22 research outputs found

    Molecular mechanism of edema formation in nephrotic syndrome: therapeutic implications

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    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

    A multidisciplinary systematic review of the use of diagrams as a means of collecting data from research subjects: application, benefits and recommendations

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    BACKGROUND: In research, diagrams are most commonly used in the analysis of data and visual presentation of results. However there has been a substantial growth in the use of diagrams in earlier stages of the research process to collect data. Despite this growth, guidance on this technique is often isolated within disciplines. METHODS: A multidisciplinary systematic review was performed, which included 13 traditional healthcare and non-health-focused indexes, non-indexed searches and contacting experts in the field. English-language articles that used diagrams as a data collection tool and reflected on the process were included in the review, with no restriction on publication date. RESULTS: The search identified 2690 documents, of which 80 were included in the final analysis. The choice to use diagrams for data collection is often determined by requirements of the research topic, such as the need to understand research subjects' knowledge or cognitive structure, to overcome cultural and linguistic differences, or to understand highly complex subject matter. How diagrams were used for data collection varied by the degrees of instruction for, and freedom in, diagram creation, the number of diagrams created or edited and the use of diagrams in conjunction with other data collection methods. Depending on how data collection is structured, a variety of options for qualitative and quantitative analysis are available to the researcher. The review identified a number of benefits to using diagrams in data collection, including the ease with which the method can be adapted to complement other data collection methods and its ability to focus discussion. However it is clear that the benefits and challenges of diagramming depend on the nature of its application and the type of diagrams used. DISCUSSION/CONCLUSION: The results of this multidisciplinary systematic review examine the application of diagrams in data collection and the methods for analyzing the unique datasets elicited. Three recommendations are presented. Firstly, the diagrammatic approach should be chosen based on the type of data needed. Secondly, appropriate instructions will depend on the approach chosen. And thirdly, the final results should present examples of original or recreated diagrams. This review also highlighted the need for a standardized terminology of the method and a supporting theoretical framework

    Hyperaldosteronemia and activation of the epithelial sodium channel are not required for sodium retention in puromycin-induced nephrosis

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    Edema and ascites in nephrotic syndrome mainly result from increased Na+ reabsorption along connecting tubules and cortical collecting ducts (CCD). In puromycin aminonucleoside (PAN)-induced nephrosis, increased Na+ reabsorption is associated with increased activity of the epithelial sodium channel (ENaC) and Na+,K+-ATPase, two targets of aldosterone. Because plasma aldosterone increases in PAN-nephrotic rats, the aldosterone dependence of ENaC activation in PAN nephrosis was investigated. For this purpose, (1) the mechanism of ENaC activation was compared in nephrotic and sodium-depleted rats, and (2) ENaC activity in PAN-nephrotic rats was evaluated in the absence of hyperaldosteronemia. The mechanism of ENaC activation was similar in CCD from nephrotic and sodium-depleted rats, as demonstrated by (1) increased number of active ENaC evaluated by patch clamp, (2) recruitment of ENaC to the apical membrane determined by immunohistochemistry, (3) shift in the electrophoretic profile of gamma-ENaC, and (4) increased abundance of beta-ENaC mRNA. Corticosteroid clamp fully prevented all PAN-induced changes in ENaC but did not alter the development of a full-blown nephrotic syndrome with massive albuminuria, amiloride-sensitive sodium retention, induction of CCD Na+,K+-ATPase, and ascites. It is concluded that in PAN-nephrosis, (1) ENaC activation in CCD is secondary to hyperaldosteronemia, (2) sodium retention and induction of Na+,K+-ATPase in CCD are independent of hyperaldosteronemia, and (3) ENaC is not necessarily limiting for sodium reabsorption in the distal nephron

    YAP protects the eye from uveitic glaucoma by preserving retinal and anterior chamber homeostases

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    https://iovs.arvojournals.org/article.aspx?articleid=2775349International audienceThe role of the transcription coactivator YAP has been studied during eye development but its implication in ocular homeostasis and diseases is much less documented. YAP is expressed by several ocular cell types including the non-pigmented cells of the ciliary body (CB) as well as MĂŒller glial cells (MGs) of the neuroretina. Here, we assessed whether postnatal Yap deletion in these two cell types could affect eye homeostasis during aging.Methods : Specific Yap deletion in CB and MGs was induced in a conditional mouse model (Yap cKO) at P10. The phenotype was investigated by western-blot, immunohistochemistry, and RNA-sequencing (RNA-seq). Blood defects were identified by fluorescein angiography. Optic nerve degeneration was assessed by optical coherence tomography. Intraocular pressure (IOP) was recorded by a rebound tonometer. Imaging of the CB in healthy and uveitic human patients was performed by ultrasound biomicroscopy

    Late-onset glaucoma in Yap conditional knockout mouse

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    Abstract Glaucoma is an optic neuropathy often referred to as “the silent thief of sight”, due to its late diagnosis, which is generally made when degeneration of the optic nerve and retinal ganglion cells is already well under way. It is thus of utmost importance to have a better understanding of the disease, and to investigate more deeply the early causes of glaucoma. The transcriptional coactivator YAP recently emerged as an important regulator of eye homeostasis and is drawing attention in the glaucoma research field. Here we show that Yap conditional knockout mice ( Yap cKO), in which the deletion of Yap is induced in both MĂŒller glia ( i.e . the only retinal YAP-expressing cells) and the non-pigmented epithelial cells of the ciliary body, exhibit breakdown of the aqueous-blood barrier accompanied by progressive collapse of the ciliary body as we observed in human uveitic patients. In addition, aged Yap cKO mice harbor glaucoma features, including alteration of glutamate recycling, deregulation of key homeostatic MĂŒller-derived proteins, retinal vascular defects, optic nerve degeneration, and retinal ganglion cell death. Together, our findings reveal the essential role of YAP in preserving the ciliary body and the retinal ganglion cells, thereby preventing the onset of glaucoma features

    Nanostructured and Conventional Cr2O3, TiO2, and TiO2-Cr2O3 Thermal-Sprayed Coatings for Metal-Seated Ball Valve Applications in Hydrometallurgy

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    A detailed characterization project was undertaken by Velan, an international industrial valve designer and manufacturer, in collaboration with the National Research Council of Canada, Boucherville, and Polytechnique Montr\ue9al. The purpose was to assess the mechanical and tribological resistances of promising ceramic coatings for hydrometallurgy applications, including a novel n-TiO\u2082-Cr\u2082O\u2083 blend. Hardness and shear strength were determined using microhardness indentation testers and universal tensile testing equipment. Wear resistance of the coatings under sliding wear, abrasion, and galling conditions were measured by standard pin-on-disk tests, abrasion tests, and custom-designed galling tests. The main result is that the synergy between Cr\u2082O\u2083 and n-TiO\u2082 produced abrasion performance exceeding that of these materials alone. Also, an optimized balance between the hard and brittle Cr\u2082O\u2083 phases and the soft and ductile n-TiO\u2082 phases resulted in higher abrasion, sliding, and galling resistance. The novel n-TiO\u2082-Cr\u2082O\u2083 blend is therefore considered as a promising evolution of the current TiO\u2082-Cr\u20822O\u20833 blend.Peer reviewed: YesNRC publication: Ye
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