Biomedical subjects
A Basdevant
Publications and source records attributed to A Basdevant.
Compound heterozygote for lipoprotein lipase deficiency: Ser----Thr244 and transition in 3' splice site of intron 2 (AG----AA) in the lipoprotein lipase gene.
Cloning and sequencing of translated exons and intron-exon boundaries of the lipoprotein lipase gene in a patient of French descent who has the chylomicronemia syndrome revealed that he was a compound heterozygote for two nucleotide substitutions. One (TCC----ACC) leads to an amino acid substitution (Ser----Thr244), while the other alters the 3' splice site of intron 2 (AG----AA). The functional significance of the Thr244 amino acid substitution was established by in vitro expression in cultured mammalian cells.
[Contraception in the diabetic woman].
The metabolic and vascular effect of oestroprogestative treatments make the choice of a contraception difficult for the diabetic women. More than the action on blood glucose it is the effect of Ethynyl-oestradiol on blood pressure, blood lipids and hemostasis which makes problem in case of diabetes. Local contraceptive methods are generally preferred owing to the absence of systemic effect and their good tolerance in a diabetic women. The choice of a method must take into consideration not only the type of diabetes but also the existence or absence of micro and macro-angiopathy.
[Drugs acting on feeding behavior].
The pharmacology of food intake has made considerable progress due to recent developments in neurobiology and to advances in the final analysis of eating behaviour. In this way, the pharmacology of food intake has risen to the rank of a more global pharmacology of eating behaviour. It is now possible to evaluate the points of impact of catecholaminergic, serotoninergic and opioid agents in terms of central or peripheral mode of action and also in terms of behavioral sequence. Some serotoninergic and opioid agents currently under development are opening new therapeutic vistas.
Increased basal glucose production and utilization in children with recent obesity versus adults with long-term obesity.
To characterize the abnormalities of glucose homeostasis and insulin action early in the course of human obesity, we studied in vivo glucose kinetics in seven children who were recently massively overweight. At time of study they were gaining weight at a rate of 13.5 +/- 1.4 kg/yr. They were compared with six age-matched control subjects. Six adults with long-term obesity and five normal adults were studied in parallel. The obese children and adults were normoglycemic and hyperinsulinemic. We found that glucose production and utilization were remarkably higher in obese children (295 +/- 18 mg/min; 7.6 mg.kg-1 lean body mass.min-1) than in control children (129 +/- 13 mg/min; 4.4 mg.kg-1 lean body mass.min-1, P less than .01) and obese adults (151 +/- 8 mg/min; 3.1 +/- 0.3 mg.kg-1 lean body mass.min-1, P less than .01). Obese adults had normal rates of glucose production and utilization. Insulin- and non-insulin-mediated glucose uptake, estimated with somatostatin-induced suppression of endogenous insulin secretion, contributed almost equally to the excess glucose utilization observed in the obese children. When studied with the euglycemic-hyperinsulinemic clamp, obese children could not increase glucose disposal to the same extent as normal children and were not able to adequately suppress their endogenous glucose production. Recently obese children are therefore characterized by an increased basal glucose turnover rate and an already established insulin resistance of the liver and probably the skeletal muscles.
[Contraception in a diabetic woman].
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Effect of intranasal glucagon on blood glucose levels in healthy subjects and hypoglycaemic patients with insulin-dependent diabetes.
Glucagon in solution with a surfactant (deoxycholic acid 1% w/v) was administered by intranasal spray to 6 healthy fasting subjects and 6 insulin-dependent diabetics with insulin-induced hypoglycaemia. In the normal subjects, intranasal glucagon increased plasma glucose levels, with a dose-response effect. In the diabetic patients, plasma glucose levels showed a mean increase of 100% above nadir values in approximately 26 min in response to 7.5 mg intranasal glucagon; hypoglycaemic symptoms were relieved within about 7 min. These results suggest that intranasal glucagon is effective and may represent an alternative to parenteral glucagon or glucose or to oral sugar as the first-line treatment of hypoglycaemic episodes in insulin-dependent diabetics.
Regional variations in cholesterol-esterase activity in rat adipocytes.
Cholesterol esterase and lipoprotein lipase activities were examined in different fat depots in adult male rats. Both were significantly higher in the retroperitoneal and epididymal regions than in the subcutaneous abdominal depots.
Regional differences in adipose tissue lipoprotein lipase activity in relation to body fat distribution and menopausal status in obese women.
Adipose tissue lipoprotein lipase (LPL) activity was determined in the abdominal and femoral regions in 25 pre- and 25 post-menopausal obese women, matched for body mass index and fat distribution. LPL activity was not different in pre- and post-menopausal women. Regional differences of the same magnitude were observed in pre- and post-menopausal women with femoral obesity. Such differences were not found in women with abdominal obesity either pre- or post-menopausal. Furthermore the abdominal/femoral ratio of LPL activity was positively correlated (P less than 0.05) to waist/hip ratio, independently of age, body mass index, fat cell size ratio and menopausal status. These data indicate that in obese women the regional differences in LPL activity are related to body fat distribution. The menopausal status does not seem to be a sufficient and necessary condition to abolish the typical female regional differences in LPL activity in adipose tissue from obese women.
Glycosylation of human fibrinogen and fibrin in vitro. Its consequences on the properties of fibrin(ogen).
As observed for many proteins, glucose has been shown to bind non enzymatically to fibrinogen and to fibrin. The in vitro degree of glycosylation depends upon the concentration of glucose added to fibrinogen and also on the incubation period. This glycosylation induces a decrease in fibrin lysis by plasmin. On the contrary, it does not influence either fibrinogen activity as cofactor in ADP-induced platelet aggregation or the binding of thrombin onto a clot. Despite the 4 day half life of fibrinogen, since clearance of fibrinogen is exponential, it is assumed that very small quantities of fibrinogen may remain for a long time in the circulation leading to the presence of a low level of a highly glycosylated form of fibrinogen. Consequently, poorly degradable fibrin might be derived from this highly glycosylated fibrinogen and thus be responsible for capillary occlusion and also for atherosclerotic complications in the diabetic patient.
[Relation between adipose tissue distribution and and circulating lipids in obese women].
Adipose tissue distribution was determined in 50 pre--or post--menopausal women by measuring the waist/hip and arm/thigh circumference ratios and the brachial-femoral adipo-muscular ratio. These three ratios correlated with plasma triglycerides levels irrespective of the women's age and degree of obesity. Total cholesterol, LDL-cholesterol and HDL-cholesterol were related to age and not to weight or adipose tissue distribution. Compared to pre-menopausal women with the same weight excess, post-menopausal women had a more android type of body fat distribution and higher plasma triglycerides and total cholesterol values. The influences of age and menopause are difficult to separate, since the three distribution ratios are age-related. The correlation between plasma triglycerides and adipose tissue distribution in obese women reflects the metabolic consequences of an abdominal predominance of fat.
[Influence of the distribution of body fat on vascular risk].
The metabolic and cardiovascular complications of obesity are dependent upon the distribution of body fat excess: predominantly abdominal or "android" obesity is more pathogenic than "gynoid" obesity which predominates in the lower part of the body. Adipose tissue overloads localized to the abdomen are associated with hypermortality from vascular diseases, even in patients who are not overweight. The metabolic characteristics of abdominal adipocytes, which have increased lipolytic capacity, might account for this situation, as they would facilitate hyperinsulinism, insulin resistance and such-metabolic disturbances as arterial hypertension, diabetes mellitus and dyslipidemia. Androgens seem to play a key role in the development of obesity morphotypes. These notions have important practical applications: an excess of body fat is not necessarily pathogenic; as regards vascular and metabolic risks, body fat distribution seems to be more important than overweight.
Transdermal estradiol.
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Hypolipidaemia in fire-eaters.
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Biological effects of estradiol-17 beta in postmenopausal women: oral versus percutaneous administration.
To determine whether the route of administration or the type of estrogen used in estrogen replacement therapy (ERT) is more important in avoiding effects on hepatic function, 24 postmenopausal women were studied before and at the end of 2 months of oral or percutaneous administration of the same estrogen, estradiol-17 beta (E2). The treatments studied were oral micronized E2, 2 mg/day (9 women); oral E2 valerate, 2 mg/day (5 women), and percutaneous E2, 3 mg/day (10 women). Specific plasma biological and biochemical markers of estrogenic action were evaluated, namely, E2, estrone (E1), LH, FSH, sex steroid binding protein (SBP), renin substrate, antithrombin activity, and lipoproteins (high density lipoprotein cholesterol, low density lipoprotein cholesterol, very low density lipoprotein triglycerides). Both oral and percutaneous administration of E2 increased plasma E2 levels up to midfollicular values and decreased LH and FSH levels into the same range. Oral administration of E2 led to substantial increases in plasma E1, SBP, renin substrate, and VLDL levels, whereas AT decreased significantly. Percutaneous administration of E2 led to a physiological plasma E1/E2 ratio and did not induce any change in hepatic proteins. These data suggest that the route of administration of E2 determines the biochemical response to ERT in postmenopausal women. SBP is the most sensitive marker of the liver action of estrogen, and triglycerides also are simple and useful markers for this effect. Percutaneous E2 therapy is an effective method of ERT, and has no measurable effects on hepatic markers of estrogen action.
Contraception in hypertensive women using a vaginal ring delivering estradiol and levonorgestrel.
Contraception with a vaginal ring (CVR) that delivers estradiol and levonorgestrel was used during a mean of 15.6 menstrual cycles in 12 hypertensive women. Blood pressure (BP) was measured 5 times on each visit during 2 pretreatment control cycles; during the 1st, 2nd, 4th, 6th, and from the 9th to 12th cycles of CVR use; and again after a 1-month recovery period. No significant change in BP occurred during CVR use in any of the subjects. Plasma renin substrate and antithrombin III activity did not vary significantly, which suggests the utility of administering natural estradiol via the vagina, thus avoiding the first pass effect that occurs with oral contraceptives. Significant decreases in plasma sex hormone-binding globulin, cholesterol, high density lipoprotein cholesterol, phospholipids, and triglycerides occurred, indicating an androgenic effect of levonorgestrel. We conclude that the CVR is a method of contraception that does not elevate BP in hypertensive women.
[Metabolism of sex hormones and adipose tissue].
Adipose tissue is a catchment area for storing, converting and releasing the sex hormones. The role of adipose tissue in the general metabolism of endogenous and exogenous steroids deserves to be considered seeing how big the volume of fat is in the human body. The fatty pool of sex steroids seems to be greater than the plasma pool. Hormones which have been stored can be released by adipocytes into the general circulation even if they have been converted while in the adipocytes. Similarly, androgens are changed by adipose tissue into oestrogens by aromatisation and are liberated. This extraglandular production of oestrogens can have clinical and pathological consequences.
[Diabetes in adolescence. The adult diabetes physician point of view].
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