Search PubMed⌕ Search

Biomedical subjects

M Laville

Publications and source records attributed to M Laville.

At least 55 records · Page 3Linked to original sources
PubMed2001

[How to measure insulin sensitivity in clinical practice?].

Insulin resistance is common and cluster with glucose intolerance, dyslipidaemia and high blood pressure,. in type 2 diabetes mellitus it play a key role in the occurence of hyperglycemia. The importance of the insulin-resistant phenotype for the assessment of cardiovascular risk and response to intervention is increasingly being recognized. Therefore there is a need for accurate, reproducible and simple methods for measuring insulin resistance in vivo. The euglycemic hyperinsulinemic clamp is currently the best available standard technique but is not suitable for clinical practice. Thus, numerous index for insulin resistance estimation from fasting or post-load OGTT glycemia and insulinemia have been proposed. Although their simplicity is an obvious advantage, their application is subject to numerous limitations. The choice of the method to evaluate insulin sensitivity thus depend on objectives and available means. For clinical research, euglycemic clamp is the gold standard. In the case of epidemiologic studies, validated models like HOMA model are suitable. Finally in clinical practice, for type 2 diabetic patients, evaluation of insulin resistance should be made from clinical and biological context eventually associated with an estimation of respectives roles of insulinopenia and insulin resistance with a validated index like the HOMA model.

Blood Glucose↗
PubMed2001

RPR 119990, a novel alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid antagonist: synthesis, pharmacological properties, and activity in an animal model of amyotrophic lateral sclerosis.

Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptor antagonists are of potential interest for the treatment of certain acute and chronic neurodegenerative diseases, including amyotrophic lateral sclerosis. Here, we describe the synthesis and pharmacological properties of 9-carboxymethyl-4-oxo-5H,10H-imidazo[1,2-a]indeno[1,2-e]pyrazin-2-phosphonic acid (RPR 119990). The compound displaced [3H]AMPA from rat cortex membranes with a K(i) of 107 nM. In oocytes expressing human recombinant AMPA receptors, RPR 119990 depressed ion flux with a K(B) of 71 nM. The antagonist properties of this compound were confirmed on rat native AMPA receptors in cerebella granule neurons in culture and in hippocampal slices where it antagonized electrophysiological responses with IC50 values of 50 and 93 nM, respectively. RPR 119990 antagonized hippocampal evoked responses in vivo, demonstrating brain penetration at active concentrations. RPR 119990 is a potent anticonvulsant in the supramaximal electroshock in the mouse with an ED50 of 2.3 mg/kg 1 h post s.c. administration, giving it a workably long action. Pharmacokinetic studies show good passage into the plasma after subcutaneous administration, whereas brain penetration is low but with slow elimination. This compound was found active in a transgenic mouse model of familial amyotrophic lateral sclerosis (SOD1-G93A) where it was able to improve grip muscle strength and glutamate uptake from spinal synaptosomal preparations, and prolong survival with a daily dose of 3 mg/kg s.c.

Amyotrophic Lateral Sclerosis↗
PubMed2000

Low protein diets delay end-stage renal disease in non diabetic adults with chronic renal failure.

BACKGROUND: Since more than fifty years, low protein diets are proposed to patients with kidney failure. However, the effects of these diets in preventing severe renal failure and the need for maintenance dialysis is still controversial. OBJECTIVES: To determine the efficacy of low protein diets in delaying the need to start maintenance dialysis. SEARCH STRATEGY: Medline and Embase search from January 1966 through June 1999. Congress abstracts (American Society of Nephrology since 1990, European Dialysis Transplant Association since1985, International Society of Nephrology since 1987). Direct contacts with investigators. SELECTION CRITERIA: Randomised trials comparing two different levels of protein intake in adult patients suffering from moderate to severe renal failure, followed for at least one year. Exclusion of patients with diabetic nephropathy. DATA COLLECTION AND ANALYSIS: Seven trials selected over 40 studies since 1975. A total of 1494 patients analysed, 753 receiving a reduced protein intake and 741 a larger protein intake. Collection of the number of "renal death" being the need for starting dialysis, the death of a patient or the transplantation of a kidney during the trials. MAIN RESULTS: 242 renal deaths were recorded, 101 in the low protein diet and 141 in the larger protein diet group, giving an odds ratio of low protein to control of 0.62 with a 95% confidence interval of 0.46 to 0.83 (p<0.001, Peto odds ratio). To spare one extra renal death, 17 patients need to be treated (NNT) with a low protein diet for approximately two years. REVIEWER'S CONCLUSIONS: Reducing protein intake in patients with chronic renal failure do reduce the occurence of renal death by about 40% as compared with larger or unrestricted protein intake and therefore should be warmly recommended to patients. The optimal level of protein intake cannot be deduced from the present work. However, based on other nutritional studies perfomed in patients having chronic renal failure, we recommend a protein intake of 0.6 g/kg/day and an energy intake no less than 35 kcal/kg/day. Skilled dietitian survey should be offered to closely monitor these values and the patient's nutritional status.

Adult↗
PubMed2000

Regulation of gene expression during severe caloric restriction: lack of induction of p85 alpha phosphatidylinositol 3-kinase mRNA in skeletal muscle of patients with type II (non-insulin-dependent) diabetes mellitus.

AIMS/HYPOTHESIS: Alterations in the regulation of gene expression could be involved in the development of Type II (non-insulin-dependent) diabetes mellitus. METHODS: We compared the mRNA concentrations of eight genes encoding proteins involved in insulin action and intermediary metabolism in skeletal muscle of healthy volunteers and Type II diabetic patients. The in vivo regulation of the expression of these genes was investigated after 5 days of hypocaloric diet (1045 kJ/day). RESULTS: In the basal state, diabetic muscle showed reduced insulin receptor (-38%), hexokinase II (-73%), glycogen synthase (-45%) and lipoprotein lipase (-70%) mRNA expression. There was no difference in the mRNA abundances of IRS-1, GLUT 4, p85 alpha phosphatidylinositol-3-kinase (p85 alpha PI3K) or Rad. In both groups, caloric restriction induced weight loss, reduced glycaemia and increased plasma ketone body concentrations. The diet also increased plasma concentrations of fatty acids and decreased whole-body insulin sensitivity in control subjects. In control subjects, the diet increased p85 alpha PI3K (+146%), insulin receptor (+100%) and Rad (+40%) mRNA concentrations in muscle. In Type II diabetic patients, the diet increased insulin receptor (+41%) and Rad (+31%) mRNAs but the expression of p85 alpha PI3K was not modified. CONCLUSION/INTERPRETATION: The regulation of the expression of p85 alpha PI3K is altered during caloric restriction in skeletal muscle of Type II diabetic patients. Because we have shown in an earlier study that there is also a defective regulation of p85 alpha PI3K gene expression in response to insulin, these data support the hypothesis that alterations in the regulation of gene expression could be involved in the pathogenesis of Type II diabetes.

Adult↗
PubMed2000

Enhanced long-term potentiation in mice lacking cannabinoid CB1 receptors.

Marijuana is known to affect learning and memory in humans, and cannabinoids block long-term potentiation in the hippocampus, a model for the synaptic changes that are believed to underlie memory at the cellular level. We have now examined the physiological properties of the Schaffer collateral-CA1 synapses in mutant mice in which the CB1 receptor gene has been invalidated and found that these animals exhibit a half-larger long-term potentiation than wild-type controls. Other properties of these synapses, such as paired-pulse facilitation, remained unchanged. This indicates that disrupting CB1 receptor-mediated neurotransmission at the genome level produces mutant mice with an enhanced capacity to strengthen synaptic connections in a brain region crucial for memory formation.

Animals↗
PubMed2000

Is advice for breakfast consumption justified? Results from a short-term dietary and metabolic experiment in young healthy men.

Short-term (2 weeks) effects of the consumption of a high-energy (2920 kJ (700 kcal)) or low-energy (418 kJ (100 kcal)) breakfast on dietary patterns, blood variables and energy expenditure (indirect calorimetry) were compared in ten free-living healthy young men in a crossover study. During the high-energy breakfast, total energy intake was increased, the intake of protein and lipids was unchanged but the intake of carbohydrates was increased. Thus, 48 (sd 4)% of energy came from carbohydrates in the high-energy breakfast compared with 42 (sd 5)% in the low-energy breakfast. Excluding breakfast, the macronutrient composition of the diet remained identical in the two situations. After the high-energy breakfast, fasting serum triacylglycerol concentration was higher and HDL-cholesterol concentration was lower than after the low-energy breakfast. A high glycaemic response was observed in the morning after the high-energy breakfast period, while there was a peak of free fatty acids after the low-energy breakfast. The high-energy breakfast induced a strong inhibition of fat oxidation throughout the day. Although long-term adaptation to a high-energy breakfast cannot be excluded, the high-energy breakfast in this study did not appear to be favourable to health. Our results do not support the current advice to consume more energy at breakfast.

Adult↗
PubMed2000

Methodological approaches to assess body-weight regulation and aetiology of obesity.

Obesity, which is becoming one of the major health hazards in developed and developing societies, results from a long-term positive energy balance. Body-weight regulation and stability depend on an axis with three interrelated components: food intake, energy expenditure and adipogenesis, although there are still many unknown features concerning fuel homeostasis and energy balance. Biochemical processes are interconnected, and a separate consideration of each component is often useful for methodological purposes and to achieve a better understanding of the whole system. Thus, many different experimental approaches can be applied by using laboratory animals, cell culture or human subjects to unravel the molecular mechanisms which participate in body-weight regulation. Thus, both in vitro (cellular and subcellular models) and in vivo methods have dramatically increased our knowledge of weight control. Several strategies in obesity research are reported here, exploiting the opportunities of the molecular era as well as novel whole-body approaches, which will impact on the development of new targets for obesity management and prevention.

Animals↗
PubMed2000

Subcutaneous adipose tissue expression of tumour necrosis factor-alpha is not associated with whole body insulin resistance in obese nondiabetic or in type-2 diabetic subjects.

BACKGROUND: An association with subcutaneous adipose tissue TNFalpha expression and insulin resistance has been suggested in obesity/type-2 diabetes, but this has not been examined directly. In the first part of the study we investigated whether this association is present in 7 lean, 10 obese nondiabetic and 9 type-2 diabetic men. In the second part of the study we examined the relationship between adipose tissue TNFalpha mRNA levels and BMI in 81 nondiabetic subjects spanning a wide range of BMIs. METHODS: Subcutaneous adipose tissue TNFalpha mRNA levels and insulin sensitivity were determined with quantitative RT-competitive PCR and hyperinsulinaemic clamp, respectively. RESULTS: Subcutaneous adipose tissue TNFalpha mRNA levels were similar in 7 lean and 10 obese nondiabetic and 9 type-2 diabetic men (P = 0.68), and did not change in response to 240-min hyperinsulinaemia. TNFalpha mRNA levels and insulin sensitivity were not correlated. Unexpectedly, no correlation between TNFalpha mRNA and BMI was found. The relationship between adipose tissue TNFalpha mRNA and BMI was examined further in 31 male and 50 female nondiabetic subjects. The subcutaneous adipose tissue TNFalpha mRNA level correlated with BMI in all subjects (rS = 0.32, P < 0.01), and in a subgroup analysis in men (rS = 0.55, P < 0.01) but not in women (rS = - 0.08). The correlation in men was dependent on a fourfold higher TNFalpha mRNA level in 5 morbidly obese men while there was no difference in TNFalpha mRNA levels in lean or obese men. CONCLUSIONS: Subcutaneous adipose tissue TNFalpha expression does not correlate with insulin sensitivity in nondiabetic or type-2 diabetic men; is not regulated by acute hyperinsulinaemia; and is increased only in morbidly obese men.

Adipose Tissue↗
PubMed2000

Renal blood flow measurement by positron emission tomography using 15O-labeled water.

BACKGROUND: Only few noninvasive methods have the potential to quantitate renal blood flow (RBF) in humans. Positron emission tomography (PET) is a clinical imaging method that can be used to measure the tissue blood flow noninvasively. The purpose of this study was to validate PET measurement of RBF using 15O-labeled water (H215O), a tracer that allows repeated measurements at short time intervals. METHODS: RBF was measured in six pigs by PET and by radioactive microspheres (MS). Three measurements were performed in each pig at baseline (BL), during vascular expansion and dopamine infusion (DA; 20 microg. kg-1. min-1 intravenously), and during angiotensin II (Ang II) infusion (50 ng. kg-1. min-1 intravenously). RBF was estimated from aortic and renal tracer kinetics using a model adapted from the blood flow model described by Kety and Smith. RESULTS: PET and MS values correlated strongly (y = 0.79x + 42, r = 0.93, P < 0.0001) over the RBF range from 100 to 500 mL. min-1. 100 g-1. Pharmacologically induced changes were significant and were measured equally well by PET and MS: 38 and 39%, respectively, below BL (P < 0.005 and P < 0.05) under Ang II, and 47 and 48%, respectively, above BL (P < 0.005 and P < 0.01) under DA. A Bland and Altman representation showed a low average difference of -17 +/- 45 mL. min-1. 100 g-1 (mean +/- SD). CONCLUSION: To our knowledge, this study provides the first validation of RBF measurement by PET using H215O over a large range of RBF values (100 to 500 mL. min-1. 100 g-1), which correspond to RBF values in both healthy subjects and in patients suffering from chronic renal failure.

Animals↗
PubMed2000

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↗
PubMed2000

Nutritional aspects in hemodialysis.

The results of cross sectional studies throughout the world indicate that maintenance hemodialysis patients are at risk of malnutrition. Longitudinal studies show that malnutrition is associated with a reduced life expectancy mainly because of cardiovascular and infectious complications. Several factors are responsible for malnutrition of hemodialysis patients. Protein-energy intake is often reduced because of inappropriate dietary restrictions, anorexia, and taste alterations, promoting malnutrition in most patients entering dialysis. Intercurrent illnesses and frequent hospitalizations add to meal disturbances. A state of persistent catabolism may result from acidosis, resistance to anabolic factors such as growth hormone, insulin, and insulin-like growth factor-1, as well as a chronic inflammatory state caused by dialysis membrane and fluid bioincompatibility. In addition, losses of nutrients, including glucose, amino acids, proteins, and vitamins, occur during the dialysis treatment. Careful monitoring of dietary intakes is mandatory even in predialysis patients. In hemodialysis patients, the dose of dialysis should be adapted to correct acidosis and to relieve anorexia caused by accumulation of uremic toxins and hyperleptinemia. When malnutrition is established, active therapeutic interventions should take place, including intradialytic parenteral nutrition if oral supplementation has failed to improve nutritional status. Anabolism has been observed during the administration of recombinant growth hormone and insulin-like growth factor-1. Emerging therapeutic strategies against malnutrition may also involve a short period of daily dialysis.

Humans↗
PubMed2000

Heparins and blood polymorphonuclear stimulation in haemodialysis: an expansion of the biocompatibility concept.

BACKGROUND: At the concentrations used in haemodialysis and in a dose-dependent way, unfractionated heparin (UFH) and, to a lesser degree, a low-molecular-weight heparin (LMWH) stimulate polymorphonuclear cells (PMN) in vitro, and could act in synergy with the stimulatory effect of dialysis membranes in vivo. To examine this hypothesis, we studied the effects of different heparin types and regimens on blood PMNs during haemodialysis sessions. METHODS: Ten haemodialysed patients were studied during regular dialysis sessions on a cellulose triacetate membrane (CT 110 G; 1.10 m(2); Baxter), with four different random heparin protocols: one high-UFH regimen (HHR) at 90 IU/kg body-weight (b.w.) and one low-UFH regimen (LHR) at 50 IU/kg b.w., and with a LMWH (nadroparin calcium) at 85 (HHR) or 45 (LHR) IU/kg b.w. Blood granulocytes, platelet counts, and plasma granulocyte degranulation products (elastase, lactoferrin) were measured serially during 4 h dialysis sessions. RESULTS: After 10 min, the reduction in PMNs with UFH was 29.5% for HHR (P<0.01) and 28.5% for LHR (P<0.01), and only 16.8 and 18.6% with LMWH (NS), significantly higher for HHR with UFH than with LMWH (P<0.01). At 60 min, the elastase increase with HHR was greater, 61% with UFH (P<0.01) and 37.8% with LMWH (P<0.01), significantly higher than LHR for UFH (P<0.05) or LMWH (P<0.05). The overall decrease in platelets (with LMWH P<0.01) and the overall increase in lactoferrin (P<0.001) were not different between heparinization procedures. CONCLUSION: Under a conventional heparin regimen, the PMN variation during the course of the dialysis session suggests a more biocompatible effect of LMWH over UFH. In addition, the variation of elastase favours the lower dose, whatever the type of heparin. Heparin type and dose should therefore be considered in studies addressing biocompatibility in haemodialysis: a low dose of LMWH may be viewed as a better biocompatible treatment with regard to leukocyte stimulation.

Adult↗
PubMed2000

Low protein diets delay end-stage renal disease in non-diabetic adults with chronic renal failure.

BACKGROUND: The objective of this study was to determine the efficacy of low protein diets in delaying the need to start maintenance dialysis based on an analysis of published literature. METHODS: The search strategy involved a Medline and Embase search from January 1966 through to June 1999, congress abstracts (American Society of Nephrology since 1990, European Dialysis Transplant Association since 1985, International Society of Nephrology since 1987) and direct contacts with investigators. The selection criteria included randomized trials comparing two different levels of protein intake in adult patients suffering from moderate to severe renal failure, followed for at least 1 year. Patients with diabetic nephropathy were excluded. Seven trials were selected from 40 studies since 1975. A total of 1494 patients were analysed: 753 had received reduced protein intake and 741 a higher protein intake. The numbers of 'renal deaths' (defined as the need for starting dialysis, the death of a patient or kidney transplant during the trial) were collected. RESULTS: 242 renal deaths were recorded, 101 in the low protein diet and 141 in the higher protein diet group, giving an odds ratio of 0.61 with a 95% confidence interval of 0.46 to 0.83 (P=0.006). CONCLUSION: Reducing protein intake in patients with chronic renal failure reduces the occurrence of renal death by about 40% as compared with larger or unrestricted protein intake. The optimal level of protein intake cannot be confirmed from these studies.

Chronic Disease↗
PubMed2000

Fatty acid transport protein-1 mRNA expression in skeletal muscle and in adipose tissue in humans.

Fatty acid transporter protein (FATP)-1 mRNA expression was investigated in skeletal muscle and in subcutaneous abdominal adipose tissue of 17 healthy lean, 13 nondiabetic obese, and 16 obese type 2 diabetic subjects. In muscle, FATP-1 mRNA levels were higher in lean women than in lean men (2.2 +/- 0.1 vs. 0.6 +/- 0.2 amol/microg total RNA, P < 0.01). FATP-1 mRNA expression was decreased in skeletal muscle in obese women both in nondiabetic and in type 2 diabetic patients (P < 0.02 vs. lean women in both groups), and in all women there was a negative correlation with basal FATP-1 mRNA level and body mass index (r = -0.74, P < 0.02). In men, FATP-1 mRNA was expressed at similar levels in the three groups both in skeletal muscle (0.6 +/- 0.2, 0.6 +/- 0.2, and 0.8 +/- 0.2 amol/microg total RNA in lean, obese, and type 2 diabetic male subjects) and in adipose tissue (0.9 +/- 0.2 amol/microg total RNA in the 3 groups). Insulin infusion (3 h) reduced FATP-1 mRNA levels in muscle in lean women but not in lean men. Insulin did not affect FATP-1 mRNA expression in skeletal muscle in obese nondiabetic or in type 2 diabetic subjects nor in subcutaneous adipose tissue in any of the three groups. These data show a gender-related difference in the expression of the fatty acid transporter FATP-1 in skeletal muscle of lean individuals and suggest that changes in FATP-1 expression may not contribute to a large extent to the alterations in fatty acid uptake in obesity and/or type 2 diabetes.

Abdomen↗
PubMed2000

Mental stress-induced increase in blood pressure is not related to baroreflex sensitivity in middle-aged healthy men.

The baroreflex that acts to blunt blood pressure (BP) variations through opposite variations in heart rate should limit the BP increase produced by an emotional challenge. However, relations between baroreflex sensitivity and BP reactivity induced by a psychological stress in a large group of adults have never been firmly established. In 280 healthy men, rest (10 minutes) and stress (5 minutes) BP and heart rate were recorded beat to beat by a blood pressure monitor. The mental stress was elicited by a well-standardized computerized version of a word color conflict stress test (Stroop Color Test). Rest and stress baroreflex sensitivity was assessed by the cross-spectral analysis of BP and heart rate and by the sequence method. The stress-induced increase in systolic BP (22.4+/-0.1 mm Hg) was not correlated with resting baroreflex sensitivity but was slightly correlated (r=0.2, P<0.001) with BP variability assessed either by standard deviation or by mid-frequency band spectral power. Our results suggested that a centrally mediated sympathetic stimulation overcame cardiac autonomic regulation and emphasized the role of the sympathetic vasoconstriction in the pressure response at the onset of the stressing stimulation. During the sustained sympathoexcitatory phase, the cardiac baroreflex blunts BP variations but at a lower sensitivity.

Adolescent↗
PubMed2000

Normal reproductive function in leptin-deficient patients with lipoatropic diabetes.

To further examine the relationships between leptin and female reproductive axis, we conducted hormonal studies in two patients with lipoatropic diabetes that occurred before puberty. Despite complete atrophy of sc and visceral adipose tissue, menarche occurred in these two patients between 11-12 yr of age, followed by regular menstrual cycles. One patient had been pregnant three times, giving birth to children who did not develop the disease. In our two patients, repeated analysis revealed leptin levels below 1 ng/mL (normal range for 20 insulin-treated diabetic women, 2-23 ng/mL for body mass index of 14-39 kg/m2; personal data). We measured peripheral levels of estradiol, progesterone, FSH, LH, free testosterone, and androstenedione within the first 5 days of the menstrual cycle, and we tested the reactivity of pituitary after iv injection of 100 microg GnRH. The variation in body temperature in the morning before arising was also analyzed. We showed that 1) all measured levels of hormones were in the normal range for both patients; and 2) low levels of leptin did not impair the development of reproductive function in one patient and was associated with normal gonadal function in both patients. We conclude that puberty and fertility can occur despite chronic low serum levels of leptin. This suggests that leptin is not fundamental to the maintenance of normal reproductive function in humans.

Adult↗