RARgamma and TRbeta expressions are decreased in PBMC and SWAT of obese subjects in weight gain.

In order to evaluate the expression of nuclear receptors at the peripheral level in obese subjects, messenger RNA (mRNA) levels of different isoforms of retinoic acid receptor (RAR), triiodothyronine (TR), and peroxisome proliferator-activated receptor (PPAR) were determined and compared in peripheral mononuclear blood cells (PBMC) and subcutaneous white adipose tissue (SWAT). Twelve lean subjects and 68 obese subjects divided into weight gain (WG), weight-stable (WS), and weight loss (WL) groups were studied. Nuclear receptor mRNA levels were assessed in PBMC and SWAT using a quantitative real-time reverse transcription polymerase chain reaction method. mRNA levels of RARgamma were significantly lower in PBMC of obese subjects (WG -19%, WS -30%, and WL -24.7%) as in SWAT of WG (-50%). Lower mRNA levels of TRbeta were observed in PBMC and SWAT of WG (-50.7% and -28%, respectively) just as for TRalpha in PBMC of WG (-19%). In contrast, retinoid X receptors alpha (RXRalpha) and RARalpha mRNA levels were higher in PBMC of obese subjects (+53% and +54.5% in WG, +56% and +67% in WS, and +68% and +49.7% in WL, respectively), while expression of RXRalpha was lower in SWAT of WG (-24.5%). As for PPARgamma, its mRNA level was significantly higher in PBMC of WG subjects (+34%) while its expression was not modified in SWAT, contrary to the PPARgamma2 isoform which was significantly higher. These data show that in both adipose tissue and blood compartment of obese subjects, expressions of RARgamma and TRbeta were downregulated. Thus, we suggest that the expression in PBMC of obese subjects may constitute new cellular indicators of nuclear receptor retinoid and thyroid status.

RARã and TRBeta expressions are decreased in PBMC and SWAT of obese subjects in weight gain

No disponible

In order to evaluate the expression of nuclear receptors at the peripheral level in obese subjects,messenger RNA (mRNA) levels of different isoforms of retinoic acid receptor (RAR), triiodothyronine(TR), and peroxisome proliferator-activated receptor (PPAR) were determined and compared in peripheral mononuclear blood cells (PBMC) and subcutaneous white adipose tissue (SWAT). Twelve lean subjects and 68 obese subjects divided into weight gain (WG), weight-stable (WS), and weight loss (WL) groups were studied. Nuclear receptor mRNA levels were assessed in PBMC and SWAT using a quantitative real-time reverse transcription polymerase chain (..) (AU)

Reduction of dietary saturated fatty acids correlates with increased plasma lecithin cholesterol acyltransferase activity in humans.

OBJECTIVE: Increased HDL-cholesterol (HDL-C) concentrations have been associated with lower coronary heart disease risk. On the other hand, dietary fats are known to influence the fatty acid profile of plasma lipids, including phospholipids that are substrates of lecithin cholesterol acyltransferase (LCAT), an important enzyme in HDL metabolism. The purpose of this study was to examine the association between the saturated fatty acid (SFA) intake and LCAT activity. DESIGN: An interventional study was performed in a monk community of 25 men. SETTING: A French monk community, South West of France. SUBJECTS AND INTERVENTIONS: The basal diet of the study cohort contained SFA in a proportion of 13.5% of their total energy intake (TEI). They were submitted to two experimental isocaloric diets containing either 8.4% of the TEI in SFA (diet A) or 11% (diet B), each lasting 5 weeks. RESULTS: The elevation of SFA in diet B was mainly obtained by decreasing carbohydrates. The only significant difference among total fats between diets A and B was the myristic acid content (0.6 and 1.2% of TEI, respectively). The elevation in SFA in diet B resulted in a significant increase of HDL-C (P<0.04), while plasma apo A-I concentration and LCAT activity both decreased (P<0.02). CONCLUSION: Altogether, these results are consistent with a negative effect of SFA on reverse cholesterol transport.

Relationship between peroxisome proliferator-activated receptor gamma and retinoic acid receptor alpha gene expression in obese human adipose tissue.

OBJECTIVE: To investigate in human adipose tissue a possible relationship between per oxisome proliferator-activated receptor gamma (PPARgamma) and retinoic acid receptor alpha (RARalpha) gene expression, two genes involved in the control of adipocyte differentiation. SUBJECTS: Ten lean control women (age 31-60 y, body mass index (BMI) 18-24.7 kg/m(2)) and an obese group of 15 women (age 27-62 y, BMI 30-57.5 kg/m(2)), of whom 10 subjects were in weight-gain phase and five were in weight-loss phase. MEASUREMENTS: We assessed the relative PPARgamma and RARalpha mRNA levels in subcutaneous abdominal adipose tissue using a real-time PCR method. RESULTS: PPARgamma mRNA level were significantly increased (+91%; P<0.01) in obese women compared to lean control women. In the obese group, we observed a PPARgamma mRNA level 42% lower in weight-loss obese than in weight-gain obese subjects. We obtained a positive correlation (r=0.56; P<0.01) between PPARgamma mRNA level and the BMI of all subjects. Relative mRNA abundance level of RARalpha in subcutaneous adipose tissue of obese subjects is significantly lower than in control subjects (-56%, P<0.01), and a negative correlation was found between PPARgamma and RARalpha mRNA levels in subcutaneous adipose tissue of subjects study (r=-0.75; P<0.01). CONCLUSION: Our findings suggest that obesity is associated with an inverse relationship between PPARgamma and RARalpha expressions in human subcutaneous adipose tissue. Modulations of nuclear receptor profile could be an important event in the body's early adaptive mechanisms promoting adipose tissue plasticity and leading to the onset of obesity.

Erythropoietin can deteriorate glucose control in uraemic non-insulin-dependent diabetic patients.

Two patients with non-insulin-dependent diabetes mellitus (NIDDM) and moderate chronic renal failure experienced a worsening of glycaemic control when recombinant human erythropoietin (r-HuEPO) was introduced, leading to insulin therapy. A 71-year-old woman with a 20-year history of NIDDM had presented histologically documented diabetic nephropathy for 2 years during which glucose control was stabilized by a diet and glibenclamide 10 mg. In the 6 months following introduction of r-HuEPO, hyperglycaemic symptoms developed, and HbA1C increased from 8.9% to 12.3%. During this period, no intercurrent events occurred, except epistaxis due to accelerated hypertension one month after r-HuEPO was started. A 62-year-old man had a 15-year history of NIDDM, with proliferative retinopathy, macroproteinuria and chronic renal failure for 4 years. The day after the first injection of r-HuEPO, capillary glucose level rose dramatically. In both of these cases, antihypertensive treatment was increased and insulin introduced. The role of r-HuEPO in hyperglycaemia was probable in the first case and highly probable in the second. Reports about the effects of r-HuEPO on glucose metabolism in uraemic patients are conflicting. Short- and long-term effects can differ, although long-term benefit is likely. The fact that our patients were not dialized may have been important. Clinicians should be aware that glucose control may deteriorate with r-HuEPO, requiring some uraemic NIDDM patients to undergo insulin therapy.

Identification of tryptamine and tryptamine-serotonin neurons in the rat dorsal raphe nuclei using specific antibodies.

Previous studies have shown that tryptamine (T) is closely associated with the serotonergic system but have failed to determine whether neurons containing only T exist in the raphe nuclei (RN) and/or if T colocalizes with serotonin (5-HT). The use of rabbit-conjugated T antisera (TAS) and rat-conjugated 5-HT antisera (5-HTAS) in a double-labelling technique has made the study of the colocalization of T and 5-HT in neurons of the rat dorsal RN (DR) possible. Slices taken from the same zone of the DR were treated following four different procedures of double-immunolabelling: DAB coloration for the rabbit TAS and DAB-nickel coloration for the rat 5-HTAS either first or second; or DAB coloration for the 5-HTAS and DAB-nickel coloration for the TAS first or second. Control sections were treated according to a single immunoperoxidase staining in the same zone. The immunolabelled neurons were computed using the Biocom 200 program at the same magnification. The results of this double-immunolabelling show that three different cell types exist in the rat DR: (1) T-only-containing neurons, (2) 5-HT-only-containing neurons displaying either homogeneous DAB or homogeneous DAB-nickel, and (3) neurons where T colocalizes with 5-HT (T-positive/5-HT-positive neurons) displaying heterogeneous DAB-nickel coloration. The results were identical whatever the procedure performed or the order of the DAB-nickel revelation.(ABSTRACT TRUNCATED AT 250 WORDS)

[Is nutritional intervention influencing lipid allowances beneficial?]. / L'intervention nutritionnelle portant sur les apports lipidiques est-elle bénéfique?

An earlier study (consumption study) has shown that in subjects eating normally: 1) the amount of fat consumed per day corresponds to 4/5 of the fat contained in the portions served; 2) the distribution of the fatty acids (FA) consumed is unfavorable because of the use of saturated FA for food preparation and cooking and because of the elimination of mono- and polyunsaturated FA in the unconsumed food. In order to determine whether a simple nutritional intervention might favorably modify the distribution of FA consumed, a computer simulation of a decrease in allowances of saturated FA in exchange for an increase in mono- and polyunsaturated FA was tested. The laboratory results were compared to those of the computer program. Comparison of the intervention study with the consumption study revealed that: 1) the fat content was identical; 2) there were the same number of total calories, but there were more lipidic calories consumed during the intervention (38% instead of 35%); 3) the distribution of FA more nearly approached the recommended amounts: 40% saturated FA (-25%), 39% monounsaturated FA (+8%), 21% polyunsaturated FA (+91%) and a P/S ratio of .60 (instead of .21); 4) these proportions can be explained by a decrease in palmitic (-30%) and stearic (-20%) acids and by an increase in linoleic (+100%) and linolenic (+40%) acids; 5) the allowances of elaidic acid was on the average 4.3 g per day and had little influence on the P/S ratio; 6) the omega 6/omega 3 ratio (ratio of 7) was higher than that of the consumption study (ratio of 5); 7) there was a 16% decrease in cholesterol intake (260 mg instead of 310 mg). The laboratory findings corresponded on the whole to those of the computer program that only faulted by overestimating lipid and cholesterol allowances.

First characterization of 6-hydroxytryptamine in the rat midbrain by using specific antibodies.

The visualization of serotonin, 5-methoxytryptamine, and tryptamine in the rat midbrain has been made possible by the development of antibodies raised against these conjugated molecules. It has been suggested that 6-hydroxytryptamine (6-HT) might also be a neurotransmitter in this region. To test this hypothesis, 6-HT was synthesized and antibodies were raised in the rabbit. The high avidity (IC50 = 5 x 10(-9) M) and specificity [cross-reactivity ratio between 6-HT-glutaraldehyde (G)-bovine serum albumin (BSA) and 5-HT-G-BSA, the most immunoreactive compound, was 1,500] rendered these antibodies reliable tools for specific molecular detection of 6-HT in the G-fixed tissues. In the dopaminergic region, 6-HT immunoreactivity was noted in the substantia nigra but was particularly intense in the red nuclei, where it seems to be localized in the magnocellular division in the form of large 6-HT neurons. In contrast, there were few 6-HT neurons in the raphe nuclei. Thus, 6-HT may be a new putative neurotransmitter existing in the red nuclei, in addition to the other neurotransmitters already described in this region, in the nigro-rubral pathway, and in the rubral projection from the dorsal raphe nuclei. 6-HT is possibly implicated in motor control and might exert hallucinogenic properties as do other 6-hydroxylated indoleamines.

[Recurrent hematemesis caused by paraprosthetic aorto-digestive fistula]. / Hématémèse récidivante par fistule aorto-digestive paraprothétique.

The authors report the observation of a paraprosthetic fistula revealed by three episodes of digestive haemorrhage, illustrating the diagnostic and therapeutic difficulties brought about by the erosion of the duodenum by a sub-renal aortic prosthesis. A review of the literature confirms the rarity and the gravity of this pathology, and underlines the per-operative preventive measures.

[Simultaneous detection of tryptamine and dopamine in the substantia nigra and raphe nuclei in rats using specific antibodies]. / Détection simultanée par anticorps spécifiques de tryptamine et dopamine dans la substance noire et les noyaux du raphé chez le rat.

Using a double-labelling procedure, morphological relationships existing between dopaminergic and indoleaminergic neuronal systems in rat brain were investigated. Firstly, thanks to a tryptamine (T) antiserum, we visualized this indoleamine in all mesencephalic regions and showed that the T-immunoreactivity (IR) seems to overlap with the staining observed from serotonin (HT) and 5-methoxytryptamine (MT) antisera. Secondly, using a monoclonal anti-dopamine (DA) antibody and our anti-T antibodies, the simultaneous and specific detection of these compounds enabled us to define the chemically relationships existing between the dopaminergic and tryptaminergic neuronal systems from substantia nigra to raphe nuclei. No co-localization exists. But, the intensity of T-IR decreases from the back to the front, whereas the DA-staining decreases in the opposite way, indicating possible interactions at the end of substantia nigra and B9 area.

[Acamprosate. From pharmacology to therapeutics]. / L'acamprosate. De la pharmacologie à la clinique.

Acamprosate is an homotaurine derivative, structural analogue of Gamma amino butyric acid and upper homologue of taurine. Its crossing through the blood brain barrier is facilitated by acetylation and calcium salification. Acamprosate has a very weak toxicity attributable to the ingested dose of calcium. Acamprosate is a GABAagonist showing pharmacological activity on direct and indirect tests of GABA activity and a high binding capacity with GABA receptors. Acamprosate also shows beta-adrenergic and serotoninergic activity, probably due to its GABAergic activity. Acamprosate is neither and antidepressant, nor a neuroleptic or a tranquillizer. In experimental alcohology, on different animal models (alcohol preferring or alcohol dependent) acamprosate induces a very clear and highly significant reduction of alcohol consumption. This effect is progressive and dose dependent, antagonized by bicuculine which is a GABA agonist. Besides, acamprosate reduces the intensity of the alcohol withdrawal syndrome. Clinical alcohology is a very difficult field for strict methodology in therapeutic trials: determination of inclusion characters, choice of judgment criteria, reduction of the number of drop out and lost subjects, length of evaluation... Different clinical controlled studies, most in double blind against placebo, on patients suffering from signs of physical or psychical alcohol addiction as well as biological modifications due to their ethylic consumption showed beneficial effects of acamprosate (in weaned alcoholics after withdrawal) according to clinical criteria (the number of abstinents after 3 months was doubled: 60% with active drug--30% with placebo) and for biological criteria (Normalization of Gamma Glutamyl Transpeptidase level in blood). The tolerance is good.(ABSTRACT TRUNCATED AT 250 WORDS)

Simultaneous detection of tryptamine and dopamine in rat substantia nigra and raphe nuclei using specific antibodies.

Using a double-labelling procedure, morphological relationships existing between dopaminergic and indoleaminergic neuronal systems in the rat brain were investigated. First, thanks to a tryptamine (T) antiserum, we visualized this indoleamine in all mesencephalic regions and showed that the T-immunoreactivity (IR) seems to overlap with the stainings observed from serotonin and 5-methoxytryptamine antisera. Secondly, using a monoclonal anti-dopamine (DA) antibody and our anti-T antibodies, the simultaneous and specific detection of these compounds enabled us to define the spatial relationships existing between the dopaminergic and tryptaminergic neuronal systems from the substantia nigra (SN) to the raphe nuclei. No co-localization existed, but the intensity of T-IR decreased from back to front, whereas the DA-staining decreased in the opposite way, indicating possible interactions at the end of the SN and the B9 area.

[Qualitative and quantitative assessment of lipid consumption in the intake of a community]. / Evaluation qualitative et quantitative de la consommation lipidique dans la ration d'une collectivité.

Most nutritional studies assess the nutriment allowance of a selected population from inquiries and tables of food components. Very few of them use biochemical analysis of lipid extraction, which is a more reliable process. In other respects, the investigations on the real consumption of the population are scarce. Our study aims to assess the lipid consumption of subjects submitted to normal feeding in hospital food service, from biochemical analysis of allowances and of non-consumed food. The allowances of 10 dietary days and the whole of the non-consumed food a 10 subjects by dietary day have been assessed. The results show that: 1) the ratio of fat in the non-consumed food (7.5% in wet weight) exceeds that of the proposed intake (6.6%); 2) the consumed food (1,900 KCal/d) represents 80% of the initial total calorie allowance and includes 37.5% lipid calories (71% of initial lipid allowance); 3) the distribution of the consumed fatty acids (FA) is identical to that of the fatty acids of the initial intake and not in conformity with the recommendations of the FAO/WHO Board: 53% saturated FA, 34% mononunsaturated FA, 13% polyunsaturated FA and P/S ratio: 0.23; 4) mono and polyunsaturated FA are eliminated in the non-consumed food, more particularly in unclean plates where the distribution is very near the recommended one: 48% monounsaturated FA, 21% polyunsaturated FA, 31% saturated FA and P/S ratio: 0.8; 5) in spite of these data, the consumption of essential FA remains satisfactory: 7 g of linoleic acid, and 1.5 g of linolenic acid; 6) the consumption of cholesterol (215 mg/d), corresponding to 3/4 of the initial allowance, is satisfactory. The whole of these results are correlated with the Table of Food Components and two dietary softwares.