3,858 research outputs found
11 BETA-HSD1 ENZYME, A NEW POTENTIAL TARGET FOR THE MANAGEMENT OF TYPE 2 DIABETES AND METABOLIC DISORDERS ASSOCIATED WITH OBESITY
La 11ÎČ-hydroxystĂ©roĂŻde dĂ©shydrogĂ©nase de type 1 (11ÎČHSD1) est une enzyme intervenant dans la transformation de cortisone en cortisol, notamment dans le tissu adipeux et le foie. Elle pourrait ĂȘtre impliquĂ©e dans la physiopathologie de lâobĂ©sitĂ© abdominale, composante centrale du syndrome mĂ©tabolique, situation proche du syndrome de Cushing. Des inhibiteurs synthĂ©tiques sĂ©lectifs de la 11ÎČHSD1 sont en cours de dĂ©veloppement avec des rĂ©sultats prĂ©liminaires encourageants, mais qui doivent encore ĂȘtre amĂ©liorĂ©s avant de constituer une vĂ©ritable approche innovante dans la prise en charge pharmacologique de lâobĂ©sitĂ©, du syndrome mĂ©tabolique et du diabĂšte de type 2.The 11 beta-hydroxysteroid dehydrogenase type 1 (11ÎČHSD1) enzyme promotes the local conversion from cortisone to cortisol, especially in the adipose tissue and the liver. It may play a role in the pathophysiology of abdominal obesity and the metabolic syndrome, both showing some similarities with the Cushing syndrome. Synthetic selective inhibitors of 11ÎČHSD1 are currently in development with encouraging preliminary results that remain, however, to be further improved. Selective inhibitors of 11ÎČHSD1 may represent an innovative approach in the pharmacological management of obesity, metabolic syndrome and type 2 diabetes.Peer reviewe
Anti-cancer activity of metformin: new perspectives for an old drug
Type 2 diabetes is associated with a higher risk of cancer, which appears more obvious since the reduction of cardiovascular mortality. All glucose-lowering oral agents do not have the same impact on cancer: the risk is increased with sulfonylureas and decreased with metformin (and glitazones). Numerous epidemiological observational and case-control studies showed that metformin is associated with a lower incidence of cancer and a lower cancer-related death rate. A dose-response relationship and a relation between duration of prior treatment with metformin and the protective effect against cancer have been reported. Mechanisms involved are the activation of the AMPK enzyme and the inhibition of the mTOR pathway. Studies with metformin are ongoing in the field of oncology, especially as adjunct to treatment of breast cancer.Le diabĂšte de type 2 est associĂ© Ă un risque accru de cancer, dâautant plus Ă©vident quâon
maĂźtrise mieux la mortalitĂ© cardio-vasculaire. Tous les traitements antidiabĂ©tiques nâont pas le
mĂȘme impact sur le cancer : le risque est accru avec les sulfonylurĂ©es et diminuĂ© avec la
metformine (et les glitazones). De nombreuses études épidémiologiques observationnelles et
cas-tĂ©moins rĂ©centes rĂ©vĂšlent quâun traitement par metformine est associĂ© Ă une nette
rĂ©duction de lâincidence de nĂ©oplasies et de la mortalitĂ© par cancer. Il existe une relation doserĂ©ponse
et une relation entre la durĂ©e prĂ©alable du traitement par metformine et lâeffet
protecteur observĂ©. Les mĂ©canismes invoquĂ©s sont lâactivation de lâenzyme AMPK et
lâinhibition de la voie mTOR. Des Ă©tudes avec la metformine sont en cours en oncologie,
notamment dans le cancer du sein
Modeling and Optimization of M-cresol Isopropylation for Obtaining N-thymol: Combining a Hybrid Artificial Neural Network with a Genetic Algorithm
The application of a hybrid framework based on the combination, artificial neural network-genetic algorithm (ANN-GA), for n-thymol synthesis modeling and optimization has been developed. The effects of molar ratio propylene/cresol (X1), catalyst mass (X2) and temperature (X3) on n-thymol selectivity Y1 and m-cresol conversion Y2 were studied. A 3-8-2 ANN model was found to be very suitable for reaction modeling. The multiobjective optimization, led to optimal operating conditions (0.55 â€X1â€0.77; 1.773 g †X2 â€1.86 g; 289.74 °C †X3 â€291.33 °C) representing good solutions for obtaining high n-thymol selectivity and high m-cresol conversion. This optimal zone corresponded to n-thymol selectivity and m-cresol conversion ranging respectively in the interval [79.3; 79.5]% and [13.4 %; 23.7]%. These results were better than those obtained with a sequential method based on experimental design for which, optimum conditions led to n-thymol selectivity and m-cresol conversion values respectively equal to 67%and 11%. The hybrid method ANN-GA showed its ability to solve complex problems with a good fitting
Paradigmatic well posedness in some generalized characteristic Cauchy problems
By means of convenient regularization for an ill posed Cauchy problem, we deĂŻÂŹne an associated generalized problem and discuss the conditions for the solvability of it. To illustrate this, starting from the semilinear unidirectional wave equation with data given on a characteristic curve, we show existence and uniqueness of the solution.
Oc031--Generic Substitution Of Antiepileptic Drug (Aed) And Loss Of Seizure Control: A Population-Based Case-Crossover Study
Open access CC-BYInternational audienceThere are still controversies over pill substitution among AEDs: some studies claimed that switching between brand and generic AED (generic substitution) can lead to breakthrough seizures; other studies have refuted these concerns. France and some US states recommend limiting substitution of generic AED. We aimed at further estimating the association between generic substitution and loss of seizure control
Doubled haploids of Coffea canephora : development, fertility and agronomic characteristics
Des haploĂŻde-doublĂ©s (HD) de #Coffea canephora ont Ă©tĂ© dĂ©veloppĂ©s en utilisant les embryons haploĂŻdes qui apparaissent spontanĂ©ment en association avec la polyembryonie. Les frĂ©quences de graines polyembryonĂ©es et d'embryons haploĂŻdes varient en fonction du gĂ©notype parental. Cependant la production d'un grand nombre de HD semble possible Ă partir de tous les gĂ©notypes. Plus de 750 HD produits Ă partir de diffĂ©rents gĂ©notypes ont Ă©tĂ© cultivĂ©s au champ et Ă©valuĂ©s pour plusieurs caractĂšres agronomiques. Environ la moitiĂ© des gĂ©notypes HD n'ont pas survĂ©cu, suggĂ©rant un fort et nĂ©gatif effet de l'homozygotie. La dĂ©pression de consanguinitĂ© est particuliĂšrement sĂ©vĂšre pour la vigueur vĂ©gĂ©tative et les aspects liĂ©s Ă la reproduction. Pour plusieurs caractĂšres tels que la forme des feuilles, la rĂ©sistance Ă la rouille et le poids de 100 graines, une variation gĂ©nĂ©tique considĂ©rable a Ă©tĂ© observĂ©e entre et Ă l'intĂ©rieur des groupes de gĂ©notypes HD constituĂ©s par les HD produits Ă partir d'un mĂȘme clone. MalgrĂ© leur faible vigueur et fertilitĂ© rĂ©duite, les haploĂŻde-doublĂ©s de #Coffea canephora offrent de nouvelles possibilitĂ©s pour les Ă©tudes gĂ©nĂ©tiques et l'amĂ©lioration des cafĂ©iers. (RĂ©sumĂ© d'auteur
Minimum feedback vertex set and acyclic coloring
International audienceIn the feedback vertex set problem, the aim is to minimize, in a connected graph G =(V,E), the cardinality of the set overline(V) (G) \subseteq V , whose removal induces an acyclic subgraph. In this paper, we show an interesting relationship between the minimum feedback vertex set problem and the acyclic coloring problem (which consists in coloring vertices of a graph G such that no two colors induce a cycle in G). Then, using results from acyclic coloring, as well as other techniques, we are able to derive new lower and upper bounds on the cardinality of a minimum feedback vertex set in large families of graphs, such as graphs of maximum degree 3, of maximum degree 4, planar graphs, outerplanar graphs, 1-planar graphs, k-trees, etc. Some of these bounds are tight (outerplanar graphs, k-trees), all the others differ by a multiplicative constant never exceeding 2
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