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M Krempf

Publications and source records attributed to M Krempf.

At least 73 records · Page 4Linked to original sources
PubMed1998

Production rate of acetate during colonic fermentation of lactulose: a stable-isotope study in humans.

BACKGROUND: Breath tests are currently used to qualitatively assess colonic fermentation; no quantitative estimations are available for healthy subjects. OBJECTIVE: This study describes a stable-isotope-dilution method to measure acetate production quantitatively from colonic bacterial fermentation. DESIGN: Six volunteers received a primed, constant, intravenous infusion of [1-13C]acetate at a rate of 1.01 +/- 0.04 micromol x kg(-1) x min(-1) for 7 h. They ingested 20 g pure lactulose after 1 h of the tracer infusion. Expired air and arterialized venous blood were sampled every 15 min. RESULTS: Before lactulose intake, the breath-hydrogen concentration was 7 +/- 2 ppm and the plasma acetate concentration and isotopic enrichment were 141 +/- 14 micromol/L and 14.8 +/- 1.4 moles percent excess, respectively. Whole-body acetate turnover was 6.0 +/- 0.7 micromol x kg(-1) x min(-1). After lactulose ingestion, maximum breath hydrogen and acetate concentrations reached 63 +/- 15 ppm (P = 0.004) and 313 +/- 25 micromol/L (P = 0.002), respectively, whereas [13C]acetate enrichment decreased to 9.9 +/- 1.3 moles percent excess (P = 0.03). Whole-body acetate turnover increased to 9.8 +/- 1.5 micromol x kg(-1) x min(-1) and later decreased almost to baseline values. Colonic lactulose fermentation yielded 140 +/- 12 mmol acetate over 6 h, representing 86% of the production based on stoichiometric equations. CONCLUSION: This new method provides a quantitative estimate of colonic carbohydrate fermentation via evaluation of acetate production.

Acetates↗
PubMed1998

Whole-body, peripheral and intestinal endogenous acetate turnover in dogs using stable isotopes.

Acetate metabolism supplies about 10% of energy requirements in food-deprived nonruminant animals. This study used a stable isotope dilution method to investigate the fate of acetate in 24-h food-deprived dogs free of colonic fermentation. Three dogs received intravenous bolus injections of 40 or 70 micromol/kg of [1-13C] acetate, and carotid blood was then sampled during a 15-min period to estimate the acetate distribution volume. Ten dogs received intravenous [1-13C] acetate infusions of 1.05 +/- 0.02 or 2.10 +/- 0. 10 micromol/(kg.min) for 120 or 200 min after a prime of 200 or 70 micromol/kg, respectively. Cephalic venous and carotid arterial blood were sampled for all dogs, and portal blood for five. Acetate distribution volume was 0.27 +/- 0.16 L/kg (mean +/- SEM). The concentrations of acetate in arterial (144 +/- 17 micromol/L), venous (155 +/- 20 micromol/L) and portal plasma (131 +/- 16 micromol/L) were not significantly different during infusion, whereas isotopic enrichments [mole percent excess (MPE): labeled acetate/all acetate molecules] in portal (1.2 +/- 0.2 MPE) and venous plasma (1.7 +/- 0.3 and 2.6 +/- 0.7 MPE) were lower than in arterial plasma for both infusion rates (4.9 +/- 0.6 and 7.6 +/- 0.8 MPE, respectively, P < 0.005). Whole-body acetate turnover was 24.4 +/- 2.4 micromol/(kg.min). Fractional acetate extractions for forelimb and intestine were 62 +/- 7 and 72 +/- 6%, respectively, and the production for each organ was 0.3 and 1.1 micromol/(kg.min) respectively, similar to that of utilization (P > 0.05). It is concluded that the forelimb and intestine produce and utilize acetate as an energy source in 24-h food-deprived dogs free of colonic fermentation.

Acetates↗
PubMed1998

Kinetic study of apo B100 containing lipoprotein metabolism using amino acids labeled with stable isotopes: methodological aspects.

Kinetic disturbances of lipoprotein metabolism are important to know for a better understanding of lipid diseases or effects of drugs. These kinetic aspects were previously studied with radioactive tracers. The ethical concerns related to these tracers can be now overcome at a reasonable cost with the new development of small bench top mass spectrometers and the increased production of stable isotope tracers. In this review, we will discuss some methodological aspects related to stable isotope tracers and the analysis of the data with non-compartmental or compartmental models.

Amino Acids↗
PubMed1998

[Pulmonary artery hypertension in HIV seropositive drug addicts. Apropos of 10 cases].

Pulmonary hypertension (PH) is a classic complication associated with intravenous drug addiction. Various pathogenic mechanisms may be involved but HIV infection now appears to be the main etiologic factor. We report herein 10 case of PH occurred in HIV+ intravenous drug abusers. Each patient had several pathogenic factors: HIV infection, pills crushed and intravenously injected (6 cases), heavy and repeated consumption of amphetamines and cocaine (6 cases), cirrhosis with portal hypertension (2 cases), anticardiolipid antibodies (2 cases). The clinical findings were similar to those reported for PH in HIV seronegative patients; however, in 5 cases, opiates could have alleviated dyspnea, which became perceptible only at the time of drug withdrawal. Because drug addicts usually exhibit a weak support for medical prescriptions, long term therapy needing regular follow-up such as anticoagulation appears to be hazardous and even dangerous. The prognosis remains poor, since the progression of PH led to the death of one third patients within the year following the diagnosis.

Adult↗
PubMed1997

Determination of low 13C-glutamine enrichments using gas chromatography-combustion-isotope ratio mass spectrometry.

Glutamine is an essential fuel for tissues with high rates of cell replication, such as enterocytes and lymphocytes. Infusion of 13C-labeled glutamine tracers allows for measurement of the rates of production, utilization and oxidation of glutamine's carbon skeleton in vivo. The use of this tracer, however, has been limited by its high cost and/or the difficulty is measuring low enrichments in biological fluids using conventional gas chromatography-mass spectrometry (GC/MS) techniques. We have developed a method using gas chromatography-combustion-isotope ratio mass spectrometry (GC-C-IRMS) that allows for the determination of low 13C enrichments (down to 0.06 mol.% excess) with a precision of 2% or better, and a within-day and between-day variability better than 5%, in plasma free glutamine. The method was applied to measuring the incorporation of 13C in plasma glutamine over the course of infusion of 13C-labeled acetate in a human subject.

Carbon Isotopes↗
PubMed1997

Familial ligand-defective apolipoprotein B-100: simultaneous detection of the ARG3500-->GLN and ARG3531-->CYS mutations in a French population.

Familial ligand-defective apolipoprotein B-100 (FDB) is an autosomal dominant disorder leading to plasma LDL cholesterol elevation and coronary artery disease (CAD). Two specific mutations in the APOB gene--R3500Q and R3531C--induce FDB. We report an original method to detect both mutations simultaneously, based upon PCR-mediated, site-directed mutagenesis and double restriction of a unique PCR product. With this method we have investigated the prevalence of these mutations in 1,040 French patients. The R3500Q mutation was found in five probands. Genotypes were determined for 10 APOB polymorphic markers and were consistent with the common European ancestral haplotype previously reported. The only exception was one FDB proband who did not harbor the 48 repeat allele of the 3'HVR. Additionally, the first two R3531C mutations were identified in French probands. Genotypes were consistent with a previously reported haplotype, suggesting that this is another mutation of European ancestry.

Adult↗
PubMed1997

High density lipoprotein apolipoprotein AI kinetics in NIDDM: a stable isotope study.

High density lipoprotein (HDL) kinetics were studied by infusing [5,5,5-2H3]-leucine in five subjects with normal glucose tolerance and eight patients with non-insulin-dependent diabetes mellitus (NIDDM) with poor metabolic control (HbA1c = 8.16 +/- 1.93%) (mean +/- SD). HDL were modelled as a single compartment since no kinetic differences were observed between HDL2 and HDL3 subclasses. Plasma apolipoprotein AI (apo AI) concentration was significantly lower in NIDDM patients (96.1 +/- 12.1 vs 124.4 +/- 13.1 mg.dl-1, p < 0.01). HDL composition was altered in NIDDM, as an increase in HDL-triglyceride and a decrease in HDL-cholesterol, negatively correlated (r = 0.780, p < 0.01). The mean fractional catabolic rate (FCR) of apo AI-HDL was significantly higher (0.39 +/- 0.16 vs 0.21 +/- 0.06 d-1, p < 0.05) while the apo AI-HDL absolute production rate was not significantly greater (13.6 +/- 5.1 vs 12.0 +/- 4.2 mg.kg-1.d-1) in diabetic patients compared to normal subjects. There were significant correlations between apo AI-HDL FCR and plasma apo AI concentration (r = -0.580, p < 0.05), plasma triglycerides (r = 0.839, p < 0.0001) or HDL-triglyceride levels (r = 0.597, p < 0.05). No correlation was observed between apo AI-HDL FCR and HbA1c or HDL-cholesterol level. These data support the view that the decrease in plasma apo AI level in patients with NIDDM is due to an increase of apo AI-HDL FCR, which may itself be related to changes in HDL composition.

Adult↗
PubMed1997

Lipoprotein kinetics in patients with analbuminemia. Evidence for the role of serum albumin in controlling lipoprotein metabolism.

In vitro data suggested that albumin is a key factor controlling apolipoprotein (apo) synthesis by hepatocytes. Studies in analbuminemic rats have shown an increase in secretion of apoB-containing lipoprotein from the liver. We studied the kinetic aspects of apoB- and apoAI-containing lipoprotein metabolism in two sisters with analbuminemia using a constant 14-hour infusion of leucine labeled with stable isotopes. Compared with control subjects, total cholesterol was higher in the two patients (432 and 461 versus 155 +/- 14 mg/dL), as was apoB (257 and 230 versus 72 +/- 7 mg/dL). Triglycerides were slightly increased (134 and 105 versus 89 +/- 9 mg/dL), whereas apoAI was lower (109 and 105 versus 124 +/- 6 mg/dL). VLDL-apoB production was higher, as was the production of IDL-apoB and LDL-apoB (32.8 and 36.0 versus 24.8 +/- 5.9, 32.1 and 27.2 versus 16.4 +/- 2.3, and 14.1 and 17.6 versus 10.3 +/- 1.2 mg.kg-1.d-1, respectively). The fractional catabolic rate of all the apoB-containing lipoproteins was decreased (0.23 and 0.37 versus 0.48 +/- 0.05, 0.27 and 0.28 versus 0.62 +/- 0.08, and 0.012 and 0.009 versus 0.022 +/- 0.002.h-1, respectively). A similar mechanism could explain the dyslipidemia observed in other conditions associated with low albumin levels, such as nephrotic syndrome.

Adult↗
PubMed1997

Efficacy of low-dose pravastatin in patients with mild hyperlipidemia associated with type II diabetes mellitus.

A 16 week, randomized, double-blind, parallel, placebo-controlled study was designed to determine the effects of low-dose pravastatin on cholesterol concentrations in patients with mild hypercholesterolemia and non-insulin-dependent diabetes mellitus (NIDDM). Following a 6-to 8-week dietary run-in period, a mean serum total cholesterol (TC) level > 5.2 mmol/L (200 mg/dL), but < 7.8 mmol/L (300 mg/dL) was required for entry. Metabolic control of diabetes was determined by a hemoglobin Alc (HbAlc) level less than twice the upper limit of normal on two occasions. Eighty six (86) patients recruited in 5 French diabetic clinics, were randomized in a ratio of 1:1 (pravastatin 10 mg or placebo), and 74 completed the study. There were 12 discontinuations: 5 (11.6%) in the pravastatin group and 7 (16.3%) in the placebo group. Drop-out was due to an adverse event in 1 patient (2.3%) in the pravastatin group and in 5 patients (11.6%) in the placebo group. Thirty five (35) placebo patients and 14 pravastatin patients had their dose of treatment doubled at week 8: the dose of treatment was to be doubled at week 8 in the event of non-response to treatment (TC at week 7 > 5.2 mmol/L and TC decrease < 15% from baseline). At week 16, pravastatin lowered TC from 6.4 to 5.6 mmol/L (-13.8%, p < 0.001 versus placebo), low-density lipoprotein cholesterol (LDL-C) from 4.3 to 3.4 mmol/L (-20.4%, p < 0.001 versus placebo) and slightly increased high-density lipoprotein cholesterol (HDL-C) from 1.18 to 1.25 mmol/L (+6.7%). Side effects were similar in both groups. Blood glucose control was not altered as assessed by serial HbAlc measurements which were unchanged during treatment. This study demonstrated that low-dose pravastatin is effective in lowering cholesterol levels in patients with hypercholesterolemia and NIDDM.

Adult↗
PubMed1997

[Effect of nutrition on combined hyperlipidemia].

Recent studies had underlined the expected effects of dietary changes in combined hyperlipidemia. Weight reduction is useful, but long term effect is usually moderate (10% reduction of cholesterol and 30% of triglycerides). There is no support to limit the intake of complex carbohydrates at 55% of the total calorie intake even in case of high triglyceride levels. The reduction of fat intake up to 30% of the total daily calorie intake is recommended but the quantity of saturated, mono or polyunsaturated flat is still discussed. Monoinsaturated fatty acid intake are now strongly recommended. Thus the Mediterranean diet appears to be very well adapted to the treatment of combined hyperlipidemia.

Cholesterol, Dietary↗
PubMed1996

[Alcoholism].

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Alcohol Drinking↗
PubMed1996

Kinetic aspects of acetate metabolism in healthy humans using [1-13C] acetate.

Acetate metabolism in humans is not well known. Kinetic aspects of acetate were investigated in the postabsorptive state on healthy subjects. In a first study, six subjects were infused with a primed constant infusion of [1-13C]acetate for 3 h and a prime of NaH13CO3. No difference was found between arterialized and venous tracer enrichments from the arm, although arterialized acetate concentrations were higher (74 +/- 12 vs. 59 +/- 14 mumol/l, P < 0.05), suggesting that the hand muscles used but did not produce acetate in the postabsorptive state. Total body flux of acetate was 8.4 +/- 0.6 mumol.kg-1.min-1, of which 69 +/- 5% was oxidized. Acetate contributed to 6.5 +/- 0.4% of the basal energy expenditure. In a second study, five volunteers were submitted to a gastric infusion for 3 h followed by an intravenous infusion of [1-13C]acetate for 3 h. Higher fluxes were observed with the tracer gastric infusion, and the first-pass removal of acetate within the splanchnic bed was 60 +/- 7%. Acetate contributes significantly to the energy supply of the body. It is mainly used by the liver when produced in the gut.

Acetates↗
PubMed1996

Increased cholesteryl ester transfer activity in plasma from analbuminemic patients.

Hypercholesterolemia associated with analbuminemia, an inherited disease manifesting low plasma albumin concentration, is characterized by enhanced LDL cholesterol levels and reduced HDL cholesterol levels. In addition, compared with normal counterparts, the esterified cholesterol:triglyceride ratio tends to be higher in analbuminemic apoB-containing lipoproteins and lower in analbuminemic HDL. The aim of the present study was to investigate the mechanism that may account for the association of a hypoalbuminemic state with alterations in the concentration and composition of plasma lipoprotein fractions. To this end, endogenous cholesterol esterification activity, phospholipid transfer activity, and cholesteryl ester transfer activity were measured in total plasma from three analbuminemic patients and five control subjects. Whereas endogenous cholesterol esterification and phospholipid transfer rates were not significantly affected in analbuminemia, the transfer of radiolabeled cholesteryl esters from HDL toward apoB-containing lipoproteins was constantly higher in analbuminemic plasmas than in normal control plasma (473.6+/-107.3% x h(-1) x mL(-1) versus 227.5+/-84.0% x h(-1) x mL(-1), respectively; P=.036). The rise in cholesteryl ester transfer protein (CETP) activity in analbuminemic plasma was due to a significant increase in the transfer of radiolabeled cholesteryl esters toward LDL but not toward the triglyceride-rich lipoproteins. The CETP mass was higher in analbuminemic patients than in control subjects, but the difference did not reach the significance level (5.18+/-0.82 mg/L versus 3.13+/-1.19 mg/L respectively; P=.07). Since abnormally elevated nonesterified fatty acid (NEFA) levels were shown to be associated with analbuminemic lipoproteins, mostly LDL, the direct role of lipoprotein-bound NEFA in enhancing CETP activity was suspected. In support of this view, supplementation of total plasmas with fatty acid-poor albumin was shown to reduce CETP activity to a significantly greater extent in analbuminemic plasmas than in normal control plasma. It is concluded that hyperlipidemia associated with the hypoalbuminemic state can relate, at least in part, to the combined effect of CETP and NEFA in promoting the transfer of cholesteryl esters from the antiatherogenic HDL toward the proatherogenic apoB-containing lipoproteins.

Adult↗
PubMed1996

A minimal model using stable isotopes to study the metabolism of apolipoprotein B-containing lipoproteins in humans.

A protocol using stable isotopes, developed to measure apolipoprotein B turnover in humans, was tested by intravenous infusion of [2H3]-leucine into 5 normolipidemic volunteers during a 14-h fast. Tracer-to-tracee ratio curves were analyzed by four different approaches: linear regression, monoexponential regression, a minimal compartmental model (3 compartments) and a complex model (4 compartments and two shunt pathways). The three-compartment model was validated by qualitative analysis of data obtained after injection of a [2H3]-leucine bolus. This simple model gave an FCR of 0.48 +/- 0.05 h-1 for VLDL, 0.62 +/- 0.08 h-1 for IDL and 0.022 +/- 0.002 h-1 for LDL. The total production rate of apolipoprotein B in plasma was 24.8 +/- 6.5 mg.kg-1.day-1. Kinetic parameters were similar for the complex model which showed no improvement in fit. Lower estimates were observed with the non-compartmental approaches.

Adult↗
PubMed1996

A 15N-leucine-dilution method to measure endogenous contribution to luminal nitrogen in the human upper jejunum.

OBJECTIVE: This study was done to investigate whether an intraveinous infusion of 15N-leucine was accurate to differentiate between endogenous and exogenous nitrogen in the human jejunum after meal ingestion. SUBJECTS: Four healthy human volunteers equipped with an upper jejunal tube. INTERVENTIONS: The jejunal effluents were collected both under fasting conditions and after ingestion of 300g of yoghurt. The nitrogen, amino acid composition and 15N-leucine enrichment were determined in the digesta. RESULTS: During fasting, the jejunal flow rates (mmol/h) of both total nitrogen and amino acids were stable (6.9 +/- 2.7 and 1.88 +/- 0.79, respectively). After yoghurt ingestion, the flow rate of total nitrogen increased to 28.6 +/- 5.8mmol/h at 2h. The 15N-leucine enrichment in plasma reached a plateau at 4.3 mole % excess after one hour and did not vary significantly after meal ingestion. The 15N-leucine enrichment of the endogenous secretion (Ee) in the jejunum was fitted by the equation: Ee = 2.18[1 - 2.05 x exp( - 0.42 x t)]. After yoghurt ingestion, the enrichment in jejunal secretions decreased during the first 80 min. The endogenous nitrogen, calculated from the 15N-enrichment, significantly increased from 20 to 40min after meal ingestion compared to the basal value (P < 0.05). The estimation of the exogenous nitrogen and amino acid yield 300min after yoghurt ingestion indicated that 62 +/- 30% of the exogenous nitrogen and 75 +/- 12% of the amino acids were absorbed in the upper jejunum. CONCLUSIONS: The 15N-leucine-dilution method appears to be a convenient method to differentiate between the exogenous and endogenous contributions to nitrogen fluxes in the intestinal digesta of humans. It can be used in association with dietary protein labelling or in substitution when no labelled dietary proteins are available to compare the digestion as well as the absorption of meals at different levels of the intestine.

Adult↗