Sitagliptin reduces cardiac apoptosis, hypertrophy and fibrosis primarily by insulin-dependent mechanisms in experimental type-II diabetes. Potential roles of GLP-1 isoforms

Background:Myocardial fibrosis is a key process in diabetic cardiomyopathy. However, their underlying mechanisms have not been elucidated, leading to a lack of therapy. The glucagon-like peptide-1 (GLP-1) enhancer, sitagliptin, reduces hyperglycemia but may also trigger direct effects on the heart.Methods:Goto-Kakizaki (GK) rats developed type-II diabetes and received sitagliptin, an anti-hyperglycemic drug (metformin) or vehicle (n=10, each). After cardiac structure and function assessment, plasma and left ventricles were isolated for biochemical studies. Cultured cardiomyocytes and fibroblasts were used for in vitro assays.Results:Untreated GK rats exhibited hyperglycemia, hyperlipidemia, plasma GLP-1 decrease, and cardiac cell-death, hypertrophy, fibrosis and prolonged deceleration time. Moreover, cardiac pro-apoptotic/necrotic, hypertrophic and fibrotic factors were up-regulated. Importantly, both sitagliptin and metformin lessened all these parameters. In cultured cardiomyocytes and cardiac fibroblasts, high-concentration of palmitate or glucose induced cell-death, hypertrophy and fibrosis. Interestingly, GLP-1 and its insulinotropic-inactive metabolite, GLP-1(9-36), alleviated these responses. In addition, despite a specific GLP-1 receptor was only detected in cardiomyocytes, GLP-1 isoforms attenuated the pro-fibrotic expression in cardiomyocytes and fibroblasts. In addition, GLP-1 receptor signalling may be linked to PPARδ activation, and metformin may also exhibit anti-apoptotic/necrotic and anti-fibrotic direct effects in cardiac cells.Conclusions:Sitagliptin, via GLP-1 stabilization, promoted cardioprotection in type-II diabetic hearts primarily by limiting hyperglycemia e hyperlipidemia. However, GLP-1 and GLP-1(9-36) promoted survival and anti-hypertrophic/fibrotic effects on cultured cardiac cells, suggesting cell-autonomous cardioprotective actionsThis work was supported by national funding from Ministerio de Educación y Ciencia (SAF2009-08367), Comunidad de Madrid (CCG10-UAM/ BIO-5289), and a unrestricted grant from by Merck/MS

Experimental study of a closed loop flat plate pulsating heat pipe under a varying gravity force

This paper reports on an experimental study of a closed loop Flat Plate Pulsating Heat Pipe (FPPHP) tested on ground and on board of an aircraft during the 60th ESA parabolic flight campaign, during which hyper- and microgravity conditions were reproduced. The tested FPPHP consists in two brazed copper plates, at which location a continuous rectangular channel (1.6 x 1.7 mm²) with 12 bends in the evaporator is machined. The channel is filled with FC-72 as working fluid with a volumetric filling ratio of 50%. Tests have been conducted with the FPPHP positioned both horizontally and vertically (bottom-heated). The FPPHP presents an innovative design, involving the milling of grooves between the channels. Experimental results on the ground show that the thermal device can transfer more than 180 W in both inclinations, and that the horizontal operation is characterized by repeated stop-and-start phases and lower thermal performance. The FPPHP can operate under microgravity conditions and with a transient gravity force, with global thermal resistance reaching 50% and 25% of a void only-conduction plate, in horizontal and vertical orientation respectively. The temperature homogeneity remains within 10K in the evaporator section and 3K in the condenser section with thermal power transfer up to 180 W. Minimum thermal resistance of 0.12 KW-1 was recorded, with its value rising as heating grew more powerful. A parabolic flight test demonstrated that the FPPHP in vertical inclination is rapidly influenced by variation of gravity field, even if, due to the novel geometry, it continues to operate under microgravity. In horizontal inclination, on the other hand, there was no observable parameter change during gravity field variations

Sensitivity of Clay Suspension Rheological Properties to pH, Temperature, Salinity, and Smectite-Quartz Ratio

Understanding the rheological properties of clay suspensions is critical to assessing the behavior of sediment gravity flows such as debris flow or turbidity current. We conducted rheological measurements of composite smectite-quartz suspensions at a temperature of 7 degrees C and a salt concentration of 0.6M. This is representative of smectite-bearing sediments under conditions on the seafloor. The flow curves obtained were fitted by the Bingham fluid model, from which we determined the Bingham yield stress and dynamic viscosity of each suspension. At a constant smectite-quartz mixing ratio, the yield stress and the dynamic viscosity tend to increase as the solid/water ratio of the suspension is increased. In the case of a constant solid/water ratio, these values increase with increasing smectite content in the smectite-quartz mixture. Additional experiments exploring differing physicochemical conditions (pH1.0-9.0; temperature 2-30 degrees C; and electrolyte (NaCl) concentration 0.2-0.6M) revealed that the influence of temperature is negligible, while pH moderately affects the rheology of the suspension. More significantly, the electrolyte concentration greatly affects the flow behavior. These variations can be explained by direct and/or indirect (double-layer) interactions between smectite-smectite particles as well as between smectite-quartz particles in the suspension. Although smectite is known as a frictionally weak material, our experimental results suggest that its occurrence can reduce the likelihood that slope failure initiates. Furthermore, smectite can effectively suppress the spreading distance once the slope has failed