Growth factors and malnutrition in chronic renal failure.
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Growth Hormone↗
Biomedical subjects
M Laville
Publications and source records attributed to M Laville.
Increased uncoupling protein-2 and -3 mRNA expression during fasting in obese and lean humans.
Uncoupling protein-2 and -3 (UCP2 and UCP3) are mitochondrial proteins that show high sequence homology with the brown adipocyte-specific UCP1. UCP1 induces heat production by uncoupling respiration from ATP synthesis. UCP2 is widely expressed in human tissues, whereas UCP3 expression seems restricted to skeletal muscle, an important site of thermogenesis in humans. We have investigated the regulation of UCP2 and UCP3 gene expression in skeletal muscle and adipose tissue from lean and obese humans. UCP2 and -3 mRNA levels were not correlated with body mass index (BMI) in skeletal muscle, but a positive correlation (r = 0.55, P < 0.01, n = 22) was found between UCP2 mRNA level in adipose tissue and BMI. The effect of fasting was investigated in eight lean and six obese subjects maintained on a hypocaloric diet (1,045 kJ/d) for 5 d. Calorie restriction induced a similar 2-2.5-fold increase in UCP2 and -3 mRNA levels in lean and obese subjects. To study the effect of insulin on UCP gene expression, six lean and five obese subjects underwent a 3-h euglycemic hyperinsulinemic clamp. Insulin infusion did not modify UCP2 and -3 mRNA levels. In conclusion, the similar induction of gene expression observed during fasting in lean and obese subjects shows that there is no major alteration of UCP2 and -3 gene regulation in adipose tissue and skeletal muscle of obese subjects. The increase in UCP2 and -3 mRNA levels suggests a role for these proteins in the metabolic adaptation to fasting.
Adipose Tissue↗
The organization, promoter analysis, and expression of the human PPARgamma gene.
PPARgamma is a member of the PPAR subfamily of nuclear receptors. In this work, the structure of the human PPARgamma cDNA and gene was determined, and its promoters and tissue-specific expression were functionally characterized. Similar to the mouse, two PPAR isoforms, PPARgamma1 and PPARgamma2, were detected in man. The relative expression of human PPARgamma was studied by a newly developed and sensitive reverse transcriptase-competitive polymerase chain reaction method, which allowed us to distinguish between PPARgamma1 and gamma2 mRNA. In all tissues analyzed, PPARgamma2 was much less abundant than PPARgamma1. Adipose tissue and large intestine have the highest levels of PPARgamma mRNA; kidney, liver, and small intestine have intermediate levels; whereas PPARgamma is barely detectable in muscle. This high level expression of PPARgamma in colon warrants further study in view of the well established role of fatty acid and arachidonic acid derivatives in colonic disease. Similarly as mouse PPARgammas, the human PPARgammas are activated by thiazolidinediones and prostaglandin J and bind with high affinity to a PPRE. The human PPARgamma gene has nine exons and extends over more than 100 kilobases of genomic DNA. Alternate transcription start sites and alternate splicing generate the PPARgamma1 and PPARgamma2 mRNAs, which differ at their 5'-ends. PPARgamma1 is encoded by eight exons, and PPARgamma2 is encoded by seven exons. The 5'-untranslated sequence of PPARgamma1 is comprised of exons A1 and A2, whereas that of PPARgamma2 plus the additional PPARgamma2-specific N-terminal amino acids are encoded by exon B, located between exons A2 and A1. The remaining six exons, termed 1 to 6, are common to the PPARgamma1 and gamma2. Knowledge of the gene structure will allow screening for PPARgamma mutations in humans with metabolic disorders, whereas knowledge of its expression pattern and factors regulating its expression could be of major importance in understanding its biology.
3T3 Cells↗
Multicenter study on the clinical value of fetal pulse oximetry. I. Methodologic evaluation. The French Study Group on Fetal Pulse Oximetry.
OBJECTIVE: Our purpose was to evaluate the feasibility of intrapartum fetal pulse oximetry, the distribution of fetal oxygen saturation values, and the relationship with the neonatal outcome in a population with an abnormal fetal heart rate. STUDY DESIGN: A prospective multicenter observational study was performed from June 1994 to November 1995. Fetal oxygen saturation was continuously recorded with use of a Nellcor N-400 fetal pulse oximeter in case of an abnormal fetal heart rate during labor. Simultaneous readings of fetal oxygen saturation and fetal blood analysis were obtained at inclusion and before birth. Feasibility, adverse effects, distribution of fetal oxygen saturation values, and relationship with neonatal outcome were assessed. RESULTS: One hundred seventy-four patients were included. From 172 attempted sensor placements, the procedure was impossible in three cases and fetal oxygen saturation values were obtained in 164 cases (95.3%). Physicians considered sensor placement an easier task than an attempt at fetal blood analysis (easy in 87.5% vs 78.9% for fetal blood analysis, p = 0.03). The mean reliable signal time (+/- SD) was 64.7% +/- 32% during the first stage. There were no serious adverse effects in the study population. The mean fetal oxygen saturation during the first stage of labor was 42.2% +/- 8.0% (10th to 90th percentile range 30% to 53%). Fetal oxygen saturation was significantly correlated with scalp pH (r = 0.29, p = 0.01) but not with neonatal umbilical artery pH or gas values. There was a significant association between low fetal oxygen saturation (< 30%) and poor neonatal condition. CONCLUSION: The feasibility of fetal pulse oximetry is satisfactory in clinical practice. It is easy to use and provides a fair rate of recorded values, even in a population with suspicion of fetal distress. A low fetal oxygen saturation is significantly associated with an abnormal neonatal outcome.
Adult↗
Multicenter study on the clinical value of fetal pulse oximetry. II. Compared predictive values of pulse oximetry and fetal blood analysis. The French Study Group on Fetal Pulse Oximetry.
OBJECTIVE: Our purpose was to compare the predictive value of intrapartum fetal pulse oximetry with that of fetal blood analysis for an abnormal neonatal outcome in case of an abnormal fetal heart rate. STUDY DESIGN: A prospective multicenter observational study was conducted from June 1994 to November 1995. Fetal oxygen saturation was continuously recorded with a Nellcor N-400 fetal pulse oximeter in case of an abnormal fetal heart rate during labor. Simultaneous readings of fetal oxygen saturation and fetal blood analysis obtained before birth (i.e., either at full dilatation or before cesarean section when indicated) were compared with the neonatal status. The criteria for an abnormal neonatal outcome were (1) an umbilical arterial blood pH < or = 7.15 and (2) a combined variable including 5-minute Apgar score < or = 7, umbilical arterial pH < or = 7.15, secondary respiratory distress, transfer in a neonatal care unit, or neonatal death. RESULTS: At a 7.20 threshold for fetal scalp pH and 30% for fetal oxygen saturation (i.e., the 10th percentile in the study population), the predictive value of fetal pulse oximetry was similar to that of fetal blood analysis for an arterial umbilical pH < or = 7.15 and for an abnormal neonatal outcome (positive predictive value 56% vs 55%, negative predictive value 81% vs 82%, sensitivity 29% vs 35%, and specificity 93% vs 91%, respectively). The receiver-operator characteristic curve showed similar performance of either technique for cutoff values < or = 7.20 for fetal blood pH and < or = 30% for fetal oxygen saturation, whereas fetal pulse oximetry became superior at higher thresholds. CONCLUSION: The predictive value of intrapartum fetal pulse oximetry can be favorably compared with that of fetal blood analysis. Randomized controlled management trials can now be performed to assess potential clinical benefits of this new tool.
Apgar Score↗
Fetal pulse oximetry and fetal heart rate monitoring during stage II of labour.
OBJECTIVE: This study was designed to assess the changes in fetal oxygen saturation (FSpO2) using fetal pulse oximetry when the fetal heart rate (FHR) monitoring became abnormal during stage II of labour. STUDY DESIGN: FSpO2 was recorded with the Nellcor N400 Oximeter (FS-14 sensor) and was averaged over the last 10 min of the second stage of labour. Second stage FHR patterns were assessed according to Melchior's classification. RESULTS: In terms of FHR patterns, FSpO2-10" measured 41.4% in type 0 (n = 5), 42.4% in type 1 (n = 19), 43.3% in type 2 (n = 6), 34.0% in type 3 (n = 4) and 27.6% in type 4 (n = 7) (P = 0.03). CONCLUSIONS: FSpO2-10" decreases in cases of severe FHR abnormality during the second stage of labour and could help to decide whether to perform an instrumental extraction.
Female↗
Total body water and body composition in chronic peritoneal dialysis patients.
In this investigation, total body water (TBW) in ten chronic peritoneal dialysis patients was studied by deuterium (TBW-2H), skinfold thickness (TBW-ST), Watson formula (TBW-WA), 58% of body weight (TBW-58%), and bioelectrical impedance (TBW-BIA), and these results were compared with the reference oxygen18 (TBW-18O) method. We also analyzed the fat-free mass (FFM) by skinfold thickness (FFM-ST), bioelectrical impedance (FFM-BIA), oxygen18 (FFM-18O), and creatinine kinetics method (FFM-CK). In addition, resting metabolic rate was measured by indirect calorimetry. Compared with TBW-18O, TBW-58% and TBW-BIA were significantly different (P < 0.01). TBW-2H overestimated TBW-18O by 4.3%. TBW-ST and TBW-WA gave slightly greater values than TBW-18O, although these values were nonstatistically significant. The best prediction of total body water from these methods was obtained with the Watson formula. When Kt/V was calculated from these results, the values obtained were statistically greater (BIA, P < 0.001) and smaller (58% BW, P < 0.01) than those obtained with either 18O or Watson formula. The fat-free mass estimation also led to discrepant findings. Indeed, FFM-CK was significantly lower (P < 0.05) as compared with FFM-ST, FFM-BIA, or FFM-18O. Resting metabolic rate was strongly correlated with FFM estimated by skinfold thickness (r = 0.91, P < 0.001), bioelectrical impedance (r = 0.85, P < 0.005), and 18O (r = 0.77, P < 0.01), but not when fat-free mass was estimated by the creatinine kinetic method. The water content of fat-free mass estimated by skinfold thickness was found to be 69.7 +/- 6.9% in these patients, a value lower than the standard 73.2% found in healthy adults. This study confirms that there is an abnormal water distribution in chronic peritoneal dialysis patients. However, when compared with the oxygen18 reference method, the Watson formula allows a reliable estimation of Kt/V.
Aged↗
Tissue distribution and quantification of the expression of mRNAs of peroxisome proliferator-activated receptors and liver X receptor-alpha in humans: no alteration in adipose tissue of obese and NIDDM patients.
Members of the peroxisome proliferator-activated receptor (PPAR) family might be involved in pathologies with altered lipid metabolism. They participate in the control of the expression of genes involved in lipid metabolism and adipocyte differentiation. In addition, thiazolidinediones improve insulin resistance in vivo by activating PPAR gamma. However, little is known regarding their tissue distribution and relative expression in humans. Using a quantitative and sensitive reverse transcription (RT)-competitive polymerase chain reaction (PCR) assay, we determined the distribution and relative mRNA expression of the four PPARs (alpha,beta, gamma1, and gamma2) and liver X receptor-alpha (LXR alpha) in the main tissues implicated in lipid metabolism. PPAR alpha and LXR alpha were mainly expressed in liver, while PPAR gamma1 predominated in adipose tissue and large intestine. We found that PPAR gamma2 mRNA was a minor isoform, even in adipose tissue, thus causing question of its role in humans. PPAR beta mRNA was present in all the tissues tested at low levels. In addition, PPAR gamma mRNA was barely detectable in skeletal muscle, suggesting that improvement of insulin resistance with thiazolidinediones may not result from a direct effect of these agents on PPAR gamma in muscle. Obesity and NIDDM were not associated with change in PPARs and LXR alpha expression in adipose tissue. The mRNA levels of PPAR gamma1, the predominant form in adipocytes, did not correlate with BMI, leptin mRNA levels, or fasting insulinemia in 29 subjects with various degrees of obesity. These results indicated that obesity is not associated with alteration in PPAR gene expression in abdominal subcutaneous adipose tissue in humans.
Adipocytes↗
Human plasma albumin transports [13C]docosahexaenoic acid in two lipid forms to blood cells.
Docosahexaenoic acid (22:6) decreases blood platelet function and is highly concentrated in the brain where its depletion leads to functional impairments. Because the platelets and blood brain barrier capillary endothelium cannot hydrolyze the complex lipids for fatty acid (FA) uptake, nonesterified FA (NEFA) bound to albumin are assumed to be the delivery route of FA to these cells. The supply of 13C-labeled 22:6 to blood cells by plasma albumin was studied in humans after a single ingestion of this FA esterified in a triglyceride (TG). The 22:6 13C/12C ratio, measured by gas chromatography combustion-isotope ratio mass spectrometry was measured in lipid classes from albumin, platelets, leukocytes, and erythrocytes (taken as a tentative index of the brain uptake). Nonesterified [13C]22:6 bound to albumin was rapidly produced after ingestion, as a result of the hydrolysis of very low density lipoprotein (VLDL) plus chylomicron TG. We found that albumin carried another source of 22:6, lyso-phosphatidylcholines (lyso-PC), in which [13C]22:6 accumulated while the nonesterified [13C]22:6 reached its minimal plasma concentrations. Computation of the relative contribution of NEFA and lyso-PC for the [13C]22:6 delivery to platelets and erythrocytes showed that the [13C]22:6 supply to platelets occurred uniquely through NEFA, whereas this pool was weakly involved in the delivery to erythrocytes. In contrast, lyso-PC was uniquely concerned with the 22:6 delivery to erythrocytes and represented the major part of this supply. We conclude that plasma albumin carries 22:6 in two lipid forms that are involved differently in the delivery of this FA to target cells.
Biological Transport, Active↗
The expression of ob gene is not acutely regulated by insulin and fasting in human abdominal subcutaneous adipose tissue.
The regulation of ob gene expression in abdominal subcutaneous adipose tissue was investigated using a reverse transcription-competitive PCR method to quantify the mRNA level of leptin. Leptin mRNA level was highly correlated with the body mass index of 26 subjects (12 lean, 7 non-insulin-dependent diabetic, and 7 obese patients). The effect of fasting on ob gene expression was investigated in 10 subjects maintained on a hypocaloric diet (1045 KJ/d) for 5 d. While their metabolic parameters significantly changed (decrease in insulinemia, glycemia, and resting metabolic rate and increase in plasma ketone bodies), the caloric restriction did not modify the leptin mRNA level in the adipose tissue. To verify whether insulin regulates ob gene expression, six lean subjects underwent a 3-h euglycemic hyperinsulinemic (846 +/- 138 pmol/liter) clamp. Leptin and Glut 4 mRNA levels were quantified in adipose tissue biopsies taken before and at the end of the clamp. Insulin infusion produced a significant threefold increase in Glut 4 mRNA while leptin mRNA was not affected. It is concluded that ob gene expression is not acutely regulated by insulin or by metabolic factors related to fasting in human abdominal subcutaneous adipose tissue.
Abdomen↗
Acute regulation by insulin of phosphatidylinositol-3-kinase, Rad, Glut 4, and lipoprotein lipase mRNA levels in human muscle.
We have investigated the acute regulation by insulin of the mRNA levels of nine genes involved in insulin action, in muscle biopsies obtained before and at the end of a 3-h euglycemic hyperinsulinemic clamp. Using reverse transcription-competitive PCR, we have measured the mRNAs encoding the two insulin receptor variants, the insulin receptor substrate-1, the p85alpha subunit of phosphatidylinositol-3-kinase, Ras associated to diabetes (Rad), the glucose transporter Glut 4, glycogen synthase, 6-phosphofructo-l-kinase, lipoprotein lipase, and the hormone-sensitive lipase. Insulin infusion induced a significant increase in the mRNA level of Glut 4 (+56 +/- 13%), Rad (+96 +/- 25%), the p85alpha subunit of phosphatidylinositol-3-kinase (+92 +/- 18%) and a decrease in the lipoprotein lipase mRNA level (-49 +/- 5%), while the abundance of the other mRNAs was unaffected. The relative expression of the two insulin receptor variants was not modified. These results demonstrate an acute coordinated regulation by insulin of the expression of genes coding key proteins involved in its action in human skeletal muscle and suggest that Rad and the p85alpha regulatory subunit of phosphatidylinositol-3-kinase can be added to the list of the genes controlled by insulin.
Adult↗
[How to prove the role of renal artery stenosis as a cause of arterial hypertension].
A renal artery stenosis is definitely responsible for hypertension when the correction of stenosis has resulted in the cure of hypertension. Imputability strategy consists in prior collection of indirect data allowing to predict the efficiency of surgical or angioplasty repair, leading to treatment indications. This strategy is based upon the pathophysiological link between hemodynamic abnormalities, increased renin secretion downstream the stenosis, and hypertension. Imputability methods are designed to examine the renine-dependency of hypertension, and both asymmetric renin secretion and renal hemodynamics if stenosis is unilateral. This asymmetry could be enhanced by acute converting enzyme inhibition. Imputability and screening strategies could be fruitfully associated in high risk patients.
Humans↗
Reproducibility of the cardiovascular reactivity to a computerized version of the Stroop stress test in normotensive and hypertensive subjects.
The 1-month reproducibility of haemodynamic and sympathoadrenal responses to a standardized mental stress test was studied in ten normotensive and ten hypertensive individuals. The stress test was a computerized adaptation of the Stroop test and sympathetic activity was evaluated by measuring urinary catecholamine excretion. Three-way analysis of variance (stress, session, blood pressure) revealed significant increases in systolic and diastolic blood pressures and in heart rate during the stress test. Test-retest correlation coefficients for basal stress levels, and stress-induced variations were significant (r from 0.59 to 0.88). The stress test induced a significant increase in urinary noradrenaline excretion with large intra- and interindividual variability. The significant test-retest correlations and the lack of period effect for haemodynamic parameters indicated good temporal stability. However, a slight decrease in stress-induced reactivity was observed. This standardized mental stress test may be useful in epidemiological and therapeutic trials to measure blood pressure and heart rate responses, but measurement of urinary catecholamine excretion does not provide any additional information.
Adult↗
Measurement of post-absorptive glucose kinetics in non-insulin-dependent diabetic patients: methodological aspects.
Post-absorptive glucose metabolism was studied in non-insulin-dependent diabetes mellitus (NIDDM) patients and normal subjects using dideuterated glucose as tracer. From the progressive fall in blood glucose levels and the increase in isotopic enrichment, the post-absorptive situation could not be regarded as a steady state for glucose metabolism, and non-steady-state approximations had therefore to be applied. However, this did not alter significantly the results in the 10 NIDDM patients studied. Significantly higher values of endogenous glucose production (EGP) were obtained (178 center dot 1 +/- 24 center dot 0 mg m-2 min-1 vs. 80 center dot 2 +/- 14 center dot 4; P < 0 center dot 01) if the tracer priming dose was not adapted to the degree of hyperglycaemia. Valid measurements could be made after only 1 h isotopic equilibration time if an appropriately matched priming dose was employed. Methodologically acceptable values for EGP in the 10 NIDDM patients did not differ significantly from those of 10 normal control subjects (80 center dot 2 +/- 14 center dot 4 mg m-2 min-1 vs. 85 center dot 6 +/- 3 center dot 9; not significant). The post-absorptive hyperglycaemia in these patients was assumed to stem essentially from a defect in peripheral glucose uptake.
Absorption↗
Systematic reviews and their roles in promoting evidence-based medicine in renal disease.
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Evidence-Based Medicine↗
Effects of losartan on renal function in patients with essential hypertension.
We examined the renal hemodynamic modifications induced by a selective angiotensin II (AII) AT1 receptor antagonist, losartan, in 10 patients with essential hypertension. In this single-blind study, renal hemodynamic parameters were determined twice (patients were their own controls) first after a 15-day single-blind placebo run-in period and again after a 1-month losartan period. The dosage of losartan was 50 mg/day. Glomerular filtration rate (GFR, inulin clearance), renal plasma flow [RPF; para-aminohippurate (PAH) clearance], microalbuminuria, sodium excretion, proximal sodium tubular reabsorption (lithium clearance), and acid uric metabolism were measured. After 1-month losartan treatment, systolic and diastolic BP (SBP, DBP) decreased significantly throughout the 210-min recording whereas heart rate (HR) was unchanged. GFR (100 +/- 19 vs. 96 +/- 17 ml/min/1.73 m2) and RPF (471 +/- 118 vs. 468 +/- 108 ml/ min/1.73 m2) were not altered by losartan. Rather than occurrence of any modification in filtration fraction (FF), a significant decrease in microalbuminuria was evident (57 +/- 77 vs. 40 +/- 59 mg/24 h, p < 0.05). Urinary sodium excretion was not modified, but an almost significant (p = 0.07) decrease in proximal sodium reabsorption was observed (72.9 +/- 7.7 vs. 68.1 +/- 6.4% of filtered sodium). The increase in renal uric clearance accounted for the significant decrease in serum uric acid (195 +/- 49 vs. 183 +/- 43 microM; p < 0.05). After 1-month losartan treatment, renal function was well preserved; the decrease in uric acid may be of clinical interest when adjuvent diuretic therapy is required.
Albuminuria↗
Metabolic fate of an oral long-chain triglyceride load in humans.
To determine the steps involved in the metabolism of ingested triglycerides (TG), 10 healthy women were studied during 6 h after ingestion of 30 g olive oil labeled with [1,1,1-13C3] triolein. The appearance of 13C was followed in chylomicron-TG (CM-TG), nonesterified fatty acid (NEFA), very low-density lipoprotein (VLDL)-TG, and in expired gas. Indirect calorimetry was used to determine total lipid oxidation. After 90 min, labeling was higher in CM-TG than in NEFA or VLDL. At 180 min, a plateau of enrichment was obtained for CM-TG and NEFA, demonstrating the entry of exogenous lipids in the NEFA pool. After 300 min, a plateau was observed for VLDL-TG with levels of enrichment (0.38 +/- 0.04%) similar to those observed for NEFA (0.36 +/- 0.03%), suggesting a precursor-product relationship. Only 19 +/- 2% of the load was oxidized. From 300 to 360 min, 70% of total lipid oxidation was from exogenous TG. We conclude that, after ingestion of a lipid load, a cycle of fatty acids-TG occurs from CM to NEFA and from NEFA to VLDL. Furthermore, this lipid load has a sparing effect on endogenous lipid stores.
Adult↗
Ear buzzing and lumbar pain revealing a late arteriovenous fistula of the kidney.
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Adult↗