S Fimbel

French National Centre for Scientific Research, Lutetia Parisorum, Île-de-France, France

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Publications (11)29.7 Total impact

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    ABSTRACT: The aim of this study was to determine, in the rat, the effects of chronic exposure (7-9 weeks) to normobaric hypoxia (FIO2=0.13, equivalent to 3700 m altitude) on cardiac and skeletal muscle properties, on maximal oxygen uptake (VO2max), and endurance time to exhaustion (ETE). In addition, we evaluated the impact of endurance training (90 min of treadmill running per day, 5 days per week, for 9 weeks) on these parameters. The results were compared to normoxic rats fed ad libitum (NAL) and to normoxic pair-weight (NPW) animals in order to take into account the influence of hypoxia on growth rate. It was found that, in sedentary rats, hypoxia results in stunted growth, adrenal atrophy, a significant reduction of cross-sectional area of fast-twitch (type II) fibres, a reduced capillary-to-fibre ratio (C/F), and a reduced oxidative capacity (decreases in citrate synthase and 3-hydroxy-Acyl CoA dehydrogenase activities) of the plantaris muscle. These effects are mainly related to the anorexic effects of prolonged exposure to hypoxia. Nevertheless, hypoxic (H) rats displayed higher VO2max and ETE values when compared either to NAL or to NPW animals. Endurance training resulted, in all groups (H, NAL, NPW), in a significant change of the fibre type distribution of the plantaris which displayed an increased number of type IIA fibres and a decreased proportion of type IIB fibres. In addition, the C/F ratio and cross-sectional area of fast-twitch fibres were normalized by superimposition of training on hypoxia. Both VO2max and ETE were significantly higher in trained H rats than in NAL, but these improvements were mainly related to the reduced body weight induced by hypoxia. These data suggest that the greater aerobic capacity and tolerance for prolonged exercise induced by chronic exposure to hypoxia can be mainly accounted for by the anorexic effects of hypoxia, although other factors (e.g. increase in oxygen carrying capacity induced by hypoxia acclimatization) may play a significant role in some circumstances (e.g. in sedentary rats).
    No preview · Article · Apr 1996 · Pflügers Archiv - European Journal of Physiology
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    ABSTRACT: The purpose of this study was to investigate two methods for labeling rabbit sex hormone-binding globulin (rSHBG) with non-radioactive material, biotin (B) and europium (Eu3+), in order to obtain stable labeled SHBG and measure in vivo its metabolism and distribution. The obtained half-life values were compared with [125I]rSHBG half-lives. rSHBG was first isolated by immunoaffinity chromatography using an immobilized monoclonal anti-human SHBG (hSHBG) antibody that cross-reacts with rSHBG. This purified rSHBG was labeled by either biotin-X-N-hydroxysuccinimide ester (rSHBG-B), Eu3(+)-diethylenetriaminepentaacetic dianhydride, or Eu(3+)-isothiocyanatobenzyldiethylenetriamine-tetraacetic acid reagents (rSHBG-Eu3+) or by 125I using Bolton and Hunter reagent ([125I]rSHBG). The labeling procedure preserved the main properties of native SHBG: interaction with the lectine concanavaline A-Sepharose, recognition by anti-hSHBG monoclonal antibody, and, although lower than in native SHBG, the binding affinity for 5 alpha-dihydrotestosterone. These characteristics were the prerequisite for reliable measurement of the metabolism of labeled SHBG. Labeled rSHBG was injected into various rabbits with blood sampling at 2 min and at 1, 2, 4, 8, 12, 24, 48, 72, and 96 h after injection. rSHBG-B or desiaylated rSHBG-B and rSHBG-Eu3+ were captured from serum samples by tubes coated with anti-hSHBG antibody prior to the following detection procedure: biotin was detected by luminometry with the [streptavidin-alkaline phosphatase-dioxetane (AMPPD)] system and europium by time-resolved fluorimetry. [125I]rSHBG was detected by measurement of radioactivity either directly on serum or after fixation on concanavaline A-Sepharose.(ABSTRACT TRUNCATED AT 250 WORDS)
    No preview · Article · Nov 1995 · Steroids
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    ABSTRACT: Evidence suggests that hyperinsulinemic insulin resistance may increase serum levels of ovarian androgens and reduce sex hormone-binding globulin (SHBG) levels in humans. The present study was conducted to assess the effect of administration of the biguanide metformin, a drug commonly used in the treatment of diabetes mellitus, on androgen and insulin levels in 24 hirsute patients. The patients selected for the study were obese, with a body mass index higher than 25 kg/m2 and high fasting insulin (> 90 pmol/L) and low SHBG levels (< 30 nmol/L). All patients were given a low calorie diet (1500 Cal/day) and randomized for either metformin administration at a dose of 850 mg or a placebo, twice daily for 4 months, in a double blind study. In the placebo group, diet resulted in a significant decrease in body mass index (30.8 +/- 1.0 vs. 32.7 +/- 1.5 kg/m2; P < 0.0001), fasting insulin (127 +/- 11 vs. 156 +/- 14 pmol/L; P < 0.01), non-SHBG-bound testosterone (0.19 +/- 0.02 vs. 0.28 +/- 0.03 nmol/L; P < 0.02), androstenedione (5.8 +/- 0.5 vs. 9.0 +/- 1.1 nmol/L; P < 0.03), and 3 alpha-diolglucuronide (8.6 +/- 1.1 vs. 11.7 +/- 1.9; P < 0.005) plasma concentrations and a significant increase in the glucose/insulin ratio (0.047 +/- 0.005 vs. 0.035 +/- 0.003; P < 0.001) and plasma concentrations of SHBG (26.0 +/- 3.3 vs. 19.1 +/- 1.9 nmol/L; P < 0.001) and dehydroepiandrosterone sulfate (8.7 +/- 1.5 vs. 8.4 +/- 1.3; P < 0.05). Beneficial effects of diet were not significantly different in the patients who were given metformin instead of placebo. These results confirm that weight loss induced by a low calorie diet is effective in improving hyperinsulinemia and hyperandrogenism in obese and hirsute women. With our study design, metformin administration had no additional benefit over the effect of diet.
    No preview · Article · Aug 1995 · Journal of Clinical Endocrinology & Metabolism
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    ABSTRACT: The incidence of coronary artery disease is significantly higher in men than in women, at least until menopause. This gender difference could be explained by the action of sex steroids on the lipoprotein profile. In prepubertal children, high-density lipoprotein (HDL) cholesterol and triglyceride levels are similar between sexes, while adult men have generally lower HDL cholesterol and higher triglyceride levels than premenopausal adult women. Most cross-sectional studies have reported that sex hormone binding globulin (SHBG) and testosterone levels correlate positively with HDL cholesterol levels between sexes. Thus SHBG by modulating the balance in the biodisposal of testosterone and estradiol, might have a profound effect on the risk of cardiovascular disease. However, adjustment for body weight and body fat distribution weakens the association between SHBG, testosterone and HDL cholesterol. The negative correlation of fasting insulin with SHBG and HDL cholesterol levels in both sexes, and some evidence that insulin is an inhibitor of SHBG production in vitro, has suggested that hyperinsulinism might negatively regulate SHBG and HDL levels. It remains to be determined whether the inverse relationship between SHBG and insulin levels is coincidental or has a causal effect on the increase of atherosclerosis. Decreased SHBG has been shown to be predictive of the incidence of non-insulin-dependent diabetes mellitus in women but not in men, and of subsequent development of cardiovascular disease and overall mortality in postmenopausal women. SHBG is an index of androgenism in women and of insulin-resistance in both sexes, and might be useful in epidemiological studies of cardiovascular risk. However, in men, SHBG is not predictive of the occurrence of cardiovascular disease. Whether SHBG might have an intrinsic protective effect on the arterial wall through SHBG-receptors is still highly speculative.
    No preview · Article · Jul 1995 · The Journal of Steroid Biochemistry and Molecular Biology
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    ABSTRACT: Evaluate short-term outcome of calibrated vertical gastroplasty in obese subjects. Calibrated vertical gastroplasty was performed in 55 obese subjects (BMI 43 +/- 1; age range 20-59 year). There were no post-operative complications. All the subjects were followed for 6 months and thirty one for a year. Weight loss reached 28 kg at 6 months and 36 kg at 1 year with an improvement in functional manifestations, especially for dyspnoea and, in half of the subjects, for signs of depression. New or worsened psychiatric problems were observed in 4 subjects. Post-prandial vomiting persisted for 1 year in 28 patients. Dietary intake was lowered (946 +/- 61 kcal/day) as was protein intake (43 +/- 3 g/24 hr). Impaired glucose tolerance, raised serum insulin, triglyceride and androgen levels were corrected in patients with abnormal levels before surgery. Serum vitamin B1 declined. These favourable results in the weight curve, functional problems and metabolic data should not mask the disadvantages and potential risks involved. Long-term prospective studies are required to determine the precise indications for this technique.
    No preview · Article · Mar 1995 · La Presse Médicale
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    ABSTRACT: The biological bases of endocrine alterations in ageing men are now well identified: progressive impairment of testicular function, decline in growth hormone (GH) secretion with decreased insulin-like growth factor-I (IGF-I) levels, and reduced adrenal androgen secretion. Insulin resistance and glucose intolerance also accompany male ageing. The mechanisms of these age-related changes are still unknown. There are preliminary results on the effects of hormonal replacement therapy in older males with mild hypogonadism or decreased IGF-I levels. Controlled placebo studies will in the future define the risks and benefits of long-term administration of androgens, GH or GH-releasing hormone in these patients. In view of the severe potential side effects, the generalized use of hormonal substitution in elderly men cannot, for the moment, be recommended.
    No preview · Article · Feb 1995 · Hormone Research
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    ABSTRACT: The aim of this study was to determine the impact of chronic treatment for 8 weeks with hydrocortisone acetate (5 mg kg-1 day-1) on skeletal muscles, and to evaluate whether sprint training can prevent glucocorticoid-induced muscle atrophy better than endurance training. Biochemical, histological and contractile properties were employed to determine the influence of this steroid on skeletal musculature, and the results were compared to pair-weight animals to take into account the influence of corticoids on growth rate. It was found that hydrocortisone acetate treatment results in a stunted growth, adrenal atrophy and depressed plasma corticosterone levels. Mild corticoid-induced losses of muscle mass and protein content (9%-13%) were observed in fast-twitch skeletal muscles. It appeared that the impact of corticoids is strictly directed toward type IIb fibres, which displayed a 12%-18% reduction in cross-sectional areas. No alterations occurred in plantaris contractile speed or tensions properties. Neither endurance training (30 m/min; 90 min/day; 5 days/week) nor sprint training (60 m/min; 15 min/day; 5 days/week) for 8 weeks was able to counteract the effects of corticoids. These data suggest that increased contractile activity, as induced by treadmill running, is not sufficient to counteract the muscular effects of glucocorticoids when administered at a dose of 5 mg kg-1 day-1.
    No preview · Article · Oct 1993 · Pflügers Archiv - European Journal of Physiology

  • No preview · Article · Jun 1993 · Annals of the New York Academy of Sciences
  • P Miras-Mirakian · S Fimbel · M Pugeat

    No preview · Article · Apr 1993 · La Revue du praticien
  • M H Nicolas · J C Crave · S Fimbel · A Siméan · M Pugeat
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    ABSTRACT: To investigate the relationship between overweight and hyperandrogenism, a 1500 kcal/day diet was prescribed for 4 months to 23 hirsute and obese patients. This diet decreased body mass index from 29.9 +/- 4.9 to 27.2 +/- 4.4 kg/m2 (P < 0.008), but had no significant effect on fasting insulin levels (18.9 +/- 14.2 vs. 21.1 +/- 9.6 mlU/l). Weight lost increased significantly (P < 0.008) the plasma concentration of sex-hormone binding-globulin (SHBG) from 21.2 +/- 10.6 to 26.2 +/- 13.5 nmol/l and decreased significantly (P < 0.04) the SHBG-unbound testosterone concentration from 9.3 +/- 6.2 to 7.2 +/- 4.8 ng/dl, without changing the concentrations of the main androgens measured in this study. Moreover, during diet 5 patients in amenorrhea and 8 among 13 patients with irregular menstrual cycle recovered regular menses. We concluded that the control of excess body weight in hirsute women is effective but not sufficient to improve hyperandrogenism.
    No preview · Article · Jan 1993 · La Presse Médicale
  • S Fimbel · M Pugeat

    No preview · Article · Dec 1992 · La Revue du praticien