Modulating absorption and postprandial handling of dietary fatty acids by structuring fat in the meal: a randomized crossover clinical trial.

Background: Prolonged postprandial hypertriglyceridemia is a potential risk factor for cardiovascular diseases. In the context of obesity, this is associated with a chronic imbalance of lipid partitioning oriented toward storage and not toward β-oxidation.

Objective: We tested the hypothesis that the physical structure of fat in a meal can modify the absorption, chylomicron transport, and further metabolic handling of dietary fatty acids.

[Validation of pharmaceutical quality of a [6,6-(2)H(2)]-glucose parenteral solution used for insulin-resistance measurement during human clinical trials].

Introduction: Deuterated glucose ([6,6-(2)H(2)]-glucose) is a stable isotopic tracer administered parenterally in healthy volunteers, obese or diabetic patients in clinical trial to study glucose metabolism during euglycemic hyperinsulinemic clamps. In accordance with the Health Authorities on drug safety, we evaluated the pharmaceutical quality of this preparation for biomedical research with a stability study.

Methods: After pharmaceutical qualification of the raw material, the [6,6-(2)H(2)]-glucose was dissolved in water for injection, then sterile, filtered under positive pressure of nitrogen and then autoclaved.

Comparison of high-temperature conversion and equilibration methods for the determination of d31-palmitic acid oxidation in man using continuous-flow isotope ratio mass spectrometry.

During nutritional interventions, the ingestion of d(31)-palmitic acid and H(2)(18)O allows the assessment of dietary fatty acid oxidation from cumulative (2)H recovery in urine and the estimation of the total body water pool (TBW) from (18)O dilution. Continuous-flow isotope ratio mass spectrometry (CF-IRMS) coupled to either equilibration or high-temperature conversion (HTC) techniques permits (2)H- and (18)O-enrichment measurements in biological fluids. Thus it was of great interest to compare these methods applied to the determination of dietary fatty acid oxidation.

13C tracer recovery in human stools after digestion of a fat-rich meal labelled with [1,1,1-13C3]tripalmitin and [1,1,1-13C3]triolein.

Lipid metabolism studies focus mainly on oxidation and storage but rarely on faecal elimination, which is needed to assess total lipid distribution during the postprandial period. The purpose of the present work was to set up and validate the analysis of lipid tracers in stools, with an aim of later using this methodology in studies of postprandial lipid tracer metabolism. Eight subjects received a mixture of [1,1,1-(13)C3]tripalmitin and [1,1,1-(13)C3]triolein with a fat-rich meal.

Impact of a resistant dextrin with a prolonged oxidation pattern on day-long ghrelin profile.

Objectives: The effects of a new resistant dextrin ingested at breakfast on day-long metabolic parameters and ghrelin profile at subsequent lunch were investigated.

Methods: In this randomized, single-blinded, crossover study, 12 healthy men ingested a standardized breakfast with 50 g of NUTRIOSE 10, a resistant dextrin (RD), or of maltodextrin (Malto) and a standardized lunch 5 hours later. Both products (RD and Malto) were derived from corn naturally rich in (13)C to follow their metabolic fate (by using stable isotope analysis).

Effect of postprandial modulation of glucose availability: short- and long-term analysis.

Low glycaemic index (LGI) foods have been proposed as potential means to decrease postprandial glucose excursions and thus to improve diabetes management. We modulated glucose availability of cereal products and thus their glycaemic index to study the metabolic effect of LGI foods on daylong glucose control acutely and in the long term following a 5-week GI intervention diet in free-living subjects. In this randomised, parallel trial, two groups of nineteen overweight subjects followed an ad libitum 5-week intervention diet in which usual starch was replaced by either LGI or high GI (HGI) starch.

Validation of pentaacetylaldononitrile derivative for dual 2H gas chromatography/mass spectrometry and 13C gas chromatography/combustion/isotope ratio mass spectrometry analysis of glucose.

A reference method to accurately define kinetics in response to the ingestion of glucose in terms of total, exogenous and endogenous glucose is to use stable-isotope-labelled compounds such as 2H and 13C glucose followed by gas chromatography/mass spectrometry (GC/MS) and gas chromatography/combustion/isotope ratio mass spectrometry (GC/C/IRMS) analysis. The use of the usual pentaacetyl (5Ac) derivative generates difficulties in obtaining accurate and reproducible results due to the two chromatographic peaks for the syn and anti isomers, and to the isotopic effect occurring during acetylation. Therefore, the pentaacetylaldononitrile derivative (Aldo) was validated for both isotopes, and compared with the 5Ac derivative.

Physical inactivity differentially alters dietary oleate and palmitate trafficking.

Objective: Obesity and diabetes are characterized by the incapacity to use fat as fuel. We hypothesized that this reduced fat oxidation is secondary to a sedentary lifestyle.

Research Design And Methods: We investigated the effect of a 2-month bed rest on the dietary oleate and palmitate trafficking in lean women (control group, n = 8) and the effect of concomitant resistance/aerobic exercise training as a countermeasure (exercise group, n = 8).

Modulation of the postprandial phase by beta-glucan in overweight subjects: effects on glucose and insulin kinetics.

Decreasing the postprandial glucose response is potentially of major importance to public health when low-glycemic index or high-fibre content foods are associated with a decreased risk of diabetes. We investigated in overweight subjects the effect of adding beta-glucan (BG) to a polenta (Pol) meal on postprandial metabolism and glucose bioavailability using stable isotopes. In this single-blind, randomized, crossover trial, 12 subjects ate two meals containing Pol with (Pol + BG) or without (Pol) 5 g BG.

Nutritional intervention to reduce the n-6/n-3 fatty acid ratio increases adiponectin concentration and fatty acid oxidation in healthy subjects.

Background/objectives: Consumption of n-3 polyunsaturated fatty acids (PUFA) has a favourable impact on inflammation and cardiovascular disease. However, the Western diet is characterized by a low n-3 PUFA intake and an imbalance in the n-6/n-3 PUFA ratio. Study the effect 10-week of diet modification to decrease the n-6/n-3 PUFA ratio on cardiovascular risk factors and resting energy expenditure.

Daily intake of conjugated linoleic acid-enriched yoghurts: effects on energy metabolism and adipose tissue gene expression in healthy subjects.

Conjugated linoleic acid (CLA) is a group of positional and geometric isomers of conjugated dienoic derivatives of linoleic acid. The present study was designed to determine whether 14-week CLA supplementation as triacylglycerols (3.76 g) with a 50 : 50 combination of the two main isomers (35 % cis-9, trans-11 and 35 % trans-10, cis-12) added to flavoured yoghurt-like products was able to alter body composition in healthy subjects and to alter the expression of several key adipose tissue genes (PPAR gamma, lipoprotein lipase (LPL), hormone-sensitive lipase (HSL) and uncoupling protein 2 (UCP-2)).

Effect of physical inactivity on the oxidation of saturated and monounsaturated dietary Fatty acids: results of a randomized trial.

Objectives: Changes in the way dietary fat is metabolized can be considered causative in obesity. The role of sedentary behavior in this defect has not been determined. We hypothesized that physical inactivity partitions dietary fats toward storage and that a resistance exercise training program mitigates storage.

Contamination of syringe plungers during the sampling of cyclophosphamide solutions.

The presence of cytotoxic agents in the urine of operators and in their environment has been demonstrated. The pharmacokinetics of the urinary elimination of cyclophosphamide suggests that these drugs are absorbed cutaneously during handling. In the framework of a more general study on the contamination of hospital environment, the present study addresses the possible presence of cytotoxic agents on the plungers of syringes.

The dispersion state of milk fat influences triglyceride metabolism in the rat--a 13CO2 breath test study.

Background: Milk fat, which has different structures in the various dairy products, is a major and controversial lipid source in the Western diet. However, information about the digestion fate of milk fat depending on its supramolecular structure for a given composition is scarce.

Aim Of The Study: In this study, 13CO2 breath tests were performed with fasted rats force-fed different dairy preparations of similar composition but differing in fat suprastructure in order to highlight differences of general lipid metabolism.

The effects of rosiglitazone on fatty acid and triglyceride metabolism in type 2 diabetes.

Aims/hypothesis: We investigated the effects of rosiglitazone on NEFA and triglyceride metabolism in type 2 diabetes.

Methods: In a double-blind, placebo-controlled, cross-over study of rosiglitazone in diet-treated type 2 diabetic subjects, we measured arteriovenous differences and tissue blood flow in forearm muscle and subcutaneous abdominal adipose tissue, used stable isotope techniques, and analysed gene expression. Responses to a mixed meal containing [1,1,1-(13)C]tripalmitin were assessed.

[Analysis of cyclophosphamide in the urine of antineoplastic drugs handlers].

The first study in which amounts of cyclophosphamide were found in the urine of nurses handling cytotoxic drugs using gas chromatography was published in 1984. We carried out a similar investigation on six pharmacy technicians involved in the preparation of antineoplastic agents (25,000 doses per year) but the analysis was performed with a more sensitive method: gas chromatography-mass spectrometry (LOQ = 0.1 ng/ml).

Splanchnic tissues play a crucial role in uremic glucose intolerance.

Objective: Determine the mechanism of glucose intolerance in chronically uremic subjects.

Design: Comparison of doubly labeled oral glucose tolerance tests.

Subjects: Seven nondialyzed chronically uremic subjects (creatinine, 420 +/- 104 micromol/L) and 7 healthy subjects, matched for age and body mass index.

Continuous flow isotope ratio mass spectrometry for the measurement of nanomole amounts of (13)CO(2) by a reverse isotope dilution method.

A simple method for the determination of nanomole amounts of (13)CO(2) generated from an in vitro reaction is reported. The incubation medium contains a known amount of unlabeled sodium bicarbonate and the gaseous (13)CO(2) enriches the atmosphere upon which a measurement of the isotopic enrichment ((13)CO(2)/(12)CO(2)) is made corresponding to a reverse isotope dilution. The quantification of the (13)CO(2) was performed by gas chromatography/isotope ratio mass spectrometry.

Influence of dietary fat on postprandial glucose metabolism (exogenous and endogenous) using intrinsically (13)C-enriched durum wheat.

The present study evaluates the influence of different amounts of fat added to starch on postprandial glucose metabolism (exogenous and endogenous). Nine women (24 (se 2) years old, BMI 20.4 (se 0.

The regulation of uncoupling protein-2 gene expression by omega-6 polyunsaturated fatty acids in human skeletal muscle cells involves multiple pathways, including the nuclear receptor peroxisome proliferator-activated receptor beta.

Fatty acids have been postulated to regulate uncoupling protein (UCP) gene expression in skeletal muscle in vivo. We have identified, at least in part, the mechanism by which polyunsaturated fatty acids increase UCP-2 expression in primary culture of human muscle cells. omega-6 fatty acids and arachidonic acid induced a 3-fold rise in UCP-2 mRNA levels possibly through transcriptional activation.

Detection of new propofol metabolites in human urine using gas chromatography/mass spectrometry and liquid chromatography/mass spectrometry techniques.

Using hyphenated analytical techniques, gas chromatography/mass spectrometry (GC/MS) and liquid chromatography/mass spectrometry (LC/MS), a study on minor propofol metabolites in human urine was conducted. These techniques allowed identification of two new phase I metabolites (2-(omega-propanol)-6-isopropylphenol and 2-(omega-propanol)-6-isopropyl-1,4-quinol). In addition, their four corresponding conjugates (three glucuronides and one sulphate) were detected.

Possible involvement of multiple human cytochrome P450 isoforms in the liver metabolism of propofol.

Previous studies of propofol (2,6-diisopropylphenol) pharmacology have shown that this widely used anaesthetic drug is extensively cleared from the body by conjugation of the parent molecule or its quinol metabolite. On the basis of potential influence of propofol on the metabolism of co-administered agents, many investigators have evaluated the effects of propofol on cytochrome P450 (CYP) activities. CYP isoforms involved in propofol metabolism are not defined.

Decarboxylation of [1-(13)C]leucine by hydroxyl radicals.

The decarboxylation of [1-13C]leucine by hydroxyl radicals was studied by using gas chromatography-isotope ratio mass spectrometry (GC-IRMS) to follow the production of 13CO2. A Fenton reaction between a (Fe2+)-porphyrin and hydrogen peroxide under aerobic conditions yielded hydroxyl radicals. The decarboxylation rates (VLeu) measured by GC-IRMS were dependent on [1-13C]leucine, porphyrin and hydrogen peroxide concentrations.

Oxidative decarboxylation of benzoic acid by peroxyl radicals.

A chemical model based on the thermal decomposition of AAPH (2,2'-azobis(2-amidinopropane) dihydrochloride is used for the production of peroxyl radicals. Peroxyl radicals induces the decarboxylation of [7-13C]benzoic acid and the production of 13CO2, which is measured by gas chromatography-isotope ratio mass spectrometry (GC-IRMS). The decarboxylation depends on temperature, AAPH, and benzoic acid concentrations.

Possible involvement of multiple cytochrome P450S in fentanyl and sufentanil metabolism as opposed to alfentanil.

Fentanyl, sufentanil, and alfentanil are commonly used as opioid analgesics. Alfentanil clearance has previously been shown to exhibit an important interindividual variability, which was not observed for fentanyl or sufentanil. Differences in pharmacokinetic parameters of alfentanil have previously been associated with the wide distribution of CYP3A4, the only known hepatic cytochrome P450 monooxygenase (CYP) involved in the conversion of alfentanil to noralfentanil.