Molecular mechanism of edema formation in nephrotic syndrome: therapeutic implications

Sodium retention and edema are common features of nephrotic syndrome that are classically attributed to hypovolemia and activation of the renin–angiotensin–aldosterone system. However, numbers of clinical and experimental findings argue against this underfill theory. In this review we analyze data from the literature in both nephrotic patients and experimental models of nephrotic syndrome that converge to demonstrate that sodium retention is not related to the renin–angiotensin–aldosterone status and that fluid leakage from capillary to the interstitium does not result from an imbalance of Starling forces, but from changes of the intrinsic properties of the capillary endothelial filtration barrier. We also discuss how most recent findings on the cellular and molecular mechanisms of sodium retention has allowed the development of an efficient treatment of edema in nephrotic patients

The Comparison between Circadian Oscillators in Mouse Liver and Pituitary Gland Reveals Different Integration of Feeding and Light Schedules

The mammalian circadian system is composed of multiple peripheral clocks that are synchronized by a central pacemaker in the suprachiasmatic nuclei of the hypothalamus. This system keeps track of the external world rhythms through entrainment by various time cues, such as the light-dark cycle and the feeding schedule. Alterations of photoperiod and meal time modulate the phase coupling between central and peripheral oscillators. In this study, we used real-time quantitative PCR to assess circadian clock gene expression in the liver and pituitary gland from mice raised under various photoperiods, or under a temporal restricted feeding protocol. Our results revealed unexpected differences between both organs. Whereas the liver oscillator always tracked meal time, the pituitary circadian clockwork showed an intermediate response, in between entrainment by the light regimen and the feeding-fasting rhythm. The same composite response was also observed in the pituitary gland from adrenalectomized mice under daytime restricted feeding, suggesting that circulating glucocorticoids do not inhibit full entrainment of the pituitary clockwork by meal time. Altogether our results reveal further aspects in the complexity of phase entrainment in the circadian system, and suggest that the pituitary may host oscillators able to integrate multiple time cues

Protein Phosphatase 2A Interacts with the Na+,K+-ATPase and Modulates Its Trafficking by Inhibition of Its Association with Arrestin

Background: The P-type ATPase family constitutes a collection of ion pumps that form phosphorylated intermediates during ion transport. One of the best known members of this family is the Na +,K +-ATPase. The catalytic subunit of the Na +,K +-ATPase includes several functional domains that determine its enzymatic and trafficking properties. Methodology/Principal Findings: Using the yeast two-hybrid system we found that protein phosphatase 2A (PP2A) catalytic C-subunit is a specific Na +,K +-ATPase interacting protein. PP-2A C-subunit interacted with the Na +,K +-ATPase, but not with the homologous sequences of the H +,K +-ATPase. We confirmed that the Na +,K +-ATPase interacts with a complex of A- and C-subunits in native rat kidney. Arrestins and G-protein coupled receptor kinases (GRKs) are important regulators of G-protein coupled receptor (GPCR) signaling, and they also regulate Na +,K +-ATPase trafficking through direct association. PP2A inhibits association between the Na +,K +-ATPase and arrestin, and diminishes the effect of arrestin on Na +,K +-ATPase trafficking. GRK phosphorylates the Na +,K +-ATPase and PP2A can at least partially reverse this phosphorylation. Conclusions/Significance: Taken together, these data demonstrate that the sodium pump belongs to a growing list of io

Molecular deformation mechanisms in polyethylene

adjacent labelled stems is significantly larger when the DPE guest is a copolymer molecule. Our comparative studies on various types of polyethylene lead to the conclusion that their deformation behaviour under drawing has the same basis, with additional effects imputed to the presence of tie-molecules and branches. Three major points were identified in this thesis. The changes produced by drawing imply (1) the crystallisation of some of the amorphous polymer and the subsequent orientation of the newly formed crystals, (2) the re-orientation of the crystalline ribbons and (3) the beginning of crystallite break-up. However, additional effects were observed for the high molecular weight linear sample and the copolymer sample and were attributed, respectively, to the presence of tie-molecules and of branches. It was concluded that both the tie-molecules and the branches are restricting the molecular movement during deformation, and that the branches may be acting as 'anchors'. This work is concerned with details of the molecular changes caused by deformation and also establishes any conformational differences between linear and branched polyethylene before, during and after deformation. Four blends of isotopically labelled polymers of different types, rapidly quenched from the melt, have been studied by Mixed Crystal Infra-red Spectroscopy and Small Angle Neutron Scattering (SANS), in order to clarify any differences in the molecular basis of drawing behaviour and in the initial labelled chains conformation. For all sample types, the neutron scattering results suggest that adjacent folding is not the major type of chain folding here. This point is confirmed by our infrared results where most of the crystal stems contributing to the doublet components are in groups of only 3 to 4 adjacent labelled stems. Differences in initial conformation between the linear and copolymer samples were highlighted by both SANS and FTIR techniques. The evolution of the radius of gyration as a function of molecular weight following the relationship R sub g propor to M-bar sub W sup a , determined from the SANS data, is different for linear and copolymer sample types, suggesting a more compact arrangement as the molecular weight of the copolymer DPE guest molecules increases. This was found consistent with the infrared results, where results from both curve fitting and the simulation of the infrared CD sub 2 bending profiles show that the number of small groups o

Molecular deformation mechanisms in polyethylene.

This work is concerned with details of the molecular changes caused by deformation and also establishes any conformational differences between linear and branched polyethylene before, during and after deformation. Four blends of isotopically labelled polymers of different types, rapidly quenched from the melt, have been studied by Mixed Crystal Infra-red Spectroscopy and Small Angle Neutron Scattering (SANS), in order to clarify any differences in the molecular basis of drawing behaviour and in the initial labelled chains conformation. For all sample types, the neutron scattering results suggest that adjacent folding is not the major type of chain folding here. This point is confirmed by our infrared results where most of the crystal stems contributing to the doublet components are in groups of only 3 to 4 adjacent labelled stems. Differences in initial conformation between the linear and copolymer samples were highlighted by both SANS and FTIR techniques. The evolution of the radius of gyration as a function of molecular weight following the relationship Rg ∝ Mw ∝ determined from the SANS data, is different for linear and copolymer sample types, suggesting a more compact arrangement as the molecular weight of the copolymer DPE guest molecules increases. This was found consistent with the infrared results, where results from both curve fitting and the simulation of the infrared CD2 bending profiles show that the number of small groups of adjacent labelled stems is significantly larger when the DPE guest is a copolymer molecule. Our comparative studies on various types of polyethylene lead to the conclusion that their deformation behaviour under drawing has the same basis, with additional effects imputed to the presence of tie-molecules and branches. Three major points were identified in this thesis. The changes produced by drawing imply (1) the crystallisation of some of the amorphous polymer and the subsequent orientation of the newly formed crystals, (2) the re-orientation of the crystalline ribbons and (3) the beginning of crystallite break-up. However, additional effects were observed for the high molecular weight linear sample and the copolymer sample and were attributed, respectively, to the presence of tie- molecules and of branches. It was concluded that both the tie-molecules and the branches are restricting the molecular movement during deformation, and that the branches may be acting as "anchors".</p

La voie intra-osseuse (accès vasculaire en urgence ?)

STRASBOURG-Medecine (674822101) / SudocSudocFranceF

The effect of short chain branching on local chain organisation in isotopically labelled blends of polyethylene

The complementary techniques of small angle neutron scattering (SANS) and infra-red spectroscopy have been used to determine features of molecular trajectory for isotopic blends incorporating linear polyethylene and copolymers containing butyl or hexyl branches. SANS data show both a more compact conformation for a copolymer guest molecule than for a linear guest and also a smaller molecular expansion with increasing molecular weight when both guest and host are copolymers. These blends also show the smallest proportion of {110} isolated guest stems, while wholly linear blends show the largest proportion, on the evidence of the infra-red CD2 bending band profiles. Estimates are made of the sizes of ‘groups’ of adjacent stems, and these also show a corresponding dependence on the sample type, indicating a higher proportion of adjacent re-entry for copolymer blends than for linear blends.</p