75 research outputs found

    NUTRITIONAL REGIMEN OF NEW THERAPEUTIC STRATEGIES IN CHRONIC RENAL FAILURE

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    Nowadays the number of the patients with chronic renal failure and the syndrome of end-stage renal disease permanently increases. New dietary regimens are necessary to improve the status of the patients with severe kidney diseases. Nutrition plays an essential role in the contemporary approach to the management of the patients with renal failure. Low-protein diet delays the progression of the renal failure. The meta-analysis of the effect of dietary protein restriction on the course of diabetic and non-diabetic renal diseases outlines the importance of the adequate correction of the uremic syndrome and the absence of side effects of this nutritional regimen. The development of appropriate diet therapy to be administered at the predialytic stage of the disease could prevent or at least delay the progression of chronic renal failure and, in this way, it represents a challenge for the nephrologists and hope for the patients

    The amyloid precursor protein controls PIKfyve function

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    While the Amyloid Precursor Protein (APP) plays a central role in Alzheimer's disease, its cellular function still remains largely unclear. It was our goal to establish APP function which will provide insights into APP's implication in Alzheimer's disease. Using our recently developed proteo-liposome assay we established the interactome of APP's intracellular domain (known as AICD), thereby identifying novel APP interactors that provide mechanistic insights into APP function. By combining biochemical, cell biological and genetic approaches we validated the functional significance of one of these novel interactors. Here we show that APP binds the PIKfyve complex, an essential kinase for the synthesis of the endosomal phosphoinositide phosphatidylinositol-3,5-bisphosphate. This signalling lipid plays a crucial role in endosomal homeostasis and receptor sorting. Loss of PIKfyve function by mutation causes profound neurodegeneration in mammals. Using C. elegans genetics we demonstrate that APP functionally cooperates with PIKfyve in vivo. This regulation is required for maintaining endosomal and neuronal function. Our findings establish an unexpected role for APP in the regulation of endosomal phosphoinositide metabolism with dramatic consequences for endosomal biology and important implications for our understanding of Alzheimer's disease

    Role of SNX16 in the Dynamics of Tubulo-Cisternal Membrane Domains of Late Endosomes

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    In this paper, we report that the PX domain-containing protein SNX16, a member of the sorting nexin family, is associated with late endosome membranes. We find that SNX16 is selectively enriched on tubulo-cisternal elements of this membrane system, whose highly dynamic properties and formation depend on intact microtubules. By contrast, SNX16 was not found on vacuolar elements that typically contain LBPA, and thus presumably correspond to multivesicular endosomes. We conclude that SNX16, together with its partner phosphoinositide, define a highly dynamic subset of late endosomal membranes, supporting the notion that late endosomes are organized in distinct morphological and functional regions. Our data also indicate that SNX16 is involved in tubule formation and cholesterol transport as well as trafficking of the tetraspanin CD81, suggesting that the protein plays a role in the regulation of late endosome membrane dynamics

    A Kinome RNAi Screen Identified AMPK as Promoting Poxvirus Entry through the Control of Actin Dynamics

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    Poxviruses include medically important human pathogens, yet little is known about the specific cellular factors essential for their replication. To identify genes essential for poxvirus infection, we used high-throughput RNA interference to screen the Drosophila kinome for factors required for vaccinia infection. We identified seven genes including the three subunits of AMPK as promoting vaccinia infection. AMPK not only facilitated infection in insect cells, but also in mammalian cells. Moreover, we found that AMPK is required for macropinocytosis, a major endocytic entry pathway for vaccinia. Furthermore, we show that AMPK contributes to other virus-independent actin-dependent processes including lamellipodia formation and wound healing, independent of the known AMPK activators LKB1 and CaMKK. Therefore, AMPK plays a highly conserved role in poxvirus infection and actin dynamics independent of its role as an energy regulator

    LDL - Apheresis: review of recent methods

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    Hyper cholesterolemia and the resulting atherosclerosis has been a major problem for the past few decades. Adequate control of serum cholesterol levels is generally achieved by dietary modifications and/or drug regimens. However some patients, particularly those with familial hyper cholesterolemia, fail to respond. Additional treatment methods may be necessary to reduce LDL to safer levels in these individuals who are at high risk for atherosclerotic disease complications. Reduction of lipoproteins and Lp(a), of oxidation of LDL, improvement of the procoagulatory state and disturbed hemorheology associated with atherosclerosis, as well as the stabilization of plaques and the decrease of cytokines and adhesion molecules have been induced by apheresis and are thought to favorably influence regression of artherosclerosis

    The effect of the plasma composition on characteristics of the d.c. arc - V The influence of iodine vapour on the radial temperature distribution of the arc burning in the atmosphere of nitrogen and argon

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    Considering the solutions of the Elenbaas-Heller energy balance equation it is possible to indicate how the chemical reactions among the components of added substances influence the radial temperature distribution in the arc. In the case of addition of iodine vapour to the atmosphere of nitrogen, and argon respectively, a core of higher temperature with a larger gradient of the radial temperature distribution in the arc centre is formed. These conclusions are confirmed by experimental determinations of the radial temperature distribution

    The effect of the plasma composition on characteristics of the d.c. arc - I General discussion of the effect of the chemical reactions

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    The influence of chemical reactions among the components of the arc atmosphere on the radial temperature distribution is discussed. Their effect on other arc plasma characteristics and the spectrochemieal determination of elements in the arc is considered. The discussion is made in terms of the Elenbaas-Heller equation for the energy balance of the plasma. The equation is solved according to Maecker. The arc model is a freely burning arc, under conditions usually applied in spectrochemical practice. The role of dissociation energy is discussed on the basis of a theoretical model. Experimental and theoretical data for the radial temperature distribution of an arc burning in nitrogen are compared to check the appropriateness of the applied procedures

    Sodium and body fluid homeostasis in profiling hemodialysis treatment

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    Acute adverse side-effects of hemodialysis such as hypotension, muscle cramps, osmotic imbalance and thirst are induced by the interference with fluid and electrolyte balance occurring during treatment. Changes in osmolarity due to alterations of plasma sodium concentration during hemodialysis strongly influence fluid distribution between extracellular and intracellular fluid volume. Increased sodium dialysate concentration induces fluid shift from the intracellular to the extracellular compartment. This shift leads to a more efficient ultrafiltration by increasing plasma refilling volume but also to an increased thirst. Treatment of hypotension, cramps and nausea with hypertonic saline solution leads also to a considerable retention of sodium. Profiling hemodialysis consists in deliberately changing ultrafiltration and dialysate, sodium in order to combine an efficient ultrafiltration with a balanced sodium handling and to prevent side-effects during treatment. Continuous measurement and control of blood volume seems to be the best method to prevent hypotensive episodes. Profiling of sodium should not be the cause of a positive sodium balance. The clinical benefits of sodium profiling to the patients have still to be proven

    The effect of the plasma composition on characteristics of the d.c. arc-II. Arc in argon and arc in nitrogen with water vapour

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    The experimental and theoretical curves of the radial temperature distribution of the arc burning in argon, are compared with the corresponding curves in nitrogen. The theoretical curves are obtained by solving the Elenbaas-Heller energy balance equation according to Maecker. The model of the freely burning arc, under conditions usually applied in spectrochemical praxis, is considered. In accordance with theory and in comparison with the arc burning in pure nitrogen, the brilliant zone of arcs burning in argon has a steeper radial temperature distribution. If water vapour is added to an arc burning in nitrogen, the arc plasma is narrowed and the temperature increased. These experimental data can be interpreted theoretically from the solution of the energy balance equation
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