Dietary magnesium intake can affect mechanical properties of rat carotid artery

The purpose of the present study was to determine the effects of Mg deficiency and supplementation on the mechanical properties of the rat common carotid artery. The internal diameter and intra-arterial pressure of carotid artery were measured continuously using an echo-tracking device. Systolic, diastolic and mean intra-arterial pressures were not significantly different in Mg-deficient, -supplemented or control rats. Histological examination showed a larger cross-sectional area, increased intima-media thickness and a greater media:lumen value in carotid artery of Mg-deficient rats, indicating that Mg deficiency may directly stimulate growth and/or proliferation of arterial wall components. In addition, we observed a negative linear relationship between intima-media thickness and plasma Mg concentration, suggesting that increased Mg intake may counteract arterial wall hypertrophy. Neither Mg deficiency nor supplementation modified the arterial distensibility v. intra-arterial pressure curve or the Einc v. wall stress curve, indicating that dietary Mg intake did not modify wall stiffness in young rats. At mean intra-arterial pressure, the stress and Einc values were, however, significantly lower in Mg-deficient rats (P<0·05 in both cases); this finding could be related to the alteration in the geometry of the carotid artery. In conclusion, these findings suggest that Mg deficiency modifies the mechanical properties of the common carotid artery in young rats. Since Mg deficiency is considered a risk factor, these mechanical alterations could contribute to the development of atherosclerosis, hypertension and cardiovascular disease

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Photoactivated surface grafting from PVDF surfaces

International audienceEconomic and easy methods to tune surface properties of polymers as Poly(vinylidene fluoride) (PVDF) without altering bulk properties are of major interest for different applications as biotechnological devices, medical implant device. . . UV irradiation appears as one of the simplest, easy and safe method to modify surface properties. In the case of self-initiated grafting, it is generally assumed that the pretreatment of the PVDF surface with UV irradiation can yield alkyl and per-oxy radicals originating from breaking bonds and capable of initiating the subsequent surface grafting polymerizations. Surprisingly, the present work shows that it is possible to obtain polymer grafting using low energetic UV-A irradiation (3.1-3.9 eV) without breaking PVDF bonds. An EPR study has been performed in order to investigate the nature of involved species. The ability of the activated PVDF surface to graft different kinds of hydrophilic monomers using the initiated surface polymerization method has been tested and discussed on the basis of ATR FT-IR, XPS and NMR HRMAS results

The role of water fittings in intensive care rooms as reservoirs for the colonization of patients with Pseudomonas aeruginosa

International audienceOBJECTIVE: To assess the role of the water environment in the Pseudomonas aeruginosa colonization of patients in intensive care units in the absence of a recognized outbreak. DESIGN AND SETTING: Prospective, single-centre study over an 8-week period in two adult ICUs at a university hospital. Environmental samples were taken from the water fittings of rooms once per week, during a 8-week period. Patients were screened weekly for P. aeruginosa carriage. Environmental and humans isolates were genotyped by using pulsed-field gel electrophoresis. RESULTS: P. aeruginosa was detected in 193 (86.2%) of the 224 U-bend samples and 10 of the 224 samples taken from the tap (4.5%). Seventeen of the 123 patients admitted were colonized with P. aeruginosa. Only one of the 14 patients we were able to evaluate was colonized by a clone present in the water environment of his room before the patient's first positive sample was obtained. CONCLUSION: The role of the water environment in the acquisition of P. aeruginosa by intensive care patients remains unclear, but water fittings seem to play a smaller role in non-epidemic situations than expected by many operational hospital hygiene teams

Design of a 12m stylish cruiser racer yacht.

The aim of this project was developed the full design of cruiser racer yacht with stylish design as priority. The purpose of the yacht was to be mainly a cruiser, but also IMS Rules and Regulations had been considered. The length had to be sufficiently large to have a volume inside for 6 peoples. A small market analysis was done to try to know what the customers want for a sail cruiser now and in the near future

Conception, synthèse et évaluation pharmacologique de thiadiazépines et oxathiazépines potentiellement anticancéreuses

LILLE2-BU Santé-Recherche (593502101) / SudocSudocFranceF

Conception, synthèse et évaluation pharmacologique de nouveaux ligands des PPARS

Le diabète de type II et l'obésité, problèmes majeurs de santé publique, peuvent être considérés comme apparentés. Dans la majorité des cas, le diabète de type II est maintenant considéré comme un composant du groupe de désordre appelé le syndrome métabolique. Les facteurs caractéristiques du syndrome métabolique connu aussi sous le nom de syndrome X dysmétabolique sont l'obésité abdominale, la dyslipidémie athérogénique (triglycéride élevé, LDL bas, HDL-cholestérol bas, pression sanguine élevée), la résistance à l'insuline (avec ou sans intolérance au glucose) et l'état prothrombotique et proinflammatoire. La compréhension du syndrome métabolique a été améliorée par la découverte des récepteurs nucléaires activés par les proliférateurs de peroxisomes (PPARs). Nos travaux ont consisté en la conception de ligands des PPARs alpha/gamma. A partir des recherches antérieures réalisées au laboratoire, nous avons entrepris de moduler la partie malonique du DE84 en un groupement béta-cétoester formant ainsi des composés possédant une activité antagoniste sur PPAR gamma. Puis ce motif malonate a été remplacé par des acides linéaires menant à la synthèse de dérivés montrant une activité agoniste sur PPAR gamma. La troisième partie de nos travaux consistait en la conception de composés possédant le motif alpha-alkoxyacide, commun aux ligands mixtes PPARs alpha/gamma, sur différentes hétérocycles: 5-benzoylbenzothiazolin-2-one, 6-cyclopropanoyl-3H-benzothiazolin-2-one, 6- et 7-benzoyl-4H-benzo[1,4]thiazin-3-one et 6-et7-benzoyl-4H-benzo[1,4]oxazin-3-one. Tous ces composés ont fait ou font encore l'objet d'études pharmacologiques effectuées par les laboratoires Servier.Type II diabetes and obesity are important public health problems and can be considered to be linked. In most cases, type II diabetes is nowadays considered to be a component of group disorder called metabolic syndrome. The factors characterising metabolic syndrome also know by the name syndrome X dysmetabolic are abdominal obesity, artherogenic dyslipidemea (high triglycerides, low LDL, low HDL cholesterol, high blood pressure), insulin resistance (with or without glucose tolerance) as well as prothrombotic state and proinflammatory. The understanding of metabolic syndrome has been improved by the discovery of nuclear receptors activated by the discovery of nuclear receptors activated by peroxisome proliferators (PPARs). Our work consisted of the conception of ligands for PPARs alpha/gamma. From previous research undertaken in the laboratory, we have modulated the malonic part of DE84 to a beta-ketoester thereby forming compounds wich have an antagonist activity on PPARgamma. Then this malonate motif was replaced by linear acids allowing the synthesis of derivatives wich have an agonist activity on PPARgamma. The third part of our work consisted in the conception of compounds containing the a-alkoxyacid motif, common in mixed PPAR alpha/gamma ligands, on different heterocycles: 5-benzoylbenzothiazolin-2-one, 6-cyclopropanoyl-3H-benzothiazolin-2-one, 6- et 7-benzoyl-4H-benzo[1,4]thiazin-3-one et 6- et 7-benzoyl-4H-benzo[1,4]oxazin-3-one. All our compounds have been pharmacologically tested by Les Laboratoires Servier.LILLE2-BU Santé-Recherche (593502101) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

Conception, synthèse et évaluation pharmacologique de ligands mixtes des PPAR a et g dans le traitement du diabète de type 2

Les travaux décrits dans ce mémoire ont conception et la synthèse de ligands mixtes des PPARs alpha et gamma. Après une présentation générale des PPARs (Récepteurs activés par la prolifération des peroxisomes), nous nous sommes attachés à donner des éléments de compréhension du métabolisme des lipoprotéines afin d appréhender leur implication dans des pathologies telles que le diabète de type 2 ou le syndrome métabolique. Nous avons ensuite abordé de façon plus approfondie les diffe rents ligands des sous-types des PPARs afin d en détailler leur mécanisme d actin et leur rôle physiologique. Dans la deuxième partie, nous avons relaté les différents travaux antérieurs du laboratoire sur lesquels nous nous sommes basés, puis sur la conception des molécules synthétisées, de structure de type fibrates, dans le cadre de cette thèse. Enfin, l ensemble des réactions chimiques qui ont été employées a été détaillé dans la troisième partie théorique. Les résultats pharmacologiques ont été précisés et commentés pour chaque série de molécules. L ensemble de ces molécules a été ou est encore testé, in vitro et in vivo, par les laboratoires SERVIER, afin de déterminer leurs activités sur PPAR et PPAR , ainsi que leurs effets sur des marqueurs biologiques tel que les triglycérides, le glucose, la résistance à l insuline.Our work consisted on the design, synthesis and pharmacological evaluation of PPAR and PPAR ligands. After introducing PPAR (Peroxisome Proliferated Activated Receptor), we gived some informations about the metabolism of lipoproteins in order to better understand their implication in differents pathologies as type 2 diabetes and metabolic diseases. PPAR subtypes were then approached and we have detailed the molecular mechanism of action and functional role of their ligands. In the second part, we were based on previous works of our laboratory to design and synthesize new compounds, fibrates structurally related and establish structure-activity relationships in each series. Finally all of chemical reactions will be detailled in the third part and the pharmacological results will be specified and discussed for each series. All these compounds have been or are still being studied in vitro and in vivo by les Laboratoires Servier , in order to determine their affinities and activities on PPAR and PPAR , as well as their effects on biomarkers such as triglycerides, glucose, and insulin resistance.LILLE2-BU Santé-Recherche (593502101) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

Notices biographiques, secteur Sciences humaines et sociales

International audienc

Conception, synthèse et évaluation pharmacologique de ligands des PPARs (Peroxisome Proliferator-Activated Receptors)

L'obésité, le diabète de type 2 et de nombreuses maladies inflammatoires comme l'athérosclérose, sont des pathologies en forte progression depuis ces dix dernières années. Il apparaît que les PPARs (Peroxisome Proliferator-Activated Receptors) interviennent dans la régulation de gènes influençant ces pathologies. Ces facteurs de transcription s'hétérodimérisent avec un autre récepteur nucléaire RXR (récepteur aux acides rétinoïques), après qu'ils soient activés par leurs ligands. Le complexe formé se fixe sur son PPRE (élément de réponse des PPARs) et recrute de nombreux co-facteurs. A partir de travaux antérieurs, une étude suivant le modèle de Topliss a été réalisé sur des structures diesters maloniques. La nécessité d'obtenir des ligands d'activité mixte PPARa/g, nous a conduit à moduler l'extrémité malonate des composés précédents en acides esters, amides esters, acides, amides, nitriles et tétrazoles, en série benzothiazolinone, 6-benzoylbenzothiazolinone et 5-benzoylbenzothiazolinone. L'ensemble de ces molécules a été ou est encore testé, in vitro et in vivo, par les laboratoires SERVIER, afin de déterminer leurs activités sur PPARa et PPARg, ainsi que leurs effets sur des marqueurs biologiques tel que les triglycérides, le glucose, la résistance à l'insuline.Obesity, diabetes (type 2), and many inflammatory illnesses such as arthrosclerosis have become pathologies of great interest over the last ten years. It appears that PPARs (Peroxisome Proliferator-Activated Receptors) play a role in the regulation of genes that influence these pathologies. These transcription factors heterodimerize with another nuclear receptor called RXR (Retinoidal X Receptor), after their activation by their ligands. The complex which forms fixes on PPREs (PPAR response elements) and recruits numerous co-factors. From previous work a study following Topliss was undertaken on the malonic diester structures. The need for ligands which have an activity dual PPARa/g, led us to modulate the extremity of the malonate to acid esters, amide esters, acids, amides, nitrile tetrazoles, to a series benzothiazolinone, and to 5- and 6- benzoylbenzothiazolinone. All of these molecules have or are being tested in vitro and in vivo by the laboratoires Servier , in order to determine their activities on PPARa and PPARg, as well as their effects on biomarkers such as triglycerides, glucose, and insulin resistance.LILLE2-BU Santé-Recherche (593502101) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF