocalcin-like (NC-like) activity was an effective inhibitor in this system. However, the inhibitory activity of UAP appeared to be higher than that of NC or NC-like activity. This finding suggests that NC or NC-like activity is not only urinary protein with strong inhibitory activity. UAP and probably other proteins also play a role in the control of urinary crystal growth.

Calcium Oxalate↗
PubMed1993

Impaired duodenal response to short-term dietary calcium restriction in adolescent spontaneously hypertensive rats.

The response pattern of plasma calcitriol level and related intestinal adaptation to short-term moderate calcium (Ca) restriction was examined in adolescent male, spontaneously hypertensive rats (SHR) and normotensive WKY control rats. Twelve-week-old SHR and WKY fed a low (0.1%) Ca diet for 3, 6, or 12 days were compared with rats of either strain fed a normal (1.0%) Ca diet. Plasma calcitriol response was measured and duodenal adaptation to Ca restriction was investigated by evaluating active Ca transport, calbindin-D9K (CaBP9K) protein, CaBP9K mRNA, and alkaline phosphatase activity (ALP). Under the normal Ca diet, no significant difference between strains was observed for all five parameters. In response to the low Ca diet, the SHR and WKY showed a similar increase (nearly 50%) in plasma calcitriol, starting at day 3 of this diet. However, only the WKY displayed the expected duodenal adaptation: active Ca transport increased at day 6 and CaBP9K as well as ALP increased at day 3 of the low Ca diet. The stimulation of the latter three parameters was maintained until day 12 of Ca restriction. Moreover, CaBP9K mRNA was increased in WKY after 3 days of Ca restriction. In contrast, the SHR had either no or only a minor increase of duodenal parameters in response to Ca restriction. Finally, a significant and positive correlation between Ca transport and plasma calcitriol and between Ca transport and CaBP9K was found in WKY but not in SHR.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaline Phosphatase↗
PubMed1993

A new approach to studying inhibitors of calcium oxalate crystal growth.

The nucleation and crystal growth of calcium oxalate (CaOx) were studied at pH 5.5 using turbidimetric measurements at 620 nm of suspensions produced by mixing calcium chloride and sodium oxalate (initial conditions: Ca, 3 x 10(-3) M; Ox, 0.5 x 10(-3) M). CaOx crystallization kinetics were defined first by the induction time ti and then by the slope of turbidity as a function of time during the interval corresponding to a correlation coefficient r2 > 0.99. The technique described requires only a small amount of material, is quick, convenient, and can be used to study inhibitors of CaOx crystallization by comparing ti and the rate of crystal growth in the presence and absence of inhibitors. The effects on CaOx crystal growth of several low molecular weight compounds, i.e. di- and tricarboxylic acids, were examined. The majority of these compounds were inhibitors of crystal growth, the greatest effect being seen with citric acid (50% inhibition in the presence of 1.5 x 10(-3) M citric acid), isocitric acid (50% inhibition in the presence of 0.75 x 10(-3) M isocitric acid) and pyrophosphate (30% inhibition in presence of 0.15 x 10(-3) M pyrophosphate). The inhibitors' behaviour regarding the medium was studied without any assumptions about their possible mechanisms of action. Measurements of ionized calcium before and after the reaction, as well as the observation of crystals by scanning electron microscopy, allowed us to formulate the hypothesis that the effect of citric acid and tartaric acid can be attributed mainly to ion pairing, in contrast to that of pyrophosphate and the other carboxylic acids.

Calcium↗
PubMed1993

Effects of blood pressure and antihypertensive treatment on progression of advanced chronic renal failure.

The potential role of blood pressure and antihypertensive treatment on the progression of advanced chronic renal failure was analyzed in 223 adult patients (126 males) with well-defined primary chronic renal diseases (glomerulonephritis, n = 73; angionephrosclerosis, n = 24; interstitial nephritis, n = 61; polycystic kidney disease, n = 52, Alport's syndrome, n = 13). Effect of average mean arterial pressure (MAP) obtained during follow-up, antihypertensive treatment (normotensive, conventional antihypertensive treatment, angiotensin-converting enzyme inhibitors [ACEI]), gender, type of the nephropathy, age, body mass index, and protein intake were analyzed using a multivariate analysis of variance. Mean arterial pressure was significantly and independently correlated with duration (r = -0.40, P < 0.0001) and slope of creatinine clearance (delta Ccr; r = 0.32, P < 0.0001). Mean arterial pressure and antihypertensive treatment could predict 25% of the variation in duration. Gender, type of the nephropathy, and MAP were able to predict 30% of the variation in delta Ccr. When analyzing results by type of nephropathy, MAP was significantly and inversely correlated with duration in glomerulonephritis (r = 0.29, P < 0.05), and positively with delta Ccr in angionephrosclerosis and interstitial nephritis (r = 0.49, P < 0.05 and r = 0.36, P < 0.01, respectively). In each type of nephropathy, conventional antihypertensive treatment and ACEI had grossly similar effects upon duration and slope except. In conclusion, blood pressure level is an important contributor to progression of chronic renal failure but its effect was more evident in angionephrosclerosis and interstitial nephritis at the extreme values of blood pressure distribution.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Effect of 22-oxa-calcitriol on calcium metabolism in rats with severe secondary hyperparathyroidism.

The purpose of the present study was to examine the effect of a two day and a five day administration of 22-oxa-calcitriol (OCT) on calcium metabolism in rats with advanced chronic renal failure and severe secondary hyperparathyroidism. A first series of 27 uremic rats received either placebo, OCT or calcitriol (0.3 microgram i.p./rat) 48 and 24 hours before sacrifice. A second series of 18 uremic rats received either placebo, OCT (0.3 microgram i.p./rat) or calcitriol (0.05 microgram i.p./rat) for five days. We found that after 48 hours (series 1) both calcitriol and OCT increased blood ionized calcium (Ca2+) as compared to vehicle (1.23 +/- 0.04 and 1.10 +/- 0.02 mM, P < 0.01 and P < 0.05, respectively vs. control, 1.02 +/- 0.03 mM). Duodenal Ca transport (S/M) using the everted gut sac technique was not stimulated by OCT, even though it increased from 2.8 +/- 0.4 to 7.0 +/- 0.6 (P < 0.01) with calcitriol. In contrast, duodenal calbindin-D9k mRNA expression and protein content increased to a similar extent with OCT and calcitriol. Calcitriol was more potent in reducing plasma iPTH1-34 levels than OCT: 344 +/- 75 pg/ml (calcitriol) versus 632 +/- 46 pg/ml (OCT) compared with 897 +/- 74 pg/ml (control), P < 0.01. In the second series of rats, the injection of OCT (0.3 microgram i.p./rat) over five days was less effective than the lower dose of calcitriol (0.05 microgram i.p./rat) in reducing circulating iPTH: 110 +/- 26 (calcitriol) and 281 +/- 64 (OCT) versus 624 +/- 135 pg/ml (control), P < 0.01.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Increased brush-border membrane calcium transport in the intestine, but not the kidney tubule, of spontaneously hypertensive rats.

Since we and others have found a decrease in intestinal Ca2+ absorption and renal Ca2+ reabsorption in the mature spontaneously hypertensive rat (SHR) at the tissue and cell level, we asked whether the transport defect was located at the luminal or the basolateral side of the epithelial cell. We studied intestinal and renal Ca2+ transport using isolated epithelial brush-border membrane vesicles (BBMVs) in order to examine the luminal side of this transport. For technical reasons, the preparation of intestinal BBMVs was performed using a centrifugation technique, but for renal BBMVs a precipitation method was used. The vesicles obtained with these two different techniques had markedly different aspects by electron microscopy analysis. However, no morphological difference was apparent between the two rat strains for BBMVs of either preparation. SHR and normotensive control Wistar-Kyoto (WKY) rats were studied at the age of 5 and between 12 and 14 weeks, receiving a normal Ca (1%) and P (0.46%) diet. In 5 week old SHR, duodenal BBMV Ca2+ uptake kinetics were similar to that of WKY of same age. However, in 12 week old rats mean (+/- SD) Vmax of duodenal Ca2+ uptake was significantly enhanced in SHR compared with WKY (0.59 +/- 0.21 v 0.38 +/- 0.09 nmol/mg protein and 10 s, P < .01), whereas Km was similar in the two strains. By contrast, no difference was found for Vmax or Km of Ca2+ uptake in renal BBMVs in 12 week old rats. In conclusion, Ca2+ uptake was either enhanced (duodenum) or normal (kidney tubule) in the mature SHR, compared with the WKY of same age.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Erythropoietin increases blood pressure in normotensive and hypertensive rats.

Treatment with recombinant human erythropoietin (rHuEPO) successfully reverses anemia in uremic patients. Of major concern, however, are blood pressure increases during rHuEPO therapy, observed particularly in patients with a history of hypertension. The present study was designed to determine whether high-dose rHuEPO elevates blood pressure in nonuremic rats, and if so, whether preexisting hypertension enhances this response. We examined blood pressure responses to high (100 IU/kg) and very high (200 IU/kg) doses of rHuEPO or placebo, given subcutaneously every other day for 3 weeks to male spontaneously hypertensive rats (SHR) and their normotensive genetic controls (Wistar-Kyoto rats, WKY). The high and very high doses of rHuEPO stimulated equivalent increases in hematocrit, and this increase was always larger in SHR than in WKY. In contrast to the pattern of hematocrit changes, blood pressure did not change following high-dose rHuEPO but was elevated in both strains after the very high dose of the drug. Although the rise in blood pressure tended to be greater in SHR than in WKY, this difference was not significant. The data indicate that very high-dose rHuEPO raises blood pressure comparably in normotensive and hypertensive rats and this increase is relatively independent of the increase in hematocrit.

Animals↗
PubMed1993

Renal response to angiotensin after short-term angiotensin converting enzyme inhibition.

In 13 normotensive subjects on a normal sodium diet, we studied hormonal, blood pressure, and renal vascular changes and dextran sieving profiles induced by infusion of exogenous angiotensin II (Ang II) (5 ng.kg-1.min-1). during baseline conditions and after 5 days of administration of the angiotensin converting enzyme inhibitor cilazapril. Cilazapril induced a renal vasodilative effect without affecting supine blood pressure and glomerular filtration rate. Fractional dextran clearances were significantly decreased for dextran of effective radius ranging from 3.0 to 4.0 nm. This shift was primarily related to an increase in glomerular capillary plasma flow, because no change was observed in the transcapillary glomerular pressure gradient, the ultrafiltration coefficient, or the membrane parameters. Ang II elicited a slight pressor response accompanied by hormonal, antinatriuretic, and renal hemodynamic changes that were similar during and before short-term angiotensin converting enzyme inhibition. Dextran sieving curves were unchanged by a low dose of Ang II. However, the transcapillary glomerular pressure gradient and the ultrafiltration coefficient were computed to increase by 19.4% and to decrease by 44.2%, respectively, whereas membrane parameters were unaffected. When superimposed onto short-term angiotensin converting enzyme inhibition, glomerular response to this unique dose of Ang II was similar to that induced by Ang II alone. These findings indirectly suggest that most, if not all, of the renal effects of cilazapril are mediated through suppression of Ang II formation.

Adult↗
PubMed1993

Is the process of urinary urea concentration responsible for a high glomerular filtration rate?

For subjects on a normal diet, urea is the major urinary solute and is markedly concentrated in the urine compared with in the plasma. Because urea is not known to undergo active secretion, its excretion rests on filtration lessened to a variable extent by tubular reabsorption. It is well established that the efficiency of urea excretion drops with increasing urinary concentration and decreasing urinary flow rate (from approximately 60% of filtered load, above 2 mL/min, to approximately 20% below 0.5 mL/min) because the prolonged transit time in the distal nephron favors passive urea reabsorption. Thus, a higher urinary concentration is achieved at the expense of a reduced efficiency of urea excretion. Recent experimental observations suggest that GFR could actually increase in parallel with the urinary concentrating activity, thus ensuring a normal urea excretion in the face of a high, concentration-dependent urea reabsorption, with only a moderate increase in plasma urea. A possible mechanism is proposed that could explain how the vasopressin-induced intrarenal recycling of urea (which contributes to improvement in urinary concentration), but not an exogenous urea administration, could indirectly depress the tubuloglomerular feedback and hence increase GFR. An increased concentration of an osmotically active solute in the thick ascending limb of Henle's loop (such as urea and, in some cases, glucose) could enable a lower NaCl concentration to be achieved at the macula densa by reducing the osmotically driven water leakage in this nephron segment. This mechanism could explain the hyperfiltration seen in various pathophysiologic situations such as chronic vasopressin infusion, high protein intake, severe burns, and diabetes mellitus. Whatever the mechanism, if the need to excrete relatively high amounts of urea in a concentrated urine leads to a sustained elevation of GFR, the price to pay for this water economy is higher than generally assumed. It is not limited to the energy spent in the sodium reabsorption providing the "single effect" for the urinary concentrating process. It also includes the consequences on the glomerular filter of sustained high pressure and flow and the energy spent in reabsorbing the extra load of solutes filtered. In chronic renal failure, the ability to form hypertonic urine declines but is nevertheless well preserved with respect to declining GFR, thus imposing on remnant nephrons an additional permanent stimulus for hyperfiltration.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

[Correlation between protein and sodium intake and calciuria in calcium lithiasis].

In order to assess the influence of dietary protein and salt intake on urinary calcium excretion in calcium stone formers, we simultaneously determined 24 hour urinary excretion of Urea (UU) and sodium (UNa) together with that of calcium (UCa) in 184 patients (112 males) with idiopathic calcium nephrolithiasis studied on free diet. Mean (+/- SEM) values expressed as mmol/kg BW/day of both UU and UNa were higher in hypercalciuric (UCa > or = 0.1 mmol/kg/d, mean 0.15 +/- 0.01) male patients, respectively 6.63 +/- 0.25 and 2.71 +/- 0.13, than in normocalciuric males, respectively 5.33 +/- 0.22 (p < 0.001) and 2.36 +/- 0.15 (p = 0.06), while the latter did not differ from healthy controls. Similar findings were made in female stone formers. Linear regression analysis on the whole series showed a positive but weak correlation between UU and UCa (r = 0.47, p < 0.001) and between UNa and UC a (r = 0.33, p < 0.001), but the slope of the relation UCa/UU was increased only in hypercalciurics, whereas it did not differ between normocalciurics and controls. By multiple regression analysis, variations of UU and UNa altogether accounted only for 22% of variation in UCa. We conclude that in both sexes hypercalciuric stone formers have a higher protein and sodium intake than normocalciurics, and for a given urinary urea output, their mean urinary calcium excretion is higher, thus suggesting that hypercalciuric stone formers are electively sensitive to the hypercalciuric effect of high protein intake.

Adult↗
PubMed1993

Prophylactic use of ganciclovir for allogeneic bone marrow transplant recipients.

Ganciclovir which has proved effective in the treatment of cytomegalovirus (CMV) infection was given prophylactically to 40 bone marrow transplant (BMT) patients pre and post-transplant in seropositive patients and post-transplant in seronegative patients with a seropositive donor. All patients were transfused with screened blood products and 33 received CMV hyperimmune globulin. They were compared with an historical control group consisting of 39 patients who had received significantly more unscreened blood products (p = 0.01) and less HLA-mismatched marrow transplants (p = 0.05). Toxicity of ganciclovir was hematological-neutropenia was responsible for cessation of the drug in seven patients and transfusion requirements were significantly higher in the ganciclovir group. Non-hematological toxicity did not occur in any patient. Only one patient (2.5%) experienced symptomatic CMV infection and no patient developed CMV pneumonitis. In contrast, in the control group, 23 (59%) patients had clinical symptoms of CMV infection (p < 0.0001) and 4 (10%) experienced CMV pneumonitis (p < 0.01). Ganciclovir significantly reduced the incidence of positive CMV antigenemia (7.5% in the treated group vs 72% in the control group; p < 0.01). However, ganciclovir delivery did not result in an improved overall survival due to a higher rate of regimen-related deaths and chronic GVHD mostly in patients transplanted from an HLA-mismatched donor. The prophylactic administration of ganciclovir abrogates CMV pneumonitis and considerably reduces the incidence of CMV infection in BM recipients at high risk of developing this disease after transplantation.

Adolescent↗
PubMed1993

Gastrointestinal absorption of aluminum in rats using 26Al and accelerator mass spectrometry.

Using the technique of Accelerator Mass Spectrometry (AMS), 26Al has been measured in plasma, liver, urine and bone of normal rats at 8, 24 and 48 hours after ingestion of trace amounts of Al (3.8 ng of 26Al and 63 ng of stable 27Al), both in citrate-free and citrate-containing solutions. Our data show that under physiological conditions, namely at normal levels of dietary intake, intestinal Al absorption is approximately 0.04%, and is not significantly enhanced by the presence of citrate. Interestingly, the amount of Al retained by bone (0.02%) is comparable to that excreted in urine during 48 h (0.02%). Our estimate of gastrointestinal absorption is more than two orders of magnitude smaller than that estimated by Day et al. [1991], also using 26Al, for a single human subject.

Aluminum↗
PubMed1993

[Anomalies of lipoprotein metabolism in chronic renal insufficiency].

Disturbances of the lipid metabolism in chronic renal failure (CRF) are characterized by an accumulation of serum VLDL, IDL, and remnants and also by a decrease of the HDL pool, especially for HDL2. CRF is also associated with a decrease of apolipoproteins (apo) AI and AII in relation to a preferential decrease of lipoparticles (Lp) AI-AII by comparison with the anti-atherogenic Lp AI containing no AII. It is furthermore characterized by a marked increase of apo CIII, which is disproportionate with respect to the increase of apo CII and the variation of apo E, in relation with an accumulation of Lp B-CIII (and also Lp B-E and Lp B-C-E for hemodialyzed patients) in the whole spectrum of low density lipoproteins. The abnormal distribution of apo into the various classes of lipoproteins is the consequence firstly of the relative inefficacy of the lipolytic process implicated in TG-rich lipoprotein metabolism (LPL dysfunction), and secondly of the abnormal reverse cholesterol transport (anomalies of CETP and LCAT). The hormonal, nutritional, and iatrogenic factors implicated in the uremic dyslipoproteinemia are described and the implications of such abnormalities on cardiovascular disease and on the progression of renal disease are discussed.

Apolipoproteins↗
PubMed1993

Factors affecting progression in advanced chronic renal failure.

In a series of 174 patients with advanced chronic renal failure due to well defined primary nephropathies, we retrospectively studied factors influencing the rate of progression of renal failure. Using multivariate analysis of variance, we examined the role of gender, type of nephropathy, body mass index, age, protein intake quantified from 24-hour urine urea excretion, blood pressure and need for antihypertensive treatment (including a group of patients treated with ACE inhibitors) on the rate of decline of creatinine clearance (Ccr). We found a prominent and independent influence of sex and type of nephropathy, and to a lesser extent of mean arterial pressure and protein intake. Overall, these covariates were significantly correlated with the slope of decline in creatinine clearance (n = 174; r = 0.61; r2 = 0.37; p < 0.001) indicating that nearly 40% of the total variation in the slope could be predicted by these covariates. The influence of blood pressure was more readily apparent in males, and in patients with the opposite extreme values, i.e., chronic tubulointerstitial nephritis (CIN) and hypertensive angionephrosclerosis (ANS). The effect of protein intake was marginal and limited to patients with CIN and chronic glomerulonephritis (CGN). Effect of gender was important with a progression nearly two times faster in males than in females, and was mostly apparent in polycystic kidney disease (PKD) and in CGN. Type of nephropathy was also determinant. The rate of progression was steeper in Alport's syndrome than in CGN and ANS, and in the latter than in PKD and CIN (slope: CIN = PKD < CGN = ANS < Alport).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

[Apolipoprotein C-III in nephrology].

Apolipoprotein C-III is synthesized by the liver and the small intestine. It inhibits the actions of lipoprotein lipase and hepatic triglyceride lipase. An increase of plasma apolipoprotein C-III levels has been found in patients with renal failure, in those under haemodialysis and in renal transplant recipients. The consequences of this increase correlate with the hypertriglyceridaemia observed in these patients. The responsibility of hormonal or non-hormonal factors that modulate the metabolism of apolipoprotein C-III is discussed in order to help in the understanding of the physiopathological mechanisms of lipid disorders in these renal diseases.

Apolipoprotein C-III↗
PubMed1992

Different forms of alkaline phosphatase in adult rat femur. Effect of a vitamin D3-deficient diet and of a sorbitol-enriched diet.

In the femoral extremities of the adult rat containing the metaphysis, the epiphyseal cartilage, and the epiphysis, four alkaline phosphatase (AP) forms were distinguished on polyacrylamide gel electrophoresis. Two soluble forms were present in the 160,000 g supernatant: one of Mr 165 kDa and another of Mr 110-115 kDa, which exhibited a strong catalytical activity. Moreover, from the pellet, three membrane-bound forms of Mr 130, 110-115, and 100 kDa could be extacted with sodium deoxycholate. When denaturated AP was visualized by postelectrophoretic autoradiography of the phosphorylated intermediates, subunits always appeared as three monomers of Mr 75-80, 60-70, and 50-60 kDa. As four native forms but only three types of subunits were found to be present in the femur, it seems that, apart from homodimers, some heterodimers could also occur. Three types of diets were administered to three groups of rats for 5 weeks. Two are known to disturb bone mineralization: (1) a vitamin D3-deficient diet, and (2) the same as (1) but enriched with 12% sorbitol. The third was a normal diet containing vitamin D3. Concerning the effects on AP of dietary sorbitol and the vitamin D3-deficient diet, it was found that rats receiving the diet supplemented with sorbitol showed a substantial rise in the activity of the Mr 165 kDa form with the concomitant appearance of a new monomer of Mr 100 kDa. In contrast, rats fed the vitamin D3-deficient diet always displayed an increase in enzyme activity, principally of the Mr 100 and 110 kDa forms.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaline Phosphatase↗