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Biomedical subjects

B Guy-Grand

Publications and source records attributed to B Guy-Grand.

At least 73 records · Page 4Linked to original sources

Hypersensitivity of the corticotropic axis to the serotoninergic agent clomipramine in obese women.

Serotoninergic control of food intake has been shown to be abnormal in obese persons with a decrease in serotoninergic tone. The neuroendocrine effects of intravenous I.V. administration of clomipramine (CMI), a serotonin uptake inhibitor, were studied in normal-weight (n=7) and obese subjects before (n=12) and after (n=6) dietary restriction. Under double-blind, placebo-controlled conditions, a single 12.5 mg dose of CMI was administered. There was no difference in baseline values of prolactin (PRL), corticotropin (ACTH) and cortisol in non-obese controls, obese before and obese after weight loss. CMI led to significant increases of PRL, ACTH, and cortisol concentrations in the controls as well as the obese group. The ACTH and cortisol responses to CMI in obese subjects were somewhat greater than the responses in normal-weight subjects. The area under the curve AUC for ACTH after clomipramine was 6202 +/- 976 pg/ml x 150 minutes for tile obese before weight loss and 3274 +/- 512 pg/ml x 150 minutes for the controls and the difference was significant at the level of p=0.052. The cortisol peak value after clomipramine was 163.71 +/- 14.31 ng/ml in the non-obese and 214.66 +/- 12.59 ng/ml in the obese (p=0.025). However, there was no difference in the obese subjects before and after weight loss. These data support the assumption that obese women have an abnormal sensitivity to the serotoninergic control of the hypothalamic pituitary adrenal axis (HPA), and that a mild weight loss does not significantly modify their serotoninergic tone.

Adolescent↗

Type of test-meal affects palatability and eating style in humans.

Effects of palatability on the meal as a whole or the microstructure of meals are often inconsistent or even divergent. Is this attributable to the nature of the test meals? In the present study, three frequently used types of meals were offered to seven normal-weight women: conventional courses, sandwiches and semi-liquid items. Each meal was composed of four items of either high or medium-low palatability. The type of meal appeared to be the major factor determining the level of palatability and of every dependent variable. Energy intake was influenced by palatability level in conventional meals only. The microstructure of meals was responsive to palatability only in sandwich and semi-liquid meals. The data suggest that palatability effects are detectable beyond a minimum threshold. In addition, characteristics of eating style appeared to be very stable within individuals across meal types and palatability conditions.

Adult↗

Human responses to five concentrations of sucrose in a dairy product: immediate and delayed palatability effects.

Preferences for five sucrose concentrations (0, 5, 10, 20 and 40 g of sugar per 100 g of plain yogurt) were assessed in men and women by brief-exposure sensory evaluation tests and intake tests. Ten ad-libitum yogurt intake tests (with each concentration presented twice) and two sensory evaluation tests (one before and one after the series of intake tests) were conducted. Food intake in the 24 h after each test was estimated using dietary records. Sweetness intensity ratings did not change as a function of test condition. In contrast, hedonic ratings in sensory evaluation tests were more closely correlated to actual intake in experienced than in naive subjects. In intake tests the preferred sucrose concentrations were 5 and 10%. Food intake in the first few hours after yogurt intake was significantly greater on 10%-sucrose days relative to the other concentration days in men only. Although there was a tendency to eat more over the 24 h after consumption of the preferred yogurts, this effect was not statistically significant. Total daily intake, including the calories in the yogurts, was greater on intake days than on sensory evaluation days, indicating that the energy derived from the yogurts was not compensated for by a decrease in subsequent intake.

Adult↗

Microalbuminuria and body fat distribution in obese subjects.

The aim of this work was to evaluate the prevalence of microalbuminuria in an obese population and to study the relation between albumin excretion rate (AER), various clinical (body mass index, adipose tissue distribution) nutritional (macronutrient intake) and metabolic parameters. A cross-sectional study was carried out, and AER was evaluated in 182 obese subjects (BMI > 27) with no medication, no intercurrent disease, no cardiac, pulmonary or endocrinological disorders (including diabetes and hypertension) and also in 31 control subjects at the outpatient clinic of the department of Nutrition, Hôtel Dieu, Paris, France. The following were measured: BMI, waist/hip ratio (WHR), urinary AER, blood glucose, insulin and C peptide levels, cholesterol (CT), triglycerides, HDL cholesterol (HDL-CT), apoprotein A1 and B. In the obese population, 18 subjects (9.9%) were found to have an increased AER: 13 subjects (7.1%) with microalbuminuria (AER between 30 to 300 mg/24 h) and five with AER over 300 mg/24 h. AER was normal in all control subjects but one, who was found to have microalbuminuria. Log AER was positively correlated to WHR (P < 0.001), blood pressure (P < 0.05), cholesterol (P < 0.05), Apo B levels (P < 0.01) and with fasting Insulin levels and protein intake (P < 0.001). Positive association between log AER and protein intake, insulin levels, Apo B and blood pressure were found independently of BMI and WHR. It is suggested that abdominal obesity may be associated with incipient nephropathy in some obese subjects without diabetes and hypertension. Microalbuminuria may be included among metabolic abnormalities connected with abdominal-type excess weight distribution.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗

[Treatments of massive obesity].

Treatment of massive obesity aims at somatic, psychological and social targets and therefore requires a multidisciplinary team co-ordinated by a physician. Treatment usually begins by taking care of the most worrying somatic and metabolic problems (cardio-respiratory and metabolic disorders) and by correcting the diet. It is then enhanced by a psychological assistance provided by the treating team and, in certain cases, by a psychotherapist. Massive obesity is a chronic, recurrent and severe disease. Its treatment is prolonged and implies numerous constraints (diet, drugs, treatment of a possible sleep apnoea syndrome) which are difficult to tolerate in the long term. This type of management resembles that of other chronic diseases, such as complicated diabetes. From dietetics to the most technical medicine, from the doctor-patient relationship to psychotherapy, the therapeutic methods are numerous, and the burden of using them in a coherent manner falls on the physician.

Humans↗

Snacking patterns in obese French women.

Snacking patterns were studied in 273 obese women by dietary history. Snacking was observed in 60% of the sample and occurred mainly during the afternoon. Total daily energy intake was higher in snackers than in non-snackers because of greater consumption of food at meals and between meals. A variety of foods were consumed as snacks (mean macronutrient content of snacks: 52% carbohydrate (CHO), 37% lipid and 12% proteins). CHO-rich protein-free snacks were a minority (20%). Only 7% of subjects were CHO-rich protein-free snackers. The eating pattern described by Wurtman in "carbohydrate cravers" was reported by less than 10% of these women. We conclude that, in Paris, snacking plays an important role in increasing energy consumption in obese women but macronutrient-specific snacking is not frequent.

Adolescent↗

Hemostatic and metabolic effects of lowering the ethinyl-estradiol dose from 30 mcg to 20 mcg in oral contraceptives containing desogestrel.

The metabolic and hemostatic effects of two oral contraceptives containing 150 mcg desogestrel and 20 mcg ethinyl-estradiol (EE) (MERCILON) or 30 mcg EE (MARVELON) were compared in order to examine the effect of reducing the EE dose in contraceptive pills. Forty-nine women participated in this randomized study during 6 cycles. In both groups, there was a significant increase in triglycerides, HDL-cholesterol and apoprotein A1; the same increase was observed for SBP and CBG. Slight and transient variations of fasting blood glucose levels were seen in the 30 mcg EE group and in the two groups for fasting insulin levels. The increase in renin substrate was significantly higher with the 30 mcg EE than with the 20 mcg EE pill. In both groups, plasminogen increased significantly, but antithrombin III, total and free protein S and fibrinogen decreased significantly only in women taking the 30 mcg EE pill, whereas there was no significant change in the 20 mcg EE group. Reducing the dose of EE in oral contraceptives from 30 mcg to 20 mcg minimizes their impact on renin substrate and hemostatic parameters.

Apolipoprotein A-I↗

Missense mutations in exon 5 of the human lipoprotein lipase gene. Inactivation correlates with loss of dimerization.

Most missense mutations of the lipoprotein lipase (LPL) gene identified among LPL-deficient subjects cluster in a segment of the sequence that encodes the catalytic triad as well as functional elements involved in the activation of the lipase at lipid-water interfaces. Consequently, loss of activity may result either from direct alterations of such functional elements or from less specific effects on protein folding and stability. This issue was addressed by examining biochemical properties of four such variants (A176T, G188E, G195E, and S244T) in a heterologous expression system (COS-1 cells). Variant G195E (GGA----GAA) was previously unreported. In all instances, inactive enzyme was recovered in medium, albeit at reduced levels. Cellular synthesis and extracellular degradation were similar to those for wild type, suggesting that reduced secretion resulted from increased intracellular degradation. When cell extracts were subjected to heparin-Superose affinity chromatography followed by elution on a linear salt gradient, all variants exhibited a single, inactive, low affinity immunoreactive peak. By contrast, wild-type enzyme presented an additional, high affinity, active species, which we interpret as homodimeric enzyme. Substitution of the active-site serine (S132A) led to loss of activity but maintenance of the high affinity species. When large amounts of the G188E variant were applied to the column, small but significant amounts of high affinity, active enzyme were recovered. Systematic substitutions at residue 188 showed that only glycine could accommodate structural constraints at this position. We conclude that the mutations examined did not impart lipase deficiency by affecting specific functional elements of the enzyme. Rather, they appear to affect protein folding and stability, and thereby formation and maintenance of subunit assembly.

Adult↗

Effects of bombesin, of a new bombesin agonist (BIM187) and a new antagonist (BIM189) on food intake in rats, in relation to cholecystokinin.

To study the mechanism by which bombesin induces satiety, we studied the effect of two new peptides, BIM187, a bombesin agonist, and BIM189, a bombesin antagonist, on food intake in rats fed 6 h a day. BIM187 at 4 micrograms/kg, significantly reduced food intake at 30 min, but did not change the total 6-h food intake. BIM189 (10 mg/kg), had no effect on food intake when administered alone, even at high doses (20 mg/kg). BIM189 selectively reduced bombesin-induced satiety but had no effect on satiety induced by BIM187. To examine the extent to which the satiety effect of bombesin or related peptides depends on the release of cholecystokinin (CCK), we studied the ability of CCK antagonists, BIM18216 and L364718, to reduce satiety induced by bombesin and BIM187. Neither BIM18216 nor L364718 alone had an effect on the 30-min food intake. They were not able to reverse the effect of bombesin on food intake. In our model, bombesin seems to act on satiety by a mechanism independent of CCK.

Animals↗

Clinical studies with d-fenfluramine.

d-Fenfluramine (dF) (15 mg twice daily) has been studied in controlled trials in human obesity and has been shown to increase adherence to diet, to enhance its efficacy, and most importantly, to prevent weight regain when continued over 1 y. Few side effects, mostly transient, have been observed. A long-term use of dF in the management of some obese patients could be foreseen. Additionally, evidence that dF improves eating symptoms and dysphoric impairments in obese cravers, premenstrual syndrome, seasonal affective disorder, and smoking withdrawal syndrome has been presented.

Body Weight↗

Relationships between 3-y longitudinal changes in body mass index, waist-to-hip ratio, and metabolic variables in an active French female population.

Three-year longitudinal changes in body mass index (BMI), waist-to-hip ratio (WHR), and metabolic variables were examined in 209 active French women. For the entire group, a weak but significant positive association was found between change in BMI and change in WHR. However, analysis of covariance according to the degree of abdominal fat distribution showed a heterogeneity of this association that was confined to women with abdominal fat distribution. Changes in BMI were positively associated with changes in total cholesterol (P less than 0.05), triglycerides (P less than 0.10), and blood pressure (P less than 0.001), whereas changes in WHR were associated with changes in triglycerides (P less than 0.05) and diastolic blood pressure (P less than 0.10). These longitudinal results suggest that a more favorable body-fat pattern and metabolic profile might be achieved by reducing weight, or at least by preventing weight gain, particularly in women with high abdominal-fat distribution.

Abdomen↗