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Biomedical subjects

A Hadj-Aissa

Publications and source records attributed to A Hadj-Aissa.

At least 19 recordsLinked to original sources

Mycophenolate mofetil reduces myofibroblast infiltration and collagen III deposition in rat remnant kidney.

BACKGROUND: Myofibroblasts have been shown to play a pivotal role in the synthesis of extracellular matrix components in several animal models of renal fibrosis. The purpose of the present study was to investigate whether mycophenolate mofetil (MMF) reduces interstitial myofibroblast infiltration and collagen III deposition in 5/6 nephrectomized rats. METHODS: Forty-five Wistar rats underwent 5/6 renal ablation and received by daily oral gavage either vehicle (N = 20) or MMF (N = 25) during the 60 days following surgery. Groups of five treated and five untreated rats were killed at two, four, and eight weeks after subtotal nephrectomy. Four untreated and three treated rats were killed at week 12, one month after treatment withdrawal. At the time of sacrifice, proteinuria, plasma, and urine creatinine were determined. Immunohistochemistry was performed on renal tissue for alpha-smooth muscle actin (alpha-SMA), a cytoskeletal marker of myofibroblasts, for type III collagen, and for proliferating cell nuclear antigen (PCNA). Moreover, in order to study the in vitro effects of MMF on fibroblast proliferation, rat fibroblasts were cultured in the presence or absence of mycophenolic acid (MPA). RESULTS: At all periods studied, MMF treatment improved renal functional parameters and progressively decreased remnant kidney hypertrophy and glomerular volume increment. Proliferating cells in renal tubules, interstitium, and glomeruli, as well as interstitial myofibroblast infiltration and interstitial type III collagen deposition, were also significantly reduced by MMF treatment. In addition, MPA exhibited a dose-dependent inhibitory effect on in vitro proliferation of rat fibroblasts. CONCLUSION: Reduction of interstitial myofibroblast infiltration may be an important event by which MMF significantly prevents renal injury following subtotal renal ablation. Thus, our results suggest that MMF could be useful to limit the progression of chronic renal disease toward end-stage renal failure.

Actins↗

Misoprostol in renal transplant recipients: a prospective, randomized, controlled study on the prevention of acute rejection episodes and cyclosporin A nephrotoxicity.

The aim of this prospective and randomized study was to determine whether misoprostol, an analogue of PGE1, could decrease the incidence and the number of rejection episodes and could improve the renal function over a 12-month follow-up, when given at 400 micrograms/day for 12 months in renal transplant patients. Given the known side-effects and the additive cost of misoprostol, a benefit of the therapy should be a decrease of at least 50% in the incidence of rejection episodes in the treated group. Therefore, 60 consecutive renal transplant patients were randomized to receive misoprostol or to receive aluminium and magnesium hydroxide. Patients received steroids, azathioprine, antithymocyte globulins, and cyclosporin A (CsA). CsA was randomly started on day 0 or on day 8. At 12 months, no difference in the incidence of rejection episodes was observed: 63.3% in the 30 patients of the misoprostol + group versus 70.0% in the misoprostol-group (P = 0.558 Mantel-Cox). The renal function, assessed by plasma creatinine, inulin, and para-aminohippuric acid clearances, was not significantly different between misoprostol + and misoprostol-groups. No episode of CsA nephrotoxicity was observed in any patient of group one or group two. At 12 months, the mean dosage of CsA was 4.9 +/- 0.28 mg/kg/day in the misoprostol + group versus 4.52 +/- 0.23 mg/kg/day in the misoprostol-group and the trough level was not significantly different between the two groups. The graft survival rate at 12 months was 86.7% in the Misoprostol + group and 83.33% in the misoprostol-group.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Stress-induced renal functional alterations in normotensives.

This study was performed to assess changes in renal function accompanying cardiovascular responses to mental stress. Glomerular filtration rate (GFR, inulin clearance), renal plasma flow (RPF, PAH clearance), filtration fraction (FF), sodium excretion, and segmental sodium tubular reabsorption (lithium clearance) were measured in 15 normal volunteers during rest and stress. The psychological stress test used is based on a computerized version of the Stroop word color conflict test. Stress induced a significant (P less than .05) and sustained increase in blood pressure and heart rate. During stress, GFR and RPF did not change whereas FF increased significantly (P less than .05) and sodium excretion tended to decrease. The decrease in sodium excretion was due to a significant (P less than .05) increase in proximal reabsorption, which may be mediated by renal hemodynamic changes. The observed significant increase in FF suggests an increase in postglomerular arteriolar resistances, which may account for the increase in proximal sodium reabsorption through an alteration in peritubular Starling forces. In the long run, the stress-associated increase in sodium reabsorption may contribute to the development of hypertension.

Adult↗

[Renal function during stress in hypertensive patients].

In this study, the measurement of blood pressure values, glomerular filtration rate (GFR, inulin clearance), renal plasma flow (RPF, PAH clearance), the filtration fraction (GFR/RPF), natiuresis and proximal sodium resorption (measured by lithium clearance), was performed at rest and during a computerised psychological stress test (Stroop word color conflict test) in 12 normotensive and 10 hypertensive subjects. The stress induced in the normotensives induced a significant increase of the filtration fraction and proximal tubule sodium resorption. The hypertensive kidney, submitted to a basal vasoconstriction greater than that of the normotensive kidney, does not react to stress. In the hypertensives, proximal sodium resorption occurs but is not significantly greater than at rest. In the long-term, the increased sodium resorption during stress could contribute to the development and the persistence of essential hypertension.

Adult↗

Cardiovascular reactivity to and renal impact of stress and exercise: effects of bisoprolol.

The orthosympathetic nervous system is involved in the pathogenesis of essential hypertension. In this study, we carried out tests of sympathetic stimulation using successfully an isometric exercise and a psychological stress. The efficacy of the two tests in 10 normotensive patients (NTs) was assessed by a significant increase in blood pressure and heart rate and a significant increase in metanephrine urinary excretion. These tests, repeated 2 months later, were perfectly reproducible in NTs. The cardiovascular response during exercise and stress was significantly higher in 10 hypertensive patients (HTs) than in NTs. At rest, urinary norepinephrine excretion was significantly higher in HTs. In contrast to NTs, stress in HTs significantly increased urinary excretion of epinephrine and norepinephrine, whereas exercise failed to increase urinary catecholamine excretion in both groups. In HTs, both tests induced an increase in microalbuminuria. Among functional renal parameters, only proximal sodium reabsorption (measured by lithium clearance) was significantly lower in HTs than in NTs, compensated by a higher distal reabsorption. In HTs, 2 months of treatment with bisoprolol reduced rest and peak heart rate and blood pressure, but failed to reduce blood pressure reactivity to the orthosympathetic stimulation. Proximal sodium reabsorption at rest was normalized by the treatment. Bisoprolol was also able to reduce microalbuminuria during the 24 h and in the rest period preceding the test, but the same percent increase was observed during tests.

Adrenergic beta-Antagonists↗

Effects of xamoterol on sodium excretion in volunteers.

Xamoterol has been shown to reduce the frequency of oedema and lung crepitations in heart failure. We examined its effects on blood pressure and renal function in healthy volunteers. Systolic blood pressure rose, sodium and chloride excretion increased and there was a strong correlation in individual subjects between rises in systolic blood pressure and in sodium excretion. Although no changes in glomerular filtration rates were seen, changes sufficient to explain the observed rise in sodium excretion are well within the experimental error of this study. Xamoterol may increase sodium excretion by an action on renal haemodynamics.

Adrenergic beta-Agonists↗

Antigravity suit inflation: kidney function and cardiovascular and hormonal responses in men.

To investigate the effects of lower body positive pressure (LBPP) on kidney function while controlling certain cardiovascular and endocrine responses, seven men [35 +/- 2 (SE) yr] underwent 30 min of sitting and then 4.5 h of 70 degrees head-up tilt. An antigravity suit was applied (60 Torr legs, 30 Torr abdomen) during the last 3 h of tilt. A similar noninflation experiment was conducted where the suited subjects were tilted for 3.5 h. To provide adequate urine flow, the subjects were hydrated during the course of both experiments. Immediately after inflation, mean arterial pressure increased by 8 +/- 3 Torr and pulse rate decreased by 16 +/- 3 beats/min. Plasma renin activity and aldosterone were maximally suppressed (P less than 0.05) after 2.5 h of inflation. Plasma vasopressin decreased by 40-50% (P less than 0.05) and plasma sodium and potassium remained unchanged during both experiments. Glomerular filtration rate was not increased significantly by inflation, whereas inflation induced marked increases (P less than 0.05) in effective renal plasma flow (ERPF), urine flow, osmolar and free water clearances, and total and fractional sodium excretion. No such changes occurred during control. Thus, LBPP induces 1) a significant increase in ERPF and 2) significant changes in kidney excretory patterns similar to those observed during water immersion or the early phase of bed rest, situations that also result in central vascular volume expansion.

Adult↗

Restrictions on use of creatinine clearance for measurement of renal functional reserve.

The increase of glomerular filtration rate after a 90-gram oral protein load was determined in 9 healthy individuals by simultaneous measurements of both creatinine (Ccr) and inulin (Cin) clearances, performed before and every 30 min during 4 h after the meat meal. This protein load resulted in a short 26% increase of Cin at 90 min, and a sustained 29% increase of Ccr from 90 to 240 min after load. Individual peak values of Ccr occurred later than those of Cin (Ccr: 189 +/- 19 vs. Cin: 127 +/- 19 min; p = 0.023). These discrepancies were related to an increase of serum creatinine, and a subsequent increase of the net tubular excretion of creatinine which accounted for up to 15% of the urinary creatinine. The creatinine content of red meat could lead to overestimation of renal functional reserve when measured by creatinine clearance only.

Adult↗

[Clinicobiological study of drug-induced renal diseases].

The kidney is the main organ involved in drugs elimination and thereby is particularly liable to their toxic effect. The determination of renal function is thus of importance, before and during treatment with a potentially nephrotoxic drug or during trial of new drugs. In this general review, the main methods to measure renal function are briefly analysed. They consist either of simple dosages in blood and urine which allow to roughly evaluate renal functional value and its variations, or more sophisticated investigations which allow a more precise analysis of various nephron functions: glomerular filtration rate and renal plasma flow with measurement of clearances of exogenous markers, determination of basal or maximal tubular activities. The interest of these specific tests is illustrated by the results of a study performed in patients receiving streptozotocin, an antineoplastic nephrotoxic drug. In conclusion, nephrotoxicity of drugs may be in most cases prevented owing to an accurate knowledge of their pharmacokinetics and of risk factors inherent in patients, and to survey of renal function with suitable methods which may lead to modify drug dosage and/or to choose a therapy considering the own evolution of the disease and the possible occurrence of irreversible renal impairment.

Adult↗

Magnesuria induced by thiazides and the influence of triamterene.

The effects on magnesium excretion of 4 short-term diuretic treatments (methyclothiazide 2 mg either alone or associated with increasing doses of triamterene) were evaluated in 8 normal volunteers and compared to spontaneous variations during placebo administration. The thiazide exerted a small but significant magnesuric effect, which was prevented only by the lowest dose (25 mg) of triamterene. Larger doses had no protective effect on thiazide-induced magnesuria. Independently of their absolute effects on magnesium excretion, all diuretics impaired the normal ability of the kidneys to compensate fully for the expected changes in magnesium reabsorption induced by extracellular volume contraction.

Adult↗

[Influence of acute administration of ramipril on the excretion of uric acid].

The influence of a new ACEI, Ramipril (R) on renal handling of UA was investigated. 13 hypertensives with normal renal function received either R (10 mg p.o.) or placebo (P). Arterial pressure (AP), GFR (Inulin clearance), Renal Plasma Flow (RPF, PAH clearance), UA urinary excretion (UAV) and fractional clearance (FeAU: UA clearance/GFR) were studied for seven hours after drug administration. GFR remained stable in all cases. R had no effect on sodium excretion rate. Compared to P, R significantly increased UAV by 25 p. 100, FeAU by 32 p. 100, RPF by 26.5 p. 100 and decreased mean arterial pressure (MAP) by 10 p. 100. ACE activity was maximally suppressed at 2 hours. More than 80 p. 100 of the maximal changes in UAU and FeAU were observed within the first two hours, while a progressive increase in RPF up to the fifth hour, and a progressive fall in MAP up to the fourth hour was evident. Except for PAM, all these changes were still present at the end of the study (seventh hour). In conclusion, Ramipril increases the fractional excretion of uric acid. This effect is observed independently of any change in sodium balance and preceeds by two to three hours the changes in renal hemodynamics. The simultaneous changes in FeAU and in ACE activity indicate that the effect on uric acid excretion is presumably due to the fall in angiotensin concentration.

Angiotensin-Converting Enzyme Inhibitors↗

Evolution of renal function under chronic oral administration of labetalol.

The glomerular filtration rate (GFR, inulin clearance) and renal plasma flow (RPF, PAH clearance) were measured in 35 hypertensive patients during chronic administration of an alpha-beta-blocker, labetalol. No significant changes in GFR occurred but RPF increased significantly. The increase in RPF was positively correlated with the decrease in mean arterial blood pressure. Patients with renal failure showed changes similar to patients with normal renal function. Thus chronic treatment with labetalol, unlike most beta-blockers, can increase RPF, an effect which could be related to the alpha-blocking activity of the drug.

Administration, Oral↗