The Causes and Consequences of Low Levels of High Density Lipoproteins in Patients with Diabetes

Type 2 diabetes is commonly accompanied by a low level of high density lipoprotein cholesterol (HDL-C) that contributes to the increased cardiovascular risk associated with this condition. Given that HDLs have the ability to improve increase the uptake of glucose by skeletal muscle and to stimulate the secretion of insulin from pancreatic beta cells the possibility arises that a low HDL concentration in type 2 diabetes may also contribute to a worsening of diabetic control. Thus, there is a double case for raising the level of HDL-C in patients with type 2 diabetes: to reduce cardiovascular risk and to improve glycemic control. Approaches to raising HDL-C include lifestyle factors such as weight reduction, increased physical activity and stopping smoking. Of currently available drugs, the most effective is niacin. Newer formulations of niacin are reasonably well tolerated and have the ability to increase HDL-C by up to 30%. The effect of niacin on cardiovascular events in type 2 diabetes is currently being tested in a large-scale clinical outcome trial

Patients with chronic three-vessel disease in a 15-year follow-up study: genetic and non-genetic predictors of survival.

Genetic and non-genetic predictors of 15-year survival in patients with chronic three-vessel disease (3VD) were investigated. Coronary angiography was performed on 810 subjects with symptoms of stable ischemic heart disease in 1998. The patients with 3VD were genotyped for 23 candidate polymorphisms covering the PPAR-RXR pathway, matrix metalloproteinase-2, renin-angiotensin-aldosterone system, endothelin-1, cytokine genes, MTHFR and APO E variants. Fifteen-year survival data were obtained from the national insurance registry. All data were available in the case of 150 patients with 3VD. Statistical analysis used stepwise Cox regression with dominant, recessive, or additive mode of genetic expression. Involved variables included age, sex, BMI, blood pressure, diabetes, ejection fraction, left main stenosis, previously diagnosed coronary stenosis, myocardial infarction in personal history, and coronary bypass along with polymorphisms pre-selected by log-rank tests. Out of the 23 polymorphisms, four were included in the model construction. SNP in the IL-6 gene rs1800795 (-174 G/C) has been found to be a significant predictor of survival. This SNP was in a linkage disequilibrium with rs1800797 (-597 G/A) in the same gene (D=1.0), which was also found to constitute a significant predictor of survival when rs1800795 was not included in the model construction. Age, increased BMI, diabetes, low EF, and left main stenosis were also significant predictors in all models. Age, increased BMI, diabetes, low ejection fraction, left main stenosis, and genetic variation in the IL-6 promoter were established as significant independent risk factors for the survival of patients with three-vessel disease.Genetic and non-genetic predictors of 15-year survival in patients with chronic three-vessel disease (3VD) were investigated. Coronary angiography was performed on 810 subjects with symptoms of stable ischemic heart disease in 1998. The patients with 3VD were genotyped for 23 candidate polymorphisms covering the PPAR-RXR pathway, matrix metalloproteinase-2, renin-angiotensin-aldosterone system, endothelin-1, cytokine genes, MTHFR and APO E variants. Fifteen-year survival data were obtained from the national insurance registry. All data were available in the case of 150 patients with 3VD. Statistical analysis used stepwise Cox regression with dominant, recessive, or additive mode of genetic expression. Involved variables included age, sex, BMI, blood pressure, diabetes, ejection fraction, left main stenosis, previously diagnosed coronary stenosis, myocardial infarction in personal history, and coronary bypass along with polymorphisms pre-selected by log-rank tests. Out of the 23 polymorphisms, four were included in the model construction. SNP in the IL-6 gene rs1800795 (-174 G/C) has been found to be a significant predictor of survival. This SNP was in a linkage disequilibrium with rs1800797 (-597 G/A) in the same gene (D=1.0), which was also found to constitute a significant predictor of survival when rs1800795 was not included in the model construction. Age, increased BMI, diabetes, low EF, and left main stenosis were also significant predictors in all models. Age, increased BMI, diabetes, low ejection fraction, left main stenosis, and genetic variation in the IL-6 promoter were established as significant independent risk factors for the survival of patients with three-vessel disease

D25V apolipoprotein C-III variant causes dominant hereditary systemic amyloidosis and confers cardiovascular protective lipoprotein profile

Apolipoprotein C-III deficiency provides cardiovascular protection, but apolipoprotein C-III is not known to be associated with human amyloidosis. Here we report a form of amyloidosis characterized by renal insufficiency caused by a new apolipoprotein C-III variant, D25V. Despite their uremic state, the D25V-carriers exhibit low triglyceride (TG) and apolipoprotein C-III levels, and low very-low-density lipoprotein (VLDL)/high high-density lipoprotein (HDL) profile. Amyloid fibrils comprise the D25V-variant only, showing that wild-type apolipoprotein C-III does not contribute to amyloid deposition in vivo. The mutation profoundly impacts helical structure stability of D25V-variant, which is remarkably fibrillogenic under physiological conditions in vitro producing typical amyloid fibrils in its lipid-free form. D25V apolipoprotein C-III is a new human amyloidogenic protein and the first conferring cardioprotection even in the unfavourable context of renal failure, extending the evidence for an important cardiovascular protective role of apolipoprotein C-III deficiency. Thus, fibrate therapy, which reduces hepatic APOC3 transcription, may delay amyloid deposition in affected patients

Prise en compte du temps dans la specification et le prototypage d'applications bases de donnees

SIGLEAvailable from INIST (FR), Document Supply Service, under shelf-number : TD 82079 / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

La défense et l’invasion du Cotentin en juin 1940

La bataille du Cotentin en juin 1940 -avec laquelle s'achevait l'invasion de la Normandie -doit naturellement être placée dans la situation générale de ces jours d'infortune. Les mêmes éléments pénibles ou honorables qui la tramaient - chez les soldats et chez les civils - s'y manifestent et s'y mêlent. Nous nous bornerons à en rapporter la genèse et le cours tels que nous avons pu les établir d'après les archives du Service historique de l'Armée, de nombreux témoignages recueillis sur place et une visite des lieux mêmes où s'accrochèrent quelques heures de petites troupes fermement encadrées.Nobecourt R.-G. La défense et l’invasion du Cotentin en juin 1940 . In: Études Normandes, livraison 87-88, n°263, 2e et 3e trimestres 1973. La défense et l’invasion du Cotentin en juin 1940. pp. 1-15

Les juges de Jeanne d’Arc sont-ils tous morts de «mort ignominieuse»

Nobecourt R.-G. Les juges de Jeanne d’Arc sont-ils tous morts de «mort ignominieuse» . In: Études Normandes, livraison 34, n°122, 1er trimestre 1960. Les juges de Jeanne d’Arc sont-ils tous morts de «mort ignominieuse». pp. 21-28

Le lettré, l’écrivain

Nobecourt Roger-Gérard. Le lettré, l’écrivain. In: Études Normandes, livraison 24, n°87, 3e trimestre 1957. Hommage à René Etienne. pp. 349-350