IRAS, the human homologue of Nischarin, prolongs survival of transfected PC12 cells.
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Biomedical subjects
Publications and source records attributed to G Pascal.
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The numerous food crises that Europe has experienced during the past five years have raised new consumer demands concerning the characterization, traceability, and safety of foods which are proposed on the market. The consumer has, at the same time, vigorously placed into question the modes of agricultural production in industrialized countries, as well as the structures and means of evaluating the food risks and the conditions of the consumer's participation in the public debate in these domains. For certain groups of consumers, one also attends a contestation of the expertise and the application to the food domain of the considerable progress that has taken place in the field of biotechnology. So it is that the development of genetically modified organisms (mainly plants, the raw material of food products) has experienced a slowing down in the European Union. The answers afforded to these new exigencies of consumers in matter of identity, traceability, and acceptability of the foods are dealt with in this paper, as well as the elements which may concur with the evaluation of their safety. The positive role that biotechnology can afford to the different domains is emphasized. A source of uneasiness, biotechnology is also a powerful tool for ameliorating the evaluation of the sanitary risks and for answering the hopes of the citizen in the food domain.
Most of the functions of vitamin A are mediated through the binding of retinoic acid to specific nuclear receptors that regulate genomic expression. Recent experimental work in transgenic mice showed clearly that normal embryonic development depends on the correct spatial and temporal expression of the receptors in the differentiating cells and on the binding of specific forms of retinoic acid. This implies that the parent compound, vitamin A, is available in adequate forms and quantities. Excessive dietary intake of vitamin A has been associated with teratogenicity in humans in <20 reported cases over 30 y. However, caution must be exercised to avoid unnecessary supplementation of women of childbearing age. Hypovitaminosis A affects millions of women and children worldwide. The main consequence of a poor vitamin A supply during pregnancy is a low vitamin A status at birth and in the next few months. Vitamin A deficiency is strongly associated with depressed immune function and higher morbidity and mortality due to infectious diseases such as diarrhea, measles, and respiratory infections. Vitamin A deficiency is often associated with an increased mother-to-child transmission of HIV-1. The initiation of vitamin A supplementation should be carefully examined in each case according to the risk-to-benefit ratio. The final decision should take into account the estimated vitamin A status of the woman, the availability of vitamin A-rich foods in her diet, and whether supplementation can be supervised.
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In women, sex hormone-binding globulin (SHBG) concentrations are the result of a balanced effect of stimulatory and inhibitory factors. Estrogens represent the principal stimulatory hormones, whereas androgens, insulin, excess body fat, and the pattern of body fat distribution have inhibitory effects. Menopause is characterized by major changes in blood sex steroid concentrations, notably a marked reduction of estradiol levels. In this study, we therefore investigated the relationship between hormonal and nonhormonal regulatory factors of SHBG and its blood levels in two groups of premenopausal and postmenopausal women characterized by normal-high or reduced estrogen concentrations. The data were obtained from an analysis of the cross-sectional database obtained during the first survey of the Virgilio-Menopause-Health Project, an epidemiologic longitudinal study aimed at investigating the impact of menopause on body weight, fat distribution, and related major metabolic, hormonal, and cardiovascular risk factors. A total of 329 women, 133 in premenopause and 196 in postmenopause without diabetes, thyroid diseases, or relevant cardiovascular, renal, and hepatic dysfunction, were included in the study. A clinical history (including dietary and physical-activity habits), anthropometry (body mass index [BMI], waist to hip ratio [WHR], and bioelectrical impedance analysis [BIA]), and morning blood samples in the fasting state for sex hormones, insulin, and biochemistry were available for all the women. Premenopausal and postmenopausal women showed no significant difference in SHBG concentrations (38.7 +/- 17.9 v 36.6 +/- 17.5 nmol/L, respectively). On the contrary, postmenopausal women were characterized by a marked reduction of estradiol levels and significantly lower levels of testosterone. After adjusting for age, insulin was lower and the glucose to insulin ratio was higher in postmenopause than in premenopause. Age-adjusted values for all anthropometric parameters were not significantly different in the two groups. In simple correlation models, SHBG was significantly and negatively correlated with BMI, WHR, and insulin and testosterone levels in both premenopausal and postmenopausal women, whereas estradiol levels correlated positively and significantly with SHBG only in the premenopausal group. A significant positive correlation between the glucose to insulin ratio and SHBG was present in both groups. Using multiple regression models, in the premenopausal group, SHBG levels were correlated positively with estradiol and negatively with testosterone and insulin, but not with the WHR. On the contrary, in the postmenopausal group, SHBG values had a significant negative correlation with the WHR, whereas the relationship with estradiol was not significant; moreover, the relationship with testosterone and insulin, although significant, became less marked. In conclusion, this study indicates that (1) there is no significant difference in SHBG blood concentrations between premenopause and postmenopause; (2) SHBG values are correlated positively with estradiol and negatively with insulin and testosterone concentrations, but the predictive value of these variabiles on SHBG appears to be different in premenopause and postmenopause; and (3) SHBG levels decrease with increasing WHRs, particularly in the postmenopausal group. Therefore, determinants of SHBG blood concentrations are likely to change on passing from premenopausal to postmenopausal status. In particular, there seems to be a threshold level for which estradiol is an important determinant of SHBG blood concentrations.
The current view of dietary carbohydrates as simply providing us with energy is outdated. Because of their varied chemistry and physical form the rate and extent to which the different types are digested in and absorbed from the small intestine varies. This in turn leads to affects on satiety, blood glucose and insulin, protein glycosylation, lipids and bile acids. Some carbohydrates reach the colon where they are fermented and affect many aspects of large bowel function, colonocyte and hepatic metabolism. A new framework for classifying and measuring food carbohydrates is needed to allow a greater understanding of the role of individual species in health and to inform the public of their importance. A classification based primarily on molecular size (degree of polymerisation) into sugars, oligosaccharides and polysaccharides, is suggested, with sub-groups identified by the nature of the monosaccharides. Greater knowledge of the chemical and physical properties of carbohydrates allow a more precise relation with physiology and health to be drawn. The Carbohydrate Group met in Paris in December 1995 at the invitation of Gerard Pascal, Director of CNERNA. Financial support for the meeting was provided by CNERNA.
OBJECTIVES: In this study we investigated the relationships between blood lipids and menopausal status. SETTING AND SUBJECTS: All data were obtained from the first cross-sectional examination of the Virgilio Menopause Health Project in a large cohort of middle-aged women in pre, peri-, and postmenopausal age. The data refer to 426 women without metabolic or endocrine diseases, relevant hepatic, renal and cardiovascular abnormalities, none were dieting or taking medications. MAIN OUTCOME MEASURES: A precoded questionnaire including full clinical history, socio-economic and personal information, habitual diet, physical activity, drug use and smoking habits, careful recording of gynaecological events and family history for disease was completed. Several anthropometric parameters and the bioelectrical impedance analysis was used to measure free fatty mass. Blood samples for hormones and biochemistry were also obtained. RESULTS: There were no significant differences on body mass index, fatty mass, free fatty mass and parameters of body fat distribution between the three groups. Again, there were no differences in smoking habits, dietary intake or indices of physical activity amongst the groups. There was a significant increase from pre to postmenopause of LH and FSH and a decrease of oestradiol and testosterone, whereas no difference was found in sex hormone-binding globulin. Age-adjusted values of glucose, triglycerides and high density lipoprotein (HDL-) cholesterol were similar in all groups, whereas postmenopausal women had significantly higher values of total and low density lipoprotein (LDL-) cholesterol. On the contrary, there was a significant fall in insulin levels passing from pre to postmenopause. In multiple regression models, total and LDL-cholesterol correlated positively with body mass index, waist-to-hip ratio and age, and negatively with free fatty mass and oestradiol blood levels. CONCLUSIONS: These results are consistent with the hypothesis that menopausal status may have a significant and independent effect in determining increased total and LDL-cholesterol concentrations in postmenopausal women.
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Since sex hormones are involved in the regulation of body composition and adipose tissue metabolism, in this study we investigated whether menopause may alter body weight and fat distribution in women. Data were obtained from the Virgilio-Menopause-Health Study, which is a longitudinal epidemiological project aimed at investigating the relationship between menopause and related plasma hormonal concentrations, body weight, fat distribution and health. Only data from the first cross-sectional examination are presented. Out of the 952 women living in the town of Virgilio, Mantua (Italy) and born between January 1st, 1932 and December 31st, 1946, 596 (62.6%) participated in the study. Since incomplete data were present in 19 women, 577 was the final sample size available for statistical analysis. The protocol included a collection of blood for hormones and biochemistry, a full clinical history with socioeconomic and personal information, drug use, smoking, dietary and physical activity habits, and several anthropometric measurements. According to the clinical and hormonal status, 160 women were classified as pre-menopausal, 124 as peri-menopausal and 293 as post-menopausal. After adjusting for age, we found that body mass index (BMI) was significantly higher in peri-menopausal than in pre-menopausal women and remained slightly, but again significantly, higher in post-menopausal women. Although waist-to-hip and waist-to-thigh ratios increased significantly and progressively from pre- to post-menopause, any difference was not significant after adjusting for age. Diet, physical activity and smoking habits did not explain the difference in BMI values. No difference was found in the use of estro-progestagen compounds between the groups.(ABSTRACT TRUNCATED AT 250 WORDS)
We have previously determined the dietary alpha-linolenic requirement for membrane synthesis in the developing animal. This study measures the dietary requirement for maintaining normal membrane composition in adult rats, as determined by 22:6(n-3) (docosahexaenoic acid) concentration. Sixty-day-old rats, previously fed a diet containing both linoleic and alpha-linolenic acid, were divided into nine groups, each receiving different quantities of alpha-linolenic acid but the same amount of linoleic acid. They were killed 4 wk after initiation of the new diet to determine the minimum quantity of alpha-linolenic acid required in the diet for maintaining the 22:6(n-3) tissue concentration in brain (whole tissue, myelin and nerve endings), liver and heart. The minimal amount of dietary alpha-linolenic acid that maintained the maximal 22:6(n-3) level and minimal 22:5(n-6) level in tissues was considered to be the dietary requirement. The quantity was found to be 1.30 g/kg diet (0.26% of dietary energy). It was lower than that found for the developing animal (0.4% of energy). At lower quantities of dietary alpha-linolenic acid, 22:6(n-3) was replaced by 22:5(n-6) in the organs examined, except in nervous tissue, in which 22:6(n-3) was highly preserved.
The nervous system is the organ with the second greatest concentration of lipids. These lipids participate directly in membrane functioning. Brain development is genetically programmed. It is therefore necessary to ensure that nerve cells receive an adequate supply of nutrients, especially of lipids, during their differentiation and multiplication, and throughout their lives. The effects of polyunsaturated fatty acid deficiency have been extensively studied; prolonged deficiency leads to death in animals. Linoleic acid is now universally recognized to be an essential nutrient. Until recently, however, alpha-linolenic acid was considered non-essential. Feeding animals with oils that have a low alpha-linolenic content results in all brain cells and organelles and various organs having reduced amounts of 22:6n-3, which is compensated for by an increase in 22:5n-6. The speed of recuperation from these anomalies is extremely slow for brain cells, organelles, and microvessels, in contrast to other organs. A decrease in alpha-linolenic series acids in the membranes results in a 40% reduction in the Na(+)-K(+)-ATPase of nerve terminals and a 20% reduction in 5'-nucleotidase. Some other enzymatic activities are not affected, although membrane fluidity is altered. A diet low in alpha-linolenic acid induces alterations in the electroretinogram which disappear with age; motor function and activity are little affected, but learning behavior is markedly altered. The presence of alpha-linolenic acid in the diet confers a greater resistance to certain neurotoxic agents (triethyl-lead). During the period of cerebral development, there is a linear relationship between brain content of n-3 acids and the n-3 content of the diet up to the point where alpha-linolenic levels reach 200 mg for 100 g of food intake. Beyond that level there is a plateau. For other organs, such as the liver, the relationship is also linear up to 200 mg/100 g, but then there is merely an abrupt change in slope and not a plateau. When dietary 18:2n-6 content was varied, it was noted that 20:4n-6 optimum values were obtained at 150 mg/100 g for all nerve structures, 300 mg for testicle and muscle, 800 mg for kidney, and 1200 mg for liver, lung and heart. A deficiency in alpha-linolenic acid and an excess of linoleic acid have the same main effect: an increase in 22:5n-6 levels.(ABSTRACT TRUNCATED AT 400 WORDS)
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Feeding rats a purified diet containing peanut oil with a low alpha-linolenic acid [18:3(n-3)] content resulted in lower amounts of (n-3) polyunsaturated fatty acids, mainly docosahexaenoic acid [22:6(n-3)], greater amounts of docosapentaenoic acid [22:5(n-6)] in uterus phospholipids, and altered postnatal uterus development when compared with rats fed a diet containing peanut and rapeseed oils. Maximal differences in uterine growth, as measured by uterine weight, protein and DNA content, occurred between d 24 and 30 postpartum and disappeared near the end of sexual development (d 40). The induction of the progesterone receptor was not affected, and serum estradiol concentrations were not significantly reduced in deficient animals. Moreover, growth response of the uterus to low doses of 17 beta-estradiol (less than 5 micrograms/kg) was significantly reduced in ovariectomized animals fed the diet containing only peanut oil. However, the maximal response of the uterus, observed with higher 17 beta-estradiol doses (5-50 micrograms/kg), was not affected. Because the two diets used differed in the content of alpha-linolenic acid, it is likely that alpha-linolenic acid deficiency in animals fed the diet containing only peanut oil was the cause of the affected uterine development.
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The combined effects of age and dietary n-6 and n-3 fatty acids were studied in 3-, 6- and 9-month-old rats. At each age, two groups were fed diets containing 5% (w/w) of vegetable oils rich in either 18:3n-6 (borage group) or 18:3n-6 plus 18:4n-3 (black currant group), for a period increasing with age. A control group was fed the essential fatty acids 18:2n-6 and 18:3n-3 only. For each group, delta 6, delta 5 and delta 9 desaturase activities were measured in liver microsomes, and fatty acid composition was determined in microsomal phospholipids. Desaturase activity varied as a function of age and dietary lipids. delta 6 Desaturation of 18:3n-3 was more sensitive to these factors while delta 6 desaturation of 18:2n-6 and delta 9 desaturation were more dependent on season than the other two. Desaturase activity was influenced more by the black currant than by the borage diet, especially at 6 and 9 months of age. A large proportion of arachidonic acid was maintained in the microsomes independent of the diet. Changes in the fatty acid composition did not strictly reflect the differences in desaturase activities. The effects of the two factors (age and diet) on the activities of the desaturases are complex, suggesting that the enzymes are susceptible to other factors as well.