The Rho-GTPase binding protein IQGAP2 is required for the glomerular filtration barrier.

Science.gov (United States)

Sugano, Yuya; Lindenmeyer, Maja T; Auberger, Ines; Ziegler, Urs; Segerer, Stephan; Cohen, Clemens D; Neuhauss, Stephan C F; Loffing, Johannes

2015-11-01

Podocyte dysfunction impairs the size selectivity of the glomerular filter, leading to proteinuria, hypoalbuminuria, and edema, clinically defined as nephrotic syndrome. Hereditary forms of nephrotic syndrome are linked to mutations in podocyte-specific genes. To identify genes contributing to podocyte dysfunction in acquired nephrotic syndrome, we studied human glomerular gene expression data sets for glomerular-enriched gene transcripts differentially regulated between pretransplant biopsy samples and biopsies from patients with nephrotic syndrome. Candidate genes were screened by in situ hybridization for expression in the zebrafish pronephros, an easy-to-use in vivo assay system to assess podocyte function. One glomerulus-enriched product was the Rho-GTPase binding protein, IQGAP2. Immunohistochemistry found a strong presence of IQGAP2 in normal human and zebrafish podocytes. In zebrafish larvae, morpholino-based knockdown of iqgap2 caused a mild foot process effacement of zebrafish podocytes and a cystic dilation of the urinary space of Bowman's capsule upon onset of urinary filtration. Moreover, the glomerulus of zebrafish morphants showed a glomerular permeability for injected high-molecular-weight dextrans, indicating an impaired size selectivity of the glomerular filter. Thus, IQGAP2 is a Rho-GTPase binding protein, highly abundant in human and zebrafish podocytes, which controls normal podocyte structure and function as evidenced in the zebrafish pronephros.

An in vitro model of the glomerular capillary wall using electrospun collagen nanofibres in a bioartificial composite basement membrane.

Directory of Open Access Journals (Sweden)

Sadie C Slater

Full Text Available The filtering unit of the kidney, the glomerulus, contains capillaries whose walls function as a biological sieve, the glomerular filtration barrier. This comprises layers of two specialised cells, glomerular endothelial cells (GEnC and podocytes, separated by a basement membrane. Glomerular filtration barrier function, and dysfunction in disease, remains incompletely understood, partly due to difficulties in studying the relevant cell types in vitro. We have addressed this by generation of unique conditionally immortalised human GEnC and podocytes. However, because the glomerular filtration barrier functions as a whole, it is necessary to develop three dimensional co-culture models to maximise the benefit of the availability of these cells. Here we have developed the first two tri-layer models of the glomerular capillary wall. The first is based on tissue culture inserts and provides evidence of cell-cell interaction via soluble mediators. In the second model the synthetic support of the tissue culture insert is replaced with a novel composite bioartificial membrane. This consists of a nanofibre membrane containing collagen I, electrospun directly onto a micro-photoelectroformed fine nickel supporting mesh. GEnC and podocytes grew in monolayers on either side of the insert support or the novel membrane to form a tri-layer model recapitulating the human glomerular capillary in vitro. These models will advance the study of both the physiology of normal glomerular filtration and of its disruption in glomerular disease.

Glomerular Damage in Experimental Proliferative Glomerulonephritis Under Glomerular Capillary Hypertension

Directory of Open Access Journals (Sweden)

Pei-Rong Wang

2015-03-01

Full Text Available Background/Aims: Immunologically and hemodynamically mediated the destruction of glomerular architecture is thought to be the major causes of end-stage renal failure. The purpose of this study is to evaluate the effect of glomerular hypertension on glomerular injury and the progression of glomerular sclerosis after Thy-1 nephritis was induced. Method: Thy-1 nephritis was induced in the stroke-prone spontaneously hypertensive rat strain (SHR-SP (group SP and in age-matched Wistar-Kyoto (WKY (group WKY rats, following unilateral nephrectomy (UNX, and a vehicle was injected alone in UNX SHR-SP as control (group SC. Result: The degree of glomerular damage in response to a single dose of anti-thy-1 antibody, and its functional consequences (eg. proteinuria, diminished GFR are more pronounced in group SP than normotensive group WKY and hypertensive group SC without mesangial cell injury. While normotensive group WKY rats recovered completely from mesangial cell injury on day 28-42, glomeruli in group SP kept on persistent macrophage infiltration, α-SMA expression on day 42-56. In addition, glomerular capillary repair with the GECs was rarely seen in pronouncedly proliferative and sclerostic areas. The incidence of glomerular sclerosis and the level of proteinuria were markedly increased by day 56 in the group SP. Conclusions: Our results demonstrate that glomerular hypertension aggravate glomerular damage and glomerulosclerosis in this model of Thy 1 nephritis.

Parietal cells-new perspectives in glomerular disease.

Science.gov (United States)

Miesen, Laura; Steenbergen, Eric; Smeets, Bart

2017-07-01

In normal glomeruli, parietal epithelial cells (PECs) line the inside of Bowman's capsule and form an inconspicuous sheet of flat epithelial cells in continuity with the proximal tubular epithelial cells (PTECs) at the urinary pole and with the podocytes at the vascular pole. PECs, PTECs and podocytes have a common mesenchymal origin and are the result of divergent differentiation during embryogenesis. Podocytes and PTECs are highly differentiated cells with well-established functions pertaining to the maintenance of the filtration barrier and transport, respectively. For PECs, no specific function other than a structural one has been known until recently. Possible important functions for PECs in the fate of the glomerulus in glomerular disease have now become apparent: (1) PECs may be involved in the replacement of lost podocytes; (2) PECs form the basis of extracapillary proliferative lesions and subsequent sclerosis in glomerular disease. In addition to the acknowledgement that PECs are crucial in glomerular disease, knowledge has been gained regarding the molecular processes driving the phenotypic changes and behavior of PECs. Understanding these molecular processes is important for the development of specific therapeutic approaches aimed at either stimulation of the regenerative function of PECs or inhibition of the pro-sclerotic action of PECs. In this review, we discuss recent advances pertaining to the role of PECs in glomerular regeneration and disease and address the major molecular processes involved.

A permselective CeO{sub x} coating to improve the stability of oxygen evolution electrocatalysts

Energy Technology Data Exchange (ETDEWEB)

Obata, Keisuke; Takanabe, Kazuhiro [King Abdullah University of Science and Technology (KAUST), KAUST Catalysis Center (KCC) and Physical Sciences and Engineering Division PSE, Thuwal (Saudi Arabia)

2018-02-05

Highly active NiFeO{sub x} electrocatalysts for the oxygen evolution reaction (OER) suffer gradual deactivation with time owing to the loss of Fe species from the active sites into solution during catalysis. The anodic deposition of a CeO{sub x} layer prevents the loss of such Fe species from the OER catalysts, achieving a highly stable performance. The CeO{sub x} layer does not affect the OER activity of the catalyst underneath but exhibits unique permselectivity, allowing the permeation of OH{sup -} and O{sub 2} through while preventing the diffusion of redox ions through the layer to function as a selective O{sub 2}-evolving electrode. The use of such a permselective protective layer provides a new strategy for improving the durability of electrocatalysts. (copyright 2018 Wiley-VCH Verlag GmbH and Co. KGaA, Weinheim)

Protective clothing based on permselective membrane and carbon adsorption

International Nuclear Information System (INIS)

Gottschlich, D.; Baker, R.

1995-01-01

This paper is a description of Phase I of the US DOE's program to develop improved protective clothing for use by workers engaged in decommissioning and decontamination of former DOE sites, including those used for atomic weapons research and production. Membrane Technology and Research has been developing the clothing with an innovative feature of an ultrathin, permselective outer membrane that is extremely permeable to water but impermeable to toxic organic compounds. Phase I (as described herein) includes fabric optimization, commercial-scale fabric production, and prototype suit evaluation. This phase is complete, with the results discussed in this document

Soluble CD40 ligand directly alters glomerular permeability and may act as a circulating permeability factor in FSGS.

Science.gov (United States)

Doublier, Sophie; Zennaro, Cristina; Musante, Luca; Spatola, Tiziana; Candiano, Giovanni; Bruschi, Maurizio; Besso, Luca; Cedrino, Massimo; Carraro, Michele; Ghiggeri, Gian Marco; Camussi, Giovanni; Lupia, Enrico

2017-01-01

CD40/CD40 ligand (CD40L) dyad, a co-stimulatory bi-molecular complex involved in the adaptive immune response, has also potent pro-inflammatory actions in haematopoietic and non-haematopoietic cells. We describe here a novel role for soluble CD40L (sCD40L) as modifier of glomerular permselectivity directly acting on glomerular epithelial cells (GECs). We found that stimulation of CD40, constitutively expressed on GEC cell membrane, by the sCD40L rapidly induced redistribution and loss of nephrin in GECs, and increased albumin permeability in isolated rat glomeruli. Pre-treatment with inhibitors of CD40-CD40L interaction completely prevented these effects. Furthermore, in vivo injection of sCD40L induced a significant reduction of nephrin and podocin expression in mouse glomeruli, although no significant increase of urine protein/creatinine ratio was observed after in vivo injection. The same effects were induced by plasma factors partially purified from post-transplant plasma exchange eluates of patients with focal segmental glomerulosclerosis (FSGS), and were blocked by CD40-CD40L inhibitors. Moreover, 17 and 34 kDa sCD40L isoforms were detected in the same plasmapheresis eluates by Western blotting. Finally, the levels of sCD40Lwere significantly increased in serum of children both with steroid-sensitive and steroid-resistant nephrotic syndrome (NS), and in adult patients with biopsy-proven FSGS, compared to healthy subjects, but neither in children with congenital NS nor in patients with membranous nephropathy. Our results demonstrate that sCD40L directly modifies nephrin and podocin distribution in GECs. Moreover, they suggest that sCD40L contained in plasmapheresis eluates from FSGS patients with post-transplant recurrence may contribute, presumably cooperating with other mediators, to FSGS pathogenesis by modulating glomerular permeability.

Soluble CD40 ligand directly alters glomerular permeability and may act as a circulating permeability factor in FSGS.

Directory of Open Access Journals (Sweden)

Sophie Doublier

Full Text Available CD40/CD40 ligand (CD40L dyad, a co-stimulatory bi-molecular complex involved in the adaptive immune response, has also potent pro-inflammatory actions in haematopoietic and non-haematopoietic cells. We describe here a novel role for soluble CD40L (sCD40L as modifier of glomerular permselectivity directly acting on glomerular epithelial cells (GECs. We found that stimulation of CD40, constitutively expressed on GEC cell membrane, by the sCD40L rapidly induced redistribution and loss of nephrin in GECs, and increased albumin permeability in isolated rat glomeruli. Pre-treatment with inhibitors of CD40-CD40L interaction completely prevented these effects. Furthermore, in vivo injection of sCD40L induced a significant reduction of nephrin and podocin expression in mouse glomeruli, although no significant increase of urine protein/creatinine ratio was observed after in vivo injection. The same effects were induced by plasma factors partially purified from post-transplant plasma exchange eluates of patients with focal segmental glomerulosclerosis (FSGS, and were blocked by CD40-CD40L inhibitors. Moreover, 17 and 34 kDa sCD40L isoforms were detected in the same plasmapheresis eluates by Western blotting. Finally, the levels of sCD40Lwere significantly increased in serum of children both with steroid-sensitive and steroid-resistant nephrotic syndrome (NS, and in adult patients with biopsy-proven FSGS, compared to healthy subjects, but neither in children with congenital NS nor in patients with membranous nephropathy. Our results demonstrate that sCD40L directly modifies nephrin and podocin distribution in GECs. Moreover, they suggest that sCD40L contained in plasmapheresis eluates from FSGS patients with post-transplant recurrence may contribute, presumably cooperating with other mediators, to FSGS pathogenesis by modulating glomerular permeability.

Glomerular Disease in Women

Directory of Open Access Journals (Sweden)

Kate Wiles

2018-03-01

Full Text Available Gender differences exist in the prevalence of glomerular diseases. Data based on histological diagnosis underestimate the prevalence of preeclampsia, which is almost certainly the commonest glomerular disease in the world, and uniquely gender-specific. Glomerular disease affects fertility via disease activity, the therapeutic use of cyclophosphamide, and underlying chronic kidney disease. Techniques to preserve fertility during chemotherapy and risk minimization of artificial reproductive techniques are considered. The risks, benefits, and effectiveness of different contraceptive methods for women with glomerular disease are outlined. Glomerular disease increases the risk of adverse outcomes in pregnancy, including preeclampsia; yet, diagnosis of preeclampsia is complicated by the presence of hypertension and proteinuria that precede pregnancy. The role of renal biopsy in pregnancy is examined, in addition to the use of emerging angiogenic biomarkers. The safety of drugs prescribed for glomerular disease in relation to reproductive health is detailed. The impact of both gender and pregnancy on long-term prognosis is discussed.

Cross-Linkable Polyimide Membranes for Improved Plasticization Resistance and Permselectivity in Sour Gas Separations

KAUST Repository

Kraftschik, Brian

2013-09-10

A series of cross-linkable membrane materials based on the 6FDA-DAM:DABA (3:2) polyimide backbone were synthesized for improved sour gas separation performance, in terms of both membrane stability and permselectivity. Short-chain poly(ethylene glycol) (PEG) molecules were used as cross-linking agents in an esterification-based cross-linking reaction. Pure and mixed gas permeation and pure gas sorption experiments were performed on dense films of these materials. Compared to unmodified 6FDA-DAM:DABA (3:2), higher sour gas permselectivity and membrane stability were achieved under aggressive feed conditions. H2S-induced plasticization was not evident until pure H2S feed pressures greater than approximately 6-8 bar. Pure CO 2-induced plasticization only occurred at feed pressures greater than about 25 bar. Under mixed gas feed conditions with 20% H2S, 20% CO2, and 60% CH4 at 35 C, attractive selectivities above 22 and 27 for H2S/CH4 and CO2/CH4, respectively, were observed for a feed pressure of 62 bar with both triethylene glycol and tetraethylene glycol cross-linking agents. © 2013 American Chemical Society.

Cross-Linkable Polyimide Membranes for Improved Plasticization Resistance and Permselectivity in Sour Gas Separations

KAUST Repository

Kraftschik, Brian; Koros, William J.

2013-01-01

A series of cross-linkable membrane materials based on the 6FDA-DAM:DABA (3:2) polyimide backbone were synthesized for improved sour gas separation performance, in terms of both membrane stability and permselectivity. Short-chain poly(ethylene glycol) (PEG) molecules were used as cross-linking agents in an esterification-based cross-linking reaction. Pure and mixed gas permeation and pure gas sorption experiments were performed on dense films of these materials. Compared to unmodified 6FDA-DAM:DABA (3:2), higher sour gas permselectivity and membrane stability were achieved under aggressive feed conditions. H2S-induced plasticization was not evident until pure H2S feed pressures greater than approximately 6-8 bar. Pure CO 2-induced plasticization only occurred at feed pressures greater than about 25 bar. Under mixed gas feed conditions with 20% H2S, 20% CO2, and 60% CH4 at 35 C, attractive selectivities above 22 and 27 for H2S/CH4 and CO2/CH4, respectively, were observed for a feed pressure of 62 bar with both triethylene glycol and tetraethylene glycol cross-linking agents. © 2013 American Chemical Society.

Evaluation of the Parameters and Conditions of Process in the Ethylbenzene Dehydrogenation with Application of Permselective Membranes to Enhance Styrene Yield.

Science.gov (United States)

Araújo, Paulo Jardel P; Leite, Manuela Souza; Ravagnani, Teresa M Kakuta

2016-01-01

Styrene is an important monomer in the manufacture of thermoplastic. Most of it is produced by the catalytic dehydrogenation of ethylbenzene. In this process that depends on reversible reactions, the yield is usually limited by the establishment of thermodynamic equilibrium in the reactor. The styrene yield can be increased by using a hybrid process, with reaction and separation simultaneously. It is proposed using permselective composite membrane to remove hydrogen and thus suppress the reverse and secondary reactions. This paper describes the simulation of a dehydrogenation process carried out in a tubular fixed-bed reactor wrapped in a permselective composite membrane. A mathematical model was developed, incorporating the various mass transport mechanisms found in each of the membrane layers and in the catalytic fixed bed. The effects of the reactor feed conditions (temperature, steam-to-oil ratio, and the weight hourly space velocity), the fixed-bed geometry (length, diameter, and volume), and the membrane geometry (thickness of the layers) on the styrene yield were analyzed. These variables were used to determine experimental conditions that favour the production of styrene. The simulation showed that an increase of 40.98% in the styrene yield, compared to a conventional fixed-bed process, could be obtained by wrapping the reactor in a permselective composite membrane.

Evaluation of the Parameters and Conditions of Process in the Ethylbenzene Dehydrogenation with Application of Permselective Membranes to Enhance Styrene Yield

Directory of Open Access Journals (Sweden)

Paulo Jardel P. Araújo

2016-01-01

Full Text Available Styrene is an important monomer in the manufacture of thermoplastic. Most of it is produced by the catalytic dehydrogenation of ethylbenzene. In this process that depends on reversible reactions, the yield is usually limited by the establishment of thermodynamic equilibrium in the reactor. The styrene yield can be increased by using a hybrid process, with reaction and separation simultaneously. It is proposed using permselective composite membrane to remove hydrogen and thus suppress the reverse and secondary reactions. This paper describes the simulation of a dehydrogenation process carried out in a tubular fixed-bed reactor wrapped in a permselective composite membrane. A mathematical model was developed, incorporating the various mass transport mechanisms found in each of the membrane layers and in the catalytic fixed bed. The effects of the reactor feed conditions (temperature, steam-to-oil ratio, and the weight hourly space velocity, the fixed-bed geometry (length, diameter, and volume, and the membrane geometry (thickness of the layers on the styrene yield were analyzed. These variables were used to determine experimental conditions that favour the production of styrene. The simulation showed that an increase of 40.98% in the styrene yield, compared to a conventional fixed-bed process, could be obtained by wrapping the reactor in a permselective composite membrane.

Controlling the transport of cations through permselective mesoporous alumina layers by manipulation of electric field and ionic strength

NARCIS (Netherlands)

Schmuhl, R.; Keizer, Klaas; van den Berg, Albert; ten Elshof, Johan E.; Blank, David H.A.

2004-01-01

The electric field-driven transport of ions through supported mesoporous γ-alumina membranes was investigated. The influence of ion concentration, ion valency, pH, ionic strength, and electrolyte composition on transport behavior was determined. The permselectivity of the membrane was found to be

Polypyrrole-based bilayer nitrate amperometric biosensor with an integrated permselective poly-ortho-phenylenediamine layer for exclusion of inorganic interferences.

Science.gov (United States)

Adeloju, Samuel B; Sohail, Manzar

2011-07-15

A bilayer amperometric nitrate biosensor with an integrated permselective layer has been developed for exclusion of inorganic anion and cation interferences. The inner PPy(polypyrrole)-NaR-NADH layer of the biosensor is formed by galvanostatic polymerization of pyrrole (Py) in presence of nitrate reductase (NaR) and nicotinamide adenine dinucleotide (NADH), followed by formation of the outer permselective poly-ortho-phenylenediamine (P-o-PDA) layer by potentiodynamic polymerization of ortho-phenylenediamine (o-PDA). The exclusion efficiency (E(eff)) of the outer layer in rejecting inorganic cation and anion interferences is evaluated by a new proposed relationship. 73-87% and 47-84% of anion and cation interferences, respectively, were efficiently rejected with the permselective layer. Further improvement in the exclusion efficiency for cations was accomplished by combining the use of the outer layer with the addition of 1mM EDTA into the measurement solution. The addition of EDTA improved the E(eff) achieved for cation rejection by 10-40% to give net E(eff) of 89-94%. The inclusion of the outer layer also aided the retention of NaR and NADH in the inner PPy-NaR-NADH layer and, hence, enabled improved amperometric detection of nitrate, achieving a detection limit of 0.20 μM and a linear concentration range of 10-500 μM with a 3.4%rsd (n=10). Copyright © 2011 Elsevier B.V. All rights reserved.

Effect of antibody charge and concentration on deposition of antibody to glomerular basement membrane

International Nuclear Information System (INIS)

Madaio, M.P.; Salant, D.J.; Adler, S.; Darby, C.; Couser, W.G.

1984-01-01

Fixed anionic sites within the glomerular capillary wall influence the permeation of serum proteins, the localization of various antigens, and the deposition of antibody in the subepithelial space. In anti-GBM nephritis antibody deposition occurs very rapidly to antigenic sites located relatively proximal in the glomerular capillary wall. The authors examined the influence of the glomerular charge barrier on anti-GBM antibody deposition by comparing the rate of deposition of antibodies with cationic and anionic isoelectric points. Purified sheep anti-rat GBM IgG was isolated from acid eluates of kidneys obtained 24 hr after rats were injected with sheep antiserum to rat GBM. Anti-GBM IgG was separated into cationic (pI 6.4-8.5) and anionic (pI 4.2-6.8) fractions, which were radiolabelled with 131 I and 125 I, respectively, shown to have equal antibody contents measured by in vitro binding to normal glomeruli, mixed in equal amounts, and injected in incremental doses to ten rats. At 1 hr the glomerular antibody binding of each fraction was directly related to the blood level (r . 0.95, r . 0.97) and delivery of antibody (r . 0.98, r . 0.98). Glomerular binding of cationic antibody was four times greater than anionic antibody over the entire range of deliveries studied (P less than 0.001). The authors conclude that glomerular deposition of anti-GBM antibody is directly related to blood concentration and delivery of antibody. Furthermore, the deposition of cationic antibodies to GBM antigens was significantly greater than the deposition of anionic antibodies

Haematuria as a risk factor for chronic kidney disease progression in glomerular diseases: A review.

Science.gov (United States)

Moreno, Juan Antonio; Yuste, Claudia; Gutiérrez, Eduardo; Sevillano, Ángel M; Rubio-Navarro, Alfonso; Amaro-Villalobos, Juan Manuel; Praga, Manuel; Egido, Jesús

2016-04-01

Haematuria has long been considered to be a benign condition associated with glomerular diseases. However, new evidences suggest that haematuria has a pathogenic role in promoting kidney disease progression. An increased risk for end-stage renal disease has been reported in adolescents and young adults with persistent microscopic haematuria. A persistent impairment of renal function has been also reported following macroscopic haematuria-associated acute kidney injury in immunoglobulin A nephropathy. Haematuria-induced renal damage has been related to oxidant, cytotoxic and inflammatory effects induced by haemoglobin or haem released from red blood cells. The pathophysiological origin of haematuria may be due to a more fragile and easily ruptured glomerular filtration barrier, as reported in several glomerular diseases. In this review we describe a number of the key issues associated with the epidemiology and pathogenesis of haematuria-associated diseases, provide an update of recent knowledge on the role of haematuria on renal function outcome and discuss specific therapeutic approaches in this setting. KEY SUMMARY POINTS: 1. Glomerular haematuria is a common observation in a number of renal diseases that may lead to persistent renal injury. 2. Haematuria in children differs from that in adults in specific aspects, particularly in the frequency of glomerular diseases and renal disease outcome. 3. Regular follow-up of renal function in children with isolated microhaematuria may be recommended.

A novel water perm-selective membrane dual-type reactor concept for Fischer-Tropsch synthesis of GTL (gas to liquid) technology

International Nuclear Information System (INIS)

Rahimpour, M.R.; Mirvakili, A.; Paymooni, K.

2011-01-01

The present study proposes a novel configuration of Fischer-Tropsch synthesis (FTS) reactors in which a fixed-bed water perm-selective membrane reactor is followed by a fluidized-bed hydrogen perm-selective membrane reactor. This novel concept which has been named fixed-bed membrane reactor followed by fluidized-bed membrane reactor (FMFMDR) produces gasoline from synthesis gas. The walls of the tubes of a fixed-bed reactor (water-cooled reactor) of FMFMDR configuration are coated by a high water perm-selective membrane layer. In this new configuration, two membrane reactors instead of one membrane reactor are developed for FTS reactions. In other words, two different membrane layers are used. In order to investigate the performance of FMFMDR, a one-dimensional heterogeneous model is taken into consideration. The simulation results of three schemes named fluidized-bed membrane dual-type reactor (FMDR), FMFMDR and conventional fixed-bed reactor (CR) are presented. They have been compared in terms of temperature, gasoline and CO 2 yields, H 2 and CO conversions and the water permeation rate through the membrane layer. Results show that the gasoline yield in FMFMDR is higher than the one in FMDR. The FMFMDR configuration not only decreases the undesired product such as CO 2 but also produces more gasoline. -- Research highlights: → The application of H-SOD membrane layer in FTS reactors. → Approximate 7.5% and 37% increase in the gasoline yield in terms of [g/g feed x 100] in comparison with FMDR and CR, respectively. → A remarkable decrease in CO 2 emission to the environment. → A good configuration mainly due to reduction in catalysts sintering as a result of in situ water removal.

Amperometric detection of glucose in fruit juices with polypyrrole-based biosensor with an integrated permselective layer for exclusion of interferences.

Science.gov (United States)

Ayenimo, Joseph G; Adeloju, Samuel B

2017-08-15

A novel polypyrrole (PPy)-based bilayer amperometric glucose biosensor integrated with a permselective layer has been developed for detection of glucose in the presence of interferences. It comprises of a PPy-GOx film grown, in the absence of electrolyte, as an inner layer, and a permselective PPy-Cl film as an outer layer. The PPy-GOx/PPy-Cl bilayer biosensor was effective in rejecting 98% of ascorbic acid and 100% of glycine, glutamic acid and uric acid. With an outer layer thickness of 6.6nm, the bilayer biosensor gave nearly identical glucose response to that of a single layer PPy-GOx biosensor. The biosensor also exhibited good reproducibility (1.9% rsd, n=10), high stability (more than 2months), wide linear range (0.5-24mM), low K m (8.4mM), high I max (77.2μAcm -2 ), low detection limit (26.9μM) and good sensitivity (3.5μAcm -2 mM -1 ). The bilayer biosensor was successfully employed for glucose determination in various fruit juices. Copyright © 2017 Elsevier Ltd. All rights reserved.

Permeability of peritoneal and glomerular capillaries: what are the differences according to pore theory?

Science.gov (United States)

Rippe, Bengt; Davies, Simon

2011-01-01

Pore and fiber-matrix theory can both be used to model the peritoneal and glomerular filtration barriers in an attempt to shed light on their differing structure-function relationships. The glomerular filtration barrier (GFB) is structurally more specialized, morphologically complex, and also highly dynamic; but paradoxically, because of its uniformity, it conforms more closely to the predictions of pore theory than does the peritoneum, and it in fact resembles a more simple synthetic membrane. Compared with the peritoneal capillary wall, the GFB has no transcellular "third" pores (aquaporins), and it is far less leaky and more size-selective to proteins, mainly as a result of having far fewer "large" pores. It does have charge-selective properties, although these are considered much less important in excluding albumin than was once thought, and it is also able to select polymers according to their shape and flexibility. Even this property might reflect the relative uniformity of the GFB, which has a high diffusion area and short diffusion distances, compared with the peritoneal barrier, which behaves more like a gel filtration column. Furthermore, the length of the diffusion path across the peritoneal membrane is much greater for small solutes, given the relatively high ultrafiltration coefficient for that membrane compared with the GFB--a situation that reflects both the tortuosity of the interendothelial clefts and the distribution of peritoneal capillaries within the interstitium. These comparisons reveal the peritoneal barrier as a relatively complex structure to model; and yet this model may be more representative of the general microcirculation, and thus shed light on systemic endothelial function in renal failure.

Protective clothing based on permselective membrane carbon adsorption

Energy Technology Data Exchange (ETDEWEB)

Gottschlich, D.; Baker, R. [Membrane Technology and Research, Inc., Menlo Park, CA (United States)

1995-10-01

The objective of the program is to develop improved protective clothing for use by workers engaged in decommissioning and decontamination of former Department of Energy sites, including those used for atomic weapons research and production. Such sites are contaminated with a variety of hazardous compounds, ranging from asbestos, mercury and other heavy metals, to toxic organic compounds, such as PCB and chlorinated solvents, and radioactive metals and salts. Because of the hazards of exposure to these materials, workers must wear protective garments. These garments, which are made from Saran{reg_sign}, butyl rubber or other impermeable materials, provide excellent protection against particulates, liquids, aerosols, organic vapors and gases, but are impermeable to water vapor. Consequently, humidity and temperature within the suit rise rapidly during use, causing increasing discomfort. Heat stress occurs if the suit is worn for more than brief periods without resting. The proposed technology concerns a new protective clothing fabric that combines a permselective membrane layer with a sorptive layer. If successfully developed, suits made from this fabric will offer equivalent, or better, protection than current materials, combined with a very high water vapor transmission rate (1,000 g/m{sup 2}{sm_bullet} day or more) that will dramatically improve {open_quotes}breathability,{close_quotes} comfort, and worker productivity.

Protective clothing based on permselective membrane carbon adsorption

International Nuclear Information System (INIS)

Gottschlich, D.; Baker, R.

1995-01-01

The objective of the program is to develop improved protective clothing for use by workers engaged in decommissioning and decontamination of former Department of Energy sites, including those used for atomic weapons research and production. Such sites are contaminated with a variety of hazardous compounds, ranging from asbestos, mercury and other heavy metals, to toxic organic compounds, such as PCB and chlorinated solvents, and radioactive metals and salts. Because of the hazards of exposure to these materials, workers must wear protective garments. These garments, which are made from Saran reg-sign, butyl rubber or other impermeable materials, provide excellent protection against particulates, liquids, aerosols, organic vapors and gases, but are impermeable to water vapor. Consequently, humidity and temperature within the suit rise rapidly during use, causing increasing discomfort. Heat stress occurs if the suit is worn for more than brief periods without resting. The proposed technology concerns a new protective clothing fabric that combines a permselective membrane layer with a sorptive layer. If successfully developed, suits made from this fabric will offer equivalent, or better, protection than current materials, combined with a very high water vapor transmission rate (1,000 g/m 2 sm-bullet day or more) that will dramatically improve open-quotes breathability,close quotes comfort, and worker productivity

Fouling prevention of peptides from a tryptic whey hydrolysate during electromembrane processes by use of monovalent ion permselective membranes

OpenAIRE

Persico, Mathieu; Bazinet, Laurent

2017-01-01

Peptide adsorption occurring on conventional anion- and cation-exchange membranes is one of the main technological locks in electrodialysis (ED) for hydrolysate demineralization. Hence, the peptide fouling of monovalent anion (MAP) and monovalent cation (MCP) permselective membranes was studied and compared to conventional membranes (AMX-SB and CMX-SB). It appeared that the main peptide sequences responsible for fouling were TPEVDDEALEKFDK, VAGTWY and VLVLDTDYK for both anionic membranes; and...

Podocytes regulate the glomerular basement membrane protein nephronectin by means of miR-378a-3p in glomerular diseases.

Science.gov (United States)

Müller-Deile, Janina; Dannenberg, Jan; Schroder, Patricia; Lin, Meei-Hua; Miner, Jeffrey H; Chen, Rongjun; Bräsen, Jan-Hinrich; Thum, Thomas; Nyström, Jenny; Staggs, Lynne Beverly; Haller, Hermann; Fiedler, Jan; Lorenzen, Johan M; Schiffer, Mario

2017-10-01

The pathophysiology of many proteinuric kidney diseases is poorly understood, and microRNAs (miRs) regulation of these diseases has been largely unexplored. Here, we tested whether miR-378a-3p is a novel regulator of glomerular diseases. MiR-378a-3p has two predicted targets relevant to glomerular function, the glomerular basement membrane matrix component, nephronectin (NPNT), and vascular endothelial growth factor VEGF-A. In zebrafish (Danio rerio), miR-378a-3p mimic injection or npnt knockdown by a morpholino oligomer caused an identical phenotype consisting of edema, proteinuria, podocyte effacement, and widening of the glomerular basement membrane in the lamina rara interna. Zebrafish vegf-A protein could not rescue this phenotype. However, mouse Npnt constructs containing a mutated 3'UTR region prevented the phenotype caused by miR-378a-3p mimic injection. Overexpression of miR-378a-3p in mice confirmed glomerular dysfunction in a mammalian model. Biopsies from patients with focal segmental glomerulosclerosis and membranous nephropathy had increased miR-378a-3p expression and reduced glomerular levels of NPNT. Thus, miR-378a-3p-mediated suppression of the glomerular matrix protein NPNT is a novel mechanism for proteinuria development in active glomerular diseases. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Oxidative stress in primary glomerular diseases

DEFF Research Database (Denmark)

Markan, Suchita; Kohli, Harbir Singh; Sud, Kamal

2008-01-01

To evaluate the status of oxidative stress in patients with different primary glomerular diseases (PGD) which have differential predisposition to renal failure.......To evaluate the status of oxidative stress in patients with different primary glomerular diseases (PGD) which have differential predisposition to renal failure....

Glomerular sieving of high molecular weight proteins in proteinuric rats

International Nuclear Information System (INIS)

Bertolatus, J.A.; Abuyousef, M.; Hunsicker, L.G.

1987-01-01

To characterize the permeability of the glomerular capillary wall to high molecular weight proteins in normal and proteinuric rats, we determined the glomerular sieving coefficients (GSC) of radioiodinated marker proteins of known size and charge by means of a paired label, tissue accumulation method previously validated in this laboratory. In one group of rats (Series A) the GSCs of 125 I-anionic IgG (aIgG-molecular weight [mol wt] 150,000, pI 4.9) and 131 I-neutral IgG (nIgG-pI 7.4 to 7.6) were measured simultaneously. In Series B, the GSC of a second anionic marker, 131 I-human ceruloplasmin (Crp-mol wt 137,000, pI 4.9) was compared to that of 125 I-nIgG. As in the previous report, the labeled proteins were not degraded or deiodinated during the 20 minute clearance period for GSC determination. Within Series A and B, three subgroups of rats were studied: control saline-infused rats, rats made acutely proteinuric by infusion of the polycation hexadimethrine (HDM), and rats with chronic doxorubicin (Adriamycin-Adria) nephrosis. In the control rats, GSCs for the anionic markers aIgG (Series A) or Crp (Series B) were significantly greater than that of nIgG (both series). These large proteins crossed the filtration barrier by a different pathway from that available to smaller neutral molecules the size of albumin, which in our previous study had a much higher GSC than a native, anionic albumin marker. In a third group of control rats only (Series C), the GSCs of native anionic bovine albumin (BSA) and nIgG were compared directly. The GSC of BSA (0.0029) was only slightly larger than the GSC of nIgG (0.0025), indicating that most of the native albumin crosses the glomerular capillary wall via a nonselective pathway similar to that available to nIgG. The results in the control groups are compatible with recently-described heteroporous models of glomerular size selectivity

ORGANIC PERMSELECTIVE PERVAPORATION CHARACTERISTICS OF POLY(SILYLPROPYNE) AND COPOLYMER DENSE MEMBRANES

Institute of Scientific and Technical Information of China (English)

WANG Xinwei; SHI Yanqiao; CHEN Guanwen

1997-01-01

An investigation into the organic permselective separation through poly [1-trimethylsilyl1-propyne] (PTMSP) and (1-trimethylsily1)-1-(1-penta-methyl-disilyl)-l-propyne copolymer (TMSP-PMDSP) dense membranes was made to gain an insight into the effect of the chemical structure of membrane materials on pervaporation (PV) characteristics. The results show that the copolymer has a higher separation factor αorg/water but with a relatively Lower value of flux Jt(g/m2·h)than pure PTMSP.This phenomenon may be attributed to the introduction of side chain with large bulk volume in copolymer, which brought about a decrease of excess free volume and the improvement of diffusion selectivity to some extent. With the same molar concentration of organic liquids in feed, THF/water solutions have the highest value of αorg/water as well as Jt in comparison with ethanol/water,iso-propanol/water and THF/water mixtures.

Elevated urine heparanase levels are associated with proteinuria and decreased renal allograft function.

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Itay Shafat

Full Text Available Heparanase is an endo-β-glucuronidase that cleaves heparan sulfate side chains, leading to structural modifications that loosen the extracellular matrix barrier and associated with tumor metastasis, inflammation and angiogenesis. In addition, the highly sulfated heparan sulfate proteoglycans are important constituents of the glomerular basement membrane and its permselective properties. Recent studies suggest a role for heparanase in several experimental and human glomerular diseases associated with proteinuria such as diabetes, minimal change disease, and membranous nephropathy. Here, we quantified blood and urine heparanase levels in renal transplant recipients and patients with chronic kidney disease (CKD, and assessed whether alterations in heparanase levels correlate with proteinuria and renal function. We report that in transplanted patients, urinary heparanase was markedly elevated, inversely associated with estimated glomerular filtration rate (eGFR, suggesting a relationship between heparanase and graft function. In CKD patients, urinary heparanase was markedly elevated and associated with proteinuria, but not with eGFR. In addition, urinary heparanase correlated significantly with plasma heparanase in transplanted patients. Such a systemic spread of heparanase may lead to damage of cells and tissues alongside the kidney.The newly described association between heparanase, proteinuria and decreased renal function is expected to pave the way for new therapeutic options aimed at attenuating chronic renal allograft nephropathy, leading to improved graft survival and patient outcome.

ZIF-78 membrane derived from amorphous precursors with permselectivity for cyclohexanone/cyclohexanol mixture

KAUST Repository

Fan, Lili

2014-07-01

Cyclohexanone and cyclohexanol are products of selective oxidation of cyclohexane. They are important industrial intermediates and difficult to be separated due to their close boiling points. In this work, well-intergrown ZIF-78 membrane was successfully synthesized on the porous silica substrate by secondary growth method and applied for separation of cyclohexanone/cyclohexanol mixture for the first time. Meanwhile, a facile method for seeding procedure was developed by utilizing the amorphous ZIF-78 precursors to provide better-distributed nucleation sites. Both XRD and SEM results confirmed the good quality of the membrane. The pervaporation separation of cyclohexanone/ cyclohexanol mixture were carried out at room temperature with permselectivity of 1:2 and total flux around 8.7 × 10-2 kg m-2 h-1. © 2013 Elsevier Inc. All rights reserved.

Hemodinâmica glomerular renal no roedor Calomys callosus

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Mirian A. Boim

1989-03-01

Full Text Available A função renal do roedor Calomys callosus, envolvido no ciclo de transmissão de diversos agentes patogênicos para o homem foi avaliada no animal intacto, através da técnica de depuração e micropunção renal. Os resultados mostraram que este roedor apresenta níveis pressóricos, hematócrito e proteinas plasmáticas semelhantes aos dos ratos submetidos ao mesmo procedimento experimental. Os pesos corporal e renal, bem como a filtração glomerular global e por nefro assemelham-se aos do camundongo. Surpreendentemente estes roedores apresentaram significante número de glomérulos superficiais por rim, permitindo a avaliação da hemodinàmica glomerular. Apesar da pressão arterial semelhante à dos ratos Munich-Wistar (MW, a pressão hidráulica intraglomerular no Calomys callosus foi inferior. Esta redução foi conseqüente à menor resistência pós-glomerular quando comparada à dos ratos MW. O fluxo plasmático glomerular atingiu valor bastante elevado em relação à filtração glomerular por nefro, fato que não só compensaria a reduzida pressão intraglomerular, como também seria suficiente para elevar a filtração (por g/rim a níveis superiores neste roedor, pois o coeficiente de ultrafiltração glomerular (Kj foi semelhante ao do rato MW. O presente trabalho sugere que apesar das dificuldades técnicas que este animal impõe devido ao seu reduzido tamanho, o estudo da função renal global bem como da hemodinàmica glomerular é factível, podendo portanto ser utilizado como modelo para estudo da função renal em doenças tropicais.Renal function was characterized in Calomys callosus, a rodent which can participate in the transmission of several human diseases. The results showed that the pressures levels, hematocrit and plasmatic proteins were similar to rats submitted to the same experimental maneuvers. The corporal and renal weights, whole and single nephron glomerular filtration rates were similar to the mouse

Deletion of pro-angiogenic factor vasohibin-2 ameliorates glomerular alterations in a mouse diabetic nephropathy model

Science.gov (United States)

Masuda, Kana; Ujike, Haruyo; Hinamoto, Norikazu; Miyake, Hiromasa; Tanimura, Satoshi; Sugiyama, Hitoshi; Sato, Yasufumi; Maeshima, Yohei; Wada, Jun

2018-01-01

compared with control siRNA. These results indicate that VASH2 may be involved in diabetes-induced glomerular alterations, particularly impaired filtration barrier and mesangial expansion. Therefore, VASH2 is likely to represent a promising therapeutic target for diabetic nephropathy. PMID:29641565

Muscarinic receptors modulate dendrodendritic inhibitory synapses to sculpt glomerular output.

Science.gov (United States)

Liu, Shaolin; Shao, Zuoyi; Puche, Adam; Wachowiak, Matt; Rothermel, Markus; Shipley, Michael T

2015-04-08

Cholinergic [acetylcholine (ACh)] axons from the basal forebrain innervate olfactory bulb glomeruli, the initial site of synaptic integration in the olfactory system. Both nicotinic acetylcholine receptors (nAChRs) and muscarinic acetylcholine receptors (mAChRs) are expressed in glomeruli. The activation of nAChRs directly excites both mitral/tufted cells (MTCs) and external tufted cells (ETCs), the two major excitatory neurons that transmit glomerular output. The functional roles of mAChRs in glomerular circuits are unknown. We show that the restricted glomerular application of ACh causes rapid, brief nAChR-mediated excitation of both MTCs and ETCs in the mouse olfactory bulb. This excitation is followed by mAChR-mediated inhibition, which is blocked by GABAA receptor antagonists, indicating the engagement of periglomerular cells (PGCs) and/or short axon cells (SACs), the two major glomerular inhibitory neurons. Indeed, selective activation of glomerular mAChRs, with ionotropic GluRs and nAChRs blocked, increased IPSCs in MTCs and ETCs, indicating that mAChRs recruit glomerular inhibitory circuits. Selective activation of glomerular mAChRs in the presence of tetrodotoxin increased IPSCs in all glomerular neurons, indicating action potential-independent enhancement of GABA release from PGC and/or SAC dendrodendritic synapses. mAChR-mediated enhancement of GABA release also presynaptically suppressed the first synapse of the olfactory system via GABAB receptors on sensory terminals. Together, these results indicate that cholinergic modulation of glomerular circuits is biphasic, involving an initial excitation of MTC/ETCs mediated by nAChRs followed by inhibition mediated directly by mAChRs on PGCs/SACs. This may phasically enhance the sensitivity of glomerular outputs to odorants, an action that is consistent with recent in vivo findings. Copyright © 2015 the authors 0270-6474/15/355680-13$15.00/0.

Glomerular latency coding in artificial olfaction.

Science.gov (United States)

Yamani, Jaber Al; Boussaid, Farid; Bermak, Amine; Martinez, Dominique

2011-01-01

Sensory perception results from the way sensory information is subsequently transformed in the brain. Olfaction is a typical example in which odor representations undergo considerable changes as they pass from olfactory receptor neurons (ORNs) to second-order neurons. First, many ORNs expressing the same receptor protein yet presenting heterogeneous dose-response properties converge onto individually identifiable glomeruli. Second, onset latency of glomerular activation is believed to play a role in encoding odor quality and quantity in the context of fast information processing. Taking inspiration from the olfactory pathway, we designed a simple yet robust glomerular latency coding scheme for processing gas sensor data. The proposed bio-inspired approach was evaluated using an in-house SnO(2) sensor array. Glomerular convergence was achieved by noting the possible analogy between receptor protein expressed in ORNs and metal catalyst used across the fabricated gas sensor array. Ion implantation was another technique used to account both for sensor heterogeneity and enhanced sensitivity. The response of the gas sensor array was mapped into glomerular latency patterns, whose rank order is concentration-invariant. Gas recognition was achieved by simply looking for a "match" within a library of spatio-temporal spike fingerprints. Because of its simplicity, this approach enables the integration of sensing and processing onto a single-chip.

Podocyte Number in Children and Adults: Associations with Glomerular Size and Numbers of Other Glomerular Resident Cells

Science.gov (United States)

Puelles, Victor G.; Douglas-Denton, Rebecca N.; Cullen-McEwen, Luise A.; Li, Jinhua; Hughson, Michael D.; Hoy, Wendy E.; Kerr, Peter G.

2015-01-01

Increases in glomerular size occur with normal body growth and in many pathologic conditions. In this study, we determined associations between glomerular size and numbers of glomerular resident cells, with a particular focus on podocytes. Kidneys from 16 male Caucasian-Americans without overt renal disease, including 4 children (≤3 years old) to define baseline values of early life and 12 adults (≥18 years old), were collected at autopsy in Jackson, Mississippi. We used a combination of immunohistochemistry, confocal microscopy, and design-based stereology to estimate individual glomerular volume (IGV) and numbers of podocytes, nonepithelial cells (NECs; tuft cells other than podocytes), and parietal epithelial cells (PECs). Podocyte density was calculated. Data are reported as medians and interquartile ranges (IQRs). Glomeruli from children were small and contained 452 podocytes (IQR=335–502), 389 NECs (IQR=265–498), and 146 PECs (IQR=111–206). Adult glomeruli contained significantly more cells than glomeruli from children, including 558 podocytes (IQR=431–746; P<0.01), 1383 NECs (IQR=998–2042; P<0.001), and 367 PECs (IQR=309–673; P<0.001). However, large adult glomeruli showed markedly lower podocyte density (183 podocytes per 106 µm3) than small glomeruli from adults and children (932 podocytes per 106 µm3; P<0.001). In conclusion, large adult glomeruli contained more podocytes than small glomeruli from children and adults, raising questions about the origin of these podocytes. The increased number of podocytes in large glomeruli does not match the increase in glomerular size observed in adults, resulting in relative podocyte depletion. This may render hypertrophic glomeruli susceptible to pathology. PMID:25568174

Role of albumin and its modifications in glomerular injury.

Science.gov (United States)

Agrawal, Shipra; Smoyer, William E

2017-08-01

Albuminuria is both a characteristic hallmark and a known risk factor for progressive glomerular disease. Although the molecular basis for a potential causative role for albuminuria in progressive chronic kidney disease remains poorly understood, there have been several recent advances in our understanding of the role of albumin, and its molecular modifications, in the development and progression of glomerular disease. This review discusses recent findings related to the ability of albumin and its associated factors to directly induce podocyte and glomerular injury. Additional recent studies confirming the ability and mechanisms by which podocytes endocytose albumin are also discussed. Lastly, we present several known molecular modifications in the albumin molecule itself, as well as substances bound to it, which may be important and potentially clinically relevant mediators of albumin-induced glomerular injury. These recent findings may create entirely new opportunities to develop novel future therapies directed at albumin that could potentially help reduce podocyte and renal tubular injury and slow the progression of chronic glomerular disease.

Effect of alterations in glomerular charge on deposition of cationic and anionic antibodies to fixed glomerular antigens in the rat.

Science.gov (United States)

Adler, S; Baker, P; Pritzl, P; Couser, W G

1985-07-01

Reduction of the negative charge of the glomerular capillary wall alters its charge- and size-selective properties. To investigate the effect of alteration in glomerular charge properties on antibody localization, we prepared cationic and anionic fractions of antibodies to subepithelial and glomerular basement membrane (GBM) antigens, and compared their deposition in normal rats and rats treated with protamine sulfate or aminonucleoside of puromycin to reduce capillary wall charge. IgG antibodies were eluted from kidneys of rats with active Heymann's nephritis (AICN), passive Heymann's nephritis (PHN), or anti-GBM nephritis (NTN), separated into cationic and anionic fractions, and radiolabeled with iodine 125 or iodine 131. Relative antibody content of each fraction was determined by incubation with an excess of glomerular antigen. Varying amounts of cationic and anionic IgG eluted from kidneys of rats with AICN or PHN were injected into 24 normal or protamine sulfate-treated rats. Glomerular binding of all antibodies was highly correlated with IgG delivery to the kidney. The ratio of cationic to anionic antibody deposited in the glomeruli of normal rats after 4 hours was 1.08 +/- 0.07 for AICN eluate and 0.37 +/- 0.04 for PHN eluate. The ratios were not significantly different in animals pretreated with protamine sulfate (1.15 +/- 0.06 and 0.44 +/- 0.06, respectively; P greater than 0.05). Varying amounts of cationic and anionic IgG eluted from kidneys of rats with NTN were injected into 10 normal rats and four rats treated with aminonucleoside of puromycin. Glomerular binding of antibody was again highly correlated with IgG delivery to the kidney. The ratio of cationic to anionic antibody deposited in the glomeruli of normal rats after 1 hour was 1.03 +/- 0.06, and was not significantly altered in rats treated with aminonucleoside of puromycin (1.05 +/- 0.03, P greater than 0.5). Proteinuria in PHN rats was also unaffected by treatment with protamine sulfate for

Phlorizin Prevents Glomerular Hyperfiltration but not Hypertrophy in Diabetic Rats

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Slava Malatiali

2008-01-01

Full Text Available The relationships of renal and glomerular hypertrophies to development of hyperfiltration and proteinuria early in streptozotocin-induced diabetes were explored. Control, diabetic, phlorizin-treated controls, and diabetic male Fischer rats were used. Phlorizin (an Na+-glucose cotransport inhibitor was given at a dose sufficient to normalize blood glucose. Inulin clearance (Cinulin and protein excretion rate (PER were measured. For morphometry, kidney sections were stained with periodic acid Schiff. At one week, diabetes PER increased 2.8-folds (P<.001, Cinulin increased 80% (P<.01. Kidney wet and dry weights increased 10%–12% (P<.05, and glomerular tuft area increased 9.3% (P<.001. Phlorizin prevented proteinuria, hyperfiltration, and kidney hypertrophy, but not glomerular hypertrophy. Thus, hyperfiltration, proteinuria, and whole kidney hypertrophy were related to hyperglycemia but not to glomerular growth. Diabetic glomerular hypertrophy constitutes an early event in the progression of glomerular pathology which occurs in the absence of mesangial expansion and persists even after changes in protein excretion and GFR are reversed through glycemic control.

Functional principal component analysis of glomerular filtration rate curves after kidney transplant.

Science.gov (United States)

Dong, Jianghu J; Wang, Liangliang; Gill, Jagbir; Cao, Jiguo

2017-01-01

This article is motivated by some longitudinal clinical data of kidney transplant recipients, where kidney function progression is recorded as the estimated glomerular filtration rates at multiple time points post kidney transplantation. We propose to use the functional principal component analysis method to explore the major source of variations of glomerular filtration rate curves. We find that the estimated functional principal component scores can be used to cluster glomerular filtration rate curves. Ordering functional principal component scores can detect abnormal glomerular filtration rate curves. Finally, functional principal component analysis can effectively estimate missing glomerular filtration rate values and predict future glomerular filtration rate values.

Glomerular Lesions in Proteinuric Miniature Schnauzer Dogs.

Science.gov (United States)

Furrow, E; Lees, G E; Brown, C A; Cianciolo, R E

2017-05-01

Miniature Schnauzer dogs are predisposed to idiopathic hypertriglyerceridemia, which increases risk for diseases such as pancreatitis and gallbladder mucocele. Recently, elevated triglyceride concentrations have been associated with proteinuria in this breed, although it is difficult to determine which abnormality is primary. Retrospective review of renal tissue from 27 proteinuric Miniature Schnauzers revealed that 20 dogs had ultrastructural evidence of osmophilic globules consistent with lipid in glomerular tufts. Seven of these dogs had lipid thromboemboli in glomerular capillary loops that distorted their shape and compressed circulating erythrocytes. Triglyceride concentrations were reported in 6 of these 7 dogs, and all were hypertriglyceridemic. In addition, glomerular lipidosis (defined as accumulation of foam cells within peripheral capillary loops) was identified in a single dog. The remaining 12 dogs had smaller amounts of lipid that could only be identified ultrastructurally. Neither signalment data nor clinicopathologic parameters (serum albumin, serum creatinine, urine protein-to-creatinine ratio, and blood pressure) differed among the various types of lipid lesions. During the time course of this study, all dogs diagnosed with glomerular lipid thromboemboli were Miniature Schnauzers, underscoring the importance of recognizing these clear spaces within capillary loops as lipid.

New Insights into Glomerular Parietal Epithelial Cell Activation and Its Signaling Pathways in Glomerular Diseases

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Hua Su

2015-01-01

Full Text Available The glomerular parietal epithelial cells (PECs have aroused an increasing attention recently. The proliferation of PECs is the main feature of crescentic glomerulonephritis; besides that, in the past decade, PEC activation has been identified in several types of noninflammatory glomerulonephropathies, such as focal segmental glomerulosclerosis, diabetic glomerulopathy, and membranous nephropathy. The pathogenesis of PEC activation is poorly understood; however, a few studies delicately elucidate the potential mechanisms and signaling pathways implicated in these processes. In this review we will focus on the latest observations and concepts about PEC activation in glomerular diseases and the newest identified signaling pathways in PEC activation.

Glomerular parietal epithelial cells in kidney physiology, pathology, and repair

OpenAIRE

Shankland, Stuart J.; Anders, Hans-Joachim; Romagnani, Paola

2013-01-01

Purpose of review We have summarized recently published glomerular parietal epithelial cell (PEC) research, focusing on their roles in glomerular development and physiology, and in certain glomerular diseases. The rationale is that PECs have been largely ignored until the recent availability of cell lineage tracing studies, human and murine PEC culture systems, and potential therapeutic interventions of PECs. Recent findings Several new paradigms involving PECs have emerged demonstrating thei...

Isolation and characterization of conditionally immortalized mouse glomerular endothelial cell lines.

Science.gov (United States)

Rops, Angelique L; van der Vlag, Johan; Jacobs, Cor W; Dijkman, Henry B; Lensen, Joost F; Wijnhoven, Tessa J; van den Heuvel, Lambert P; van Kuppevelt, Toin H; Berden, Jo H

2004-12-01

The culture and establishment of glomerular cell lines has proven to be an important tool for the understanding of glomerular cell functions in glomerular physiology and pathology. Especially, the recent establishment of a conditionally immortalized visceral epithelial cell line has greatly boosted the research on podocyte biology. Glomeruli were isolated from H-2Kb-tsA58 transgenic mice that contain a gene encoding a temperature-sensitive variant of the SV40 large tumor antigen, facilitating proliferative growth at 33 degrees C and differentiation at 37 degrees C. Glomerular endothelial cells were isolated from glomerular outgrowth by magnetic beads loaded with CD31, CD105, GSL I-B4, and ULEX. Clonal cell lines were characterized by immunofluorescence staining with antibodies/lectins specific for markers of endothelial cells, podocytes, and mesangial cells. Putative glomerular endothelial cell lines were analyzed for (1) cytokine-induced expression of adhesion molecules; (2) tube formation on Matrigel coating; and (3) the presence of fenestrae. As judged by immunostaining for Wilms tumor-1, smooth muscle actin (SMA), podocalyxin, and von Willebrand factor (vWF), we obtained putative endothelial, podocyte and mesangial cell lines. The mouse glomerular endothelial cell clone #1 (mGEnC-1) was positive for vWF, podocalyxin, CD31, CD105, VE-cadherin, GSL I-B4, and ULEX, internalized acetylated-low-density lipoprotein (LDL), and showed increased expression of adhesion molecules after activation with proinflammatory cytokines. Furthermore, mGEnC-1 formed tubes and contained nondiaphragmed fenestrae. The mGEnC-1 represents a conditionally immortalized cell line with various characteristics of differentiated glomerular endothelial cells when cultured at 37 degrees C. Most important, mGEnC-1 contains nondiaphragmed fenestrae, which is a unique feature of glomerular endothelial cells.

Hemodinâmica glomerular renal no roedor Calomys callosus

Directory of Open Access Journals (Sweden)

Mirian A. Boim

1989-03-01

Full Text Available A função renal do roedor Calomys callosus, envolvido no ciclo de transmissão de diversos agentes patogênicos para o homem foi avaliada no animal intacto, através da técnica de depuração e micropunção renal. Os resultados mostraram que este roedor apresenta níveis pressóricos, hematócrito e proteinas plasmáticas semelhantes aos dos ratos submetidos ao mesmo procedimento experimental. Os pesos corporal e renal, bem como a filtração glomerular global e por nefro assemelham-se aos do camundongo. Surpreendentemente estes roedores apresentaram significante número de glomérulos superficiais por rim, permitindo a avaliação da hemodinàmica glomerular. Apesar da pressão arterial semelhante à dos ratos Munich-Wistar (MW, a pressão hidráulica intraglomerular no Calomys callosus foi inferior. Esta redução foi conseqüente à menor resistência pós-glomerular quando comparada à dos ratos MW. O fluxo plasmático glomerular atingiu valor bastante elevado em relação à filtração glomerular por nefro, fato que não só compensaria a reduzida pressão intraglomerular, como também seria suficiente para elevar a filtração (por g/rim a níveis superiores neste roedor, pois o coeficiente de ultrafiltração glomerular (Kj foi semelhante ao do rato MW. O presente trabalho sugere que apesar das dificuldades técnicas que este animal impõe devido ao seu reduzido tamanho, o estudo da função renal global bem como da hemodinàmica glomerular é factível, podendo portanto ser utilizado como modelo para estudo da função renal em doenças tropicais.

Cell biology of mesangial cells: the third cell that maintains the glomerular capillary.

Science.gov (United States)

Kurihara, Hidetake; Sakai, Tatsuo

2017-03-01

The renal glomerulus consists of glomerular endothelial cells, podocytes, and mesangial cells, which cooperate with each other for glomerular filtration. We have produced monoclonal antibodies against glomerular cells in order to identify different types of glomerular cells. Among these antibodies, the E30 clone specifically recognizes the Thy1.1 molecule expressed on mesangial cells. An injection of this antibody into rats resulted in mesangial cell-specific injury within 15 min, and induced mesangial proliferative glomerulonephritis in a reproducible manner. We examined the role of mesangial cells in glomerular function using several experimental tools, including an E30-induced nephritis model, mesangial cell culture, and the deletion of specific genes. Herein, we describe the characterization of E30-induced nephritis, formation of the glomerular capillary network, mesangial matrix turnover, and intercellular signaling between glomerular cells. New molecules that are involved in a wide variety of mesangial cell functions are also introduced.

Phosphate barrier on pore-filled cation-exchange membrane for blocking complexing ions in presence of non-complexing ions

Science.gov (United States)

Chavan, Vivek; Agarwal, Chhavi; Shinde, Rakesh N.

2018-06-01

In present work, an approach has been used to form a phosphate groups bearing surface barrier on a cation-exchange membrane (CEM). Using optimized conditions, the phosphate bearing monomer bis[2-(methacryloyloxy)ethyl] phosphate has been grafted on the surface of the host poly(ethersulfone) membranes using UV light induced polymerization. The detailed characterizations have shown that less than a micron layer of phosphate barrier is formed without disturbing the original microporous structure of the host membrane. The pores of thus formed membrane have been blocked by cationic-gel formed by in situ UV-initiator induced polymerization of 2-acrylamido-2-methyl-1-propane sulphonic acid along with crosslinker ethylene glycol dimethacrylate in the pores of the membrane. UV-initiator is required for pore-filling as UV light would not penetrate the interior matrix of the membrane. The phosphate functionalized barrier membrane has been examined for permselectivity using a mixture of representative complexing Am3+ ions and non-complexing Cs+ ions. This experiment has demonstrated that complex forming Am3+ ions are blocked by phosphate barrier layer while non-complexing Cs+ ions are allowed to pass through the channels formed by the crosslinked cationic gel.

Renin-angiotensin system antagonists, glomerular filtration rate and blood pressure

Directory of Open Access Journals (Sweden)

D.D. Ivanov

2018-02-01

Full Text Available The article deals with the mModern data on the influence of renin-angiotensin system blockers on the glomerular filtration rate, the level of arterial pressure and the outcome of chronic kidney disease. The strategy of  rennin-angiotensine blockade is offered to be changed depending on the criteria va­lues of glomerular filtration rate: a combination of inhibitors of angiotensin-converting enzyme + angiotensin receptors blo­ckers, monotherapy and drug withdrawal in glomerular filtration rate under 15–30 ml/min/m2. The formula BRIMONEL for treatment of chronic kidney disease is given.

Olfactory aversive conditioning alters olfactory bulb mitral/tufted cell glomerular odor responses

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Max L Fletcher

2012-03-01

Full Text Available The anatomical organization of receptor neuron input into the olfactory bulb (OB allows odor information to be transformed into an odorant-specific spatial map of mitral/tufted cell glomerular activity at the upper level of the olfactory bulb. In other sensory systems, neuronal representations of stimuli can be reorganized or enhanced following learning. While the mammalian OB has been shown to undergo experience-dependent plasticity at the glomerular level, it is still unclear if similar representational change occurs within mitral/tufted cell glomerular odor representations following learning. To address this, odorant-evoked glomerular activity patterns were imaged in mice expressing a GFP-based calcium indicator (GCaMP2 in OB mitral/tufted cells. Glomerular odor responses were imaged before and after olfactory associative conditioning to aversive foot shock. Following conditioning, we found no overall reorganization of the glomerular representation. Training, however, did significantly alter the amplitudes of individual glomeruli within the representation in mice in which the odor was presented together with foot shock. Further, the specific pairing of foot shock with odor presentations lead to increased responses primarily in initially weakly activated glomeruli. Overall, these results suggest that associative conditioning can enhance the initial representation of odors within the olfactory bulb by enhancing responses to the learned odor in some glomeruli.

Method for forming H2-permselective oxide membranes

Science.gov (United States)

Gavalas, G.R.; Nam, S.W.; Tsapatsis, M.; Kim, S.

1995-09-26

Methods are disclosed for forming permselective oxide membranes that are highly selective to permeation of hydrogen by chemical deposition of reactants in the pore of porous tubes, such as Vycor{trademark} glass or Al{sub 2}O{sub 3} tubes. The porous tubes have pores extending through the tube wall. The process involves forming a stream containing a first reactant of the formula RX{sub n}, wherein R is silicon, titanium, boron or aluminum, X is chlorine, bromine or iodine, and n is a number which is equal to the valence of R; and forming another stream containing water vapor as the second reactant. Both of the reactant streams are passed along either the outside or the inside surface of a porous tube and the streams react in the pores of the porous tube to form a nonporous layer of R-oxide in the pores. The membranes are formed by the hydrolysis of the respective halides. In another embodiment, the first reactant stream contains a first reactant having the formula SiH{sub n}Cl{sub 4{minus}n} where n is 1, 2 or 3; and the second reactant stream contains water vapor and oxygen. In still another embodiment the first reactant stream containing a first reactant selected from the group consisting of Cl{sub 3}SiOSiCl{sub 3}, Cl{sub 3}SiOSiCl{sub 2}OSiCl{sub 3}, and mixtures thereof and the second reactant stream contains water vapor. In still another embodiment, membrane formation is carried out by an alternating flow deposition method. This involves a sequence of cycles, each cycle comprising introduction of the halide-containing stream and allowance of a specific time for reaction followed by purge and flow of the water vapor containing stream for a specific length of time. In all embodiments the nonporous layers formed are selectively permeable to hydrogen. 11 figs.

Glomerular function in sickle cell disease patients during crisis.

Science.gov (United States)

Aderibigbe, A; Arije, A; Akinkugbe, O O

1994-06-01

An 8 month prospective study was carried out in 20 adult sickle cell disease (SCD) patients 16 sickle cell anaemia (Hbss) and 4 sickle cell Hbc disease (Hbsc); who had vaso-occlusive crises within the study period to determine the extent of the effect of sickle cell crisis on glomerular function in SCD patients during crisis. The male: female ratio was 1:57 and their mean age was 21.1 +/- 7.9 years. Creatinine clearance (CCr), as an index of glomerular function, was determined at the pre-crisis, crisis, 2 and 4 weeks post-crisis and at the end of the study period. The mean values of their CCr dropped from 113.37 +/- 33.80mls/min at pre-crisis stage to 96.39 +/- 30.13mls/min during crisis (p pre-crisis stage (p > 0.05). It is concluded that glomerular dysfunction in SCD patients during crisis is potentially reversible.

Genetic Background is a Key Determinant of Glomerular Extracellular Matrix Composition and Organization.

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Randles, Michael J; Woolf, Adrian S; Huang, Jennifer L; Byron, Adam; Humphries, Jonathan D; Price, Karen L; Kolatsi-Joannou, Maria; Collinson, Sophie; Denny, Thomas; Knight, David; Mironov, Aleksandr; Starborg, Toby; Korstanje, Ron; Humphries, Martin J; Long, David A; Lennon, Rachel

2015-12-01

Glomerular disease often features altered histologic patterns of extracellular matrix (ECM). Despite this, the potential complexities of the glomerular ECM in both health and disease are poorly understood. To explore whether genetic background and sex determine glomerular ECM composition, we investigated two mouse strains, FVB and B6, using RNA microarrays of isolated glomeruli combined with proteomic glomerular ECM analyses. These studies, undertaken in healthy young adult animals, revealed unique strain- and sex-dependent glomerular ECM signatures, which correlated with variations in levels of albuminuria and known predisposition to progressive nephropathy. Among the variation, we observed changes in netrin 4, fibroblast growth factor 2, tenascin C, collagen 1, meprin 1-α, and meprin 1-β. Differences in protein abundance were validated by quantitative immunohistochemistry and Western blot analysis, and the collective differences were not explained by mutations in known ECM or glomerular disease genes. Within the distinct signatures, we discovered a core set of structural ECM proteins that form multiple protein-protein interactions and are conserved from mouse to man. Furthermore, we found striking ultrastructural changes in glomerular basement membranes in FVB mice. Pathway analysis of merged transcriptomic and proteomic datasets identified potential ECM regulatory pathways involving inhibition of matrix metalloproteases, liver X receptor/retinoid X receptor, nuclear factor erythroid 2-related factor 2, notch, and cyclin-dependent kinase 5. These pathways may therefore alter ECM and confer susceptibility to disease. Copyright © 2015 by the American Society of Nephrology.

Proximal tubular hypertrophy and enlarged glomerular and proximal tubular urinary space in obese subjects with proteinuria.

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Ana Tobar

Full Text Available BACKGROUND: Obesity is associated with glomerular hyperfiltration, increased proximal tubular sodium reabsorption, glomerular enlargement and renal hypertrophy. A single experimental study reported an increased glomerular urinary space in obese dogs. Whether proximal tubular volume is increased in obese subjects and whether their glomerular and tubular urinary spaces are enlarged is unknown. OBJECTIVE: To determine whether proximal tubules and glomerular and tubular urinary space are enlarged in obese subjects with proteinuria and glomerular hyperfiltration. METHODS: Kidney biopsies from 11 non-diabetic obese with proteinuria and 14 non-diabetic lean patients with a creatinine clearance above 50 ml/min and with mild or no interstitial fibrosis were retrospectively analyzed using morphometric methods. The cross-sectional area of the proximal tubular epithelium and lumen, the volume of the glomerular tuft and of Bowman's space and the nuclei number per tubular profile were estimated. RESULTS: Creatinine clearance was higher in the obese than in the lean group (P=0.03. Proteinuria was similarly increased in both groups. Compared to the lean group, the obese group displayed a 104% higher glomerular tuft volume (P=0.001, a 94% higher Bowman's space volume (P=0.003, a 33% higher cross-sectional area of the proximal tubular epithelium (P=0.02 and a 54% higher cross-sectional area of the proximal tubular lumen (P=0.01. The nuclei number per proximal tubular profile was similar in both groups, suggesting that the increase in tubular volume is due to hypertrophy and not to hyperplasia. CONCLUSIONS: Obesity-related glomerular hyperfiltration is associated with proximal tubular epithelial hypertrophy and increased glomerular and tubular urinary space volume in subjects with proteinuria. The expanded glomerular and urinary space is probably a direct consequence of glomerular hyperfiltration. These effects may be involved in the pathogenesis of obesity

Deficiency of the Angiotensinase Aminopeptidase A Increases Susceptibility to Glomerular Injury.

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Velez, Juan Carlos Q; Arif, Ehtesham; Rodgers, Jessalyn; Hicks, Megan P; Arthur, John M; Nihalani, Deepak; Bruner, Evelyn T; Budisavljevic, Milos N; Atkinson, Carl; Fitzgibbon, Wayne R; Janech, Michael G

2017-07-01

Aminopeptidase A (APA) is expressed in glomerular podocytes and tubular epithelia and metabolizes angiotensin II (AngII), a peptide known to promote glomerulosclerosis. In this study, we tested whether APA expression changes in response to progressive nephron loss or whether APA exerts a protective role against glomerular damage and during AngII-mediated hypertensive kidney injury. At advanced stages of FSGS, fawn-hooded hypertensive rat kidneys exhibited distinctly increased APA staining in areas of intact glomerular capillary loops. Moreover, BALB/c APA-knockout (KO) mice injected with a nephrotoxic serum showed persistent glomerular hyalinosis and albuminuria 96 hours after injection, whereas wild-type controls achieved virtually full recovery. We then tested the effect of 4-week infusion of AngII (400 ng/kg per minute) in APA-KO and wild-type mice. Although we observed no significant difference in achieved systolic BP, AngII-treated APA-KO mice developed a significant rise in albuminuria not observed in AngII-treated wild-type mice along with increased segmental and global sclerosis and/or collapse of juxtamedullary glomeruli, microcystic tubular dilation, and tubulointerstitial fibrosis. In parallel, AngII treatment significantly increased the kidney AngII content and attenuated the expression of podocyte nephrin in APA-KO mice but not in wild-type controls. These data show that deficiency of APA increases susceptibility to glomerular injury in BALB/c mice. The augmented AngII-mediated kidney injury observed in association with increased intrarenal AngII accumulation in the absence of APA suggests a protective metabolizing role of APA in AngII-mediated glomerular diseases. Copyright © 2017 by the American Society of Nephrology.

[Why? How? What for? We must measure the glomerular filtration].

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Treviño-Becerra, Alejandro

2010-01-01

The measurement of the glomerular filtration shows the degree of the functional qualities and the proficiency of the renal system. Despite new technologies, at present the best accepted technique for measuring the glomerular filtration in most countries is the clearance of creatinine in 24 hour urine. The clearance of creatinine has the advantage that it is confident, easy to reproduce, without technical limitations and low cost.

A pitfall of glomerular sieving: profibrotic and matrix proteins derive from the Bowman's capsule and not the glomerular tuft in rats with renovascular hypertension.

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Steinmetz, O M; Panzer, U; Fehr, S; Meyer-Schwesinger, C; Stahl, R A K; Wenzel, U O

2007-10-01

The glomeruli in the non-clipped kidney of rats with 2-kidney, 1-clip hypertension are a classical model for studying the mechanisms of glomerular injury. In the present study, we compared the glomerular expression of PAI-1 and collagen I alpha1 mRNA from glomeruli isolated by the classic technique of sieving with the recently developed technique of tissue laser microdissection. For quantification of mRNA from both methods, real-time PCR was used. Real-time PCR revealed a 9.0 +/- 1.3- and a 7.1 +/- 0.2-fold induction of PAI-1 and collagen I alpha 1, respectively, in the glomeruli from hypertensive rats isolated by sieving. However, in situ hybridization and microdissection revealed that expression of both mRNAs was mainly from the Bowman's capsule and not from the glomerular tuft (10.7 +/- 1.3- and 7.2 +/- 0.6-fold higher induction in whole glomeruli compared with tuft alone). This emphasizes that studies focusing on processes in the mesangium, endothelial cells or podocytes should not rely on glomeruli obtained by sieving. Rather, a technique like the laser microdissection or in situ hybridization should be applied which allows the clear separation of different glomerular and periglomerular compartments.

Pathways to nephron loss starting from glomerular diseases-insights from animal models.

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Kriz, Wilhelm; LeHir, Michel

2005-02-01

Studies of glomerular diseases in animal models show that progression toward nephron loss starts with extracapillary lesions, whereby podocytes play the central role. If injuries remain bound within the endocapillary compartment, they will undergo recovery or be repaired by scaring. Degenerative, inflammatory and dysregulative mechanisms leading to nephron loss are distinguished. In addition to several other unique features, the dysregulative mechanisms leading to collapsing glomerulopathy are particular in that glomeruli and tubules are affected in parallel. In contrast, in degenerative and inflammatory diseases, tubular injury is secondary to glomerular lesions. In both of the latter groups of diseases, the progression starts in the glomerulus with the loss of the separation between the tuft and Bowman's capsule by forming cell bridges (parietal cells and/or podocytes) between the glomerular and the parietal basement membranes. Cell bridges develop into tuft adhesions to Bowman's capsule, which initiate the formation of crescents, either by misdirected filtration (proteinaceous crescents) or by epithelial cell proliferation (cellular crescents). Crescents may spread over the entire circumference of the glomerulus and, via the glomerulotubular junction, may extend onto the tubule. Two mechanisms concerning the transfer of a glomerular injury onto the tubulointerstitium are discussed: (1) direct encroachment of extracapillary lesions and (2) protein leakage into tubular urine, resulting in injury to the tubule and the interstitium. There is evidence that direct encroachment is the crucial mechanism. Progression of chronic renal disease is underlain by a vicious cycle which passes on the damage from lost and/or damaged nephrons to so far healthy nephrons. Presently, two mechanisms are discussed: (1) the loss of nephrons leads to compensatory mechanisms in the remaining nephrons (glomerular hypertension, hyperfiltration, hypertrophy) which increase their

Nucleosomes and histones are present in glomerular deposits in human lupus nephritis

NARCIS (Netherlands)

vanBruggen, MCJ; Kramers, C; Walgreen, B; Elema, JD; Kallenberg, CGM; vandenBorn, J; Smeenk, RJT; Assmann, KJM; Muller, S; Monestier, M; Berden, JHM

Background. Recently we showed that antinuclear autoantibodies complexed to nucleosomes can bind to heparan sulphate (HS) in the glomerular basement membrane (GEM) via the histone part of the nucleosome. Histones have been identified in glomerular deposits in human and murine lupus nephritis. In

Contribution of glomerular morphometry to the diagnosis of pediatric nephropathies

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Mariana Barreto Marini

2016-01-01

Full Text Available Only a few studies describe histopathological changes in renal biopsies performed in pediatric patients. This study was conducted to identify an association between morphometric data in renal biopsies and renal function of these patients. Fifty-nine individuals with ages between 2 and 18 years old were selected, who were divided into six groups consisting of frequent nephropathies in children and adolescents and one control group. Proteinuria, urea, and creatinine values of the patients were recorded. Interactive image analysis software Leica QWin[®]was used for morpho- metric analysis of Bowman′s capsule, glomerular capillary tuft, and Bowman′s space area. The mean glomerular tuft area was higher in the membranous glomerulopathy group than in the podo- cytopathy group (57,101 ± 25,094 vs. 27,420 c ± 6279 µm2; P <0.05. The median of Bowman′s space area was higher in the control group than in the podocytopathy group and in the thin basement membrane/Alport syndrome group [12,210 (7676-26,945 vs. 5801 (3031-7852 µm2; P <0.01 and 12210 (7676-26,945 vs. 4183 (3797-7992 µm2; P <0.01, respectively]. There was a positive and significant correlation between Bowman′s capsule area and the levels of proteinuria, creatinine, and urea of the patients, as well as between the glomerular tuft area and the levels of proteinuria, creatinine, and urea in the patients, regardless of their nephropathy. Glomerular morphometry may contribute to the diagnosis of some glomerulopathies and the association between glomerular morphometric parameters, and laboratory data may promote a better understanding of the prognosis of these patients.

Nocturnal polyuria is related to absent circadian rhythm of glomerular filtration rate.

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De Guchtenaere, A; Vande Walle, C; Van Sintjan, P; Raes, A; Donckerwolcke, R; Van Laecke, E; Hoebeke, P; Vande Walle, J

2007-12-01

Monosymptomatic nocturnal enuresis is frequently associated with nocturnal polyuria and low urinary osmolality during the night. Initial studies found decreased vasopressin levels associated with low urinary osmolality overnight. Together with the documented desmopressin response, this was suggestive of a primary role for vasopressin in the pathogenesis of enuresis in the absence of bladder dysfunction. Recent studies no longer confirm this primary role of vasopressin. Other pathogenetic factors such as disordered renal sodium handling, hypercalciuria, increased prostaglandins and/or osmotic excretion might have a role. So far, little attention has been given to abnormalities in the circadian rhythm of glomerular filtration rate. We evaluated the circadian rhythm of glomerular filtration rate and diuresis in children with desmopressin resistant monosymptomatic nocturnal enuresis and nocturnal polyuria. We evaluated 15 children (9 boys) 9 to 14 years old with monosymptomatic nocturnal enuresis and nocturnal polyuria resistant to desmopressin treatment. The control group consisted of 25 children (12 boys) 9 to 16 years old with monosymptomatic nocturnal enuresis without nocturnal polyuria. Compared to the control population, children with nocturnal polyuria lost their circadian rhythm not only for diuresis and sodium excretion but also for glomerular filtration rate. Patients with monosymptomatic nocturnal enuresis and nocturnal polyuria lack a normal circadian rhythm for diuresis and sodium excretion, and the circadian rhythm of glomerular filtration rate is absent. This absence of circadian rhythm of glomerular filtration rate and/or sodium handling cannot be explained by a primary role of vasopressin, but rather by a disorder in circadian rhythm of renal glomerular and/or tubular functions.

The kinetics of glomerular deposition of nephritogenic IgA.

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Kenji Yamaji

Full Text Available Whether IgA nephropathy is attributable to mesangial IgA is unclear as there is no correlation between intensity of deposits and extent of glomerular injury and no clear mechanism explaining how these mesangial deposits induce hematuria and subsequent proteinuria. This hinders the development of a specific therapy. Thus, precise events during deposition still remain clinical challenge to clarify. Since no study assessed induction of IgA nephropathy by nephritogenic IgA, we analyzed sequential events involving nephritogenic IgA from IgA nephropathy-prone mice by real-time imaging systems. Immunofluorescence and electron microscopy showed that serum IgA from susceptible mice had strong affinity to mesangial, subepithelial, and subendothelial lesions, with effacement/actin aggregation in podocytes and arcade formation in endothelial cells. The deposits disappeared 24-h after single IgA injection. The data were supported by a fluorescence molecular tomography system and real-time and 3D in vivo imaging. In vivo imaging showed that IgA from the susceptible mice began depositing along the glomerular capillary from 1 min and accumulated until 2-h on the first stick in a focal and segmental manner. The findings indicate that glomerular IgA depositions in IgAN may be expressed under the balance between deposition and clearance. Since nephritogenic IgA showed mesangial as well as focal and segmental deposition along the capillary with acute cellular activation, all glomerular cellular elements are a plausible target for injury such as hematuria.

Changes of the glomerular size during the human fetal kidney development

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Daković-Bjelaković Marija

2006-01-01

Full Text Available Introduction. Newborns adaptation on postnatal conditions includes significant morphological and functional renal changes. Every kidney contains a constant number of nephrons, at the end of the nephrogenesis period, which extends from week 8 to 34 of gestation. Mature juxtamedullary nephrons possess higher filtration capacity than primitive superficial nephrons, which have insufficient vascularization. Objective. The objective of the study was to calculate an average glomerular diameter in cortical zones of the kidney during development, to define periods of their most intensive growth, and to record differences of glomerular size between different cortical zones. METHOD A total of 30 human fetal kidneys aged from IV to X lunar months were analyzed. Stereological methods were used for calculating the average glomerular diameter in superficial, intermediate and juxtamedullary zone of the kidney cortex. Results. Glomeruli in the superficial cortical zone had the lowest average diameter. The average glomerular diameter continually increased from IV lunar month (0.057±0.004 mm to X lunar month (0.082±0.004 mm, with highly significant correlation with gestational age (r=0.755; p<0.01. The average glomerular diameter in the intermediate zone increased from 0.081±0.004 mm (IV lunar month to 0.096±0.004 mm (X lunar month with low linear correlation with gestational age (r=0.161. Juxtamedullary glomeruli were the biggest ones. Their average diameter, during the IV LM ranged from 0.093±0.006 mm to 0.101±0.004 mm. In the newborns (X lunar month, juxtamedullary glomeruli had spherical structures with an average diameter of 0.103±0.004 mm, and low negative correlation (r=-0.032 with gestational age. In the IV and V lunar months of gestation, there was significant difference (p<0.01; p<0.05 between the average glomerular diameter in the different zones of the kidney cortex. Conclusion. Superficial glomeruli had the smallest diameter, while

Estimating individual glomerular volume in the human kidney: clinical perspectives.

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Puelles, Victor G; Zimanyi, Monika A; Samuel, Terence; Hughson, Michael D; Douglas-Denton, Rebecca N; Bertram, John F; Armitage, James A

2012-05-01

Measurement of individual glomerular volumes (IGV) has allowed the identification of drivers of glomerular hypertrophy in subjects without overt renal pathology. This study aims to highlight the relevance of IGV measurements with possible clinical implications and determine how many profiles must be measured in order to achieve stable size distribution estimates. We re-analysed 2250 IGV estimates obtained using the disector/Cavalieri method in 41 African and 34 Caucasian Americans. Pooled IGV analysis of mean and variance was conducted. Monte-Carlo (Jackknife) simulations determined the effect of the number of sampled glomeruli on mean IGV. Lin's concordance coefficient (R(C)), coefficient of variation (CV) and coefficient of error (CE) measured reliability. IGV mean and variance increased with overweight and hypertensive status. Superficial glomeruli were significantly smaller than juxtamedullary glomeruli in all subjects (P IGV mean and variability. Overall, mean IGV was particularly reliable with nine or more sampled glomeruli (R(C) > 0.95, IGV and estimated total glomerular number. Multiple comorbidities for CKD are associated with increased IGV mean and variance within subjects, including overweight, obesity and hypertension. Zonal selection and the number of sampled glomeruli do not represent drawbacks for future longitudinal biopsy-based studies of glomerular size and distribution.

[Current insights about recurrence of glomerular diseases after renal transplantation].

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Kofman, Tomek; Oniszczuk, Julie; Lang, Philippe; Grimbert, Philippe; Audard, Vincent

2018-05-01

Recurrence of glomerular disease after renal transplantation is a frequent cause of graft loss. Incidence, risk factors and outcome of recurrence are widely due to the underlying glomerular disease. Graft biopsy analysis is required to confirm the definitive diagnosis of recurrence and to start an appropriate therapy that, in some cases, remains challenging to prevent graft failure. Increased use of protocol biopsy and recent advances in our understanding of the pathogenesis of some glomerular diseases with the identification of some relevant biomarkers provide a unique opportunity to initiate kidney-protective therapy at early stages of recurrence on the graft. This review summarizes our current knowledge on the management of many recurrent primary and secondary glomerulonephritis after kidney transplantation. Copyright © 2018 Société francophone de néphrologie, dialyse et transplantation. Published by Elsevier Masson SAS. All rights reserved.

GEC-targeted HO-1 expression reduces proteinuria in glomerular immune injury.

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Duann, Pu; Lianos, Elias A

2009-09-01

Induction of heme oxygenase (HO)-1 is a key defense mechanism against oxidative stress. Compared with tubules, glomeruli are refractory to HO-1 upregulation in response to injury. This can be a disadvantage as it may be associated with insufficient production of cytoprotective heme-degradation metabolites. We, therefore, explored whether 1) targeted HO-1 expression can be achieved in glomeruli without altering their physiological integrity and 2) this expression reduces proteinuria in immune injury induced by an anti-glomerular basement membrane (GBM) antibody (Ab). We employed a 4.125-kb fragment of a mouse nephrin promoter downstream to which a FLAG-tagged hHO-1 cDNA sequence was inserted and subsequently generated transgenic mice from the FVB/N parental strain. There was a 16-fold higher transgene expression in the kidney than nonspecific background (liver) while the transprotein immunolocalized in glomerular epithelial cells (GEC). There was no change in urinary protein excretion, indicating that GEC-targeted HO-1 expression had no effect on glomerular protein permeability. Urinary protein excretion in transgenic mice with anti-GBM Ab injury (days 3 and 6) was significantly lower compared with wild-type controls. There was no significant change in renal expression levels of profibrotic (TGF-beta1) or anti-inflammatory (IL-10) cytokines in transgenic mice with anti-GBM Ab injury. These observations indicate that GEC-targeted HO-1 expression does not alter glomerular physiological integrity and reduces proteinuria in glomerular immune injury.

HIV-1 Tat reduces nephrin in human podocytes: a potential mechanism for enhanced glomerular permeability in HIV-associated nephropathy.

Science.gov (United States)

Doublier, Sophie; Zennaro, Cristina; Spatola, Tiziana; Lupia, Enrico; Bottelli, Antonella; Deregibus, Maria Chiara; Carraro, Michele; Conaldi, Pier Giulio; Camussi, Giovanni

2007-02-19

To determine whether HIV-1 Tat may directly alter glomerular permeability in HIV-associated nephropathy (HIVAN). Heavy proteinuria is a hallmark of HIVAN. The slit diaphragm is the ultimate glomerular filtration barrier critical for maintaining the efficiency of the ultrafiltration unit of the kidney. In this study, we evaluated the direct effect of Tat protein on the permeability of isolated glomeruli and on the expression of nephrin, the main slit diaphragm component, by human cultured podocytes. Permeability was studied by measuring the permeability to albumin in isolated rat glomeruli. We also evaluated the expression of nephrin in human cultured podocytes by using immunofluorescence and Western blot. We found that Tat increased albumin permeability in isolated glomeruli, and rapidly induced the redistribution and loss of nephrin in cultured podocytes. Pretreatment of glomeruli and podocytes with blocking antibodies showed that Tat reduced nephrin expression by engaging vascular endothelial growth factor receptors types 2 and 3 and the integrin alphavbeta3. Pre-incubation of podocytes with two platelet-activating factor (PAF) receptor antagonists prevented the loss and redistribution of nephrin induced by Tat, suggesting that PAF is an intracellular mediator of Tat action. Tat induced a rapid PAF synthesis by podocytes. When podocytes transfected to overexpress PAF-acetylhydrolase, the main catabolic enzyme of PAF, were stimulated with Tat, the redistribution and loss of nephrin was abrogated. The present results define a mechanism by which Tat may reduce nephrin expression in podocytes, thus increasing glomerular permeability. This provides new insights in the understanding of HIVAN pathogenesis.

Rheological Influence Upon the Glomerular Podocyte and Resultant Mechanotransduction

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Simona Pichler Sekulic

2015-03-01

Full Text Available The glomerular podocyte is exposed to numerous mechanical forces as a constituent of the glomerular filtration apparatus. This includes fluid shear stress (FSS displaced upon the podocytic foot process's apical, lateral, and basal surfaces. Even in the face of continuous flow the podocyte is capable of contributing to physiologic filtration, however with pathologic levels of hyperfiltration there is increased FSS placed upon the cell. The mechanisms by which the podocyte detects and responds to FSS are topics of recent investigations, with the aim to clarify the way these cells are injured and/or adapt in times of hyperfiltration and disease states. As the pathogenesis of numerous glomerulopathies is contingent on the status of the podocyte, understanding the manner that these cells can be modified by FSS is essential. Likewise, determination of the effect of such mechanical forces upon other resident cells of the renal corpuscle would reveal the contribution of FSS in the progression of glomerular diseases. The biochemical manner in which podocytes sense and respond to FSS, that is mechanotransduction, will be discussed.

Simple method for the estimation of glomerular filtration rate

Energy Technology Data Exchange (ETDEWEB)

Groth, T [Group for Biomedical Informatics, Uppsala Univ. Data Center, Uppsala (Sweden); Tengstroem, B [District General Hospital, Skoevde (Sweden)

1977-02-01

A simple method is presented for indirect estimation of the glomerular filtration rate from two venous blood samples, drawn after a single injection of a small dose of (/sup 125/I)sodium iothalamate (10 ..mu..Ci). The method does not require exact dosage, as the first sample, taken after a few minutes (t=5 min) after injection, is used to normilize the value of the second sample, which should be taken in between 2 to 4 h after injection. The glomerular filtration rate, as measured by standard insulin clearance, may then be predicted from the logarithm of the normalized value and linear regression formulas with a standard error of estimate of the order of 1 to 2 ml/min/1.73 m/sup 2/. The slope-intercept method for direct estimation of glomerular filtration rate is also evaluated and found to significantly underestimate standard insulin clearance. The normalized 'single-point' method is concluded to be superior to the slope-intercept method and more sophisticated methods using curve fitting technique, with regard to predictive force and clinical applicability.

Dynamics of intrarenal pressures and glomerular filtration rate after acetazolamide

DEFF Research Database (Denmark)

Leyssac, P P; Karlsen, F M; Skøtt, O

1991-01-01

-EDTA and lithium. Proximal tubular pressure (Pprox) increased initially by 1.7 +/- 0.1 mmHg after ACZ, causing a decrease in the hydrostatic pressure difference across the glomerular membrane (delta P). EDC increased, and then RBF, glomerular capillary pressure (Pgc), Pprox, and star vessel pressures (Psv) dropped......The dynamics of intrarenal pressures, early distal tubular fluid conductivity (EDC), and renal flood flow (RBF) were studied in rats given acetazolamide (ACZ), an inhibitor of proximal reabsorption. Glomerular filtration rate (GFR) and end-proximal flow were estimated by clearances of 51Cr...... as a result of afferent vasoconstriction. Pprox decreased less than Pgc, resulting in a further decrease in delta P, which after 25-30 s reached a constant level 3-4 mmHg below control. After a transient increase the pressures declined to a new steady state, in which Pprox was equal to control, Pgc...

Estimated glomerular filtration rate function in patients with and without metabolic syndrome

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María E Lizardo

2016-06-01

Full Text Available Introduction: Metabolic syndrome (MS is an independent risk factor, which affects the development of chronic kidney disease, so the glomerular filtration rate (GFR as an indicator of glomerular function in patients with and without MS who attended the outpatient clinic “los Grillitos, sector Caña de Azucar”. Materials and Methods: A comparative, correlational, cross-sectional study was conducted in a non-probability sample of convenience consisting of 60 patients with MS diagnosed according to the criteria Panel ATP III, and 60 apparently healthy individuals, whom the GFR was determined by the Cockcroft-Gault as well as clinical and biochemical parameters for the diagnosis of MS. Results: Out of the total patients evaluated, 37 (30.7% showed alterations that put them in grades G2 and G3 system risk stratification of CKD, of these 18 and 19 corresponded to patients with and without MS respectively. Glomerular Hyperfiltration (> 120 mil / min it was found in both groups 28 (46.7% and 24 (40% cases of patients with and without MS respectively. The glomerular function was strongly correlated with abdominal obesity and high levels of stress arterial. As for the number of criteria and its relationship to the level of kidney damage present, not a firm to increase the latter with respect to the first (p=0.385 trend was observed. Conclusion: The change in the glomerular function is not directly related to the MS but with its components, specifically abdominal obesity and hypertension.

Genetic analysis of intracapillary glomerular lipoprotein deposits in aging mice.

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Gerda A Noordmans

Full Text Available Renal aging is characterized by functional and structural changes like decreased glomerular filtration rate, and glomerular, tubular and interstitial damage. To gain insight in pathways involved in renal aging, we studied aged mouse strains and used genetic analysis to identify genes associated with aging phenotypes.Upon morphological screening in kidneys from 20-month-old mice from 26 inbred strains we noted intracapillary PAS-positive deposits. The severity of these deposits was quantified by scoring of a total of 50 glomeruli per section (grade 0-4. Electron microscopy and immunohistochemical staining for apoE, apoB, apoA-IV and perilipin-2 was performed to further characterize the lesions. To identify loci associated with these PAS-positive intracapillary glomerular deposits, we performed haplotype association mapping.Six out of 26 mouse strains showed glomerular PAS-positive deposits. The severity of these deposits varied: NOD(0.97, NZW(0.41, NON(0.30, B10(0.21, C3 H(0.9 and C57BR(0.7. The intracapillary deposits were strongly positive for apoE and weakly positive for apoB and apoA-IV. Haplotype association mapping showed a strong association with a 30-Kb haplotype block on Chr 1 within the Esrrg gene. We investigated 1 Mb on each site of this region, which includes the genes Spata17, Gpatch2, Esrrg, Ush2a and Kctd3.By analyzing 26 aged mouse strains we found that some strains developed an intracapillary PAS and apoE-positive lesion and identified a small haplotype block on Chr 1 within the Esrrg gene to be associated with these lipoprotein deposits. The region spanning this haplotype block contains the genes Spata17, Gpatch2, Esrrg, Ush2a and Kctd3, which are all highly expressed in the kidney. Esrrg might be involved in the evolvement of these glomerular deposits by influencing lipid metabolism and possibly immune reponses.

Development of nickel membranes deposited on ceramic materials by electroless plating: studies of the hydrogen perm-selectivity properties at elevated temperatures

International Nuclear Information System (INIS)

Amer, J.

2008-09-01

The main objective of this work was to synthesize nickel based membranes by electroless plating on materials such as alumina-α, alumina-γ and zirconia with various textures and to determine their hydrogen perm-selectivity at high temperatures. The synthesis of metal films of high purity (≥ 99% mass Ni) resulting from the choice of hydrazine with its dual role of reducing and complexing agent has revealed that the diameter of pores on the surface support has an impact on the quality of metal adherence. The various contributions of hydrogen transport through these composite membranes at low temperatures (Knudsen and surface diffusion) and at high temperatures (Knudsen and activated diffusion) was established. At its implementation in a membrane reactor (reaction of propane dehydrogenation), the layer of nickel showed a very good resistance to coking. (author)

Pattern of glomerular diseases in oman: A study based on light microscopy and immunofluorescence

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Nasar Yousuf Alwahaibi

2013-01-01

Full Text Available Light microscopy and immunofluorescence play an important part in the final diagnosis of renal biopsy. The aim of this study was to analyze the pattern of various glomerular diseases in Oman. A total of 424 renal biopsies were retrospectively analyzed at the Sultan Qaboos University Hospital between 1999 and 2010. Focal and segmental glomerulosclerosis (FSGS, minimal change disease (MCD, membranous glomerulopathy (MGN and IgA nephropathy were the most common primary glomerular diseases encountered, accounting for 21.2%, 17%, 12.3% and 8.3%, respectively, of all cases. Lupus nephritis was the most common secondary glomerular disease and was the most prevalent among all biopsies, accounting for 30.4% of all biopsies. Amyloidosis was seen in only two cases. The presence of fluorescein isothiocyanatefibrin in all renal cases was low when compared with IgG, IgA, IgM, C3 and C1q markers. In conclusion, based on the findings of this study, lupus nephritis was the most common of all glomerular diseases and FSGS was the most common primary glomerular disease. The importance of fluorescein isothiocyanate-fibrin in the diagnosis of renal biopsy needs to be further investigated.

Assessment of glomerular filtration rate and effective renal plasma flow in cystic fibrosis

International Nuclear Information System (INIS)

Spino, M.; Chai, R.P.; Isles, A.F.; Balfe, J.W.; Brown, R.G.; Thiessen, J.J.; MacLeod, S.M.

1985-01-01

A study was conducted to examine renal function in 10 healthy control subjects and eight patients with cystic fibrosis in stable condition. Sequential bolus injections of /sup 99m/Tc-DTPA and 125 I-OIH were administered to assess glomerular filtration rate and effective renal plasma flow, respectively. Blood was subsequently collected for 3 hours, and urine for 24 hours. Renal clearances of both radioisotope markers were virtually identical in patients and controls. Inasmuch as neither glomerular filtration rate nor effective renal plasma flow was enhanced in patients with cystic fibrosis, increased clearance of drugs in these patients is unlikely to be the result of enhanced glomerular filtration or tubular secretion

Loss of endogenous thymosin β4 accelerates glomerular disease.

Science.gov (United States)

Vasilopoulou, Elisavet; Kolatsi-Joannou, Maria; Lindenmeyer, Maja T; White, Kathryn E; Robson, Michael G; Cohen, Clemens D; Sebire, Neil J; Riley, Paul R; Winyard, Paul J; Long, David A

2016-11-01

Glomerular disease is characterized by morphologic changes in podocyte cells accompanied by inflammation and fibrosis. Thymosin β 4 regulates cell morphology, inflammation, and fibrosis in several organs and administration of exogenous thymosin β 4 improves animal models of unilateral ureteral obstruction and diabetic nephropathy. However, the role of endogenous thymosin β 4 in the kidney is unknown. We demonstrate that thymosin β 4 is expressed prominently in podocytes of developing and adult mouse glomeruli. Global loss of thymosin β 4 did not affect healthy glomeruli, but accelerated the severity of immune-mediated nephrotoxic nephritis with worse renal function, periglomerular inflammation, and fibrosis. Lack of thymosin β 4 in nephrotoxic nephritis led to the redistribution of podocytes from the glomerular tuft toward the Bowman capsule suggesting a role for thymosin β 4 in the migration of these cells. Thymosin β 4 knockdown in cultured podocytes also increased migration in a wound-healing assay, accompanied by F-actin rearrangement and increased RhoA activity. We propose that endogenous thymosin β 4 is a modifier of glomerular injury, likely having a protective role acting as a brake to slow disease progression. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Clinical dehydration and glomerular filtration rate in acute paediatric gastroenteritis.

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Milani, Gregorio P; Fossali, Emilio F; Perri, Alessandra; Vettori, Arianna; Grillo, Paolo; Agostoni, Carlo

2013-08-01

To evaluate changes in glomerular filtration rate in acute gastroenteritis. The correlation between two clinical diagnostic scales and glomerular filtration rate has been investigated in 113 children with acute gastroenteritis in a paediatric emergency setting. A significant reduction of GFR was found in 10% children less than, and 5% children higher than, 2 years of age with acute gastroenteritis. The differences observed as for risk of renal hypoperfusion suggests to consider the age of children as an important determinant to consider the dehydration status in acute gastroenteritis. ©2013 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

The Prediction of Key Cytoskeleton Components Involved in Glomerular Diseases Based on a Protein-Protein Interaction Network.

Science.gov (United States)

Ding, Fangrui; Tan, Aidi; Ju, Wenjun; Li, Xuejuan; Li, Shao; Ding, Jie

2016-01-01

Maintenance of the physiological morphologies of different types of cells and tissues is essential for the normal functioning of each system in the human body. Dynamic variations in cell and tissue morphologies depend on accurate adjustments of the cytoskeletal system. The cytoskeletal system in the glomerulus plays a key role in the normal process of kidney filtration. To enhance the understanding of the possible roles of the cytoskeleton in glomerular diseases, we constructed the Glomerular Cytoskeleton Network (GCNet), which shows the protein-protein interaction network in the glomerulus, and identified several possible key cytoskeletal components involved in glomerular diseases. In this study, genes/proteins annotated to the cytoskeleton were detected by Gene Ontology analysis, and glomerulus-enriched genes were selected from nine available glomerular expression datasets. Then, the GCNet was generated by combining these two sets of information. To predict the possible key cytoskeleton components in glomerular diseases, we then examined the common regulation of the genes in GCNet in the context of five glomerular diseases based on their transcriptomic data. As a result, twenty-one cytoskeleton components as potential candidate were highlighted for consistently down- or up-regulating in all five glomerular diseases. And then, these candidates were examined in relation to existing known glomerular diseases and genes to determine their possible functions and interactions. In addition, the mRNA levels of these candidates were also validated in a puromycin aminonucleoside(PAN) induced rat nephropathy model and were also matched with existing Diabetic Nephropathy (DN) transcriptomic data. As a result, there are 15 of 21 candidates in PAN induced nephropathy model were consistent with our predication and also 12 of 21 candidates were matched with differentially expressed genes in the DN transcriptomic data. By providing a novel interaction network and prediction, GCNet

World Small Animal Veterinary Association Renal Pathology Initiative: Classification of Glomerular Diseases in Dogs.

Science.gov (United States)

Cianciolo, R E; Mohr, F C; Aresu, L; Brown, C A; James, C; Jansen, J H; Spangler, W L; van der Lugt, J J; Kass, P H; Brovida, C; Cowgill, L D; Heiene, R; Polzin, D J; Syme, H; Vaden, S L; van Dongen, A M; Lees, G E

2016-01-01

Evaluation of canine renal biopsy tissue has generally relied on light microscopic (LM) evaluation of hematoxylin and eosin-stained sections ranging in thickness from 3 to 5 µm. Advanced modalities, such as transmission electron microscopy (TEM) and immunofluorescence (IF), have been used sporadically or retrospectively. Diagnostic algorithms of glomerular diseases have been extrapolated from the World Health Organization classification scheme for human glomerular disease. With the recent establishment of 2 veterinary nephropathology services that evaluate 3-µm sections with a panel of histochemical stains and routinely perform TEM and IF, a standardized objective species-specific approach for the diagnosis of canine glomerular disease was needed. Eight veterinary pathologists evaluated 114 parameters (lesions) in renal biopsy specimens from 89 dogs. Hierarchical cluster analysis of the data revealed 2 large categories of glomerular disease based on the presence or absence of immune complex deposition: The immune complex-mediated glomerulonephritis (ICGN) category included cases with histologic lesions of membranoproliferative or membranous patterns. The second category included control dogs and dogs with non-ICGN (glomerular amyloidosis or focal segmental glomerulosclerosis). Cluster analysis performed on only the LM parameters led to misdiagnosis of 22 of the 89 cases-that is, ICGN cases moved to the non-ICGN branch of the dendrogram or vice versa, thereby emphasizing the importance of advanced diagnostic modalities in the evaluation of canine glomerular disease. Salient LM, TEM, and IF features for each pattern of disease were identified, and a preliminary investigation of related clinicopathologic data was performed. © The Author(s) 2015.

Glomerular nerve endings in corial papillae of the pig lip skin.

Science.gov (United States)

Malinovský, L; Pác, L; Krivánková, L

1982-01-01

In the tops of corial papillae of the pig lip skin the authors sometimes observed besides typical sensory corpuscles also glomerular nerve endings. They are formed by one axon or they are polyaxon. The nerve fibres are richly branched in the formation. In electronogrammes a large number of axons is visible in cross sections round some of which there are more or less formed lamellous systems up to four lamellae. Between the axons there are nuclei of Schwann cells, on the surface there is a thin capsule of fibrocyte character. In non-primate mammals the typical receptor in the corium of the skin are simple corpuscles, in primates glomerular nerve endings. As concerns sensory corpuscles it is the other way round. The authors are of the opinion that the observed glomerular endings represent morphologically a transitory formation. With respect to the occurrence of lamellous complexes in the glomeruli, they can be considered as equivalent to simple sensory corpuscles with rapid adaptation.

Anti-glomerular basement membrane disease superimposed on membranous nephropathy: a case report and review of the literature

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Nivera Noel

2010-08-01

Full Text Available Abstract Introduction Anti-glomerular basement membrane disease is a rare autoimmune disorder characterized by pulmonary hemorrhage, crescentic glomerulonephritis and the presence of circulating anti-glomerular basement membrane antibodies. The simultaneous occurrence of both anti-glomerular basement membrane disease and membranous nephropathy is rare. Case presentation A 59-year-old Hispanic man presented with acute onset of nausea and vomiting and was found to have renal insufficiency. Work-up included a kidney biopsy, which revealed anti-glomerular basement membrane disease with underlying membranous nephropathy. He was treated with emergent hemodialysis, intravenous corticosteroids, plasmapheresis, and cyclophosphamide without improvement in his renal function. Conclusion Simultaneous anti-glomerular basement membrane disease and membranous nephropathy is very rare. There have been 16 previous case reports in the English language literature that have been associated with a high mortality and morbidity, and a very high rate of renal failure resulting in hemodialysis. Co-existence of membranous nephropathy and anti-glomerular basement membrane disease may be immune-mediated, although the exact mechanism is not clear.

Important clinical and laboratory correlates of glomerular filtration ...

African Journals Online (AJOL)

2015-02-03

Feb 3, 2015 ... for glomerular changes seen in sickle cell disease (SCD). These include ... sex, frequency of crises per annum, as well as steady state laboratory indices .... nephropathy in sickle cell does not arise from a vaso‑occlusive effect.

Perfil das doenças glomerulares em um hospital público do Distrito Federal Profile of glomerular diseases in a public hospital of Federal District, Brazil

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Fabio Humberto Ribeiro Paes Ferraz

2010-09-01

Full Text Available INTRODUÇÃO: As doenças glomerulares são uma causa frequente de doença renal crônica, sobretudo nos países em desenvolvimento. OBJETIVO: O objetivo deste estudo foi determinar o perfil destas glomerulopatias em um hospital público da cidade de Brasília, Distrito Federal. MÉTODOS: Foram realizadas 121 biopsias renais pela equipe de nefrologia do Hospital Regional da Asa Norte (HRAN entre agosto de 2005 e maio de 2009. Foram excluídas oito biopsias realizadas em pacientes transplantados renais e analisados os prontuários dos 113 pacientes restantes. Dados analisados: sexo, idade, exames laboratoriais, síndrome glomerular, diagnóstico clínico, grau de fibrose intersticial, uso de imunossupressores, necessidade de diálise e desfecho clínico. RESULTADOS: A média de idade foi 34,9 ± 16,2 anos, com predomínio masculino (51,3%. As principais síndromes glomerulares foram: síndrome nefrótica (41,6% e glomerulonefrite rapidamente progressiva (35,4%. Entre as glomerulopatias primárias, houve predomínio da glomeruloesclerose segmentar e focal (26,9% e da nefropatia por IgA (25% e entre as secundárias a nefrite lúpica (50% e a glomerulonefrite proliferativa exsudativa difusa (34,2%. A maioria dos pacientes fez uso de imunossupressores (68,1% e quase um terço deles (29,2% necessitou de diálise durante a internação. Evoluíram para terapia dialítica crônica 13,3% dos pacientes e 10,6% evoluíram a óbito. CONCLUSÃO: Este estudo poderá contribuir para melhor entendimento epidemiológico das doenças glomerulares no Distrito Federal, orientando na adoção de políticas públicas visando permitir rápido diagnóstico e manejo clínico das mesmas.INTRODUCTION: Glomerular diseases are a frequent etiology of chronic kidney disease, especially in the developing countries. OBJECTIVE: To determine the profile of such glomerulopathies in a public hospital located in the city of Brasilia, Federal District. METHODS: 121 renal biopsies in

Laminin α2-mediated focal adhesion kinase activation triggers Alport glomerular pathogenesis.

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Duane Delimont

Full Text Available It has been known for some time that laminins containing α1 and α2 chains, which are normally restricted to the mesangial matrix, accumulate in the glomerular basement membranes (GBM of Alport mice, dogs, and humans. We show that laminins containing the α2 chain, but not those containing the α1 chain activates focal adhesion kinase (FAK on glomerular podocytes in vitro and in vivo. CD151-null mice, which have weakened podocyte adhesion to the GBM rendering these mice more susceptible to biomechanical strain in the glomerulus, also show progressive accumulation of α2 laminins in the GBM, and podocyte FAK activation. Analysis of glomerular mRNA from both models demonstrates significant induction of MMP-9, MMP-10, MMP-12, MMPs linked to GBM destruction in Alport disease models, as well as the pro-inflammatory cytokine IL-6. SiRNA knockdown of FAK in cultured podocytes significantly reduced expression of MMP-9, MMP-10 and IL-6, but not MMP-12. Treatment of Alport mice with TAE226, a small molecule inhibitor of FAK activation, ameliorated fibrosis and glomerulosclerosis, significantly reduced proteinuria and blood urea nitrogen levels, and partially restored GBM ultrastructure. Glomerular expression of MMP-9, MMP-10 and MMP-12 mRNAs was significantly reduced in TAE226 treated animals. Collectively, this work identifies laminin α2-mediated FAK activation in podocytes as an important early event in Alport glomerular pathogenesis and suggests that FAK inhibitors, if safe formulations can be developed, might be employed as a novel therapeutic approach for treating Alport renal disease in its early stages.

Creatinine Clearance and Estimated Glomerular Filtration Rate – When are they Interchangeable

OpenAIRE

Šimetić, Lucija; Zibar, Lada; Drmić, Sandra; Begić, Ivana; Šerić, Vatroslav

2015-01-01

Study goal was to examine which of glomerular rate equations is most suitable for prediction of creatinine clearance. Using a retrospective review of data from 500 hospital patients we calculated glomerular filtration rate according to Cockcroft-Gault equation (C-G), Modification of Diet in Renal Disease Study equation (MDRD) and Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI). We determined if results of these equations were compatible with creatinine clearance, and does...

Schistosomal glomerular disease (a review

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Zilton A. Andrade

1984-12-01

Full Text Available In this review paper schistosomal glomerulopathy is defined as an immune-complex disease. The disease appears in 12-15 per cent of the individuals with hepatosplenic schistosomiasis. Portal hypertension with collateral circulation helps the by pass of the hepatic clearance process and the parasite antigens can bind to antibodies in the circulation and be trapped in the renal glomerulus. Chronic membranousproliferative glomerulonephritis is the most commom lesion present and the nephrotic syndrome is the usual form of clinical presentation. The disease can be experimentally produced, and schistosomal antigens and antibodies, as well as complement, can be demonstrated in the glomerular lesions. Specific treatment of schistosomiasis does not seem to alter the clinical course of schistosomal nephropathy.A glomerulopatia esquistossomotica e um exemplo de doenca causada por complexos imunes. Ela se manifesta em 12 a 15% dos portadores de forma hepato-eplenica da esquistossomose. A hipertensao porta, com circulacao colateral, facilita a ultrapassagem do filtro hepatico e os antigenos esquistossomoticos podem se acoplar aos anticorpos na circulacao e vir a se depositar nos glomerulos. O tipo histologico mais frequente e a glomerulonefrite cronica membrano-proliferativa, geralmente com sindrome nefrotica. A doenca e passivel de reproducao experimental e os antigenos esquistossomoticos, os anticorpos e fracoes do complemento podem ser demonstrados nas lesoes glomerulares. O tratamento especifico da esquistossomose nao mostrou ate o momento a capacidade de alterar o curso da nefropatia.

Urological disorders in chronic kidney disease in children cohort: clinical characteristics and estimation of glomerular filtration rate.

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Dodson, Jennifer L; Jerry-Fluker, Judith V; Ng, Derek K; Moxey-Mims, Marva; Schwartz, George J; Dharnidharka, Vikas R; Warady, Bradley A; Furth, Susan L

2011-10-01

Urological disorders are the most common cause of pediatric chronic kidney disease. We determined the characteristics of children with urological disorders and assessed the agreement between the newly developed bedside glomerular filtration rate estimating formula with measured glomerular filtration rate in 586 patients in the Chronic Kidney Disease in Children study. The Chronic Kidney Disease in Children study is a prospective, observational cohort of children recruited from 48 sites in the United States and Canada. Eligibility requirements include age 1 to 16 years and estimated glomerular filtration rate by original Schwartz formula 30 to 90 ml/min/1.73 m(2). Baseline demographics, clinical variables and glomerular filtration rate were assessed. Bland-Altman analysis was conducted to assess agreement between estimated and measured glomerular filtration rates. Of the 586 participants with at least 1 glomerular filtration rate measurement 348 (59%) had an underlying urological diagnosis (obstructive uropathy in 118, aplastic/hypoplastic/dysplastic kidneys in 104, reflux in 87 and other condition in 39). Among these patients median age was 9 years, duration of chronic kidney disease was 7 years and age at first visit with a urologist was less than 1 year. Of the patients 67% were male, 67% were white and 21% had a low birth weight. Median height was in the 24th percentile. Median glomerular filtration rate as measured by iohexol plasma disappearance was 44.8 ml/min/1.73 m(2). Median glomerular filtration rate as estimated by the Chronic Kidney Disease in Children bedside equation was 44.3 ml/min/1.73 m(2) (bias = -0.5, 95% CI -1.7 to 0.7, p = 0.44). Underlying urological causes of chronic kidney disease were present in 59% of study participants. These children were diagnosed early in life, and many had low birth weight and growth delay. There is good agreement between the newly developed Chronic Kidney Disease in Children estimating equations and measured

Clinical use of estimated glomerular filtration rate for evaluation of kidney function

DEFF Research Database (Denmark)

Broberg, Bo; Lindhardt, Morten; Rossing, Peter

2013-01-01

is a significant predictor for cardiovascular disease and may along with classical cardiovascular risk factors add useful information to risk estimation. Several cautions need to be taken into account, e.g. rapid changes in kidney function, dialysis, high age, obesity, underweight and diverging and unanticipated......Estimating glomerular filtration rate by the Modification of Diet in Renal Disease or Chronic Kidney Disease Epidemiology Collaboration formulas gives a reasonable estimate of kidney function for e.g. classification of chronic kidney disease. Additionally the estimated glomerular filtration rate...

Transitory cell attachments in the differentiating glomerular epithelium of the opossum metanephros.

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Krause, W J; Cutts, J H

1980-01-01

Numerous transitory intercellular attachments are observed between the central, lateral surfaces of adjacent glomerular epithelial cells in the differentiating renal corpuscle. The junctions are characterized by an increased electron density of the adjacent cell membranes and cytoplasm. The intervening intercellular space may contain an amorphous material of moderate electron density. The distribution and position of such temporary cell attachments, together with their modification and subsequent loss during the differentiation of podocytes, suggest that they play an important role in the histogenesis of the glomerular epithelium.

Abdominal Adipose Tissue was Associated with Glomerular Hyperfiltration among Non- Diabetic and Normotensive Adults with a Normal Body Mass Index.

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Jeonghwan Lee

Full Text Available Glomerular hyperfiltration is recognized as an early marker of progressive kidney dysfunction in the obese population. This study aimed to identify the relationship between glomerular hyperfiltration and body fat distribution measured by computed tomography (CT in healthy Korean adults. The study population included individuals aged 20-64 years who went a routine health check-up including an abdominal CT scan. We selected 4,378 individuals without diabetes and hypertension. Glomerular filtration rate was estimated using the CKD-EPI equation, and glomerular hyperfiltration was defined as the highest quintile of glomerular filtration rate. Abdominal adipose tissue areas were measured at the level of the umbilicus using a 16-detector CT scanner, and the cross-sectional area was calculated using Rapidia 2.8 CT software. The prevalence of glomerular hyperfiltration increased significantly according to the subcutaneous adipose tissue area in men (OR = 1.74 (1.16-2.61, P for trend 0.016, for the comparisons of lowest vs. highest quartile and visceral adipose tissue area in women (OR = 2.34 (1.46-3.75, P for trend < 0.001 in multivariate analysis. After stratification by body mass index (normal < 23 kg/m2, overweight ≥ 23 kg/m2, male subjects with greater subcutaneous adipose tissue, even those in the normal BMI group, had a higher prevalence of glomerular hyperfiltration (OR = 2.11 (1.17-3.80, P for trend = 0.009. Among women, the significance of visceral adipose tissue area on glomerular hyperfiltration resulted from the normal BMI group (OR = 2.14 (1.31-3.49, P for trend = 0.002. After menopause, the odds ratio of the association of glomerular hyperfiltration with subcutaneous abdominal adipose tissue increased (OR = 2.96 (1.21-7.25, P for trend = 0.013. Subcutaneous adipose tissue areas and visceral adipose tissue areas are positively associated with glomerular hyperfiltration in healthy Korean adult men and women, respectively. In post

Measurement of glomerular filtration rate by impulse synthesis: Clinical validation and optimization

International Nuclear Information System (INIS)

Palagi, B.; Verga, P.; Broggi, A.; Picozzi, R.; Villa, F.; Guzzini, F.; Cozzi, C.; Tomasi, A.

1988-01-01

Impulse synthesis is a technique which relies upon the logic of continuous infusion but extracts the clearance value from single-injection data by shifting and adding them until an asymptotic value is attained. This study has been aimed at validating and optimizing clinically the measurement of glomerular filtration rate by impulse synthesis. A single intravenous injection of 51 Cr-EDTA has been made in 32 patients and plasma activity monitored over the next 6 h. Glomerular filtration rate computed by a single-exponential fit method (GFR-SEF) has been shown to be significantly (p [de

The future of hemodialysis membranes.

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Humes, H D; Fissell, W H; Tiranathanagul, K

2006-04-01

Hemodialytic treatment of patients with either acute or chronic renal failure has had a dramatic impact on the mortality rates of these patients. Unfortunately, this membrane-based therapy is still incomplete renal replacement, as the mortality and morbidity of these patients remain unacceptably high. Much progress must be made to improve the biocompatibility of hemodialysis membranes as well as their hydraulic and permselective properties to remove small solutes and 'middle molecules' in compact cartridges. The next directions of development will leverage materials and mechanical engineering technology, including microfluidics and nanofabrication, to further improve the clearance functions of the kidney to replicate glomerular permselectivity while retaining high rates of hydraulic permeability. The extension of membrane technology to biohybrid devices utilizing progenitor/stem cells will be another substantive advance for renal replacement therapy. The ability to not only replace solute and water clearance but also active reabsorptive transport and metabolic activity will add additional benefit to the therapy of patients suffering from renal failure. This area of translational research is rich in creative opportunities to improve the unmet medical needs of patients with either chronic or acute renal failure.

Expression of Toll-Like Receptor 4 in Glomerular Endothelial Cells under Diabetic Conditions

International Nuclear Information System (INIS)

Takata, Shunsuke; Sawa, Yoshihiko; Uchiyama, Takanobu; Ishikawa, Hiroyuki

2013-01-01

Diabetic conditions promote glomerulosclerosis by mesangial cells but the mechanisms are not fully elucidated. The present study evaluated the expression of toll-like receptor 4 in glomerular endothelial cells in the streptozotocin (STZ)-induced type 1 diabetic mouse (ICR-STZ) and the type 2 diabetic KK/TaJcl mouse which were fed a high fat diet feed (KK/Ta-HF). In the ICR-STZ and KK/Ta-HF almost glomeruli were immunostained with anti-TLR4 but there was no glomerulus immunostained by ani-TLR4 in the control ICR and KK/Ta. Laser-scanning confocal microscopy showed that the TLR4-positive region did not coincide with the podoplanin-positive region but coincide with the PECAM-1- and VE-cadherin-positive regions in the glomeruli of the ICR-STZ and KK/Ta-HF. The in situ hybridization showed that almost signals for TLR4 mRNA were present in the glomerulus of the ICR-STZ and KK/Ta-HF to a stronger extent than in the control ICR and KK/Ta. These suggest that glomerular endothelial cells usually express the TLR4 gene and hyperglycemia in the diabetic condition induces the TLR4 protein expression in the glomerular capillary endothelial cells. Cytokine productions through the TLR signaling pathway in glomerular endothelial cells may allow mesangial cells to produce extracellular matrix proteins in the diabetic milieu

Multiple Factors Influence Glomerular Albumin Permeability in Rats

Science.gov (United States)

Sandoval, Ruben M.; Wagner, Mark C.; Patel, Monica; Campos-Bilderback, Silvia B.; Rhodes, George J.; Wang, Exing; Wean, Sarah E.; Clendenon, Sherry S.

2012-01-01

Different laboratories recently reported incongruous results describing the quantification of albumin filtration using two-photon microscopy. We investigated the factors that influence the glomerular sieving coefficient for albumin (GSCA) in an effort to explain these discordant reports and to develop standard operating procedures for determining GSCA. Multiple factors influenced GSCA, including the kidney depth of image acquisition (10–20 μm was appropriate), the selection of fluorophore (probes emitting longer wavelengths were superior), the selection of plasma regions for fluorescence measurements, the size and molecular dispersion characteristics of dextran polymers if used, dietary status, and the genetic strain of rat. Fasting reduced the GSCA in Simonsen Munich Wistar rats from 0.035±0.005 to 0.016±0.004 (Palbumin transcytosis with vesicular and tubular delivery to and fusion with the basolateral membrane in S1 proximal tubule cells. In summary, these results help explain the previously conflicting microscopy and micropuncture data describing albumin filtration and highlight the dynamic nature of glomerular albumin permeability. PMID:22223875

Estimated glomerular filtration rate in patients with type 2 diabetes mellitus

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Paula Caitano Fontela

2014-12-01

Full Text Available Objective: to estimate the glomerular filtration using the Cockcroft-Gault (CG, Modification of Diet in Renal Disease (MDRD, and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI equations, and serum creatinine in the screening of reduced renal function in patients with type two diabetes (T2DM enrolled in the Family Health Strategy (ESF, Brazilian federal health-care program. Methods: a cross-sectional descriptive and analytical study was conducted. The protocol consisted of sociodemographics, physical examination and biochemical tests. Renal function was analyzed through serum creatinine and glomerular filtration rate (GFR estimated according to the CG, MDRD and CKD-EPI equations, available on the websites of the Brazilian Nephrology Society (SBN and the (NKF. Results: 146 patients aged 60.9±8.9 years were evaluated; 64.4% were women. The prevalence of serum creatinine >1.2 mg/dL was 18.5% and GFR <60 mL/min/1.73m2 totaled 25.3, 36.3 and 34.2% when evaluated by the equations CG, MDRD and CKD-EPI, respectively. Diabetic patients with reduced renal function were older, had long-term T2DM diagnosis, higher systolic blood pressure and higher levels of fasting glucose, compared to diabetics with normal renal function. Creatinine showed strong negative correlation with the glomerular filtration rate estimated using CG, MDRD and CKD-EPI (-0.64, -0.87, -0.89 equations, respectively. Conclusion: the prevalence of individuals with reduced renal function based on serum creatinine was lower, reinforcing the need to follow the recommendations of the SBN and the National Kidney Disease Education Program (NKDEP in estimating the value of the glomerular filtration rate as a complement to the results of serum creatinine to better assess the renal function of patients.

Prevalence of glomerular hyperfiltration and nephromegaly in normo- and microalbuminuric type 2 diabetic patients.

Science.gov (United States)

Gragnoli, G; Signorini, A M; Tanganelli, I; Fondelli, C; Borgogni, P; Borgogni, L; Vattimo, A; Ferrari, F; Guercia, M

1993-01-01

Glomerular hyperfiltration, correlated with nephromegaly, is a frequent finding in type 1 (insulin-dependent) diabetes. In type 2 (non-insulin-dependent) diabetes, very few studies have been performed, and the results have been inconclusive. Glomerular filtration rate (GFR) and kidney volume, using 99mTc-DTPA scintigraphy and ultrasonography, respectively, were evaluated in 58 control subjects and 163 type 2 diabetic patients; 79 of whom were normoalbuminuric and 84 microalbuminuric. In the two groups of patients, these parameters did not differ significantly from those of controls, even when hypertensive subjects were excluded. Glomerular hyperfiltration was observed in 10 cases; all were normotensive (9.8%), of whom 7 were normoalbuminuric and 3 microalbuminuric. Nephromegaly was observed in 3 other normotensive microalbuminuric diabetic patients. Hypertensive subjects showed a lower GFR than normotensive patients and control subjects. Multivariate analysis showed a negative correlation between glomerular filtrate and systolic blood pressure (BP) in the overall population of patients and in normo- and microalbuminuric patients taken separately. It is concluded that the relationship between these variables forms a continuum in our type 2 diabetic patients; it may also be important in determining the low prevalence of hyperfiltration and nephromegaly found in our patients, who had BP levels higher than those of controls.

Nanoscale protein architecture of the kidney glomerular basement membrane

Science.gov (United States)

Suleiman, Hani; Zhang, Lei; Roth, Robyn; Heuser, John E; Miner, Jeffrey H; Shaw, Andrey S; Dani, Adish

2013-01-01

In multicellular organisms, proteins of the extracellular matrix (ECM) play structural and functional roles in essentially all organs, so understanding ECM protein organization in health and disease remains an important goal. Here, we used sub-diffraction resolution stochastic optical reconstruction microscopy (STORM) to resolve the in situ molecular organization of proteins within the kidney glomerular basement membrane (GBM), an essential mediator of glomerular ultrafiltration. Using multichannel STORM and STORM-electron microscopy correlation, we constructed a molecular reference frame that revealed a laminar organization of ECM proteins within the GBM. Separate analyses of domains near the N- and C-termini of agrin, laminin, and collagen IV in mouse and human GBM revealed a highly oriented macromolecular organization. Our analysis also revealed disruptions in this GBM architecture in a mouse model of Alport syndrome. These results provide the first nanoscopic glimpse into the organization of a complex ECM. DOI: http://dx.doi.org/10.7554/eLife.01149.001 PMID:24137544

Effects of CTLA4-Fc on glomerular injury in humorally-mediated glomerulonephritis in BALB/c mice.

Science.gov (United States)

Kitching, A R; Huang, X R; Ruth, A-J; Tipping, P G; Holdsworth, S R

2002-06-01

The effect of cytotoxic T-lymphocyte-associated molecule 4-immunoglobulin fusion protein (CTLA4-Fc) on humorally-mediated glomerulonephritis was studied in accelerated anti-glomerular basement membrane (anti-GBM) glomerulonephritis induced in BALB/c mice. This strain of mice develops antibody and complement dependent glomerulonephritis under this protocol. Sensitized BALB/c mice developed high levels of circulating autologous antibody titres, intense glomerular deposition of mouse immunoglobulin and complement, significant proteinuria, renal impairment, significant glomerular necrosis and a minor component of crescent formation 10 days after challenge with a nephritogenic antigen (sheep anti-GBM globulin). Early treatment during the primary immune response, or continuous treatment throughout the disease with CTLA4-Fc, significantly suppressed mouse anti-sheep globulin antibody titres in serum, and immunoglobulin and complement deposition in glomeruli. The degree of glomerular necrosis was improved and proteinuria was reduced, particularly in the earlier stages of disease. Late treatment by CTLA4-Fc starting one day after challenge with sheep anti-mouse GBM did not affect antibody production and did not attenuate glomerulonephritis. The low level of crescent formation found in BALB/c mice developing glomerulonephritis was not prevented by the administration of CTLA4-Fc. These results demonstrate that CTLA4-Fc is of benefit in this model of glomerulonephritis by its capacity to attenuate antibody production, without affecting the minor degree of cell-mediated glomerular injury.

Sleep duration and quality in relation to chronic kidney disease and glomerular hyperfiltration in healthy men and women.

Directory of Open Access Journals (Sweden)

Chan-Won Kim

Full Text Available It is unclear whether sleep duration and quality are associated with chronic kidney disease (CKD and glomerular hyperfiltration. The aim of this study was to examine the association of sleep duration and quality with CKD and glomerular hyperfiltration in young and middle-aged adults.We conducted a cross-sectional study of men and women who underwent a health checkup examination, including assessment of sleep duration and quality (n = 241,607. Chronic kidney disease (CKD was defined as an estimated glomerular filtration rate (eGFR less than 60 ml/min/1.73 m2, and glomerular hyperfiltration was defined as eGFR above the age-/sex-specific 95th percentile.In a multinomial logistic regression analysis adjusting for relevant confounders, the adjusted prevalence ratios for CKD (95% confidence interval comparing sleep durations of ≤ 5, 6, 8, and 9 hours with 7 hours were 1.22 (0.95-1.55, 0.93 (0.75-1.14, 0.97 (0.75-1.26, and 1.56 (1.06-2.30 in men and 0.98 (0.68-1.43, 1.03 (0.72-1.46, 1.39 (0.97-2.00, and 1.31 (0.78-2.22 in women, respectively. The corresponding prevalence ratios (95% confidence interval for glomerular hyperfiltration were 1.00 (0.93-1.08, 0.97 (0.91-1.03, 1.03 (0.94-1.13, and 1.39 (1.13-1.72 in men and 1.04 (0.95-1.14, 0.96 (0.90-1.04, 1.11 (1.02-1.20, and 1.28 (1.14-1.45 in women, respectively. Poor subjective sleep quality was associated with glomerular hyperfiltration in men and women.In this large study of young and middle-aged adults, we found that long sleep duration was associated with CKD and glomerular hyperfiltration. Additionally, poor subjective sleep quality was associated with increased prevalence of glomerular hyperfiltration, suggesting the importance of adequate quantity and quality of sleep for kidney function.

Circadian Rhythm of Glomerular Filtration and Solute Handling Related to Nocturnal Enuresis.

Science.gov (United States)

Dossche, L; Raes, A; Hoebeke, P; De Bruyne, P; Vande Walle, J

2016-01-01

Although nocturnal polyuria in patients with monosymptomatic enuresis can largely be explained by the decreased nocturnal vasopressin secretion hypothesis, other circadian rhythms in the kidney also seem to have a role. We recently documented an absent day/night rhythm in a subgroup of desmopressin refractory cases. We explore the importance of abnormal circadian rhythm of glomerular filtration and tubular (sodium, potassium) parameters in patients with monosymptomatic enuresis. In this retrospective study of a tertiary enuresis population we collected data subsequent to a standardized screening (International Children's Continence Society questionnaire), 14-day diary for nocturnal enuresis and diuresis, and 24-hour concentration profile. The study population consisted of 139 children with nocturnal enuresis who were 5 years or older. Children with nonmonosymptomatic nocturnal enuresis were used as controls. There was a maintained circadian rhythm of glomerular filtration, sodium, osmotic excretion and diuresis rate in children with monosymptomatic and nonmonosymptomatic nocturnal enuresis, and there was no difference between the 2 groups. Secondary analysis revealed that in patients with nocturnal polyuria (with monosymptomatic or nonmonosymptomatic nocturnal enuresis) circadian rhythm of glomerular filtration, sodium and osmotic excretion, and diuresis rate was diminished in contrast to those without nocturnal polyuria (p Circadian rhythm of the kidney does not differ between patients with nonmonosymptomatic and monosymptomatic enuresis. However, the subgroup with enuresis and nocturnal polyuria has a diminished circadian rhythm of nocturnal diuresis, sodium excretion and glomerular filtration in contrast to children without nocturnal polyuria. This observation cannot be explained by the vasopressin theory alone. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Treatment of resistant glomerular diseases with adrenocorticotropic hormone gel: a prospective trial.

Science.gov (United States)

Bomback, Andrew S; Canetta, Pietro A; Beck, Laurence H; Ayalon, Rivka; Radhakrishnan, Jai; Appel, Gerald B

2012-01-01

Adrenocorticotropic hormone (ACTH) has shown promising results in glomerular diseases resistant to conventional therapies, but the reported data have solely been from retrospective, observational studies. In this prospective, open-label study (NCT01129284), 15 subjects with resistant glomerular diseases were treated with ACTH gel (80 units subcutaneously twice weekly) for 6 months. Resistant membranous nephropathy (MN), minimal change disease (MCD), and focal segmental glomerulosclerosis (FSGS) were defined as failure to achieve sustained remission of proteinuria off immunosuppressive therapy with at least 2 treatment regimens; resistant IgA nephropathy was defined as >1 g/g urine protein:creatinine ratio despite maximally tolerated RAAS blockade. Remission was defined as stable or improved renal function with ≥50% reduction in proteinuria to 50% reductions in proteinuria while on ACTH, with proteinuria consistently <1 g/g by 6 months. Three of 15 subjects reported significant steroid-like adverse effects with ACTH, including weight gain and hyperglycemia, prompting early termination of therapy without any clinical response. ACTH gel is a promising treatment for resistant glomerular diseases and should be studied further in controlled trials against currently available therapies for resistant disease. Copyright © 2012 S. Karger AG, Basel.

Morphological aspects of the rat kidney preserved by cold storage. I. Glomerular morphometric changes.

Science.gov (United States)

Neagu, S; Chirculescu, A R; Ranga, V; Popescu, F

1983-01-01

The absolute density of glomeruli in the microscopic field was determined in the rat kidney preserved by cold storage for 24, 48, 72 and 96 hrs in two different media: Sacks (hyperosmolar electrolytic solution of intracellular type) and Plasmagel (gelatin solution 4%). Progressive, statistically significant (p less than 0.01) decrease of glomerular density at 24 and 48 hrs was followed by return to initial values at 96 hrs. Decrease of the glomerular density was greater with Plasmagel.

Pattern of glomerular disease in the Saudi population: A single-center, five-year retrospective study

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Z Nawaz

2013-01-01

Full Text Available Glomerular diseases continue to be the leading cause of end-stage renal disease (ESRD globally. Hence, it is important to recognize the pattern of glomerular diseases in different geographical areas in order to understand the patho-biology, incidence and progression of the disorder. Published studies from different centers in Saudi Arabia have reported contradicting results. In this retrospective study, we report our experience at the Armed Forces Hospital, Riyadh, Saudi Arabia. A total of 348 native renal biopsies performed at our center on patients with proteinuria >1 g, hematuria and/or renal impairment during a period of 5 years (between January 2005 and December 2009 were studied by a histopathologist using light microscopy, immunofluorescence and electron microscopy, and were categorized. Results showed that primary glomerular disease accounted for 55.1% of all renal biopsies. The most common histological lesion was focal and segmental glomerulosclerosis (FSGS (27.6%, followed by minimal change disease (MCD (17.7% and membrano-proliferative glomerulonephritis (MPGN (13.0%. Secondary glomerular disease accounted for 37.9% of the glomerular diseases, with lupus nephritis (LN being the most common lesion (54.5%, followed by hypertensive nephrosclerosis (22%, post-infectious glomerulonephritis (7.5%, diabetic nephropathy (DN (6.8% and vasculitides (4.5%. Four percent of all biopsies turned out to be ESRD while biopsy was inadequate in 2.8% of the cases. In conclusion, our study showed that FSGS was the most common primary GN encountered, while LN was the most common secondary GN. We encountered 14 cases of crescentic glomerulonephritis. Also, the prevalence of MPGN, MCD, IgA nephropathy and membranous GN was many folds higher in males when compared with the Western data. We believe that it is mandatory to maintain a Saudi Arabian Renal Biopsy Registry to understand better the pattern of glomerular disease in the Saudi population and to follow

Plasma Gelsolin Induced Glomerular Fibrosis via the TGF-β1/Smads Signal Transduction Pathway in IgA Nephropathy

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Lei Zhang

2017-02-01

Full Text Available Glomerular fibrosis has been shown to be closely related to the progression and prognosis of IgA nephropathy (IgAN. However, mechanism underlying IgAN glomerular fibrosis remains unclear. Recently, our study showed that plasma gelsolin (pGSN was decreased in the serum of an IgAN mouse model and that pGSN deposition was found in the glomeruli. Another cytokine, TGF-β1, which is closely related to glomerular fibrosis, was also found to be highly expressed in the glomeruli. In the present study, we report that pGSN induces glomerular fibrosis through the TGF-β1/Smads signal transduction pathway. This is supported by the following findings: human mesangial cells (HMCs show remarkable morphological changes and proliferation in response to co-stimulation with pGSN and polymeric IgA1 (pIgA1 from IgAN patients compared to other controls. Moreover, ELISA assays showed that more TGF-β1 secretion was found in HMCs supernatants in the co-stimulation group. Further experiments showed increased TGF-β1, Smad3, p-Smad2/3, Smad4, and collagen 1 and decreased Smad7 expression in the co-stimulation group. Our present study implied that the synergistic effect of pGSN and pIgA induced glomerular fibrosis via the TGF-β1/Smads signal transduction pathway. This might be a potential mechanism for the glomerular fibrosis observed in IgAN patients.

Plasma Gelsolin Induced Glomerular Fibrosis via the TGF-β1/Smads Signal Transduction Pathway in IgA Nephropathy

Science.gov (United States)

Zhang, Lei; Han, Changsong; Ye, Fei; He, Yan; Jin, Yinji; Wang, Tianzhen; Wu, Yiqi; Jiang, Yang; Zhang, Fengmin; Jin, Xiaoming

2017-01-01

Glomerular fibrosis has been shown to be closely related to the progression and prognosis of IgA nephropathy (IgAN). However, mechanism underlying IgAN glomerular fibrosis remains unclear. Recently, our study showed that plasma gelsolin (pGSN) was decreased in the serum of an IgAN mouse model and that pGSN deposition was found in the glomeruli. Another cytokine, TGF-β1, which is closely related to glomerular fibrosis, was also found to be highly expressed in the glomeruli. In the present study, we report that pGSN induces glomerular fibrosis through the TGF-β1/Smads signal transduction pathway. This is supported by the following findings: human mesangial cells (HMCs) show remarkable morphological changes and proliferation in response to co-stimulation with pGSN and polymeric IgA1 (pIgA1) from IgAN patients compared to other controls. Moreover, ELISA assays showed that more TGF-β1 secretion was found in HMCs supernatants in the co-stimulation group. Further experiments showed increased TGF-β1, Smad3, p-Smad2/3, Smad4, and collagen 1 and decreased Smad7 expression in the co-stimulation group. Our present study implied that the synergistic effect of pGSN and pIgA induced glomerular fibrosis via the TGF-β1/Smads signal transduction pathway. This might be a potential mechanism for the glomerular fibrosis observed in IgAN patients. PMID:28208683

Do Anesthetic Techniques Influence the Threshold for Glomerular Capillary Hemorrhage Induced in Rats by Contrast-Enhanced Diagnostic Ultrasound?

Science.gov (United States)

Miller, Douglas L; Lu, Xiaofang; Fabiilli, Mario; Dou, Chunyan

2016-02-01

Glomerular capillary hemorrhage can be induced by ultrasonic cavitation during contrast-enhanced diagnostic ultrasound (US) exposure, an important nonthermal US bioeffect. Recent studies of pulmonary US exposure have shown that thresholds for another nonthermal bioeffect of US, pulmonary capillary hemorrhage, is strongly influenced by whether xylazine is included in the specific anesthetic technique. The objective of this study was to determine the influence of xylazine on contrast-enhanced diagnostic US-induced glomerular capillary hemorrhage. In this study, anesthesia with ketamine only was compared to ketamine plus xylazine for induction of glomerular capillary hemorrhage in rats by 1.6-MHz intermittent diagnostic US with a microsphere contrast agent (similar to Definity; Lantheus Medical Imaging, Inc, North Billerica, MA). Glomerular capillary hemorrhage was measured as a percentage of glomeruli with hemorrhage found in histologic sections for groups of rats scanned at different peak rarefactional pressure amplitudes. There was a significant difference between the magnitude of the glomerular capillary hemorrhage between the anesthetics at 2.3 MPa, with 45.6% hemorrhage for ketamine only, increasing to 63.2% hemorrhage for ketamine plus xylazine (P Ultrasound in Medicine.

HUMAN GLOMERULAR VOLUME QUANTIFICATIONDURING THE AGING PROCESS

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Dejan Zdravković

2004-12-01

Full Text Available Kidney function is directly related to the changes of renal tissue, especially glomeruli, which is particularly distinct during the aging process. The impossibility of kidney function substitution points to the need for glomerular morphologic and functional characteristics estimation during the aging process.Human cadaveric kidney tissue samples were used as material during research. Age of cadavers ranged from 20 to 70 years and they were classified according to the scheme: I (20–29; II (30–39; III (40–49; IV (50–59; V (60–69 i VI (older than 70. After the routine histologic preparation of the renal tissue the slices were analized stereologicaly under the light microscope with projection screen (Reichert Visopan with 40 x lens magnification. M42 test system was used and 100, by unbased method selected glomeruli, were analyzed.Average glomerular capillary network volume shows significant increase (p< 0,001 as far as to the age of 50 years in regard to the age of 20 to 29 years. This parameter shows insignificant decrease after the age of 50 until the age of 70 years. This decrease was significant after the age of 70 years in regard to the period of the 20 to 29 (p< 0,05 and the period of 40 to 49 years (p<0,01.

Glomerular hyperfiltration in children with cancer: prevalence and a hypothesis

Energy Technology Data Exchange (ETDEWEB)

Kwatra, Neha S. [Children' s National Medical Center, Division of Diagnostic Imaging and Radiology, Washington, DC (United States); Boston Children' s Hospital, Department of Radiology, Boston, MA (United States); Meany, Holly J. [Children' s National Medical Center, Department of Hematology/Oncology, Washington, DC (United States); Ghelani, Sunil J. [Boston Children' s Hospital, Department of Cardiology, Boston, MA (United States); Zahavi, David [The Johns Hopkins University School of Medicine, Department of Pathology, Baltimore, MD (United States); Pandya, Nayan; Majd, Massoud [Children' s National Medical Center, Division of Diagnostic Imaging and Radiology, Washington, DC (United States)

2017-02-15

Glomerular hyperfiltration has recently been reported in children with malignancies and has been attributed to increased solute from breakdown of tumor tissues. To evaluate the prevalence of hyperfiltration in the pediatric oncology population and explore its pathophysiological mechanism. Tc-99 m diethylenetriaminepentaacetic acid (DTPA) glomerular filtration rate (GFR) examinations (437 studies) and medical records of 177 patients <21 years of age diagnosed with a malignancy between January 2005 and October 2013 were retrospectively reviewed. Hyperfiltration was defined as a GFR ≥ 160 ml/min/1.73 m{sup 2}. Seventy-seven (43.5%) patients had hyperfiltration in at least one GFR exam. A significantly higher percentage of patients with central nervous system (CNS) tumors (63.6%) had hyperfiltration when compared to other tumor types (27.3%, P < 0.001). No association was found between hyperfiltration and age, gender, race or bone marrow involvement. There was a significant trend toward decreasing hyperfiltration after the second cycle of chemotherapy (P = 0.006) and a significant increase in subjects with low GFR (<100 ml/min/1.73 m{sup 2}) with increasing number of cycles of chemotherapy (P = 0.005). Glomerular hyperfiltration is common in children with malignancies at diagnosis and during initial cycles of chemotherapy. It is particularly prevalent in patients with central nervous tumors, which are frequently smaller in volume. Therefore, the pathophysiological mechanism of hyperfiltration cannot be explained solely on the basis of large tumor volume and subsequent cell breakdown. We hypothesize that host hypermetabolic state plays an important role in pathophysiology of hyperfiltration. (orig.)

Glomerular filtration rate by {sup 51}chomium and {sup 113m}indium labeled EDTA in horses; Taxa de filtracao glomerular pelo EDTA marcado com {sup 51}cromo e com {sup 113m}indio em equinos

Energy Technology Data Exchange (ETDEWEB)

Maliska, C.; D' Almeida, J.; Pellegrini, P.M.; Schimit, T.S. [Hospital Central do Exercito (HCE), Rio de Janeiro, RJ (Brazil). Servico de Medicina Nuclear; Pinho, W.R. [Centro de Ensino Superior, Valenca, RJ (Brazil). Fac. de Medicina Veterinaria; Lima, J.E.T. [Instituto Nacional do Cancer (INCa), Rio de Janeiro, RJ (Brazil). Servico de Medicina Nuclear

2009-07-01

The glomerular filtration rate was determined in nine healthy horses, six male and three female, aged two to 12-year-old, by means of {sup 51}Cr and {sup 113m}In labeled EDTA single injection technique. The glomerular filtration rate was calculated from the plasma disappearance curve and the volume of distribution of the radiotracer, {sup 51}Cr-EDTA or {sup 113m}In-EDTA. The result (mean +- standard deviation) was 148.80 +- 26.42 m L.min{sup -1}.100 kg. It is concluded that the measurement of glomerular filtration rate by {sup 51}Cr-EDTA or {sup 113m}In-EDTA by single injection technique eliminates the bladder catheterization, and for its simplicity, convenience, accuracy, and low dose of radiation, can be used in horses as a method of choice in clinical routine. (author)

Glomerular and Mitral-Granule Cell Microcircuits Coordinate Temporal and Spatial Information Processing in the Olfactory Bulb.

Science.gov (United States)

Cavarretta, Francesco; Marasco, Addolorata; Hines, Michael L; Shepherd, Gordon M; Migliore, Michele

2016-01-01

The olfactory bulb processes inputs from olfactory receptor neurons (ORNs) through two levels: the glomerular layer at the site of input, and the granule cell level at the site of output to the olfactory cortex. The sequence of action of these two levels has not yet been examined. We analyze this issue using a novel computational framework that is scaled up, in three-dimensions (3D), with realistic representations of the interactions between layers, activated by simulated natural odors, and constrained by experimental and theoretical analyses. We suggest that the postulated functions of glomerular circuits have as their primary role transforming a complex and disorganized input into a contrast-enhanced and normalized representation, but cannot provide for synchronization of the distributed glomerular outputs. By contrast, at the granule cell layer, the dendrodendritic interactions mediate temporal decorrelation, which we show is dependent on the preceding contrast enhancement by the glomerular layer. The results provide the first insights into the successive operations in the olfactory bulb, and demonstrate the significance of the modular organization around glomeruli. This layered organization is especially important for natural odor inputs, because they activate many overlapping glomeruli.

Glomerular and mitral-granule cell microcircuits coordinate temporal and spatial information processing in the olfactory bulb

Directory of Open Access Journals (Sweden)

Francesco Cavarretta

2016-07-01

Full Text Available The olfactory bulb processes inputs from olfactory receptor neurons (ORNs through two levels: the glomerular layer at the site of input, and the granule cell level at the site of output to the olfactory cortex. The sequence of action of these two levels has not yet been examined. We analyze this issue using a novel computational framework that is scaled up, in three-dimensions (3D, with realistic representations of the interactions between layers, activated by simulated natural odors, and constrained by experimental and theoretical analyses. We suggest that the postulated functions of glomerular circuits have as their primary role transforming a complex and disorganized input into a contrast-enhanced and normalized representation, but cannot provide for synchronization of the distributed glomerular outputs. By contrast, at the granule cell layer, the dendrodendritic interactions mediate temporal decorrelation, which we show is dependent on the preceding contrast enhancement by the glomerular layer. The results provide the first insights into the successive operations in the olfactory bulb, and demonstrate the significance of the modular organization around glomeruli. This layered organization is especially important for natural odor inputs, because they activate many overlapping glomeruli.

Structural Alterations of the Glomerular Wall And Vessels in Early ...

African Journals Online (AJOL)

Structural Alterations of the Glomerular Wall And Vessels in Early Stages of Diabetes Mellitus: Light and Transmission Electron Microscopic Study. ... The second group of 20 (the experimental group) was injected intraperitoneally by a single dose of streptozotocin to induce hyperglycemia. Rats were sacrificed after ten days, ...

PROTECTIVE CLOTHING BASED ON PERMSELECTIVE MEMBRANE AND CARBON ADSORPTION

Energy Technology Data Exchange (ETDEWEB)

J.G. Wijmans; J.O. Stull

2001-11-07

The goal of this project was to develop chemical protective clothing for use by DOE decontamination and decommissioning workers that is sufficiently water vapor permeable to keep the workers cool, thereby enhancing their productivity. This report describes the results of Phase II of a two-phase project to complete development of the novel permselective material and to test protective clothing made from the fabric. In Phase I a novel material incorporating a nonporous hydrophilic polyvinylacohol (PVA) layer, which is water vapor permeable but relatively impermeable to organic vapors, was developed. The results of the Phase I tests showed that the chemical resistance of the MTR material is comparable to that of Saranex/Tyvek materials, and that the comfort properties are closer to those of Tyvek (as measured in terms of CLO and permeability). Chemical resistance was measured using permeation tests against liquid dichloromethane. Comfort properties were ascertained by measuring the water vapor transmission of the material and by sweating manikin tests on whole protective suits. In addition, a cost/benefit analysis demonstrated that use of MTR's material technology could result in significant improvements in work productivity and cost savings if protective clothing items made from the new material were used more than once. In Phase II, MTR undertook a program to optimize the performance and production engineering for the new material technology. A partnership was formed with Kimberly-Clark Corporation to assist with a detailed evaluation of the MTR technology, and MTR used the services of Mr. Jeff Stull, President of the consulting firm International Personnel Protection, Inc., who conducted a detailed economic and application analysis for the developed fabric. The protective fabric manufacturing steps were simplified significantly, resulting in a 30% reduction in manufacturing costs and eliminating the necessity for capital investment in production equipment

PROTECTIVE CLOTHING BASED ON PERMSELECTIVE MEMBRANE AND CARBON ADSORPTION

International Nuclear Information System (INIS)

Wijmans, J.G.; Stull, J.O.

2001-01-01

The goal of this project was to develop chemical protective clothing for use by DOE decontamination and decommissioning workers that is sufficiently water vapor permeable to keep the workers cool, thereby enhancing their productivity. This report describes the results of Phase II of a two-phase project to complete development of the novel permselective material and to test protective clothing made from the fabric. In Phase I a novel material incorporating a nonporous hydrophilic polyvinylacohol (PVA) layer, which is water vapor permeable but relatively impermeable to organic vapors, was developed. The results of the Phase I tests showed that the chemical resistance of the MTR material is comparable to that of Saranex/Tyvek materials, and that the comfort properties are closer to those of Tyvek (as measured in terms of CLO and permeability). Chemical resistance was measured using permeation tests against liquid dichloromethane. Comfort properties were ascertained by measuring the water vapor transmission of the material and by sweating manikin tests on whole protective suits. In addition, a cost/benefit analysis demonstrated that use of MTR's material technology could result in significant improvements in work productivity and cost savings if protective clothing items made from the new material were used more than once. In Phase II, MTR undertook a program to optimize the performance and production engineering for the new material technology. A partnership was formed with Kimberly-Clark Corporation to assist with a detailed evaluation of the MTR technology, and MTR used the services of Mr. Jeff Stull, President of the consulting firm International Personnel Protection, Inc., who conducted a detailed economic and application analysis for the developed fabric. The protective fabric manufacturing steps were simplified significantly, resulting in a 30% reduction in manufacturing costs and eliminating the necessity for capital investment in production equipment

Aluminum-containing dense deposits of the glomerular basement membrane: identification by energy dispersive X-ray analysis

International Nuclear Information System (INIS)

Smith, D.M. Jr.; Pitcock, J.A.; Murphy, W.M.

1982-01-01

Heavy metals, including gold, mercury, lead, bismuth, and cadmium, have the potential to cause renal disease. With the development of X-ray microanalysis, these heavy metals can now be identified in tissue deposits. This report describes a case of renal failure, probably related to dysproteinemia, in which granular, electron-opaque dense deposits were present in the glomerular basement membranes. Energy dispersive X-ray analysis demonstrated that these dense deposits contained aluminum. An analysis of this patient's history in relation to the current knowledge of aluminum metabolism suggests that the aluminum deposition occurred secondary to previous glomerular injury. This case emphasizes the need to utilize heavy metal identification technology whenever granular, electron-opaque dense deposits are identified and represents, to our knowledge, the first study to document aluminum deposits within the glomerular basement membrane of humans

Reduced glomerular filtration rate as a predictor of coronary artery ...

African Journals Online (AJOL)

Tarek A. Ghonemy

2016-07-09

Jul 9, 2016 ... Internal Medicine Department, Nephrology Unit, Zagazig University ... glomerular filtration rate (eGFR) and risk of coronary artery disease ... ing of eGFR may have a pivotal role in early detection and management of CAD in those types of ..... position statement from kidney disease improving global out-.

[Could isolated mesangial deposits of C3 be responsible of glomerular hematuric nephropathies (author's transl)].

Science.gov (United States)

Saint-Andre, J P; Touzard, D; Houssin, A; Simard, C

1982-01-01

This communication presents three cases of prolonged macroscopic hematuria in young subjects. Complementary explorations eliminated urologic or vascular causes. Renal biopsies showed minimal glomerular lesions with light microscopy, normal basement membranes in electron microscopy and mesangial deposits of C3 and properdine in immunofluorescence. Although the mesangial deposits of C3 lack specificity and the number of observations is small, it appears useful to report such cases so as to indicate their frequency and perhaps their autonomy, in glomerular hematuric nephropathies.

Creatinine clearance during cimetidine administration for measurement of glomerular filtration rate

NARCIS (Netherlands)

van Acker, B. A.; Koomen, G. C.; Koopman, M. G.; de Waart, D. R.; Arisz, L.

1992-01-01

Creatinine clearance inaccurately estimates true glomerular filtration rate (GFR) because of tubular secretion of creatinine. We studied the ability of oral cimetidine, a blocker of tubular creatinine secretion, to improve the accuracy of measuring creatinine clearance. Clearances of inulin and

Early-Onset Diabetic E1-DN Mice Develop Albuminuria and Glomerular Injury Typical of Diabetic Nephropathy

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Mervi E. Hyvönen

2015-01-01

Full Text Available The transgenic E1-DN mice express a kinase-negative epidermal growth factor receptor in their pancreatic islets and are diabetic from two weeks of age due to impaired postnatal growth of β-cell mass. Here, we characterize the development of hyperglycaemia-induced renal injury in the E1-DN mice. Homozygous mice showed increased albumin excretion rate (AER at the age of 10 weeks; the albuminuria increased over time and correlated with blood glucose. Morphometric analysis of PAS-stained histological sections and electron microscopy images revealed mesangial expansion in homozygous E1-DN mice, and glomerular sclerosis was observed in the most hyperglycaemic mice. The albuminuric homozygous mice developed also other structural changes in the glomeruli, including thickening of the glomerular basement membrane and widening of podocyte foot processes that are typical for diabetic nephropathy. Increased apoptosis of podocytes was identified as one mechanism contributing to glomerular injury. In addition, nephrin expression was reduced in the podocytes of albuminuric homozygous E1-DN mice. Tubular changes included altered epithelial cell morphology and increased proliferation. In conclusion, hyperglycaemic E1-DN mice develop albuminuria and glomerular and tubular injury typical of human diabetic nephropathy and can serve as a new model to study the mechanisms leading to the development of diabetic nephropathy.

Common histological patterns in glomerular epithelial cells in secondary focal segmental glomerulosclerosis.

Science.gov (United States)

Kuppe, Christoph; Gröne, Hermann-Josef; Ostendorf, Tammo; van Kuppevelt, Toin H; Boor, Peter; Floege, Jürgen; Smeets, Bart; Moeller, Marcus J

2015-11-01

Parietal epithelial cells (PECs) are involved in the development of sclerotic lesions in primary focal and segmental glomerulosclerosis (FSGS). Here, the role of PECs was explored in the more common secondary FSGS lesions in 68 patient biopsies, diagnosed with 11 different frequently or rarely encountered glomerular pathologies and additional secondary FSGS lesions. For each biopsy, one section was quadruple stained for PECs (ANXA3), podocytes (synaptopodin), PEC matrix (LKIV69), and Hoechst (nuclei), and a second was quadruple stained for activated PECs (CD44 and cytokeratin-19), PEC matrix, and nuclei. In all lesions, cellular adhesions (synechiae) between Bowman's capsule and the tuft were formed by cells expressing podocyte and/or PEC markers. Cells expressing PEC markers were detected in all FSGS lesions independent of the underlying glomerular disease and often stained positive for markers of activation. Small FSGS lesions, which were hardly identified on PAS sections previously, were detectable by immunofluorescent staining using PEC markers, potentially improving the diagnostic sensitivity to identify these lesions. Thus, similar patterns of cells expressing podocyte and/or PEC markers were found in the formation of secondary FSGS lesions independent of the underlying glomerular disease. Hence, our findings support the hypothesis that FSGS lesions follow a final cellular pathway to nephron loss that includes involvement of cells expressing PEC markers.

Efectos de la circulación extracorpórea sobre el filtrado glomerular en la cirugía cardiovascular pediátrica Effects of extracorporeal circulation on glomerular filtration in pediatric cardiovascular surgery

OpenAIRE

Abel Facenda; Antolín Romero; Junior M Lima; Cruz M Contreras; Heilyn del Valle Montero; Manuel G Lima Montero

2011-01-01

Objetivo: conocer como afecta la circulación extracorpórea la función renal tomando como marcador la alteración del filtrado glomerular. Material y método: se realizó un estudio prospectivo, analítico y observacional en 63 pacientes pediátricos sometidos a cirugía cardiaca electiva con circulación extracorpórea en el Cardiocentro Pediátrico «William Soler» entre octubre de 2009 y abril de 2010. Se calcularon las variaciones del filtrado glomerular durante la circulación extracorpórea por el m...

Crescentic glomerular nephritis associated with rheumatoid arthritis: a case report.

Science.gov (United States)

Balendran, K; Senarathne, L D S U; Lanerolle, R D

2017-07-21

Rheumatoid arthritis is a systemic disorder where clinically significant renal involvement is relatively common. However, crescentic glomerular nephritis is a rarely described entity among the rheumatoid nephropathies. We report a case of a patient with rheumatoid arthritis presenting with antineutrophil cytoplasmic antibody-negative crescentic glomerular nephritis. A 54-year-old Sri Lankan woman who had recently been diagnosed with rheumatoid arthritis was being treated with methotrexate 10 mg weekly and infrequent nonsteroidal anti-inflammatory drugs. She presented to our hospital with worsening generalized body swelling and oliguria of 1 month's duration. Her physical examination revealed that she had bilateral pitting leg edema and periorbital edema. She was not pale or icteric. She had evidence of mild synovitis of the small joints of the hand bilaterally with no deformities. No evidence of systemic vasculitis was seen. Her blood pressure was 170/100 mmHg, and her jugular venous pressure was elevated to 7 cm with an undisplaced cardiac apex. Her urine full report revealed 2+ proteinuria with active sediment (dysmorphic red blood cells [17%] and granular casts). Her 24-hour urinary protein excretion was 2 g. Her serum creatinine level was 388 μmol/L. Abdominal ultrasound revealed normal-sized kidneys with acute parenchymal changes and mild ascites. Her renal biopsy showed renal parenchyma containing 20 glomeruli showing diffuse proliferative glomerular nephritis, with 14 of 20 glomeruli showing cellular crescents, and the result of Congo red staining was negative. Her rheumatoid factor was positive with a high titer (120 IU/ml), but results for antinuclear antibody, double-stranded deoxyribonucleic acid, and antineutrophil cytoplasmic antibody (perinuclear and cytoplasmic) were negative. Antistreptolysin O titer rheumatoid arthritis, awareness of which would facilitate early appropriate investigations and treatment.

Transcriptional landscape of glomerular parietal epithelial cells.

Directory of Open Access Journals (Sweden)

Sina A Gharib

Full Text Available Very little is known about the function of glomerular parietal epithelial cells (PECs. In this study, we performed genome-wide expression analysis on PEC-enriched capsulated vs. PEC-deprived decapsulated rat glomeruli to determine the transcriptional state of PECs under normal conditions. We identified hundreds of differentially expressed genes that mapped to distinct biologic modules including development, tight junction, ion transport, and metabolic processes. Since developmental programs were highly enriched in PECs, we characterized several of their candidate members at the protein level. Collectively, our findings confirm that PECs are multifaceted cells and help define their diverse functional repertoire.

Reduced glomerular angiotensin II receptor density in diabetes mellitus in the rat: time course and mechanism

International Nuclear Information System (INIS)

Wilkes, B.M.

1987-01-01

Glomerular angiotensin II receptors are reduced in number in early diabetes mellitus, which may contribute to hyperfiltration and glomerular injury. The time course and role of the renin-angiotensin-aldosterone system in the pathogenesis of the receptor abnormality were studied in male Sprague-Dawley rats made diabetic with streptozotocin (65 mg, iv). Glomerular angiotensin II receptors were measured by Scatchard analysis; insulin, renin activity, angiotensin II, and aldosterone were measured by RIA. Diabetes mellitus was documented at 24 h by a rise in plasma glucose (vehicle-injected control, 133 +/- 4; diabetic, 482 +/- 22 mg/dl and a fall in plasma insulin (control, 53.1 +/- 5.7; diabetic, 35.6 +/- 4.0 microIU/ml. At 24 h glomerular angiotensin II receptor density was decreased by 26.5% in diabetic rats (control, 75.5 +/- 9.6 X 10(6); diabetic, 55.5 +/- 8.3 X 10(6) receptors/glomerulus. Receptor occupancy could not explain the defect, because there was reduced binding in diabetic glomeruli after pretreatment with 3 M MgCl 2 , a maneuver that caused dissociation of previously bound hormone. There was a progressive return of the receptor density toward normal over the 60 days following induction of diabetes, with diabetic glomeruli measuring 22.7%, 14.8%, and 3.7% fewer receptors than age-matched controls at 11 days, 1 month, and 2 months, respectively

estimated glomerular filtration rate and risk of survival in acute stroke

African Journals Online (AJOL)

2014-03-03

Mar 3, 2014 ... ESTIMATED GLOMERULAR FILTRATION RATE AND RISK OF SURVIVAL IN ACUTE STROKE. E. I. Okaka, MBBS, FWACP, F. A. Imarhiagbe, MBChB, FMCP, F. E. Odiase, MBBS, FMCP, O. C. A. Okoye, MBBS, FWACP,. Department of Medicine, University of Benin Teaching Hospital, Benin City, Nigeria.

Glomerular and tubular damage markers are elevated in patients with diabetes

NARCIS (Netherlands)

Nauta, Ferdau L.; Boertien, Wendy E.; Bakker, Stephan J. L.; van Goor, Harry; van Oeveren, Wim; de Jong, Paul E.; Bilo, Henk; Gansevoort, Ron T.

OBJECTIVE: We investigated in a cross-sectional study the levels of serum and urinary damage markers in diabetic patients (n = 94) and nondiabetic control subjects (n = 45) to study the association of glomerular (IgG), proximal tubular (kidney injury molecule [KIM]-1, N-acetyl-β-d-glucosaminidase

The associations of Bmi-1 with progression of glomerular chronic kidney disease
.

Science.gov (United States)

Yang, Xiaoxia; Bai, Ming; Ning, Xiaoxuan; Ma, Feng; Liu, Limin; Liu, Ting; Liu, Minna; Wang, Hanmin; Sun, Shiren

2018-02-01

Our previous studies indicated that Bmi-1 plays an important role in hypoxia-induced tubular epithelial-mesenchymal transition and the development of kidney fibrosis in cellular and animal models. However, circulating Bmi-1 levels in human chronic kidney disease (CKD) and their relation to progression remains unknown. We conducted a post-hoc analysis of a prospective cohort study. The blood samples and clinical data of 230 patients with glomerular CKD and 67 healthy adults were prospectively collected between January 2010 and June 2012. Serum Bmi-1 was measured using enzyme-linked immunosorbent assay (ELISA). CKD patients had significantly higher serum Bmi-1 concentrations than the healthy controls (496.4 (363.1 - 675.4) pg/mL compared with 257.3 (235.4 - 303.8) pg/mL, p Bmi-1 level inversely correlated with the estimated glomerular filtration rate (eGFR) (r = -0.346, p Bmi-1 levels and serum creatinine, blood urea nitrogen, cystatin C concentration, and the severity of tubulointerstitial fibrosis (r = 0.248, p Bmi-1 level was associated with a shorter duration of renal survival. Cox multivariate analyses further demonstrated that serum Bmi-1 concentration was an independent prognostic factor for CKD patients (HR = 6.48, p Bmi-1 levels were associated with adverse kidney disease outcome, suggesting that Bmi-1 is a novel biomarker for glomerular CKD progression. More data from larger longitudinal studies are required to validate our findings.
.

Associations between age, body size and nephron number with individual glomerular volumes in urban West African males.

Science.gov (United States)

McNamara, Bridgette J; Diouf, Boucar; Hughson, Michael D; Hoy, Wendy E; Bertram, John F

2009-05-01

Glomerulomegaly has been associated with an increased risk of renal disease. Few reports have investigated the heterogeneity of glomerular size within kidneys and associated risk factors. This study measured the individual glomerular volume (IGV) of 720 non-sclerotic glomeruli in kidneys of adult West African males, and investigated associations of IGV with age, total glomerular (nephron) number and body surface area (BSA). IGVs were determined in the kidneys of 24 Senegalese males from two age groups (12 subjects aged 20- 30 years and 12 subjects aged 50-70 years). Subjects were randomly chosen at autopsies performed at Le Dantec Hospital in Dakar. Volumes of 30 glomeruli per subject were determined using the disector/Cavalieri stereological method. IGVs ranged from 1.31 x 10(6) microm3 to 12.40 x 10(6) microm3 (a 9.4-fold variation). IGV varied up to 5.3-fold within single kidneys. The trimmed range of IGV within subjects (10th to 90th percentile of IGV) was directly correlated with median glomerular size. The mean and standard deviation (SD) of IGV did not differ significantly between age groups or between subjects with higher (> or =1.78 m2) and lower BSA (IGV was significantly and directly correlated with BSA. Kidneys with less than 1 million nephrons had significantly larger mean IGV than kidneys with more than 1 million nephrons, and the trimmed range of IGVs within subjects was inversely correlated with total glomerular number. There was a considerable variation in IGV within kidneys of Senegalese males at autopsy. The heterogeneity of IGV was increased in association with low nephron number and increased BSA, with more pronounced effects in older subjects.

A fine structural localization of the non-specific cholinesterase activity in glomerular nerve formations (endings).

Science.gov (United States)

Dubový, P

1990-01-01

Snout glabrous skin (rhinarium) of the cat is innervated not only by typical simple lamellar corpuscles but also glomerular formations. In contrast to simple lamellar corpuscles, glomerular nerve formations are located away the dermal papillae. In cross sections, glomerular nerve formation consists of several axonal profiles enveloped by 1-2 cytoplasmic lamellae of Schwann cells. The space among them is filled by collagenous microfibrils and the basal lamina-like material. Capsule was composed from fibroblast-like cells without definite basal lamina. An electron-dense reaction product due to non-specific cholinesterase activity was associated with Schwann cells and their processes surrounding unmyelinated terminal portion of the sensory axons. Abundant reaction product was bound to the collagenous microfibrils and was deposited in extracellular matrix between Schwann cell processes. These results are further evidence for the presence of the non-specific cholinesterase molecules as integral component of the extracellular matrix in sensory corpuscles. On the basis of histochemical study two possible explanation are considered for functional involving of this enzyme in sensory nerve formations.

Opposite regulation of type II and III receptors for immunoglobulin G in mouse glomerular mesangial cells and in the induction of anti-glomerular basement membrane (GBM) nephritis

NARCIS (Netherlands)

Radeke, HH; Janssen-Graalfs, [No Value; Sowa, EN; Chouchakova, N; Skokowa, J; Loscher, F; Schmidt, RE; Heeringa, P; Gessner, JE

2002-01-01

We examined the capacity of mouse glomerular mesangial cells (MC) to express and function through two different low affinity FcgammaRs, the activating FcgammaRIII and the inhibitory FcgammaRII. Immunohistochemistry identified FcgammaRII as the prominent FcgammaR in the kidney, and low levels of

Cell renewal of glomerular cell types in normal rats. An autoradiographic analysis

International Nuclear Information System (INIS)

Pabst, R.; Sterzel, R.B.

1983-01-01

Normal adult Sprague-Dawley rats received either a single or repetitive injection of the DNA precursor 3 H-thymidine ( 3 H-TdR). For autoradiography semi-thin sections were prepared 2 hr to 14 days after labeling. The majority of labeled cells noted in glomerular tufts were endothelial cells. Mesangial cells had a lower production rate. Podocytes revealed no evidence of proliferation. Bowman's capsule cells showed a higher labeling index than tuft cells at all times. Neither the urinary nor the vascular pole was found to be a proliferative zone for Bowman's capsule cells. The flash and repetitive labeling experiments demonstrated a constant rate of cell renewal of about 1% per day, resulting in a long life span for endothelial and mesangial cells as well as Bowman's capsule cells. These data provide a basis for cell kinetic studies in models of glomerular diseases

Creatinine Clearance Is Not Equal to Glomerular Filtration Rate and Cockcroft-Gault Equation Is Not Equal to CKD-EPI Collaboration Equation.

Science.gov (United States)

Fernandez-Prado, Raul; Castillo-Rodriguez, Esmeralda; Velez-Arribas, Fernando Javier; Gracia-Iguacel, Carolina; Ortiz, Alberto

2016-12-01

Direct oral anticoagulants (DOACs) may require dose reduction or avoidance when glomerular filtration rate is low. However, glomerular filtration rate is not usually measured in routine clinical practice. Rather, equations that incorporate different variables use serum creatinine to estimate either creatinine clearance in mL/min or glomerular filtration rate in mL/min/1.73 m 2 . The Cockcroft-Gault equation estimates creatinine clearance and incorporates weight into the equation. By contrast, the Modification of Diet in Renal Disease and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations estimate glomerular filtration rate and incorporate ethnicity but not weight. As a result, an individual patient may have very different renal function estimates, depending on the equation used. We now highlight these differences and discuss the impact on routine clinical care for anticoagulation to prevent embolization in atrial fibrillation. Pivotal DOAC clinical trials used creatinine clearance as a criterion for patient enrollment, and dose adjustment and Federal Drug Administration recommendations are based on creatinine clearance. However, clinical biochemistry laboratories provide CKD-EPI glomerular filtration rate estimations, resulting in discrepancies between clinical trial and routine use of the drugs. Copyright © 2016 Elsevier Inc. All rights reserved.

HYDROXYUREA TREATMENT DECREASES GLOMERULAR HYPERFILTRATION IN CHILDREN WITH SICKLE CELL ANEMIA

Science.gov (United States)

Aygun, Banu; Mortier, Nicole A.; Smeltzer, Matthew P.; Shulkin, Barry L.; Hankins, Jane S.; Ware, Russell E.

2015-01-01

Background Glomerular hyperfiltration and microalbuminuria/proteinuria are early manifestations of sickle nephropathy. The effects of hydroxyurea therapy on these renal manifestations of sickle cell anemia (SCA) are not well defined. Objective To investigate the effects of hydroxyurea on glomerular filtration rate (GFR) measured by 99mTc-DTPA clearance, and on microalbuminuria/proteinuria in children with SCA. Study Design Hydroxyurea Study of Long-Term Effects (HUSTLE) is a prospective study (NCT00305175) with the goal of describing the long-term cellular, molecular, and clinical effects of hydroxyurea therapy in SCA. Glomerular filtration rate, urine microalbumin, and serum cystatin C were measured before initiating hydroxyurea therapy and then repeated after 3 years. Baseline and Year 3 values for HUSTLE subjects were compared using the Wilcoxon Signed Rank test. Associations between continuous variables were evaluated using Spearman correlation coefficient. Results Twenty-three children with SCA (median age 7.5 years, range 2.5–14.0 years) received hydroxyurea at maximum tolerated dose (MTD, 24.4 ± 4.5 mg/kg/day, range 15.3–30.6 mg/kg/day). After three years of treatment, GFR measured by 99mTc-DTPA decreased significantly from 167 ± 46 mL/min/1.73m2 to 145 ± 27 mL/min/1.73m2 (p=0.016). This decrease in GFR was significantly associated with increase in fetal hemoglobin (p= 0.042) and decrease in lactate dehydrogenase levels (p=0.035). Urine microalbumin and cystatin C levels did not change significantly. Conclusions Hydroxyurea at MTD is associated with a decrease in hyperfiltration in young children with SCA. PMID:23255310

Consensus Recommendations for the Diagnostic Investigation of Dogs with Suspected Glomerular Disease

NARCIS (Netherlands)

Littman, M.P.; Daminet, S.; Grauer, G.F.; Lees, G.E.; van Dongen, A.M.|info:eu-repo/dai/nl/097672637

2013-01-01

Background The International Renal Interest Society (IRIS) offers guidelines for chronic kidney disease and acute kidney injury. As dogs with glomerular disease may present differently and require different treatment than those with whole nephron or tubular disease, the IRIS Canine

Radiation-induced changes in glomerular and tubular cell kinetics and morphology following irradiation of a single kidney in the pig

International Nuclear Information System (INIS)

Robbins, Mike E. C.; Bonsib, Stephen M.; Ikeda, Andrea; Soranson, Julie A.; Wilson, George D.; Rezvani, Mohi; Golding, Stephen J.; Whitehouse, Elizabeth; Hopewell, John W.

1995-01-01

Purpose: Radiation-induced changes in glomerular and tubular cell kinetics and morphology following irradiation of a single pig kidney were assessed. Methods and Materials: The right kidney of 13 adult female Large White pigs was irradiated with a single dose of 9.8 Gy γ rays. Animals were serially killed between 2 and 24 weeks postirradiation (PI); 1 h prior to postmortem each pig received 500 mg bromodeoxyuridine (BrdUrd). At postmortem, both kidneys were removed and tissue taken to prepare cell suspensions. The labeling index (LI) of these suspensions was measured using flow cytometry; in vivo BrdUrd incorporation in glomerular and tubular cells was determined immunohistochemically. The kidneys were also assessed histologically. Results: Irradiation of the right kidney alone resulted in a significant increase in renal cell LI in both the irradiated and the contralateral unirradiated kidney within 2 weeks of irradiation; peak values of 1.57 ± 0.32% and 1.04 ± 0.13%, respectively, were seen 4 weeks PI, significantly greater p < 0.001) than the preirradiation value of 0.18 ± 0.01%. The LI values then declined with time, but remained greater than those seen prior to irradiation. A similar pattern of response was determined from counts of labeled glomerular and tubular cells identified immunohistochemically. The increase in labeled glomerular cells was seen 2 weeks PI, whereas that for the tubular cells did not occur until 4 weeks PI. The irradiated kidney exhibited diffuse, progressive glomerular alterations. In contrast, tubular damage was focal; the irradiated kidney also exhibited a prominent vasculopathy, involving arteriolar and peripheral interlobular artery thickening. The contralateral unirradiated kidney appeared unchanged. Conclusion: These findings confirm the hypothesis that the morphologic and kinetic responses observed after irradiation of a single kidney are similar to those observed after irradiation of both kidneys. Renal irradiation results in

Indexing Glomerular Filtration Rate to Body Surface Area

DEFF Research Database (Denmark)

Redal-Baigorri, Belén; Rasmussen, Knud; Heaf, James Goya

2014-01-01

BACKGROUND: Kidney function is mostly expressed in terms of glomerular filtration rate (GFR). A common feature is the expression as ml/min per 1.73 m(2) , which represents the adjustment of the individual kidney function to a standard body surface area (BSA) to allow comparison between individuals....... We investigated the impact of indexing GFR to BSA in cancer patients, as this BSA indexation might affect the reported individual kidney function. METHODS: Cross-sectional study of 895 adults who had their kidney function measured with (51) chrome ethylene diamine tetraacetic acid. Mean values of BSA...

Glomerular filtration rate estimated from the uptake phase of 99mTc-DTPA renography in chronic renal failure

DEFF Research Database (Denmark)

Petersen, L J; Petersen, J R; Talleruphuus, U

1999-01-01

The purpose of the study was to compare the estimation of glomerular filtration rate (GFR) from 99mTc-DTPA renography with that estimated from the renal clearance of 51Cr-EDTA, creatinine and urea.......The purpose of the study was to compare the estimation of glomerular filtration rate (GFR) from 99mTc-DTPA renography with that estimated from the renal clearance of 51Cr-EDTA, creatinine and urea....

Changes in glomerular parietal epithelial cells in mouse kidneys with advanced age

Science.gov (United States)

Roeder, Sebastian S.; Stefanska, Ania; Eng, Diana G.; Kaverina, Natalya; Sunseri, Maria W.; McNicholas, Bairbre A.; Rabinovitch, Peter; Engel, Felix B.; Daniel, Christoph; Amann, Kerstin; Lichtnekert, Julia; Pippin, Jeffrey W.

2015-01-01

Kidney aging is accompanied by characteristic changes in the glomerulus, but little is known about the effect of aging on glomerular parietal epithelial cells (PECs), nor if the characteristic glomerular changes in humans and rats also occur in very old mice. Accordingly, a descriptive analysis was undertaken in 27-mo-old C57B6 mice, considered advanced age. PEC density was significantly lower in older mice compared with young mice (aged 3 mo), and the decrease was more pronounced in juxtamedullary glomeruli compared with outer cortical glomeruli. In addition to segmental and global glomerulosclerosis in older mice, staining for matrix proteins collagen type IV and heparan sulfate proteoglycan were markedly increased in Bowman's capsules of older mouse glomeruli, consistent with increased extracellular matrix production by PECs. De novo staining for CD44, a marker of activated and profibrotic PECs, was significantly increased in aged glomeruli. CD44 staining was more pronounced in the juxtamedullary region and colocalized with phosphorylated ERK. Additionally, a subset of aged PECs de novo expressed the epithelial-to-mesenchymal transition markers α-smooth muscle and vimentin, with no changes in epithelial-to-mesenchymal transition markers E-cadherin and β-catenin. The mural cell markers neural/glial antigen 2, PDGF receptor-β, and CD146 as well as Notch 3 were also substantially increased in aged PECs. These data show that mice can be used to better understand the aging kidney and that PECs undergo substantial changes, especially in juxtamedullary glomeruli, that may participate in the overall decline in glomerular structure and function with advancing age. PMID:26017974

Glomerular hypertrophy in subjects with low nephron number: contributions of sex, body size and race.

Science.gov (United States)

Puelles, Victor G; Douglas-Denton, Rebecca N; Zimanyi, Monika A; Armitage, James A; Hughson, Michael D; Kerr, Peter G; Bertram, John F

2014-09-01

We have shown that low nephron number (Nglom) is a strong determinant of individual glomerular volume (IGV) in male Americans. However, whether the same pattern is present in female Americans remains unclear. The contributions of body surface area (BSA) and race to IGV in the context of Nglom also require further evaluation. Kidneys without overt renal disease were collected at autopsy in Mississippi, USA. The extremes of female Nglom were used to define high and low Nglom for both sexes. Nglom and IGV were estimated by design-based stereology. A total of 24 African and Caucasian American females (n = 12 per race; 6 per Nglom extreme) were included. These subjects were subsequently matched to 24 comparable males by age and Nglom and to 18 additional males by age, Nglom and BSA. IGV average and variance were very similar in female African and Caucasian Americans with high and low Nglom. Males with low Nglom from both races showed greater IGV average and variance than comparable females matched by age and Nglom. These differences in IGV between sexes were not observed in Caucasian Americans with low Nglom that were matched by age, Nglom and BSA. In contrast, glomeruli from African Americans were larger than those from Caucasian Americans, especially in subjects with high Nglom. While female Americans with low Nglom did not show glomerular hypertrophy, comparable males with low Nglom showed marked glomerular hypertrophy that was closely associated with high BSA. Glomerular size in African Americans may be confounded by multiple additional factors. © The Author 2014. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Glomerular parietal epithelial cell activation induces collagen secretion and thickening of Bowman's capsule in diabetes.

Science.gov (United States)

Holderied, Alexander; Romoli, Simone; Eberhard, Jonathan; Konrad, Lukas A; Devarapu, Satish K; Marschner, Julian A; Müller, Susanna; Anders, Hans-Joachim

2015-03-01

The metabolic and hemodynamic alterations in diabetes activate podocytes to increase extracellular matrix (ECM) production, leading to thickening of the glomerular basement membrane (GBM). We hypothesized that diabetes would activate parietal epithelial cells (PECs) in a similar manner and cause thickening of Bowman's capsules. Periodic acid Schiff staining of human kidney biopsies of 30 patients with diabetic nephropathy (DN) revealed a significantly thicker Bowman's capsule as compared with 20 non-diabetic controls. The average thickness was 4.55±0.21 μm in the group of patients with DN compared with 2.92±0.21 μm in the group of non-diabetic controls (PBowman's capsule showed strong association with CD44-positive PECs. In summary, metabolic alterations in diabetes activate PECs to increase the expression and secretion of Bowman's capsule proteins. This process may contribute to the thickening of the Bowman's capsule, similar to the thickening of the GBM that is driven by activated podocytes. These data may also imply that activated PECs contribute to ECM production once they migrate to the glomerular tuft, a process resulting in glomerular scaring, for example, in diabetic glomerulosclerosis.

Glomerular Podocytes Express Type 1 Adenylate Cyclase: Inactivation Results in Susceptibility to Proteinuria

Science.gov (United States)

Xiao, Zhijie; He, Liqun; Takemoto, Minoru; Jalanko, Hannu; Chan, Guy C.; Storm, Daniel R.; Betsholtz, Christer; Tryggvason, Karl; Patrakka, Jaakko

2011-01-01

Background/Aims The organization of actin cytoskeleton in podocyte foot processes plays a critical role in the maintenance of the glomerular filtration barrier. The cAMP pathway is an important regulator of the actin network assembly in cells. However, the role of the cAMP pathway in podocytes is not well understood. Type 1 adenylate cyclase (Adcy1), previously thought to be specific for neuronal tissue, is a member of the family of enzymes that catalyses the formation of cAMP. In this study, we characterized the expression and role of Adcy1 in the kidney. Methods Expression of Adcy1 was studied by RT-PCR, Northern blotting and in situ hybridization. The role of Adcy1 in podocytes was investigated by analyzing Adcy1 knockout mice (Adcy1–/–). Results and Conclusion: Adcy1 is expressed in the kidney specifically by podocytes. In the kidney, Adcy1 does not have a critical role in normal physiological functioning as kidney histology and function are normal in Adcy1–/– mice. However, albumin overload resulted in severe albuminuria in Adcy1–/– mice, whereas wild-type control mice showed only mild albumin leakage to urine. In conclusion, we have identified Adcy1 as a novel podocyte signaling protein that seems to have a role in compensatory physiological processes in the glomerulus. PMID:21196775

Clinical study of GFR and split renal GFR in evaluating the glomerular function in patients with type 2 diabetes

International Nuclear Information System (INIS)

Fu Hongliang; Li Jinsong; Li Jianing; Wu Jingchuan; Yang Shurong; Gu Zhenhui; Zou Renjian; Shi Haihong

2003-01-01

Objective: To assess glomerular filtration function in patients with type 2 diabetes by glomerular filtration rate (GFR) and split GFR, namely left GFR (LGFR) and right GFR (RGFR). Methods: Fifty-one patients with type 2 diabetes were classified by urine albumin analysis into three groups, normalalbuminuria group (NA), microalbuminuria group(MA) and macroalbuminuria group (MAA) . Twelve patients without diabetes were included into control group. 99 Tc m -DTPA renography was performed on all these cases. GFR and split GFR were calculated by Gates formula. Results: 1) GFR, LGFR and RGFR of NA group were lower than that of the control group. 2) GFR, LGFR and RGFR were significantly correlated with the urine albumin level (r=-0.457, -0.412, -0.424, respectively, P all < 0.01). 3) In all 51 cases, there were 5 cases whose GFR were normal while split GFR were abnormal. Conclusions: 1) GFR and split GFR measurement can detect the incipient damage of glomerular function more sensitively than urine albumin analysis and show the degree of the damage correctly. 2) Split GFR measurement can improve the evaluation of the glomerular function in type 2 diabetes patients

Coexistence of anti-glomerular basement membrane antibodies and myeloperoxidase-ANCAs in crescentic glomerulonephritis

NARCIS (Netherlands)

Rutgers, Abraham; Slot, Marjan; van Paassen, Pieter; van Breda Vriesman, Peter; Heeringa, Peter; Tervaert, Jan Willem Cohen

BACKGROUND: In a substantial proportion of patients with crescentic glomerulonephritis (CGN), both anti-glomerular basement membrane (GBM) antibodies and antineutrophil cytoplasmic antibodies (ANCAs) with specificity for myeloperoxidase (MPO-ANCA) are detected. In the present study, we questioned

Quantitation of renal function with glomerular and tubular agents

International Nuclear Information System (INIS)

Dubovsky, E.V.; Russell, C.D.

1982-01-01

Quantitative methods to measure the glomerular and tubular function of the kidneys with radionuclides have been available for many years. They have not been widely used because the techniques and the calculations exceeded the scope of routine nuclear medicine practice. Validation of simplified methods and the introduction of computer technology have made measurement of the effective renal plasma flow (ERPF) and the glomerular filtration rate (GFR) simple enough so that they can be performed reproducibly in most nuclear medicine departments. The estimation of ERPF with radioiodinated OIH and GFR with /sup 99m/TcDTPA can be achieved in many ways, all of which yield clinically useful results. How to get the best results using the simplest methods is still unclear. The required accuracy depends on the intended clinical use. Our preference at the present time is to use a single or double plasma sample to calculate global ERPF or GFR, and to use the 1-2 min OIH or 1-3 min Tc-DTPA uptake to calculate relative function of the two kidneys (split function ERPF or GFR). The choice of method will be influenced by local factors, such as the nature of the patient population, the case volume, and the resources available. A desirable goal for future studies is to document carefully the capabilities and limitations of each alternative method, so that the choice can be rational

Implementation of Olfactory Bulb Glomerular Layer Computations in a Digital Neurosynaptic Core

Directory of Open Access Journals (Sweden)

Nabil eImam

2012-06-01

Full Text Available We present a biomimetic system that captures essential functional properties of the glomerular layer of the mammalian olfactory bulb, specifically including its capacity to decorrelate similar odor representations without foreknowledge of the statistical distributions of analyte features. Our system is based on a digital neuromorphic chip consisting of 256 leaky-integrate-and-fire neurons, 1024x256 crossbar synapses, and AER communication circuits. The neural circuits configured in the chip reflect established connections among mitral cells, periglomerular cells, external tufted cells and superficial short axon cells within the olfactory bulb, and accept input from convergent sets of sensors configured as olfactory sensory neurons. This configuration generates functional transformations comparable to those observed in the glomerular layer of the mammalian olfactory bulb. Our circuits, consuming only 45 pJ of active power per spike with a power supply voltage of 0.85V, can be used as the first stage of processing in low-power artificial chemical sensing devices inspired by natural olfactory systems.

Measurement of renal glomerular filtration rate using labelled substances with compartmental analysis

International Nuclear Information System (INIS)

Eberstadt, P.L.

1981-10-01

Using a model for the two-compartmental open system and experiments on animals (rabbits and dogs) as well as on human healthy volunteers, an attempt was made to study the advantages and limitations of different radionuclide methods for glomerular filtration rate determination. Labelled compounds used in different combinations were: 3 H-inulin, sup(113m)In-EDTA, 131 I-iothalamate, sup(99m)Tc-DTPA and 14 C-creatinine. The results of the study lead to some working hypotheses concerning the value of creatinine and other labelled substances in the measurement of glomerular filtration rate in clinical practice. The advantages and disadvantages of individual methods summarized in the final report are generally in agreement with the present views of many research workers. Also the hypothesis can be justified that the different labelled compounds which have been studied might be handled independently by the membranes involved but at the long run produce similar homeostatic balance

Glomerular filtration values obtained with 99mTc-DTPA v/s measurements of creatinine Clearance and calculation of the filtered glomerular using the Schwartz formula in a pediatric population

International Nuclear Information System (INIS)

Opazo, Claudio; Gutierrez, Elisa; Zamorano, Julio; Troncoso, TM

2005-01-01

We compare glomerular filtration rate by DTPA Renogram (DTPA-GFR) with creatinine clearance (CC) and Glomerular filtration rate from Schwartz formula (Schwartz-GFR). The need for using (DTPA-GFR) method raised from the practical difficulties in getting an accurate (CC) in pediatric population. From Sep-2001 to May-2005, 48 patients aged 1month to 18 years, underwent (DTPA-GFR) and (Schwartz-GFR). 18 had also (CC). Comparison were made among these measurements also accounting for age groups. We found a better correlation between (DTPA-GFR) and (CC) Pearson = 0,895. (Schwartz)/(CC) comparison showed a slightly lower correlation Pearson = 0,857. The worst correlation was found comparing (DTPA-GFR)/(Schwartz-GFR) in children < 3 yr Pearson = 0,560. As we found a better correlation between (DTPA-GFR)/(CC) than (DTPA-GFR)/(Schwartz-GFR), DTPA-GFR could be considered reliable method in evaluating renal function in children having difficulties to get a Creatinine Clearance (au)

Changes in glomerular parietal epithelial cells in mouse kidneys with advanced age.

Science.gov (United States)

Roeder, Sebastian S; Stefanska, Ania; Eng, Diana G; Kaverina, Natalya; Sunseri, Maria W; McNicholas, Bairbre A; Rabinovitch, Peter; Engel, Felix B; Daniel, Christoph; Amann, Kerstin; Lichtnekert, Julia; Pippin, Jeffrey W; Shankland, Stuart J

2015-07-15

Kidney aging is accompanied by characteristic changes in the glomerulus, but little is known about the effect of aging on glomerular parietal epithelial cells (PECs), nor if the characteristic glomerular changes in humans and rats also occur in very old mice. Accordingly, a descriptive analysis was undertaken in 27-mo-old C57B6 mice, considered advanced age. PEC density was significantly lower in older mice compared with young mice (aged 3 mo), and the decrease was more pronounced in juxtamedullary glomeruli compared with outer cortical glomeruli. In addition to segmental and global glomerulosclerosis in older mice, staining for matrix proteins collagen type IV and heparan sulfate proteoglycan were markedly increased in Bowman's capsules of older mouse glomeruli, consistent with increased extracellular matrix production by PECs. De novo staining for CD44, a marker of activated and profibrotic PECs, was significantly increased in aged glomeruli. CD44 staining was more pronounced in the juxtamedullary region and colocalized with phosphorylated ERK. Additionally, a subset of aged PECs de novo expressed the epithelial-to-mesenchymal transition markers α-smooth muscle and vimentin, with no changes in epithelial-to-mesenchymal transition markers E-cadherin and β-catenin. The mural cell markers neural/glial antigen 2, PDGF receptor-β, and CD146 as well as Notch 3 were also substantially increased in aged PECs. These data show that mice can be used to better understand the aging kidney and that PECs undergo substantial changes, especially in juxtamedullary glomeruli, that may participate in the overall decline in glomerular structure and function with advancing age. Copyright © 2015 the American Physiological Society.

A novel podocyte gene, semaphorin 3G, protects glomerular podocyte from lipopolysaccharide-induced inflammation.

Science.gov (United States)

Ishibashi, Ryoichi; Takemoto, Minoru; Akimoto, Yoshihiro; Ishikawa, Takahiro; He, Peng; Maezawa, Yoshiro; Sakamoto, Kenichi; Tsurutani, Yuya; Ide, Shintaro; Ide, Kana; Kawamura, Harukiyo; Kobayashi, Kazuki; Tokuyama, Hirotake; Tryggvason, Karl; Betsholtz, Christer; Yokote, Koutaro

2016-05-16

Kidney diseases including diabetic nephropathy have become huge medical problems, although its precise mechanisms are still far from understood. In order to increase our knowledge about the patho-physiology of kidney, we have previously identified >300 kidney glomerulus-enriched transcripts through large-scale sequencing and microarray profiling of the mouse glomerular transcriptome. One of the glomerulus-specific transcripts identified was semaphorin 3G (Sema3G) which belongs to the semaphorin family. The aim of this study was to analyze both the in vivo and in vitro functions of Sema3G in the kidney. Sema3G was expressed in glomerular podocytes. Although Sema3G knockout mice did not show obvious glomerular defects, ultrastructural analyses revealed partially aberrant podocyte foot processes structures. When these mice were injected with lipopolysaccharide to induce acute inflammation or streptozotocin to induce diabetes, the lack of Sema3G resulted in increased albuminuria. The lack of Sema3G in podocytes also enhanced the expression of inflammatory cytokines including chemokine ligand 2 and interleukin 6. On the other hand, the presence of Sema3G attenuated their expression through the inhibition of lipopolysaccharide-induced Toll like receptor 4 signaling. Taken together, our results surmise that the Sema3G protein is secreted by podocytes and protects podocytes from inflammatory kidney diseases and diabetic nephropathy.

QUANTIFICATION OF GLOMERULAR EPITHELIAL-CELL ADHESION BY USING ANTI-DNA ANTIBODIES IN ELISA

NARCIS (Netherlands)

COERS, W; SMEENK, RJT; SALANT, DJ; WEENING, JJ

A sensitive and reproducible microassay is described for quantification of adhesion of cells to matrix-coated 96-wells plates under different experimental conditions. For this purpose glomerular visceral epithelial cells (GVEC) were used. Attached GVEC were fixed with methanol and incubated with a

Clinical Relevance of Differences in Glomerular Filtration Rate Estimations in Frail Older People by Creatinine- vs. Cystatin C-Based Formulae.

Science.gov (United States)

Jacobs, Anne; Benraad, Carolien; Wetzels, Jack; Rikkert, Marcel Olde; Kramers, Cornelis

2017-06-01

The risk of incorrect medication dosing is high in frail older people. Therefore, accurate assessment of the glomerular filtration rate is important. The objective of this study was to compare the estimated glomerular filtration rate using creatinine- and cystatin C-based formulae, the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations, in frail older people. We hypothesized that frailty determines the difference between the creatinine- and cystatin C-based formulae. The mean difference between CKD-EPI creatinine and cystatin C was determined using (cross-sectional) data of 55 patients (mean age 73 years) admitted to a psychiatric ward for older adults. The level of agreement of these estimations was assessed by a Bland-Altman analysis. In all patients, the Rockwood's Frailty Index was derived and correlated with the mean difference between CKD-EPI creatinine and cystatin C. The mean difference between CKD-EPI creatinine (mean 71.2 mL/min/1.73 m 2 ) and CKD-EPI cystatin C (mean 57.6 mL/min/1.73 m 2 ) was 13.6 mL/min/1.73 m 2 (p creatinine- and cystatin C-based glomerular filtration rate (Pearson correlation coefficient 0.182, p = 0.184). There was a significant gap between a creatinine- and cystatin C-based estimation of glomerular filtration rate, irrespective of frailty. The range of differences between the commonly used estimated glomerular filtration rate formulae might result in clinically relevant differences in drug prescription and differences in chronic kidney disease staging.

Implementation of olfactory bulb glomerular-layer computations in a digital neurosynaptic core.

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Imam, Nabil; Cleland, Thomas A; Manohar, Rajit; Merolla, Paul A; Arthur, John V; Akopyan, Filipp; Modha, Dharmendra S

2012-01-01

We present a biomimetic system that captures essential functional properties of the glomerular layer of the mammalian olfactory bulb, specifically including its capacity to decorrelate similar odor representations without foreknowledge of the statistical distributions of analyte features. Our system is based on a digital neuromorphic chip consisting of 256 leaky-integrate-and-fire neurons, 1024 × 256 crossbar synapses, and address-event representation communication circuits. The neural circuits configured in the chip reflect established connections among mitral cells, periglomerular cells, external tufted cells, and superficial short-axon cells within the olfactory bulb, and accept input from convergent sets of sensors configured as olfactory sensory neurons. This configuration generates functional transformations comparable to those observed in the glomerular layer of the mammalian olfactory bulb. Our circuits, consuming only 45 pJ of active power per spike with a power supply of 0.85 V, can be used as the first stage of processing in low-power artificial chemical sensing devices inspired by natural olfactory systems.

Agrin is a major heparan sulfate proteoglycan in the human glomerular basement membrane

NARCIS (Netherlands)

Groffen, Alexander J.; Ruegg, Markus A.; Dijkman, Henri; Van De Velden, Thea J.; Buskens, Carin A.; Van Den Born, Jacob; Assmann, Karel J.; Monnens, Leo A.; Veerkamp, Jacques H.; Van Den Heuvel, Lambert P.

Agrin is a heparan sulfate proteoglycan (HSPG) that is highly concentrated in the synaptic basal lamina at the neuromuscular junction (NMJ). Agrin-like immunoreactivity is also detected outside the NMJ. Here we show that agrin is a major HSPG component of the human glomerular basement membrane

Learning-dependent and -independent enhancement of mitral/tufted cell glomerular odor responses following olfactory fear conditioning in awake mice.

Science.gov (United States)

Ross, Jordan M; Fletcher, Max L

2018-04-18

Associative fear learning produces fear toward the conditioned stimulus (CS) and often generalization, the expansion of fear from the CS to similar, unlearned stimuli. However, how fear learning affects early sensory processing of learned and unlearned stimuli in relation to behavioral fear responses to these stimuli remains unclear. We subjected male and female mice expressing the fluorescent calcium indicator GCaMP3 in olfactory bulb mitral and tufted cells to a classical olfactory fear conditioning paradigm. We then used awake, in vivo calcium imaging to quantify learning-induced changes in glomerular odor responses, which constitute the first site of olfactory processing in the brain. The results demonstrate that odor-shock pairing non-specifically enhances glomerular odor representations in a learning-dependent manner and increases representational similarity between the CS and non-conditioned odors, potentially priming the system towards generalization of learned fear. Additionally, CS-specific glomerular enhancements remain even when associative learning is blocked, suggesting two separate mechanisms lead to enhanced glomerular responses following odor-shock pairings. SIGNIFICANCE STATEMENT In the olfactory bulb (OB), odors are uniquely coded in a spatial map that represents odor identity, making the OB a unique model system for investigating how learned fear alters sensory processing. Classical fear conditioning causes fear of the conditioned stimulus (CS) and of neutral stimuli, known as generalization. Combining fear conditioning with fluorescent calcium imaging of OB glomeruli, we found enhanced glomerular responses of the CS as well as neutral stimuli in awake mice, which mirrors fear generalization. We report that CS and neutral stimuli enhancements are, respectively, learning- independent and learning-dependent. Together, these results reveal distinct mechanisms leading to enhanced OB processing of fear-inducing stimuli and provide important

Radiation induced changes in the expression of fibronectin, Pai-1, MMP in rat glomerular epithelial cell

International Nuclear Information System (INIS)

Park, Woo Yoon; Kim, Won Dong; Zheng, Ying; Ha, Tae Sun; Kim, Jae Sung; Cho, Moon June

2006-01-01

Renal irradiation can lead to the development of radiation nephropathy, and this is characterized by the accumulation of extracellular matrix and final fibrosis. To determine the possible role of the glomerular epithelial cell, the radiation-induced changes in the expression of its genes associated with the extracellular matrix were analyzed. Rat glomerular epithelial cells (GEpC) were irradiated with a single dose of 0, 2, 5, 10 and 20 Gy with using 6 MV LINAC (Siemens, USA), and the samples were collected 6, 24, 48 and 72 hours post-irradiation, respectively. Northern blotting, western blotting and zymography were used to measure the expression level of fibronectin (Fn), plasminogen activator inhibitor-1 (Pai-1), matrix metalloproteinases-2, 9 (MMP-2, 9), tissue inhibitor of metalloproteinases-2 (TIMP-2), tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA). Irradiation with a single dose of 10 Gy resulted in a significant increase in Fn mRNA since 24 hours post-irradiation, and a single dose of 5 and 10 Gy significantly increased the Fn immunoreactive protein measured 48 hours post-irradiation. An increase in Pai-mRNA and protein was also observed and especially, a single dose of 10 Gy significantly increased the mRNA measured 24 and 48 hours post-irradiation. The active MMP-2 measured 24 hours post-irradiation slightly increased in a dose dependent manner, but this increase did not reach statistical significance. The levels of MMP-9, TIMP-2, t-PA and u-PA appeared unaltered after irradiation. Irradiation of the glomerular epithelial cells altered the expression of genes associated with the extracellular matrix, implying that the glomerular epithelial cell may be involved in the development of radiation nephropathy

Radiation induced changes in the expression of fibronectin, Pai-1, MMP in rat glomerular epithelial cell

Energy Technology Data Exchange (ETDEWEB)

Park, Woo Yoon; Kim, Won Dong; Zheng, Ying; Ha, Tae Sun [Chungbuk National University, Cheongju (Korea, Republic of); Kim, Jae Sung [Seoul National University, Seoul (Korea, Republic of); Cho, Moon June [Chungnam National University, Daejeon (Korea, Republic of)

2006-03-15

Renal irradiation can lead to the development of radiation nephropathy, and this is characterized by the accumulation of extracellular matrix and final fibrosis. To determine the possible role of the glomerular epithelial cell, the radiation-induced changes in the expression of its genes associated with the extracellular matrix were analyzed. Rat glomerular epithelial cells (GEpC) were irradiated with a single dose of 0, 2, 5, 10 and 20 Gy with using 6 MV LINAC (Siemens, USA), and the samples were collected 6, 24, 48 and 72 hours post-irradiation, respectively. Northern blotting, western blotting and zymography were used to measure the expression level of fibronectin (Fn), plasminogen activator inhibitor-1 (Pai-1), matrix metalloproteinases-2, 9 (MMP-2, 9), tissue inhibitor of metalloproteinases-2 (TIMP-2), tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA). Irradiation with a single dose of 10 Gy resulted in a significant increase in Fn mRNA since 24 hours post-irradiation, and a single dose of 5 and 10 Gy significantly increased the Fn immunoreactive protein measured 48 hours post-irradiation. An increase in Pai-mRNA and protein was also observed and especially, a single dose of 10 Gy significantly increased the mRNA measured 24 and 48 hours post-irradiation. The active MMP-2 measured 24 hours post-irradiation slightly increased in a dose dependent manner, but this increase did not reach statistical significance. The levels of MMP-9, TIMP-2, t-PA and u-PA appeared unaltered after irradiation. Irradiation of the glomerular epithelial cells altered the expression of genes associated with the extracellular matrix, implying that the glomerular epithelial cell may be involved in the development of radiation nephropathy.

Diffuse glomerular nodular lesions in diabetic pigs carrying a dominant-negative mutant hepatocyte nuclear factor 1-alpha, an inheritant diabetic gene in humans.

Directory of Open Access Journals (Sweden)

Satoshi Hara

Full Text Available Glomerular nodular lesions, known as Kimmelstiel-Wilson nodules, are a pathological hallmark of progressive human diabetic nephropathy. We have induced severe diabetes in pigs carrying a dominant-negative mutant hepatocyte nuclear factor 1-alpha (HNF1α P291fsinsC, a maturity-onset diabetes of the young type-3 (MODY3 gene in humans. In this model, glomerular pathology revealed that formation of diffuse glomerular nodules commenced as young as 1 month of age and increased in size and incidence until the age of 10 months, the end of the study period. Immunohistochemistry showed that the nodules consisted of various collagen types (I, III, IV, V and VI with advanced glycation end-product (AGE and Nε-carboxymethyl-lysine (CML deposition, similar to those in human diabetic nodules, except for collagen type I. Transforming growth factor-beta (TGF-β was also expressed exclusively in the nodules. The ultrastructure of the nodules comprised predominant interstitial-type collagen deposition arising from the mesangial matrices. Curiously, these nodules were found predominantly in the deep cortex. However, diabetic pigs failed to show any of the features characteristic of human diabetic nephropathy; e.g., proteinuria, glomerular basement membrane thickening, exudative lesions, mesangiolysis, tubular atrophy, interstitial fibrosis, and vascular hyalinosis. The pigs showed only Armanni-Ebstein lesions, a characteristic tubular manifestation in human diabetes. RT-PCR analysis showed that glomeruli in wild-type pigs did not express endogenous HNF1α and HNF1β, indicating that mutant HNF1α did not directly contribute to glomerular nodular formation in diabetic pigs. In conclusion, pigs harboring the dominant-negative mutant human MODY3 gene showed reproducible and distinct glomerular nodules, possibly due to AGE- and CML-based collagen accumulation. Although the pathology differed in several respects from that of human glomerular nodular lesions, the

Glomerular prostaglandins modulate vascular reactivity of the downstream efferent arterioles.

Science.gov (United States)

Arima, S; Ren, Y; Juncos, L A; Carretero, O A; Ito, S

1994-03-01

The balance of vascular resistance in afferent (Af-) and efferent arterioles (Ef-Arts) is a crucial factor that determines glomerular hemodynamics. We have recently reported that when Ef-Arts were perfused from the distal end of the Af-Art through the glomerulus (orthograde perfusion; OP), both angiotensin II (Ang II) and norepinephrine (NE) induced much weaker constriction than they did when Ef-Arts were perfused from the distal end (retrograde perfusion; RP). This difference was not affected by inhibiting synthesis of nitric oxide. In the present study, we tested the hypothesis that glomerular prostaglandins (PGs) may modulate vascular reactivity of the downstream Ef-Art. In addition, we examined the possible modulatory role of PGs in the Af-Art responses to Ang II or NE. Both Ang II and NE caused dose-dependent constriction of Ef-Arts with either OP or RP; however, the constriction was stronger in RP. At 10(-8) M, Ang II decreased Ef-Art diameter by 35 +/- 3.5% in OP (N = 9) compared to 73 +/- 3.9% in RP (N = 5), while 10(-6) M NE decreased the diameter by 25 +/- 3.6% in OP (N = 9) compared to 62 +/- 7.2% in RP (N = 5). Pretreatment with 5 x 10(-5) M indomethacin (Indo) did not alter basal diameter with either method of perfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Detection of diffuse glomerular lesions in rats: II. Comparison of indium-111 cationic small macromolecules with technetium-99m DTPA

International Nuclear Information System (INIS)

McAfee, J.G.; Thomas, F.D.; Subramanian, G.; Schneider, R.D.; Lyons, B.; Roskopf, M.; Zapf-Longo, C.; Whaley, D.

1986-01-01

Dextrans with average molecular weights of 5000, 10,000, and 17,500 and inulin were rendered cationic by amination with 2-bromoethylamine hydrobromide. After limited coupling with DTPA cyclic dianhydride, they were labeled with 111In. A good correlation was found between their early renal uptake quantitated by camera-computer techniques and their renal clearance from multiple plasma samples in rats with glomerular damage induced by puromycin aminonucleoside and controls. However, there was poor correlation between the early renal uptake of these agents and the clearance of simultaneously injected [/sup 99m/Tc]DTPA. The 2-hr organ distribution and urinary excretion of these agents were compared with the corresponding values of DTPA. The differences in clearance between rats with glomerular damage and controls were greater with aminated dextran (mol wt 5000) than with DTPA, confirming previous work with infusions of nonradioactive charged dextrans and neutral inulin. The cationic dextrans appear to reflect the presence or absence of the normal anionic charge of the glomerular membrane as well as changes in filtration rate. Aminated inulin did not differentiate between controls and rats with glomerular disease any better than DTPA, probably because the number of amino groups conjugated was insufficient to produce the charge effect

Changes in glomerular filtration rate, lithium clearance and plasma protein clearances in the early phase after unilateral nephrectomy in living healthy renal transplant donors

DEFF Research Database (Denmark)

Strandgaard, S; Kamper, A; Skaarup, P

1988-01-01

1. Glomerular and tubular function was studied before and 2 months after unilateral nephrectomy in 14 healthy kidney donors by measurement of the clearances of 51Cr-labelled ethylenediaminetetra-acetate, lithium, beta 2-microglobulin, albumin and immunoglobulin G. 2. The glomerular filtration rat...

Effects of a K+ channel blocker on glomerular filtration rate and electrolyte excretion in conscious rats.

Science.gov (United States)

Ludens, J H; Clark, M A; Lawson, J A

1995-06-01

Effects of a K+ channel blocker on glomerular filtration rate and electrolyte excretion in conscious rats were observed. Effects of K+ channel modulation on glomerular filtration rate and electrolyte excretion were studied using the adenosine-triphosphate- (ATP)-sensitive K+ channel blocker 4-morpholinecarboximidine-N-1-adamantyl-N'-cyclohexylhydr ochloride (U-37883A) in conscious rats previously equipped with catheters for clearance studies. In saline-loaded rats, i.v. doses of U-37883A of 1.7, 5.0 and 15 mg/kg increased absolute and fractional Na+ excretion dose-dependently without changing K+ excretion. The glomerular filtration rate remained constant during diuresis. In water-loaded (hypotonic dextrose) rats, free-water clearance studies revealed that the ATP-sensitive K+ channel blocker significantly decreased an index of solute reabsorption (free-water clearance adjusted for chloride clearance) in the diluting segment during peak natriuretic activity. In addition, U-37883A significantly decreased the osmolality of renal papillary interstitial fluid, indicative of an effect in the medullary portion of the diluting segment. Together, these findings suggest that ATP-sensitive K+ channels, possibly those located at the apical boarder, play a pivotal role in Na+ reabsorption in the thick ascending limb of the loop of Henle.

Aldosterone and glomerular filtration--observations in the general population.

Science.gov (United States)

Hannemann, Anke; Rettig, Rainer; Dittmann, Kathleen; Völzke, Henry; Endlich, Karlhans; Nauck, Matthias; Wallaschofski, Henri

2014-03-10

Increasing evidence suggests that aldosterone promotes renal damage. Since data on the association between aldosterone and renal function in the general population are sparse, we chose to address this issue. We investigated the associations between the plasma aldosterone concentration (PAC) or the aldosterone-to-renin ratio (ARR) and the estimated glomerular filtration rate (eGFR) in a sample of adult men and women from Northeast Germany. A study population of 1921 adult men and women who participated in the first follow-up of the Study of Health in Pomerania was selected. None of the subjects used drugs that alter PAC or ARR. The eGFR was calculated according to the four-variable Modification of Diet in Renal Disease formula. Chronic kidney disease (CKD) was defined as an eGFR < 60 ml/min/1.73 m2. Linear regression models, adjusted for sex, age, waist circumference, diabetes mellitus, smoking status, systolic and diastolic blood pressures, serum triglyceride concentrations and time of blood sampling revealed inverse associations of PAC or ARR with eGFR (ß-coefficient for log-transformed PAC -3.12, p < 0.001; ß-coefficient for log-transformed ARR -3.36, p < 0.001). Logistic regression models revealed increased odds for CKD with increasing PAC (odds ratio for a one standard deviation increase in PAC: 1.35, 95% confidence interval: 1.06-1.71). There was no statistically significant association between ARR and CKD. Our study demonstrates that PAC and ARR are inversely associated with the glomerular filtration rate in the general population.

Glomerular diseases associated with HBV and HCV infection

Directory of Open Access Journals (Sweden)

Boriana Kiperova

2014-03-01

Full Text Available Hepatitis B and C viruses are human pathogens of major significance. Their extrahepatic manifestations are global health problem. HBV is a well-known cause of membranous nephropathy, membranoproliferative GN and IgA nephropathy, frequently in Asian populations. Polyarteritis nodosa is a rare, but serious systemic complication of chronic HBV. Immunosuppressive therapy in HBV-related GN is not recommended. Interferon alpha treatment produces sustained remission of porteinuria, often associated with clearance of HBeAg and/or HBsAg, however, it has many side effects. Compared to interferon, nucleos(tide analogues offer some advantages. These antiviral agents suppress HBV replication through their inhibitory effect on viral DNA polymerase. They have convenient administration and high tolerability. Lamivudine is well tolerated and safe in long-term studies, but the resistance of HBV is an escalating problem. The resistance to newer polymerase inhibitors Entecavir and Tenofovir is significantly lower. Hepatitis C virus causes cryoglobulinemia-mediated glomerulonephritis and other immune complex forms of GN. The renal manifestations are usually associated with long-lasting HCV infection. HCV glomerular disease is more frequent in adult males, and often leads to chronic renal insufficiency. The first line treatment in patients with mild to moderate clinical and histological kidney damage is the antiviral therapy with pegylated INF alpha and ribavirin. In case of severe HCV-associated cryoglobulinemic GN - nephrotic syndrome, nephritic syndrome and/or progressive renal failure, high activity score of glomerulonephritis on light microscopy, the initial treatment might consist of sequential administration of antiviral and immunosuppressive agents (corticosteroids, cyclophosphamide and plasma exchange, or rituximab. The treatment of HCV-related glomerular disease is still under debate and based on scant experimental evidence. Large randomized and controlled

Antibody response against the glomerular basement membrane protein agrin in patients with transplant glomerulopathy.

NARCIS (Netherlands)

Joosten, S.A.; Sijpkens, Y.W.; Ham, V. van; Trouw, L.A.; Vlag, J. van der; Heuvel, L.P.W.J. van den; Kooten, C. van; Paul, L.C.

2005-01-01

Chronic allograft nephropathy (CAN) of renal allografts is still the most important cause of graft loss. A subset of these patients have transplant glomerulopathy (TGP), characterized by glomerular basement membrane (GBM) duplications, but of unknown etiology. Recently, a role for the immune system

Sinomenine alleviates high glucose-induced renal glomerular endothelial hyperpermeability by inhibiting the activation of RhoA/ROCK signaling pathway

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Yin, Qingqiao [Renal Department of Internal Medicine, The Third Hospital of Wuhan (China); Xia, Yuanyu, E-mail: xiayuanyu.wh@gmail.com [Renal Department of Internal Medicine, The Third Hospital of Wuhan (China); Wang, Guan [Department of Cardiology, The Second Affiliated Hospital of Guangzhou Medical University (China)

2016-09-02

As an early sign of diabetic cardiovascular disease, endothelial dysfunction may contribute to progressive diabetic nephropathy (DN). Endothelial hyperpermeability induced by hyperglycemia (HG) is a central pathogenesis for DN. Sinomenine (SIN) has strong anti-inflammatory and renal protective effects, following an unknown protective mechanism against HG-induced hyperpermeability. We herein explored the role of SIN in vitro in an HG-induced barrier dysfunction model in human renal glomerular endothelial cells (HRGECs). The cells were exposed to SIN and/or HG for 24 h, the permeability of which was significantly increased by HG. Moreover, junction protein occludin in the cell-cell junction area and its total expression in HRGECs were significantly decreased by HG. However, the dysfunction of tight junction and hyperpermeability of HRGECs were significantly reversed by SIN. Furthermore, SIN prevented HG-increased reactive oxygen species (ROS) by activating nuclear factor-E2-related factor 2 (Nrf2). Interestingly, activation of RhoA/ROCK induced by HG was reversed by SIN or ROCK inhibitor. HG-induced hyperpermeability was prevented by SIN. High ROS level, tight junction dysfunction and RhoA/ROCK activation were significantly attenuated with knockdown of Nrf2. Mediated by activation of Nrf2, SIN managed to significantly prevent HG-disrupted renal endothelial barrier function by suppressing the RhoA/ROCK signaling pathway through reducing ROS. We successfully identified a novel pathway via which SIN exerted antioxidative and renal protective functions, and provided a molecular basis for potential SIN applications in treating DN vascular disorders.

Sinomenine alleviates high glucose-induced renal glomerular endothelial hyperpermeability by inhibiting the activation of RhoA/ROCK signaling pathway.

Science.gov (United States)

Yin, Qingqiao; Xia, Yuanyu; Wang, Guan

2016-09-02

As an early sign of diabetic cardiovascular disease, endothelial dysfunction may contribute to progressive diabetic nephropathy (DN). Endothelial hyperpermeability induced by hyperglycemia (HG) is a central pathogenesis for DN. Sinomenine (SIN) has strong anti-inflammatory and renal protective effects, following an unknown protective mechanism against HG-induced hyperpermeability. We herein explored the role of SIN in vitro in an HG-induced barrier dysfunction model in human renal glomerular endothelial cells (HRGECs). The cells were exposed to SIN and/or HG for 24 h, the permeability of which was significantly increased by HG. Moreover, junction protein occludin in the cell-cell junction area and its total expression in HRGECs were significantly decreased by HG. However, the dysfunction of tight junction and hyperpermeability of HRGECs were significantly reversed by SIN. Furthermore, SIN prevented HG-increased reactive oxygen species (ROS) by activating nuclear factor-E2-related factor 2 (Nrf2). Interestingly, activation of RhoA/ROCK induced by HG was reversed by SIN or ROCK inhibitor. HG-induced hyperpermeability was prevented by SIN. High ROS level, tight junction dysfunction and RhoA/ROCK activation were significantly attenuated with knockdown of Nrf2. Mediated by activation of Nrf2, SIN managed to significantly prevent HG-disrupted renal endothelial barrier function by suppressing the RhoA/ROCK signaling pathway through reducing ROS. We successfully identified a novel pathway via which SIN exerted antioxidative and renal protective functions, and provided a molecular basis for potential SIN applications in treating DN vascular disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

Assessment of glomerular filtration rate measurement with plasma sampling: a technical review.

Science.gov (United States)

Murray, Anthony W; Barnfield, Mark C; Waller, Michael L; Telford, Tania; Peters, A Michael

2013-06-01

This article reviews available radionuclide-based techniques for glomerular filtration rate (GFR) measurement, focusing on clinical indications for GFR measurement, ideal GFR radiopharmaceutical tracer properties, and the 2 most common tracers in clinical use. Methods for full, 1-compartment, and single-sample renal clearance characterization are discussed. GFR normalization and the role of GFR measurement in chemotherapy dosing are also considered.

Compound effects of aging and experimental FSGS on glomerular epithelial cells.

Science.gov (United States)

Schneider, Remington R S; Eng, Diana G; Kutz, J Nathan; Sweetwyne, Mariya T; Pippin, Jeffrey W; Shankland, Stuart J

2017-02-17

Advanced age portends a poorer prognosis in FSGS. To understand the impact of age on glomerular podocytes and parietal epithelial cells (PECs), experimental FSGS was induced in 3m-old mice (20-year old human age) and 27m-old mice (78-year old human age) by abruptly depleting podocytes with a cytopathic anti-podocyte antibody. Despite similar binding of the disease-inducing antibody, podocyte density was lower in aged FSGS mice compared to young FSGS mice. Activated PEC density was higher in aged versus young FSGS mice, as was the percentage of total activated PECs. Additionally, the percentage of glomeruli containing PECs with evidence of phosphorylated ERK and EMT was higher in aged FSGS mice. Extracellular matrix, measured by collagen IV and silver staining, was higher in aged FSGS mice along Bowman's capsule. However, collagen IV accumulation in the glomerular tufts alone and in glomeruli with both tuft and Bowman's capsule accumulation were similar in young FSGS and aged FSGS mice. Thus, the major difference in collagen IV staining in FSGS was along Bowman's capsule in aged mice. The significant differences in podocytes, PECs and extracellular matrix accumulation between young mice and old mice with FSGS might explain the differences in outcomes in FSGS based on age.

Barriers to effective communication between veterans with chronic kidney disease and their healthcare providers.

Science.gov (United States)

Lederer, Swati; Fischer, Michael J; Gordon, Howard S; Wadhwa, Anuradha; Popli, Subhash; Gordon, Elisa J

2015-12-01

Many patients with chronic kidney disease (CKD) have insufficient knowledge about CKD, which is associated with poorer health outcomes. Effective patient-provider communication can improve CKD patients' knowledge, thereby augmenting their participation in self-care practices. However, barriers to addressing CKD patients' information needs have not been previously characterized. Adults with an estimated glomerular filtration rate (eGFR) of communication dynamics. Thirty-two patients participated. The mean age of participants was 63 years; most were male (94%) and non-Hispanic white (53%). CKD severity groups represented included CKD-3 (eGFR 30-59 mL/min/1.73 m(2); 34%), CKD-4 (eGFR 15-29 mL/min/1.73 m(2); 25%), CKD-5 (eGFR barriers to patient-provider communication based on patients' reported care at both VA and non-VA facilities, including patients perceived their role as a 'listener', reported limited CKD knowledge, did not understand physicians' explanations and were dissatisfied with the patient-provider relationship. Several barriers to patient-provider communication prevent patients from meeting their information needs and perpetuate patient passivity. Future research should evaluate whether interventions that empower CKD patients to actively participate in their care increase knowledge and improve health outcomes.

Comparative evaluation of quantitative glomerular filtration rate measured by isotopic and nonisotopic methods

International Nuclear Information System (INIS)

Balachandran, S.; Toguri, A.G.; Petrusick, T.W.; Abbott, L.C.

1981-01-01

Good correlation of glomerular filtration rate (GFR) measured isotopically from plasma disappearance of Tc-99m-DTPA (Sn) was shown with inulin clearance, creatinine clearance, and graded radionuclide imaging. The isotopic GFR is a simple, urineless technique not requiring continuous infusion that enables one to perform simultaneous renal imaging with one radiotracer

TLR4 links podocytes with the innate immune system to mediate glomerular injury

DEFF Research Database (Denmark)

Banas, Miriam C; Banas, Bernhard; Hudkins, Kelly L

2008-01-01

profile of chemokines. In conclusion, it was demonstrated that TLR4 is constitutively expressed by podocytes and is upregulated in MPGN, where it may mediate glomerular injury by modulating expression of chemokines; therefore, TLR4 may link podocytes with the innate immune system to mediate MPGN triggered...... by the deposition of immune complexes....

Mutation in the key enzyme of sialic acid biosynthesis causes severe glomerular proteinuria and is rescued by N-acetylmannosamine.

Science.gov (United States)

Galeano, Belinda; Klootwijk, Riko; Manoli, Irini; Sun, MaoSen; Ciccone, Carla; Darvish, Daniel; Starost, Matthew F; Zerfas, Patricia M; Hoffmann, Victoria J; Hoogstraten-Miller, Shelley; Krasnewich, Donna M; Gahl, William A; Huizing, Marjan

2007-06-01

Mutations in the key enzyme of sialic acid biosynthesis, uridine diphospho-N-acetylglucosamine 2-epimerase/N-acetylmannosamine (ManNAc) kinase (GNE/MNK), result in hereditary inclusion body myopathy (HIBM), an adult-onset, progressive neuromuscular disorder. We created knockin mice harboring the M712T Gne/Mnk mutation. Homozygous mutant (Gne(M712T/M712T)) mice did not survive beyond P3. At P2, significantly decreased Gne-epimerase activity was observed in Gne(M712T/M712T) muscle, but no myopathic features were apparent. Rather, homozygous mutant mice had glomerular hematuria, proteinuria, and podocytopathy. Renal findings included segmental splitting of the glomerular basement membrane, effacement of podocyte foot processes, and reduced sialylation of the major podocyte sialoprotein, podocalyxin. ManNAc administration yielded survival beyond P3 in 43% of the Gne(M712T/M712T) pups. Survivors exhibited improved renal histology, increased sialylation of podocalyxin, and increased Gne/Mnk protein expression and Gne-epimerase activities. These findings establish this Gne(M712T/M712T) knockin mouse as what we believe to be the first genetic model of podocyte injury and segmental glomerular basement membrane splitting due to hyposialylation. The results also support evaluation of ManNAc as a treatment not only for HIBM but also for renal disorders involving proteinuria and hematuria due to podocytopathy and/or segmental splitting of the glomerular basement membrane.

Focused ultrasound-modulated glomerular ultrafiltration assessed by functional changes in renal arteries.

Directory of Open Access Journals (Sweden)

Feng-Yi Yang

Full Text Available This study demonstrates the feasibility of using focused ultrasound (FUS to modulate glomerular ultrafiltration by renal artery sonication and determine if protein-creatinine ratios are estimated through vascular parameters. All animal experiments were approved by our Animal Care and Use Committee. The renal arteries of Sprague-Dawley rats were surgically exposed and sonicated at various acoustic power levels using a FUS transducer with a resonant frequency of 1 MHz. The mean peak systolic velocity (PSV of the blood flow was measured by Doppler ultrasound imaging. Urinary protein-creatinine ratios were calculated during the experiments. Histological examination of renal arteries and whole kidneys was performed. The PSV, pulsatility index, and resistance index of blood flow significantly increased in the arteries after FUS sonication without microbubbles (p<0.05. The change in normalized protein-creatinine ratios significantly increased with increasing acoustic power, but such was not observed when microbubbles were administered. Furthermore, no histological changes were observed in the hematoxylin- and eosin-stained sections. Glomerular ultrafiltration is regulated temporarily by renal artery sonication without microbubbles. Monitoring vascular parameters are useful in estimating the normalized change in protein-creatinine ratios.

Tubular markers do not predict the decline in glomerular filtration rate in type 1 diabetic patients with overt nephropathy

DEFF Research Database (Denmark)

Nielsen, Stine E; Andersen, Steen; Zdunek, Dietmar

2011-01-01

of neutrophil gelatinase-associated lipocalin (NGAL), liver-fatty acid-binding protein (LFABP), and kidney injury molecule-1 (KIM-1) in a 3-year intervention study of 63 type 1 diabetic patients with kidney disease. The baseline mean glomerular filtration rate (GFR) was 87 ml/min per 1.73 m(2) and urinary......Recent studies have shown that both glomerular and tubulointerstitial damage are important factors in the pathophysiology and progression of diabetic nephropathy. To examine whether markers of tubular damage are useful in monitoring the progression of disease, we measured urinary levels...

The glomerular parietal epithelial cell's responses are influenced by SM22 alpha levels.

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Naito, Shokichi; Pippin, Jeffrey W; Shankland, Stuart J

2014-11-06

Studies have shown in several diseases initially affecting podocytes, that the neighboring glomerular parietal epithelial cells (PECs) are secondarily involved. The PEC response might be reparative under certain circumstances, yet injurious under others. The factors governing these are not well understood. We have shown that SM22α, an actin-binding protein considered a marker of smooth muscle differentiation, is upregulated in podocytes and PECs in several models of podocyte disease. However, the impact of SM22α levels on PECs is not known. Experimental glomerular disease, characterized by primary podocyte injury, was induced in aged-matched SM22α+/+ and SM22α-/-mice by intraperitoneal injection of sheep anti-rabbit glomeruli antibody. Immunostaining methods were employed on days 7 and 14 of disease. The number of PEC transition cells, defined as cells co-expressing a PEC protein (PAX2) and podocyte protein (Synaptopodin) was higher in diseased SM22α-/-mice compared with SM22α+/+mice. WT1 staining along Bowman's capsule is higher in diseased SM22α-/-mice. This was accompanied by increased PEC proliferation (measured by ki-67 staining), and an increase in immunostaining for the progenitor marker NCAM, in a subpopulation of PECs in diseased SM22α-/-mice. In addition, immunostaining for vimentin and alpha smooth muscle actin, markers of epithelial-to-mesenchymal transition (EMT), was lower in diseased SM22α-/-mice compared to diseased SM22α+/+mice. SM22α levels may impact how PECs respond following a primary podocyte injury in experimental glomerular disease. Absent/lower levels favor an increase in PEC transition cells and PECs expressing a progenitor marker, and a lower EMT rate compared to SM22α+/+mice, where SM22 levels are markedly increased in PECs.

[Expression of glomerular heparan sulfate domains in pediatric patients with minimal change nephrotic syndrome].

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Dong, Li-Qun; Wang, Zheng; Yu, Ping; Guo, Yan-Nan; Wu, Jin; Feng, Shi-Pin; Li, Sha

2009-01-01

To investigate the expression of glomerular heparin sulfate (HS) in paediatric patients with minimal change nephritic syndrome (MCNS). The kidyney tissues were collected by biopsy from 13 paediatric patients with MCNS, while 5 normal renal biopsy samples were used as control. HS in glomeruli was analysed by indirect immunofluorescence staining using four different monoclonal antibodies, Hepss1, 3G10, JM403 and 10E4, which all recognize distinct HS species and each interacts with a specific HS domain. The concentrations of urine heparan sulfate also were measured by enzyme-linked immunosorbent assay (Elisa). Expression of HS fine domains was aberrant in paediatric patients compared with control subjects. Children with MCNS in replase showed a decreased glomerular expression of 10E4, JM403 and Hepss1 (P peadiatric patients with MCNS when compared with that in control subjects (P < 0.01). These results suggest that loss of heparan sulphate in renal tissue may play a role in the pathogenesis of MCNS proteinuria.

Proteinuria: The diagnostic strategy based on urine proteins differentiation

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Stojimirović Biljana B.

2004-01-01

Full Text Available Basal glomerular membrane represents mechanical and electrical barrier for passing of the plasma proteins. Mechanical barrier is composed of cylindrical pores and filtration fissure, and negative layer charge in exterior and interior side of basal glomerular membrane, made of heparan sulphate and sialoglicoproteine, provides certain electrical barrier. Diagnostic strategy based on different serum and urine proteins enables the differentiation of various types of proteinuria. Depending on etiology of proteinuria it can be prerenal, renal and postrenal. By analyzing albumin, armicroglobulin, immunoglobulin G and armacroglobulin, together with total protein in urine, it is possible to detect and differentiate causes of prerenal, renal (glomerular, tubular, glomerulo-tubular and postrenal proteinuria. The adequate and early differentiation of proteinuria type is of an immense diagnostic and therapeutic importance.

Albuminuria and Glomerular Filtration Rate in Individuals with Type 1 Diabetes Mellitus: Contribution of Metabolic Syndrome.

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Uribe-Wiechers, Ana Cecilia; Janka-Zires, Marcela; Almeda-Valdés, Paloma; López-Gutiérrez, Joel; Gómez-Pérez, Francisco J

2015-01-01

The development of metabolic syndrome has been described in patients with type 1 diabetes mellitus as the disease progresses over time. The purpose of this study is to assess the relationship between metabolic syndrome, albuminuria, and glomerular filtration rate, as well as to determine the prevalence of metabolic syndrome, in a group of Mexican patients with type 1 diabetes mellitus. We conducted a cross-sectional study that included patients with type 1 diabetes mellitus who were diagnosed over 10 years ago and who are seen at the Diabetes Intensive Control Clinic of the Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran in Mexico City. The presence of metabolic syndrome was determined by using the National Cholesterol Education Program-Adult Treatment Panel III (ATP III) criteria. A total of 81 individuals were studied. The prevalence of metabolic syndrome was 18.5% (n = 15). A higher albuminuria was found in subjects with metabolic syndrome (34.9 mg/24 hours; 8.3-169.3) than in those without metabolic syndrome (9.0 mg/24 hours; 5.0-27.0; p = 0.02). Glomerular filtration rate was lower in patients with metabolic syndrome (95.3 ml/minute; [64.9-107.2] vs. 110.2 ml/minute [88.1-120.3]; p = 0.04). After classifying the population according to the number of metabolic syndrome criteria, a progressive increase in albuminuria and a progressive decrease in glomerular filtration rate were found with each additional metabolic syndrome criterion (p = 0.008 and p = 0.032, respectively). After adjusting for age, time from diagnosis, systolic blood pressure, triglycerides, HDL-cholesterol, and treatment with angiotensin receptor blockers or angiotensin converting enzyme inhibitors, we found that age, time from diagnosis, triglycerides, and HDL-cholesterol were independent factors associated with glomerular filtration rate (R2 = 0.286; p diabetes mellitus. Metabolic syndrome was present in 18.5% of this group of Mexican individuals with type 1 diabetes

Experimental autoimmune glomerulonephritis induced by anti-glomerular basement membrane antibody. II. Effects of injecting heterologous, homologous, or autologous glomerular basement membranes and complete Freund's adjuvant into sheep.

OpenAIRE

Steblay, R. W.; Rudofsky, U. H.

1983-01-01

The effects of injecting human, rabbit, rat, or single-kidney homologous glomerular basement membrane (GBM) or autologous GBM, each in complete Freund's adjuvant (CFA), into 15- to 18-month-old sheep are compared. All sheep receiving heterologous GBM and 3 of 6 sheep receiving homologous GBM had anti-GBM nephritis, but such sheep did not bind autoantibodies or have Goodpasturelike lesions in their lungs. Sheep given injections of human GBM had autoantibodies to antigenic determinants shared b...

Diabetic kidney lesions of GIPRdn transgenic mice: podocyte hypertrophy and thickening of the GBM precede glomerular hypertrophy and glomerulosclerosis.

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Herbach, Nadja; Schairer, Irene; Blutke, Andreas; Kautz, Sabine; Siebert, Angela; Göke, Burkhard; Wolf, Eckhard; Wanke, Ruediger

2009-04-01

Diabetic nephropathy is the leading cause of end-stage renal disease and the largest contributor to the total cost of diabetes care. Rodent models are excellent tools to gain more insight into the pathogenesis of diabetic nephropathy. In the present study, we characterize the age-related sequence of diabetes-associated kidney lesions in GIPR(dn) transgenic mice, a novel mouse model of early-onset diabetes mellitus. Clinical-chemical analyses as well as qualitative and quantitative morphological analyses of the kidneys of GIPR(dn) transgenic animals and nontransgenic littermate controls were performed at 3, 8, 20, and 28 wk of age. Early renal changes of transgenic mice consisted of podocyte hypertrophy, reduced numerical volume density of podocytes in glomeruli, and homogenous thickening of the glomerular basement membrane, followed by renal and glomerular hypertrophy as well as mesangial expansion and matrix accumulation. At 28 wk of age, glomerular damage was most prominent, including advanced glomerulosclerosis, tubulointerstitial lesions, and proteinuria. Real-time PCR demonstrated increased glomerular expression of Col4a1, Fn1, and Tgfb1. Immunohistochemistry revealed increased mesangial deposition of collagen type IV, fibronectin, and laminin. The present study shows that GIPR(dn) transgenic mice exhibit renal changes that closely resemble diabetes-associated kidney alterations in humans. Data particularly from male transgenic mice indicate that podocyte hypertrophy is directly linked to hyperglycemia, without the influence of mechanical stress. GIPR(dn) transgenic mice are considered an excellent new tool to study the mechanisms involved in onset and progression of diabetic nephropathy.

A SAGE based approach to human glomerular endothelium: defining the transcriptome, finding a novel molecule and highlighting endothelial diversity.

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Sengoelge, Guerkan; Winnicki, Wolfgang; Kupczok, Anne; von Haeseler, Arndt; Schuster, Michael; Pfaller, Walter; Jennings, Paul; Weltermann, Ansgar; Blake, Sophia; Sunder-Plassmann, Gere

2014-08-27

Large scale transcript analysis of human glomerular microvascular endothelial cells (HGMEC) has never been accomplished. We designed this study to define the transcriptome of HGMEC and facilitate a better characterization of these endothelial cells with unique features. Serial analysis of gene expression (SAGE) was used for its unbiased approach to quantitative acquisition of transcripts. We generated a HGMEC SAGE library consisting of 68,987 transcript tags. Then taking advantage of large public databases and advanced bioinformatics we compared the HGMEC SAGE library with a SAGE library of non-cultured ex vivo human glomeruli (44,334 tags) which contained endothelial cells. The 823 tags common to both which would have the potential to be expressed in vivo were subsequently checked against 822,008 tags from 16 non-glomerular endothelial SAGE libraries. This resulted in 268 transcript tags differentially overexpressed in HGMEC compared to non-glomerular endothelia. These tags were filtered using a set of criteria: never before shown in kidney or any type of endothelial cell, absent in all nephron regions except the glomerulus, more highly expressed than statistically expected in HGMEC. Neurogranin, a direct target of thyroid hormone action which had been thought to be brain specific and never shown in endothelial cells before, fulfilled these criteria. Its expression in glomerular endothelium in vitro and in vivo was then verified by real-time-PCR, sequencing and immunohistochemistry. Our results represent an extensive molecular characterization of HGMEC beyond a mere database, underline the endothelial heterogeneity, and propose neurogranin as a potential link in the kidney-thyroid axis.

Glomerular Epithelial Cells-Targeted Heme Oxygenase-1 Over Expression in the Rat: Attenuation of Proteinuria in Secondary But Not Primary Injury.

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Atsaves, Vassilios; Makri, Panagiota; Detsika, Maria G; Tsirogianni, Alexandra; Lianos, Elias A

2016-01-01

Induction of heme oxygenase 1 (HO-1) in glomerular epithelial cells (GEC) in response to injury is poor and this may be a disadvantage. We, therefore, explored whether HO-1 overexpression in GEC can reduce proteinuria induced by puromycin aminonucleoside (PAN) or in anti-glomerular basement membrane (GBM) antibody (Ab)-mediated glomerulonephritis (GN). HO-1 overexpression in GEC (GECHO-1) of Sprague-Dawley rats was achieved by targeting a FLAG-human (h) HO-1 using transposon-mediated transgenesis. Direct GEC injury was induced by a single injection of PAN. GN was induced by administration of an anti-rat GBM Ab and macrophage infiltration in glomeruli was assessed by immunohistochemistry and western blot analysis, which was also used to assess glomerular nephrin expression. In GECHO-1 rats, FLAG-hHO-1 transprotein was co-immunolocalized with nephrin. Baseline glomerular HO-1 protein levels were higher in GECHO-1 compared to wild type (WT) rats. Administration of either PAN or anti-GBM Ab to WT rats increased glomerular HO-1 levels. Nephrin expression markedly decreased in glomeruli of WT or GECHO-1 rats treated with PAN. In anti-GBM Ab-treated WT rats, nephrin expression also decreased. In contrast, it was preserved in anti-GBM Ab-treated GECHO-1 rats. In these, macrophage infiltration in glomeruli and the ratio of urine albumin to urine creatinine (Ualb/Ucreat) were markedly reduced. There was no difference in Ualb/Ucreat between WT and GECHO-1 rats treated with PAN. Depending on the type of injury, HO-1 overexpression in GEC may or may not reduce proteinuria. Reduced macrophage infiltration and preservation of nephrin expression are putative mechanisms underlying the protective effect of HO-1 overexpression following immune injury. © 2016 S. Karger AG, Basel.

DISTRIBUTION OF GBM HEPARAN-SULFATE PROTEOGLYCAN CORE PROTEIN AND SIDE-CHAINS IN HUMAN GLOMERULAR-DISEASES

NARCIS (Netherlands)

VANDENBORN, J; VANDENHEUVEL, LPWJ; BAKKER, MAH; VEERKAMP, JH; ASSMANN, KJM; WEENING, JJ; BERDEN, JHM

Using monoclonal antibodies (mAbs) recognizing either the core protein or the heparan sulfate (HS) side chain of human GBM heparan sulfate proteoglycan (HSPG), we investigated their glomerular distribution on cryostat sections of human kidney tissues. The study involved 95 biopsies comprising twelve

Curcumin Induces Nrf2 Nuclear Translocation and Prevents Glomerular Hypertension, Hyperfiltration, Oxidant Stress, and the Decrease in Antioxidant Enzymes in 5/6 Nephrectomized Rats

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Edilia Tapia

2012-01-01

Full Text Available Renal injury resulting from renal ablation induced by 5/6 nephrectomy (5/6NX is associated with oxidant stress, glomerular hypertension, hyperfiltration, and impaired Nrf2-Keap1 pathway. The purpose of this work was to know if the bifunctional antioxidant curcumin may induce nuclear translocation of Nrf2 and prevents 5/6NX-induced oxidant stress, renal injury, decrease in antioxidant enzymes, and glomerular hypertension and hyperfiltration. Four groups of rats were studied: (1 control, (2 5/6NX, (3 5/6NX +CUR, and (4 CUR (n=8–10. Curcumin was given by gavage to NX5/6 +CUR and CUR groups (60 mg/kg/day starting seven days before surgery. Rats were studied 30 days after NX5/6 or sham surgery. Curcumin attenuated 5/6NX-induced proteinuria, systemic and glomerular hypertension, hyperfiltration, glomerular sclerosis, interstitial fibrosis, interstitial inflammation, and increase in plasma creatinine and blood urea nitrogen. This protective effect was associated with enhanced nuclear translocation of Nrf2 and with prevention of 5/6NX-induced oxidant stress and decrease in the activity of antioxidant enzymes. It is concluded that the protective effect of curcumin against 5/6NX-induced glomerular and systemic hypertension, hyperfiltration, renal dysfunction, and renal injury was associated with the nuclear translocation of Nrf2 and the prevention of both oxidant stress and the decrease of antioxidant enzymes.

A systematic review of glomerular hyperfiltration assessment and definition in the medical literature.

Science.gov (United States)

Cachat, Francois; Combescure, Christophe; Cauderay, Michel; Girardin, Eric; Chehade, Hassib

2015-03-06

Evaluation of glomerular hyperfiltration (GH) is difficult; the variable reported definitions impede comparisons between studies. A clear and universal definition of GH would help in comparing results of trials aimed at reducing GH. This study assessed how GH is measured and defined in the literature. Three databases (Embase, MEDLINE, CINAHL) were systematically searched using the terms "hyperfiltration" or "glomerular hyperfiltration". All studies reporting a GH threshold or studying the effect of a high GFR in a continuous manner against another outcome of interest were included. The literature search was performed from November 2012 to February 2013 and updated in August 2014. From 2013 retrieved studies, 405 studies were included. Threshold use to define GH was reported in 55.6% of studies. Of these, 88.4% used a single threshold and 11.6% used numerous thresholds adapted to participant sex or age. In 29.8% of the studies, the choice of a GH threshold was not based on a control group or literature references. After 2004, the use of GH threshold use increased (Psex-matched control group should be used to define a GH threshold. Copyright © 2015 by the American Society of Nephrology.

Mechanistic studies of ocular peptide absorption and its enhancement by various penetration enhancers

International Nuclear Information System (INIS)

Rojanasakul, Y.

1989-01-01

Two major aspects of corneal peptide absorption, namely the transport mechanisms and the promoting effect of some penetration enhancers, were investigated. Studies on transport mechanisms involve (a) identification of transport pathways of peptides across the cornea, (b) determination of rate-limiting barrier(s) for peptide absorption, and (c) permselective properties of the cornea. To study the transport pathways of peptides, four model peptides differing in molecular size and charge were either fluorescently or radioactively labeled and their movement across the cornea was detected by laser scanning confocal microscopy and autoradiography. Results from these studies indicate that peptides can penetrate the cornea via different pathways, depending on the physicochemical properties and membrane specificity of the peptides. In all cases, the outermost layer of the corneal epithelium presents the rate-limiting barrier for peptide absorption. The results also indicate a charge discrimination effect to transport of negatively charged peptides. In permselectivity studies, it has been shown that the cornea, due to the presence of ionizable charged groups, is amphoteric and exhibits dual selective characteristics to transport of charged molecules. At pH's above the isoelectric point, 3.2, the cornea carries a net negative charge and is selective to positively-charged molecules. Below the isoelectric pH, the reverse is valid. The promoting mechanisms of penetration enhancers were studied microscopically using confocal fluorescence microscopy with the aid of a specific fluorescent membrane probe (3,3'-dioctadecyloxacarbocyanine) and a non-permeating polar tracer. All enhancers, including chelators, non-ionic surfactants, bile salts, and cytoskeleton-active agents, significantly increase membrane permeability depending on concentration and exposure time

Rapid decline in glomerular filtration rate during the first weeks following heart transplantation

DEFF Research Database (Denmark)

Hornum, M; Andersen, Mads Jønsson; Gustafsson, F

2011-01-01

We hypothesized that a decrease in renal function is seen immediately after heart transplantation (HTX) with little recovery over time. Twelve consecutive patients had their glomerular filtration rate (GFR) measured using (51)Cr-ethylenediaminetetraacetic acid (EDTA) measured GFR (mGFR) before tr...... risk factor for the rapid and sustained decrease in renal function supports the need for more studies on renoprotective strategies immediately after HTX....

Short-term inhibition of prostaglandin synthesis has no effect on the elevated glomerular filtration rate of early insulin-dependent diabetes

DEFF Research Database (Denmark)

Christiansen, J S; Feldt-Rasmussen, B; Parving, H H

1985-01-01

Glomerular filtration rate and renal plasma flow (constant infusion technique using 125I-iothalamate and 131I-hippuran) were measured twice within a 1-week interval in nine young males with insulin-dependent diabetes of short duration (2-5 years). The study was performed in a randomized double...... +/- 43 versus 560 +/- 52 ml/min X 1.73 m2), when measured during placebo or indomethacin treatment, respectively. It is concluded that the steady-state enhancement of glomerular filtration rate and renal plasma flow found in early insulin-dependent diabetes is not due to an excessive activity...

Did Creatinine Standardization Give Benefits to the Evaluation of Glomerular Filtration Rate?

OpenAIRE

Piéroni, Laurence; Bargnoux, Anne-Sophie; Cristol, Jean-Paul; Cavalier, Etienne; Delanaye, Pierre

2017-01-01

During the last decade, a lot of efforts has been made to improve the evaluation of renal functions. Measured Glomerular Filtration Rate (GFR) remains the only valuable test to confirm or confute the status of chronic kidney disease (CKD) and is recommended by Kidney Disease Global Outcomes guidelines when estimation of GFR is not reliable. However, in routine clinical practice, serum creatinine remains the one of the most prescribed biological parameters and is an undeniable factor, alone or...

Physiopathology glomerular hyperfiltration in diabetes. Part 1

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Claudio A. Mascheroni

2014-09-01

Full Text Available Glomerular hyperfiltration (HF in diabetic kidney disease is a complex hemodynamic phenomenon which occurs in early stages of the disease’s progress and probably has negative influences, regarding the progression to the occurrence of microalbuminuria and the progress of evident diabetic nephropathy (DN. Factors involved in its physiopathology are numerous, they include: diabetic biochemical environment and several humoral factors like nitric oxide, prostaglandins, renin-angiotensin-aldosterone system, atrial natriuretic peptide, reactive oxygen species, other humoral and growth factors. These factors cause or enhance the vasodilatation of the afferent arteriole (AA. Factors with vasoconstriction function over the efferent arteriole, all considered primary vascular factors. However, these factors cannot explain other observed alterations and they constitute primary tubular abnormalities such as the increased reabsorption at the proximal tubule, probably conditioned by kidney growth in DBT and by the overexpression of the SGLT2 cotransporter. This higher proximal reabsorption would produce a lower arrival of solutes to the macula densa (MD. This would be incompatible with an action of the tubuloglomerular balance system, but it would be compatible with an action performed by the tubuloglomerular feedback system (TGFB that senses the decrease of the ClNa concentration at the MD. Also deactivating the TGFB and causing vasodilatation of the AA, resulting in an increase of glomerular filtration (GF and renal plasma flow (RPF, characteristic of the HF process. These two processes (vascular and tubular could act in synergy or simultaneously, depending on the metabolic and progressing conditions of the diabetic kidney disease. Similar mechanisms could explain the salt paradox, whereby a lowsalt diet would exacerbate the HF phenomenon and a high-salt diet would decrease the GF and the RPF, which could result in unexpected clinical implications. The

Glomerular filtration rate measured by 51Cr-EDTA clearance: evaluation of captopril-induced changes in hypertensive patients with and without renal artery stenosis

International Nuclear Information System (INIS)

Chaves, Anna Alice Rolim; Buchpiguel, Carlos Alberto; Praxedes, Jose Nery; Bortolotto, Luiz Aparecido; Sapienza, Marcelo Tatit

2010-01-01

Introduction: renal artery stenosis can lead to renovascular hypertension; however, the detection of stenosis alone does not guarantee the presence of renovascular hypertension. Renovascular hypertension depends on activation of the renin-angiotensin system, which can be detected by functional tests such as captopril renal scintigraphy. A method that allows direct measurement of the baseline and post-captopril glomerular filtration rate using chromium-51 labeled ethylenediamine tetraacetic acid ( 51 Cr-EDTA) could add valuable information to the investigation of hypertensive patients with renal artery stenosis. The purposes of this study were to create a protocol to measure the baseline and post-captopril glomerular filtration rate using 51 Cr-EDTA, and to verify whether changes in the glomerular filtration rate permit differentiation between hypertensive patients with and without renal artery stenosis. Methods: this prospective study included 41 consecutive patients with poorly controlled severe hypertension. All patients had undergone a radiological investigation of renal artery stenosis within the month prior to their inclusion. The patients were divided into two groups: patients with (n=21) and without renal artery stenosis, (n=20). In vitro glomerular filtration rate analysis ( 51 Cr-EDTA) and 99m Tc-DMSA scintigraphy were performed before and after captopril administration in all patients. Results: the mean baseline glomerular filtration rate was 48.6±21.8 ml/kg/1.73 m 2 in the group with renal artery stenosis, which was significantly lower than the GFR of 65.1±28.7 ml/kg/1.73m 2 in the group without renal artery stenosis (p=0.04). Captopril induced a significant reduction of the glomerular filtration rate in the group with renal artery stenosis (to 32.6±14.8 ml/kg/1.73m 2 , p=0.001) and an insignificant change in the group without RAS (to 62.2±23.6 ml/kg/1.73m 2 , p=0.68). Scintigraphy with technetium-99m dimercapto-succinic acid (DMSA) did not show

Olfactory bulb glomerular NMDA receptors mediate olfactory nerve potentiation and odor preference learning in the neonate rat.

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Rebecca Lethbridge

Full Text Available Rat pup odor preference learning follows pairing of bulbar beta-adrenoceptor activation with olfactory input. We hypothesize that NMDA receptor (NMDAR-mediated olfactory input to mitral cells is enhanced during training, such that increased calcium facilitates and shapes the critical cAMP pattern. Here, we demonstrate, in vitro, that olfactory nerve stimulation, at sniffing frequencies, paired with beta-adrenoceptor activation, potentiates olfactory nerve-evoked mitral cell firing. This potentiation is blocked by a NMDAR antagonist and by increased inhibition. Glomerular disinhibition also induces NMDAR-sensitive potentiation. In vivo, in parallel, behavioral learning is prevented by glomerular infusion of an NMDAR antagonist or a GABA(A receptor agonist. A glomerular GABA(A receptor antagonist paired with odor can induce NMDAR-dependent learning. The NMDA GluN1 subunit is phosphorylated in odor-specific glomeruli within 5 min of training suggesting early activation, and enhanced calcium entry, during acquisition. The GluN1 subunit is down-regulated 3 h after learning; and at 24 h post-training the GluN2B subunit is down-regulated. These events may assist memory stability. Ex vivo experiments using bulbs from trained rat pups reveal an increase in the AMPA/NMDA EPSC ratio post-training, consistent with an increase in AMPA receptor insertion and/or the decrease in NMDAR subunits. These results support a model of a cAMP/NMDA interaction in generating rat pup odor preference learning.

Anti-glomerular basement membrane: A rare cause of renal failure in children

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Indira Agarwal

2017-01-01

Full Text Available Anti-glomerular basement membrane (GBM disease is a rare cause of acute renal failure and known to have bad prognosis regarding renal functions recovery and patient survival specially when diagnosed late and presents with severe renal failure that requires dialysis. We report a case of 11-year-old child with acute renal failure secondary to anti-GBM disease and associated with antineutrophil cytoplasmic antibody-positive vasculitis. He was treated with plasmapheresis, steroids, and cyclophosphamide with recovery of his kidney functions.

RENAL GLOMERULAR NUMBER AND SIZE IN AUSTRALIAN ABORIGINES, AFRICAN AMERICANS AND WHITE POPULATIONS FROM THE SAME LOCATIONS: A PRELIMINARY REPORT

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John F Bertram

2011-05-01

Full Text Available End stage renal disease is a major health problem for Australian Aborigines and African Americans. Abnormally enlarged glomeruli are commonly observed in biopsies from Aborigines and African Americans and may represent a compensatory hypertrophic response to reduced nephron endowment. We have commenced a study examining glomerular number and size, and their associations in Australian Aborigines and whites, and US African Americans and whites. Kidneys at autopsy are perfusion-fixed and subsampled for stereological estimation of total glomerular number (Nglom; using the physical disector/fractionator combination, and mean renal corpuscle (Vcorp and glomerular volume (Vglom. Kidneys from 58 people have been studied to date with ages ranging from newborn to 84 years. Preliminary findings are: (1 an almost 9-fold range in Nglom (from 210,332 to 1,825,380 with a mean of 762,302; (2 Nglom decreased with age in adult life (p = 0.014; (3 Vcorp varied 19-fold in the series and 5.5-fold in adults; (4 Vglom was inversely correlated with Nglom (p = 0.004; (5 total renal corpuscle volume (Nglom × Vcorp ranged by a factor of 13.2; (6 kidney weight was correlated with body surface area (BSA at all ages (p < 0.001; (7 BSA-corrected kidney weight did not vary with age, it ranged from 47 g/m2 to 175 g/m2, a 3.7 fold difference, with an average of 92 ± 25 g/m2. These preliminary results have revealed several new and important correlations. No racial differences in glomerular number or size have yet been identified, but with greater sample sizes such differences may be revealed.

Salt sensitivity of renin secretion, glomerular filtration rate and blood pressure in conscious Sprague-Dawley rats

DEFF Research Database (Denmark)

Isaksson, G L; Stubbe, J; Hansen, Per Lyngs

2014-01-01

We hypothesized that in normal rats in metabolic steady state, (i) the plasma renin concentration (PRC) is log-linearly related to Na(+) intake (NaI), (ii) the concurrent changes in mean arterial pressure (MABP) and glomerular filtration rate (GFR) are negligible and (iii) the function PRC...

Estimated glomerular filtration rate is an early biomarker of cardiac surgery-associated acute kidney injury.

Science.gov (United States)

Candela-Toha, Ángel; Pardo, María Carmen; Pérez, Teresa; Muriel, Alfonso; Zamora, Javier

2018-04-20

and objective Acute kidney injury (AKI) diagnosis is still based on serum creatinine and diuresis. However, increases in creatinine are typically delayed 48h or longer after injury. Our aim was to determine the utility of routine postoperative renal function blood tests, to predict AKI one or 2days in advance in a cohort of cardiac surgery patients. Using a prospective database, we selected a sample of patients who had undergone major cardiac surgery between January 2002 and December 2013. The ability of the parameters to predict AKI was based on Acute Kidney Injury Network serum creatinine criteria. A cohort of 3,962 cases was divided into 2groups of similar size, one being exploratory and the other a validation sample. The exploratory group was used to show primary objectives and the validation group to confirm results. The ability to predict AKI of several kidney function parameters measured in routine postoperative blood tests, was measured with time-dependent ROC curves. The primary endpoint was time from measurement to AKI diagnosis. AKI developed in 610 (30.8%) and 623 (31.4%) patients in the exploratory and validation samples, respectively. Estimated glomerular filtration rate using the MDRD-4 equation showed the best AKI prediction capacity, with values for the AUC ROC curves between 0.700 and 0.946. We obtained different cut-off values for estimated glomerular filtration rate depending on the degree of AKI severity and on the time elapsed between surgery and parameter measurement. Results were confirmed in the validation sample. Postoperative estimated glomerular filtration rate using the MDRD-4 equation showed good ability to predict AKI following cardiac surgery one or 2days in advance. Copyright © 2018 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

Glomerular filtration rate estimation from plasma creatinine after inhibition of tubular secretion: relevance of the creatinine assay

NARCIS (Netherlands)

Kemperman, F. A.; Silberbusch, J.; Slaats, E. H.; van Zanten, A. P.; Weber, J. A.; Krediet, R. T.; Arisz, L.

1999-01-01

BACKGROUND: Estimation of glomerular filtration rate (GFR) from plasma creatinine concentration after inhibition of tubular creatinine secretion with cimetidine provides a good assessment in patients with various nephropathies and with non-insulin-dependent diabetes mellitus (NIDDM). The aim of this

A prospective study of glomerular filtration rate and arterial blood pressure in insulin-dependent diabetics with diabetic nephropathy

DEFF Research Database (Denmark)

Parving, H H; Smidt, U M; Friisberg, B

1981-01-01

Glomerular filtration rate (GFR, single bolus 51Cr-EDTA technique), serum creatinine, proteinuria and arterial blood pressure have been measured prospectively in 14 young onset insulin-dependent diabetics selected by of persistent proteinuria (greater than 0.5 g/day) secondary to diabetic...... in arterial blood pressure to a hypertensive level is an early feature of diabetic nephropathy in young insulin-dependent diabetics....... and 112/mumol/l (NS), proteinuria increased from 1.8 to 3.3 g/day (p less than 0.001) and arterial blood pressure rose from 132/88 to 153/101 mmHg (p less than 0.001). Glomerular filtration rate decreased linearly with time (slope = -0.75, r = 0.99, p less than 0.001) by a mean of 0.75 ml/min/month (range...

Increased kidney size, glomerular filtration rate and renal plasma flow in short-term insulin-dependent diabetics

DEFF Research Database (Denmark)

Christiansen, JS; Gammelgaard, J; Frandsen, M

1981-01-01

Glomerular filtration rate (GFR), renal plasma flow (RPF) and kidney volume were measured in thirteen male subjects (mean age 30 years) with short-term insulin-dependent diabetes (mean duration of disease 2.4 years) and fourteen normal male subjects (mean age 29 years). GFR and RPF were measured...

Novel therapeutic approaches for chronic kidney disease due to glomerular disorders.

Science.gov (United States)

Del Nogal-Avila, Maria; Donoro-Blazquez, Hector; Saha, Manish K; Marshall, Caroline B; Clement, Lionel C; Macé, Camille E A; Chugh, Sumant S

2016-07-01

Improved understanding of glomerular disease mechanisms over the past decade has led to the emergence of new and targeted therapeutic strategies for chronic kidney disease (CKD). Most promising among these are the administration of recombinant mutated human angiopoietin-like 4, sialic acid-related sugars that induce sialylation in vivo, compounds related to Bis-T-23, and immune depletion of the soluble urokinase receptor from the circulation. Taking these therapeutic strategies into clinical trials will be the first step away from repurposed and relatively toxic drugs currently used for treating kidney disease. Copyright © 2016 the American Physiological Society.

Long-term expression of glomerular genes in diabetic nephropathy.

Science.gov (United States)

Chittka, Dominik; Banas, Bernhard; Lennartz, Laura; Putz, Franz Josef; Eidenschink, Kathrin; Beck, Sebastian; Stempfl, Thomas; Moehle, Christoph; Reichelt-Wurm, Simone; Banas, Miriam C

2018-01-11

Although diabetic nephropathy (DN) is the most common cause for end-stage renal disease in western societies, its pathogenesis still remains largely unclear. A different gene pattern of diabetic and healthy kidney cells is one of the probable explanations. Numerous signalling pathways have emerged as important pathophysiological mechanisms for diabetes-induced renal injury. Glomerular cells, as podocytes or mesangial cells, are predominantly involved in the development of diabetic renal lesions. While many gene assays concerning DN are performed with whole kidney or renal cortex tissue, we isolated glomeruli from black and tan, brachyuric (BTBR) obese/obese (ob/ob) and wildtype mice at four different timepoints (4, 8, 16 and 24 weeks) and performed an mRNA microarray to identify differentially expressed genes (DEGs). In contrast to many other diabetic mouse models, these homozygous ob/ob leptin-deficient mice develop not only a severe type 2 diabetes, but also diabetic kidney injury with all the clinical and especially histologic features defining human DN. By functional enrichment analysis we were able to investigate biological processes and pathways enriched by the DEGs at different disease stages. Altered expression of nine randomly selected genes was confirmed by quantitative polymerase chain reaction from glomerular RNA. Ob/ob type 2 diabetic mice showed up- and downregulation of genes primarily involved in metabolic processes and pathways, including glucose, lipid, fatty acid, retinol and amino acid metabolism. Members of the CYP4A and ApoB family were found among the top abundant genes. But more interestingly, altered gene loci showed enrichment for processes and pathways linked to angioneogenesis, complement cascades, semaphorin pathways, oxidation and reduction processes and renin secretion. The gene profile of BTBR ob/ob type 2 diabetic mice we conducted in this study can help to identify new key players in molecular pathogenesis of diabetic kidney

Zea mays L. extracts modify glomerular function and potassium urinary excretion in conscious rats.

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Velazquez, D V O; Xavier, H S; Batista, J E M; de Castro-Chaves, C

2005-05-01

Diuretic and uricosuric properties have traditionally been attributed to corn silk, stigma/style of Zea mays L. Although the diuretic effect was confirmed, studies of the plant's effects on renal function or solute excretion were lacking. Thus, we studied the effects of corn silk aqueous extract on the urinary excretion of water, Na+, K+, and uric acid. Glomerular and proximal tubular function and Na+ tubular handling were also studied. Conscious, unrestrained adult male rats were housed in individual metabolic cages (IMC) with continuous urine collection for 5 and 3 h, following two protocols. The effects of 25, 50, 200, 350, and 500 mg/kg body wt. corn silk extract on urine volume plus Na+ and K+ excretions were studied in water-loaded conscious rats (2.5 ml/100 g body wt.) in the IMC for 5 h (Protocol 1). Kaliuresis was observed with doses of 350 (100.42 +/- 22.32-120.28 +/- 19.70 microEq/5 h/100 g body wt.; n = 13) and 500 mg/kg body wt. (94.97+/- 29.30-134.32 +/- 39.98 microEq/5h/100 g body wt.; n = 12; pcorn silk extract on urine volume, Na+, K+ and uric acid excretions, and glomerular and proximal tubular function, were measured respectively by creatinine (Cler) and Li+ (ClLi) clearances and Na+ tubular handling, in water-loaded rats (5 ml/100 g body wt.) in the IMC for 3 h (Protocol 2). Clcr (294.6 +/- 73.2, n = 12, to 241.7 +/- 48.0 microl/ min/100 g body wt.; n = 13; pcorn silk aqueous extract is diuretic at a dose of 500 mg/kg body wt. and kaliuretic at doses of 350 and 500 mg/kg body wt. In water-loaded conscious rats (5.0 ml/100 g body wt.), corn silk aqueous extract is kaliuretic at a dose of 500 mg/kg body wt., but glomerular filtration and filtered load decrease without affecting proximal tubular function, Na+, or uric acid excretion.

Estimating Glomerular Filtration Rate in Older People

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Sabrina Garasto

2014-01-01

Full Text Available We aimed at reviewing age-related changes in kidney structure and function, methods for estimating kidney function, and impact of reduced kidney function on geriatric outcomes, as well as the reliability and applicability of equations for estimating glomerular filtration rate (eGFR in older patients. CKD is associated with different comorbidities and adverse outcomes such as disability and premature death in older populations. Creatinine clearance and other methods for estimating kidney function are not easy to apply in older subjects. Thus, an accurate and reliable method for calculating eGFR would be highly desirable for early detection and management of CKD in this vulnerable population. Equations based on serum creatinine, age, race, and gender have been widely used. However, these equations have their own limitations, and no equation seems better than the other ones in older people. New equations specifically developed for use in older populations, especially those based on serum cystatin C, hold promises. However, further studies are needed to definitely accept them as the reference method to estimate kidney function in older patients in the clinical setting.

Glomerular filtration rate measured by {sup 51}Cr-EDTA clearance: evaluation of captopril-induced changes in hypertensive patients with and without renal artery stenosis

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Chaves, Anna Alice Rolim; Buchpiguel, Carlos Alberto; Praxedes, Jose Nery; Bortolotto, Luiz Aparecido; Sapienza, Marcelo Tatit, E-mail: annaalice100@yahoo.com.b [Universidade de Sao Paulo (USP), SP (Brazil). Faculdade de Medicina. Dept. de Neurologia

2010-07-01

Introduction: renal artery stenosis can lead to renovascular hypertension; however, the detection of stenosis alone does not guarantee the presence of renovascular hypertension. Renovascular hypertension depends on activation of the renin-angiotensin system, which can be detected by functional tests such as captopril renal scintigraphy. A method that allows direct measurement of the baseline and post-captopril glomerular filtration rate using chromium-51 labeled ethylenediamine tetraacetic acid ({sup 51}Cr-EDTA) could add valuable information to the investigation of hypertensive patients with renal artery stenosis. The purposes of this study were to create a protocol to measure the baseline and post-captopril glomerular filtration rate using {sup 51}Cr-EDTA, and to verify whether changes in the glomerular filtration rate permit differentiation between hypertensive patients with and without renal artery stenosis. Methods: this prospective study included 41 consecutive patients with poorly controlled severe hypertension. All patients had undergone a radiological investigation of renal artery stenosis within the month prior to their inclusion. The patients were divided into two groups: patients with (n=21) and without renal artery stenosis, (n=20). In vitro glomerular filtration rate analysis ({sup 51}Cr-EDTA) and {sup 99m}Tc-DMSA scintigraphy were performed before and after captopril administration in all patients. Results: the mean baseline glomerular filtration rate was 48.6+-21.8 ml/kg/1.73 m{sup 2} in the group with renal artery stenosis, which was significantly lower than the GFR of 65.1+-28.7 ml/kg/1.73m{sup 2} in the group without renal artery stenosis (p=0.04). Captopril induced a significant reduction of the glomerular filtration rate in the group with renal artery stenosis (to 32.6+-14.8 ml/kg/1.73m{sup 2}, p=0.001) and an insignificant change in the group without RAS (to 62.2+-23.6 ml/kg/1.73m{sup 2}, p=0.68). Scintigraphy with technetium-99m dimercapto

The effects of cimetidine on creatinine excretion, glomerular filtration rate and tubular function in renal transplant recipients

DEFF Research Database (Denmark)

Olsen, N V; Ladefoged, S D; Feldt-Rasmussen, B

1989-01-01

The renal clearance of endogenous creatinine (CCr), sodium (CNa) and lithium (CLi) was determined before and after a single intravenous bolus of cimetidine in nine renal transplant recipients. The glomerular filtration rate (GFR) was measured with 125I-iothalamate clearance (CTh). The initial CCr...... of 65 ml/min (median) was reduced to a nadir of 46 ml/min (p less than 0.01) during the first 2 h after infusion of cimetidine. GFR remained unchanged, and thus the fractional clearance of creatinine (CCr/CTh) was reduced from 1.43 (median) to 1.03 (p less than 0.01). CNa and the fractional excretion...... of sodium decreased throughout the study (p less than 0.05); CLi was unchanged. In conclusion cimetidine, when measured during 1-h clearance periods, interferes with tubular creatinine secretion in the denervated kidney of transplant recipients without affecting the glomerular filtration rate or proximal...

Role of the immune system in the pathogenesis of idiopathic nephrotic syndrome

NARCIS (Netherlands)

van den Berg, José G.; Weening, Jan J.

2004-01-01

Idiopathic NS (nephrotic syndrome) is characterized by massive proteinuria, due to a leak in the glomerular barrier to proteins. Genetic defects that affect the function and the composition of the glomerular capillary wall, in particular of the visceral epithelial cells, have recently been

Contrast media and glomerular filtration: dose dependence of clearance for three agents

International Nuclear Information System (INIS)

Baeck, S.E.K.; Krutzen, E.; Nilsson-Ehle, P.

1988-01-01

Determination of plasma clearance of contrast agents has been advocated as a means to assess glomerular filtration rate. To evaluate the feasibility of different agents for this purpose, we have compared, in healthy volunteers, the dose dependence of plasma clearance for three contrast media (iohexol, a nonionic agent, and iothalamate and metrizoate, which are ionic substances), with special emphasis on the lower dose range (2-20 mL corresponding to 0.9-12.9 g, depending on dose and agent). Iohexol and iothalamate were cleared at constant rates, irrespective of given dose, whereas metrizoate clearance increased significantly at lower doses. In general, the clearances or iothalamate and metrizoate were, respectively, moderately and markedly higher than that of iohexol. The clearance of different doses of metrizoate (2 mL versus a radiographic dose of 40 mL or more) was also compared with the clearance of [ 51 Cr]EDTA in two groups of patients with reduced renal function. When compared with [ 51 Cr]EDTA in patients with renal dysfunction, metrizoate was cleared significantly faster after a 2-mL dose, whereas clearances were identical when the metrizoate dose was 40 mL or more. These findings indicate that tubular secretion plays an active role in the elimination of metrizoate. The pharmacokinetic properties of iohexol, in combination with its low toxicity, make it a suitable agent for determination of glomerular filtration rate in clinical practice

Focal glomerular immune complex deposition: possible role of periglomerular fibrosis/atubular glomeruli.

Science.gov (United States)

Satoskar, Anjali A; Calomeni, Edward; Bott, Cherri; Nadasdy, Gyongyi M; Nadasdy, Tibor

2009-02-01

Consensus exists among renal pathologists that, in biopsies with immune complex glomerulonephritis, even a single glomerulus with open capillary loops may be sufficient for immunofluorescence and/or electron microscopy evaluation because immune complex deposition is a diffuse phenomenon. However, we have encountered renal biopsies with focal absence of immune complexes in glomeruli on either immunofluorescence or electron microscopy examination despite presence of open glomerular capillary loops. To evaluate renal biopsies with focal immune complex deposition and look for any subtle or unusual morphologic changes in the glomeruli (and in the biopsy in general). Native and transplant renal biopsies were reviewed. All biopsies had been triaged and processed according to our routine protocol for light microscopy, immunofluorescence, and electron microscopy examination. Of 2018 renal biopsies from December 2005 to December 2007, we found 10 such biopsies; 5 native and 5 transplant kidney biopsies. We found that the glomeruli with absent immune complex deposits had periglomerular fibrosis with open, albeit, wrinkled appearing capillary loops but no glomerular sclerosis. We hypothesize that these histologic features are indicative of nonfunctional glomeruli and may be associated with disconnection between the Bowman capsule and proximal tubule (atubular glomeruli). These glomeruli may not have effective filtration, despite some degree of circulation through the open capillary loops, and therefore are unable to accumulate immune complex deposits. If biopsies are small and only such glomeruli are available for immunofluorescence or electron microscopy examination, the absence of immune complex deposition in them should be evaluated carefully.

Glomerular Filtration Rate Estimation in Renal and Non-Renal Solid Organ Transplantation

DEFF Research Database (Denmark)

Hornum, Mads; Feldt-Rasmussen, Bo

2017-01-01

Following transplantation (TX) of both renal and non-renal organs, a large proportion of patients have renal dysfunction. There are multiple causes for this. Chronic nephrotoxicity and high doses of calcineurin inhibitors are important factors. Preoperative and perioperative factors like...... or estimates of renal function in these patients, in order to accurately and safely dose immunosuppressive medication and perform and adjust the treatment and prophylaxis of renal dysfunction. This is a short overview and discussion of relevant studies and possible caveats of estimated glomerular filtration...... rate methods for use in renal and non-renal TX....

Expression of Toll-Like Receptor 2 in Glomerular Endothelial Cells and Promotion of Diabetic Nephropathy by Porphyromonas gingivalis Lipopolysaccharide

Science.gov (United States)

Hatakeyama, Yuji; Ishikawa, Hiroyuki; Tsuruga, Eichi

2014-01-01

The toll-like receptor (TLR) has been suggested as a candidate cause for diabetic nephropathy. Recently, we have reported the TLR4 expression in diabetic mouse glomerular endothelium. The study here investigates the effects of the periodontal pathogen Porphyromonas gingivalis lipopolysaccharide (LPS) which is a ligand for TLR2 and TLR4 in diabetic nephropathy. In laser-scanning microscopy of glomeruli of streptozotocin- and a high fat diet feed-induced type I and type II diabetic mice, TLR2 localized on the glomerular endothelium and proximal tubule epithelium. The TLR2 mRNA was detected in diabetic mouse glomeruli by in situ hybridization and in real-time PCR of the renal cortex, the TLR2 mRNA amounts were larger in diabetic mice than in non-diabetic mice. All diabetic mice subjected to repeated LPS administrations died within the survival period of all of the diabetic mice not administered LPS and of all of the non-diabetic LPS-administered mice. The LPS administration promoted the production of urinary protein, the accumulation of type I collagen in the glomeruli, and the increases in IL-6, TNF-α, and TGF-β in the renal cortex of the glomeruli of the diabetic mice. It is thought that blood TLR ligands like Porphyromonas gingivalis LPS induce the glomerular endothelium to produce cytokines which aid glomerulosclerosis. Periodontitis may promote diabetic nephropathy. PMID:24835775

Basement membrane-specific chondroitin sulfate proteoglycan is abnormally associated with the glomerular capillary basement membrane of diabetic rats

DEFF Research Database (Denmark)

McCarthy, K J; Abrahamson, D R; Bynum, K R

1994-01-01

exception being the normal glomerular capillary basement membrane (GBM), where it is absent. In the present study of mature kidneys we examined the distribution of BM-CSPG in streptozocin-induced diabetes mellitus in rats. We found BM-CSPG atypically associated with the GBM of diabetic animals as early as 1...... month after induction of diabetes mellitus. Immunoelectron microscopy (IEM) of affected capillary loops showed BM-CSPG present in the subendothelial matrix in areas of GBM thickening and absent in areas where the GBM appears to be of normal thickness. Moreover, the association of BM-CSPG with regions...... of the pericapillary GBM affects the morphology of the capillary endothelial cells within these areas, directly displacing the cell body from the GBM proper and causing loss of fenestrae. These new data on BM-CSPG distribution reflect abnormal glomerular extracellular matrix protein biosynthesis/turnover in diabetes...

Pentoxifylline Ameliorates Glomerular Basement Membrane Ultrastructural Changes Caused by Gentamicin Administration in Rats

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Nenad Stojiljković

2009-08-01

Full Text Available Gentamicin is commonly used for the treatment of severe gram negative bacterial infections but inevi-tably cause renal failure during prolonged use. The aim of our study was to emphasize protective effects of pentoxifylline on glomerular basement membrane (GBM alterations induced by gentamicin in rats. Experiments were done on 40 male Wistar rats divided in three experimental groups. GM-group was treated daily with gentamicin in dose of 100 mg/kg during 8 days. PTX-group was treated daily with pentoxifylline in dose of 45 mg/kg and the same dose of gentamicin as in GM-group during 8 days. The control group received 1 ml/day saline intraperitoneally. Morphometric parameter measured during the analysis was glomerular basement membrane thickness. In GM-group of animals glomeruli were en-larged and GMB was diffusely and unequally thickened with neutrophil cells infiltration. In proximal tu-bules epithelial cells, vacuolization of cytoplasm with coagulation-type necrosis were observed. In PTX-group of animals glomeruli were somewhat enlarged and GBM was thickened only in some segments. Coagulation-type necrosis was not found. Blood urea and serum creatinine concentration in GM-group were significantly elevated in comparison with PTX-group while potassium level was decreased. Our results suggest that PTX has protective effects on GBM and proximal tubules in GM-treated rats.

Rat glomerular epithelial cells in culture. Parietal or visceral epithelial origin

International Nuclear Information System (INIS)

Norgaard, J.O.

1987-01-01

Isolated glomeruli from rats were explanted under standard culture conditions and outgrowths were studied by light and electron microscopy in order to identify the cells. Rat glomerular samples contained 20 to 30% structurally well-preserved encapsulated glomeruli which had a large rate of attachment to the substrate and very constantly gave rise to cellular outgrowth. In order to label cells from which outgrowth originated the glomerular incorporation of [ 3 H]thymidine was studied in the preattachment phase. By light and electron microscope autoradiograph it was demonstrated that label was located only over visceral and parietal epithelial cells during the first 3 days of culture. Incorporation of [ 3 H]thymidine was seen in mesangial cells after 5 days, i.e., after the glomeruli had attached to the culture vessels and the initial outgrowth had appeared. Consequently the first cells to grow out were of epithelial origin. Glomeruli were then incubated with [ 3 H]thymidine for the first 2 1/2 days of culture in order to label the epithelial cells, then were allowed to attach to the substrate and induce cell outgrowth. By light microscope autoradiography performed with the outgrowths in situ two types of cells with labeled nuclei were seen: (a) a small, polyhedral ciliated cell which grew in colonies where the cells were joined by junctional complexes (type I), and (b) a second very large, often multinucleated cell (type II). Based on the structural resemblance with their counterparts in situ and on comparisons with positively identified visceral epithelial cells in outgrowths from other species it is suggested that type I cells are derived from the parietal epithelium of Bowman's capsule and type II cells from the visceral epithelium

Ischemia-induced glomerular parietal epithelial cells hyperplasia: Commonly misdiagnosed cellular crescent in renal biopsy.

Science.gov (United States)

Zeng, Yeting; Wang, Xinrui; Xie, Feilai; Zheng, Zhiyong

2017-08-01

Ischemic pseudo-cellular crescent (IPCC) that is induced by ischemia and composed of hyperplastic glomerular parietal epithelial cells resembles cellular crescent. In this study, we aimed to assess the clinical and pathological features of IPCC in renal biopsy to avoid over-diagnosis and to determine the diagnostic basis. 4 IPCC cases diagnosed over a 4-year period (2012-2015) were evaluated for the study. Meanwhile, 5 cases of ANCA-associated glomerulonephritis and 5 cases of lupus nephritis (LN) were selected as control. Appropriate clinical data, morphology, and immunohistochemical features of all cases were retrieved. Results showed that the basement membrane of glomerulus with IPCC appeared as a concentric twisted ball, and glomerular cells of the lesion were reduced even entirely absent, and the adjacent afferent arterioles showed sclerosis or luminal stenosis. Furthermore, immune globulin deposition, vasculitis, and fibrinous exudate have not been observed in IPCC. While the cellular crescents showed diverse characteristics in both morphology and immunostaining in the control group. Therefore, these results indicated that IPCC is a sort of ischemic reactive hyperplasia and associated with sclerosis, stenosis, or obstruction of adjacent afferent arterioles, which is clearly different from cellular crescents result from glomerulonephritis. Copyright © 2017 Elsevier GmbH. All rights reserved.

Automatic Reporting of Creatinine-Based Estimated Glomerular Filtration Rate in Children: Is this Feasible?

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Andrew Lunn

2016-07-01

Full Text Available Creatinine, although widely used as a biomarker to measure renal function, has long been known as an insensitive marker of renal impairment. Patients with reduced renal function can have a creatinine level within the normal range, with a rapid rise when renal function is significantly reduced. As of 1976, the correlation between height, the reciprocal of creatinine, and measured glomerular filtration rate (GFR in children has been described. It has been used to derive a simple formula for estimated glomerular filtration rate (eGFR that could be used at the bedside as a more sensitive method of identifying children with renal impairment. Formulae based on this association, with modifications over time as creatinine assay methods have changed, are still widely used clinically at the bedside and in research studies to assess the degree of renal impairment in children. Adult practice has moved in many countries to computer-generated results that report eGFR alongside creatinine results using more complex, but potentially more accurate estimates of GFR, which are independent of height. This permits early identification of patients with chronic kidney disease. This review assesses the feasibility of automated reporting of eGFR and the advantages and disadvantages of this in children.

Sex steroids do not affect shigatoxin cytotoxicity on human renal tubular or glomerular cells

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Kohan Donald E

2002-08-01

Full Text Available Abstract Background The greater susceptibility of children to renal injury in post-diarrheal hemolytic-uremic syndrome (HUS may be related, at least in part, to heightened renal cell sensitivity to the cytotoxic effect of Shiga toxin (Stx, the putative mediator of kidney damage in HUS. We hypothesized that sexual maturation, which coincides with a falling incidence of HUS, may induce a relatively Stx-resistant state in the renal cells. Methods Cultured human glomerular endothelial (HGEN, human glomerular visceral epithelial (HGEC and human proximal tubule (HPT cells were exposed to Stx-1 after pre-incubation with progesterone, β-estradiol or testosterone followed by determination of cytotoxicity. Results Under basal conditions, Stx-1 potently and dose-dependently killed HPT and HGEC, but had relatively little effect on HGEN. Pre-incubation for 1, 2 or 7 days with physiologic or pharmacologic concentrations of progesterone, β-estradiol or testosterone had no effect on Stx-1 cytotoxicity dose-response on any cell type. In addition, no steroid altered Gb3 expression (Stx receptor by any cell type at any time point. Conclusion These data do not support the notion that hormonal changes associated with puberty induce an Stx-resistant state within kidney cells.

The Effect of Alium Satium Extract on the Glomerular Diameter of STZ -induced Sprague dawley Rats

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Susilorini Susilorini

2013-06-01

Full Text Available Hyperglycemia exert toxic effect in kidney.The aim of this study was to investigate the short term effect of ethanolic extract of garlic in preventing nephropathy following streptozotocin (STZ induced rats. Twenty male Sprague dawley rats were randomly divided into 4 group, all group induced induced by single dose intraperitoneal injection of 40 mg kg-1 of streptozotocin (STZ. Treatment with 3 doses ethanolic extract of garlic (0,1; 0,25; 0,5 mg kg-1 day-1 was followed for 14 days, then the left kidneys were excised and histhopathological studies were carried out using scanner 3D Hitech and Panoramic view software. Statistical analysis have been done using non parametric analysis Kruskall Wallis. The study revealed that glomerular diameter of the treatment rats was significantly different from the control group (p=0,0001. Increasing doses didn’t make difference. The ethanolic extract of garlic (Allium sativum influences the diameter glomeruli but increasing doses has no effect on the glomerular diameter.

Ultrastructural Characterization of the Glomerulopathy in Alport Mice by Helium Ion Scanning Microscopy (HIM).

Science.gov (United States)

Tsuji, Kenji; Suleiman, Hani; Miner, Jeffrey H; Daley, James M; Capen, Diane E; Păunescu, Teodor G; Lu, Hua A Jenny

2017-09-15

The glomerulus exercises its filtration barrier function by establishing a complex filtration apparatus consisting of podocyte foot processes, glomerular basement membrane and endothelial cells. Disruption of any component of the glomerular filtration barrier leads to glomerular dysfunction, frequently manifested as proteinuria. Ultrastructural studies of the glomerulus by transmission electron microscopy (TEM) and conventional scanning electron microscopy (SEM) have been routinely used to identify and classify various glomerular diseases. Here we report the application of newly developed helium ion scanning microscopy (HIM) to examine the glomerulopathy in a Col4a3 mutant/Alport syndrome mouse model. Our study revealed unprecedented details of glomerular abnormalities in Col4a3 mutants including distorted podocyte cell bodies and disorganized primary processes. Strikingly, we observed abundant filamentous microprojections arising from podocyte cell bodies and processes, and presence of unique bridging processes that connect the primary processes and foot processes in Alport mice. Furthermore, we detected an altered glomerular endothelium with disrupted sub-endothelial integrity. More importantly, we were able to clearly visualize the complex, three-dimensional podocyte and endothelial interface by HIM. Our study demonstrates that HIM provides nanometer resolution to uncover and rediscover critical ultrastructural characteristics of the glomerulopathy in Col4a3 mutant mice.

SGLT2 inhibitor empagliflozin reduces renal growth and albuminuria in proportion to hyperglycemia and prevents glomerular hyperfiltration in diabetic Akita mice

Science.gov (United States)

Gerasimova, Maria; Rose, Michael A.; Masuda, Takahiro; Satriano, Joseph; Mayoux, Eric; Koepsell, Hermann; Thomson, Scott C.; Rieg, Timo

2013-01-01

Our previous work has shown that gene knockout of the sodium-glucose cotransporter SGLT2 modestly lowered blood glucose in streptozotocin-diabetic mice (BG; from 470 to 300 mg/dl) and prevented glomerular hyperfiltration but did not attenuate albuminuria or renal growth and inflammation. Here we determined effects of the SGLT2 inhibitor empagliflozin (300 mg/kg of diet for 15 wk; corresponding to 60–80 mg·kg−1·day−1) in type 1 diabetic Akita mice that, opposite to streptozotocin-diabetes, upregulate renal SGLT2 expression. Akita diabetes, empagliflozin, and Akita + empagliflozin similarly increased renal membrane SGLT2 expression (by 38–56%) and reduced the expression of SGLT1 (by 33–37%) vs. vehicle-treated wild-type controls (WT). The diabetes-induced changes in SGLT2/SGLT1 protein expression are expected to enhance the BG-lowering potential of SGLT2 inhibition, and empagliflozin strongly lowered BG in Akita (means of 187–237 vs. 517–535 mg/dl in vehicle group; 100–140 mg/dl in WT). Empagliflozin modestly reduced GFR in WT (250 vs. 306 μl/min) and completely prevented the diabetes-induced increase in glomerular filtration rate (GFR) (255 vs. 397 μl/min). Empagliflozin attenuated increases in kidney weight and urinary albumin/creatinine ratio in Akita in proportion to hyperglycemia. Empagliflozin did not increase urinary glucose/creatinine ratios in Akita, indicating the reduction in filtered glucose balanced the inhibition of glucose reabsorption. Empagliflozin attenuated/prevented the increase in systolic blood pressure, glomerular size, and molecular markers of kidney growth, inflammation, and gluconeogenesis in Akita. We propose that SGLT2 inhibition can lower GFR independent of reducing BG (consistent with the tubular hypothesis of diabetic glomerular hyperfiltration), while attenuation of albuminuria, kidney growth, and inflammation in the early diabetic kidney may mostly be secondary to lower BG. PMID:24226524

A comparison of co-current and counter-current modes of operation for a novel hydrogen-permselective membrane dual-type FTS reactor in GTL technology

Energy Technology Data Exchange (ETDEWEB)

Rahimpour, M.R.; Forghani, A.A.; Mostafazadeh, A. Khosravanipour; Shariati, A. [Chemical Engineering Department, School of Chemical and Petroleum Engineering, Shiraz University, Shiraz 71345 (Iran)

2010-01-15

In this work, a comparison of co-current and counter-current modes of operation for a novel hydrogen-permselective membrane reactor for Fischer-Tropsch Synthesis (FTS) has been carried out. In both modes of operations, a system with two-catalyst bed instead of one single catalyst bed is developed for FTS reactions. In the first catalytic reactor, the synthesis gas is partly converted to products in a conventional water-cooled fixed-bed reactor, while in the second reactor which is a membrane fixed-bed reactor, the FTS reactions are completed and heat of reaction is used to preheat the feed synthesis gas to the first reactor. In the co-current mode, feed gas is entered into the tubes of the second reactor in the same direction with the reacting gas stream in shell side while in the counter-current mode the gas streams are in the opposite direction. Simulation results for both co-current and counter-current modes have been compared in terms of temperature, gasoline and CO{sub 2} yields, H{sub 2} and CO conversion, selectivity of components as well as permeation rate of hydrogen through the membrane. The results showed that the reactor in the co-current configuration operates with lower conversion and lower permeation rate of hydrogen, but it has more favorable profile of temperature. The counter-current mode of operation decreases undesired products such as CO{sub 2} and CH{sub 4} and also produces more gasoline. (author)

Evidence for the existence of multiple heparan sulfate proteoglycans in the human glomerular basement membrane and mesangial matrix

NARCIS (Netherlands)

Groffen, Alexander J A; Hop, Frank W H; Tryggvason, Karl; Dijkman, Henri; Assmann, Karel J M; Veerkamp, Jacques H.; Monnens, Leo A H; Van Den Heuvel, Lambert P W J

1997-01-01

Heparan sulfate proteoglycans (HSPGs) are essential components of the glomerular basement membrane (GBM) carrying a strong anionic charge. A well- characterized extracellular HSPG is perlecan, ubiquitously expressed in basement membranes. A cDNA construct encoding domains I and II of human perlecan

Comparative evaluation of iohexol and inulin clearance for glomerular filtration rate determinations

International Nuclear Information System (INIS)

Lindblad, H.G.; Berg, U.B.

1994-01-01

The authors have evaluated iohexol as a filtration marker in 150 children. The clearance of iohexol was compared with that of inulin or with a formula clearance. The single-sample clearance of iohexol showed a good correlation with the clearance of inulin. The clearance of iohexol correlated well with the formula clearance. The optimal blood sampling time for iohexol clearance determinations appears to be between 120 and 180 min after injection, at least in patient with relatively normal filtration rates. It is concluded that iohexol clearance is an accurate method of determining the glomerular filtration rate in clinical practice. 25 refs., 5 figs

Glomerular cell death and inflammation with high-protein diet and diabetes.

Science.gov (United States)

Meek, Rick L; LeBoeuf, Renee C; Saha, Sandeep A; Alpers, Charles E; Hudkins, Kelly L; Cooney, Sheryl K; Anderberg, Robert J; Tuttle, Katherine R

2013-07-01

Overfeeding amino acids (AAs) increases cellular exposure to advanced glycation end-products (AGEs), a mechanism for protein intake to worsen diabetic kidney disease (DKD). This study assessed receptor for AGE (RAGE)-mediated apoptosis and inflammation in glomerular cells exposed to metabolic stressors characteristic of high-protein diets and/or diabetes in vitro with proof-of-concept appraisal in vivo. Mouse podocytes and mesangial cells were cultured under control and metabolic stressor conditions: (i) no addition; (ii) increased AAs (4-6-fold>control); (iii) high glucose (HG, 30.5 mM); (iv) AA/HG combination; (v) AGE-bovine serum albumin (AGE-BSA, 300 µg/mL); (vi) BSA (300 µg/mL). RAGE was inhibited by blocking antibody. Diabetic (streptozotocin) and nondiabetic mice (C57BL/6J) consumed diets with protein calories of 20 or 40% (high) for 20 weeks. People with DKD and controls provided 24-h urine samples. In podocytes and mesangial cells, apoptosis (caspase 3/7 activity and TUNEL) increased in all metabolic stressor conditions. Both inflammatory mediator expression (real-time reverse transcriptase-polymerase chain reaction: serum amyloid A, caspase-4, inducible nitric oxide synthase, and monocyte chemotactic protein-1) and RAGE (immunostaining) also increased. RAGE inhibition prevented apoptosis and inflammation in podocytes. Among mice fed high protein, podocyte number (WT-1 immunostaining) decreased in the diabetic group, and only these diabetic mice developed albuminuria. Protein intake (urea nitrogen) correlated with AGE excretion (carboxymethyllysine) in people with DKD and controls. High-protein diet and/or diabetes-like conditions increased glomerular cell death and inflammation, responses mediated by RAGEs in podocytes. The concept that high-protein diets exacerbate early indicators of DKD is supported by data from mice and people.

Agrin is a major heparan sulfate proteoglycan in the human glomerular basement membrane.

Science.gov (United States)

Groffen, A J; Ruegg, M A; Dijkman, H; van de Velden, T J; Buskens, C A; van den Born, J; Assmann, K J; Monnens, L A; Veerkamp, J H; van den Heuvel, L P

1998-01-01

Agrin is a heparan sulfate proteoglycan (HSPG) that is highly concentrated in the synaptic basal lamina at the neuromuscular junction (NMJ). Agrin-like immunoreactivity is also detected outside the NMJ. Here we show that agrin is a major HSPG component of the human glomerular basement membrane (GBM). This is in addition to perlecan, a previously characterized HSPG of basement membranes. Antibodies against agrin and against an unidentified GBM HSPG produced a strong staining of the GBM and the NMJ, different from that observed with anti-perlecan antibodies. In addition, anti-agrin antisera recognized purified GBM HSPG and competed with an anti-GBM HSPG monoclonal antibody in ELISA. Furthermore, both antibodies recognized a molecule that migrated in SDS-PAGE as a smear and had a molecular mass of approximately 200-210 kD after deglycosylation. In immunoelectron microscopy, agrin showed a linear distribution along the GBM and was present throughout the width of the GBM. This was again different from perlecan, which was exclusively present on the endothelial side of the GBM and was distributed in a nonlinear manner. Quantitative ELISA showed that, compared with perlecan, the agrin-like GBM HSPG showed a sixfold higher molarity in crude glomerular extract. These results show that agrin is a major component of the GBM, indicating that it may play a role in renal ultrafiltration and cell matrix interaction. (J Histochem Cytochem 46:19-27, 1998)

Preliminary Findings of Serum Creatinine and Estimated Glomerular Filtration Rate (eGFR) in Adolescents with Intellectual Disabilities

Science.gov (United States)

Lin, Jin-Ding; Lin, Lan-Ping; Hsieh, Molly; Lin, Pei-Ying

2010-01-01

The present study aimed to describe the kidney function profile--serum creatinine and estimated glomerular filtration rate (eGFR), and to examine the relationships of predisposing factors to abnormal serum creatinine in people with intellectual disabilities (ID). Data were collected by a cross-sectional study of 827 aged 15-18 years adolescents…

B Cell Depletion: Rituximab in Glomerular Disease and Transplantation

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S. Marinaki

2013-12-01

Full Text Available B cells play a central role in the pathogenesis of many autoimmune diseases. Selective targeting can be achieved with the use of the monoclonal antibody rituximab. In addition to being a drug for non-Hodgkin's lymphoma, rituximab is also an FDA-approved treatment for refractory rheumatoid arthritis and, since recently, ANCA vasculitis. It has shown efficacy in many autoimmune diseases. This review will discuss current evidence and the rationale of the use of rituximab in glomerular diseases, including randomized controlled trials. The focus will be on the use of rituximab in idiopathic membranous nephropathy, systemic lupus erythematosus and ANCA-associated vasculitis. The emerging role of rituximab in renal transplantation, where it seems to be important for the desensitization protocols for highly sensitized patients as well as for the preconditioning of ABO-incompatible recipients and the treatment of antibody-mediated rejection, will also be addressed.

Combined effects of moderately elevated blood glucose and locally produced TGF-beta1 on glomerular morphology and renal collagen production

DEFF Research Database (Denmark)

Krag, Søren; Nyengaard, Jens R; Wogensen, Lise

2007-01-01

BACKGROUND: There is a correlation between renal graft rejection and blood glucose (BG) levels. Furthermore, diabetic patients may develop non-diabetic renal diseases, which in some circumstances progress rapidly. Since transforming growth factor-beta1 (TGF-beta) levels are elevated in many renal...... diseases, the accelerated progression may be due to interactions between glucose and locally produced TGF-beta1. Therefore, we investigated the effect of mild hyperglycaemia on glomerular morphology and collagen production in TGF-beta1 transgenic mice. METHODS: To achieve BG concentrations of approximately...... 15 mmol/l in TGF-beta1 transgenic and non-transgenic mice, we used multiple streptozotocin (STZ) injections, and after 8 weeks, we measured the changes in glomerular morphology and total collagen content. We also analysed extracellular matrix (ECM) and protease mRNA levels using real-time polymerase...

A SAGE based approach to human glomerular endothelium : defining the transcriptome, finding a novel molecule and highlighting endothelial diversity

NARCIS (Netherlands)

Sengoelge, Guerkan; Winnicki, Wolfgang; Kupczok, Anne; von Haeseler, Arndt; Schuster, Michael; Pfaller, Walter; Jennings, Paul; Weltermann, Ansgar; Blake, Sophia; Sunder-Plassmann, Gere

2014-01-01

BACKGROUND: Large scale transcript analysis of human glomerular microvascular endothelial cells (HGMEC) has never been accomplished. We designed this study to define the transcriptome of HGMEC and facilitate a better characterization of these endothelial cells with unique features. Serial analysis

The giraffe kidney tolerates high arterial blood pressure by high renal interstitial pressure and low glomerular filtration rate

DEFF Research Database (Denmark)

Damkjær, Mads; Wang, T; Brøndum, E

2015-01-01

BACKGROUND: The tallest animal on earth, the giraffe (Giraffa camelopardalis) is endowed with a mean arterial blood pressure (MAP) twice that of other mammals. The kidneys reside at heart level and show no sign of hypertension-related damage. We hypothesized that a species-specific evolutionary...... cava generated a pressure drop of 12 ± 2 mmHg. RI was 0.27. The renal capsule was durable with a calculated burst pressure of 600 mmHg. Plasma renin and AngII were 2.6 ± 0.5 mIU L(-1) and 9.1 ± 1.5 pg mL(-1) respectively. CONCLUSION: In giraffes, GFR, ERPF and RI appear much lower than expected based...... adaption in the giraffe kidney allows normal for size renal haemodynamics and glomerular filtration rate (GFR) despite a MAP double that of other mammals. METHODS: Fourteen anaesthetized giraffes were instrumented with vascular and bladder catheters to measure glomerular filtration rate (GFR) and effective...

Rapid decline in glomerular filtration rate during the first weeks following heart transplantation

DEFF Research Database (Denmark)

Hornum, M; Andersen, M; Gustafsson, F

2011-01-01

We hypothesized that a decrease in renal function is seen immediately after heart transplantation (HTX) with little recovery over time. Twelve consecutive patients had their glomerular filtration rate (GFR) measured using (51)Cr-ethylenediaminetetraacetic acid (EDTA) measured GFR (mGFR) before...... transplantation and at 1, 2, 3, and 26 weeks after transplantation. The mGFR decreased by 28% and 24% during the first 3 and 26 weeks, respectively, with mean blood cyclosporine concentration as an independent risk factor for the decrease in mGFR. The identification of cyclosporine A (CsA) as the most important...

Glomerular parietal epithelial cells contribute to adult podocyte regeneration in experimental focal segmental glomerulosclerosis

Science.gov (United States)

Eng, Diana G.; Sunseri, Maria W.; Kaverina, Natalya; Roeder, Sebastian S.; Pippin, Jeffrey W.; Shankland, Stuart J.

2015-01-01

Since adult podocytes cannot adequately proliferate following depletion in disease states there has been interest in the potential role of progenitors in podocyte repair and regeneration. To determine if parietal epithelial cells (PECs) can serve as adult podocyte progenitors following disease-induced podocyte depletion, PECs were permanently labeled in adult PECrtTA/LC1/R26 reporter mice. In normal mice, labeled PECs were confined to Bowman's capsule, while in disease (cytotoxic sheep anti-podocyte antibody), labeled PECs were found in the glomerular tuft in progressively higher numbers by days 7, 14 and 28. Early in disease, the majority of PECs in the tuft co-expressed CD44. By day 28, when podocyte numbers were significantly higher and disease severity was significantly lower, the majority of labeled PECs co-expressed podocyte proteins but not CD44. Neither labeled PECs on the tuft, nor podocytes stained for the proliferation marker BrdU. The de novo expression of phospho-ERK colocalized to CD44 expressing PECs, but not to PECs expressing podocyte markers. Thus, in a mouse model of focal segmental glomerulosclerosis typified by abrupt podocyte depletion followed by regeneration, PECs undergo two phenotypic changes once they migrate to the glomerular tuft. Initially these cells are predominantly activated CD44 expressing cells coinciding with glomerulosclerosis, and later they predominantly exhibit a podocyte phenotype which is likely reparative. PMID:25993321

Clinico-pathological study of glomerular diseases in patients with significant proteinuria in North India

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Irneet Mundi

2014-01-01

Full Text Available Proteinuria is a common manifestation of renal disease. The present study was carried out to analyze the clinic-pathological correlation, assess the value of histopathology and immunofluorescence (IF as well as note the spectrum of renal diseases in patients with significant proteinuria. Fifty consecutive patients having proteinuria >1 g/24 h underwent ultrasound-guided percutaneous renal biopsy. Clinical information was correlated with the pathological findings and the results were analyzed. The patients were in the age range of 12-79 years. Males (60% outnumbered females (40% in all the disease categories except lupus nephritis and IgA nephropathy. The most common clinical presentation was the nephrotic syndrome, seen in 31 cases (62%. Primary glomerular diseases (72% were more common than secondary glomerular diseases (24% and tubulointerstitial diseases (4%. Overall, the most common pathological diag-nosis was focal and segmental glomerulosclerosis (FSGS (20%, followed by membranous glomerulonephritis (MGN (18%. In young patients (age 60 years it was FSGS (60%. IF modified the diagnosis in 12% of the cases. The concordance between clinical diagnosis and pathological diagnosis was 66%. The difference between clinical diagnosis and final diagnosis was statistically significant. Our study further reinforces the knowledge that renal biopsy helps in accurate diagnosis and, thus, helps in appropriate management of the patients. IF provides additional information that can make the morphologic diagnosis considerably more precise.

Glomerular parietal epithelial cells contribute to adult podocyte regeneration in experimental focal segmental glomerulosclerosis.

Science.gov (United States)

Eng, Diana G; Sunseri, Maria W; Kaverina, Natalya V; Roeder, Sebastian S; Pippin, Jeffrey W; Shankland, Stuart J

2015-11-01

As adult podocytes cannot adequately proliferate following depletion in disease states, there has been interest in the potential role of progenitors in podocyte repair and regeneration. To determine whether parietal epithelial cells (PECs) can serve as adult podocyte progenitors following disease-induced podocyte depletion, PECs were permanently labeled in adult PEC-rtTA/LC1/R26 reporter mice. In normal mice, labeled PECs were confined to Bowman's capsule, whereas in disease (cytotoxic sheep anti-podocyte antibody) labeled PECs were found in the glomerular tuft in progressively higher numbers by days 7, 14, and 28. Early in disease, the majority of PECs in the tuft coexpressed CD44. By day 28, when podocyte numbers were significantly higher and disease severity was significantly lower, the majority of labeled PECs coexpressed podocyte proteins but not CD44. Neither labeled PECs on the tuft nor podocytes stained for the proliferation marker BrdU. The de novo expression of phospho-ERK colocalized to CD44 expressing PECs, but not to PECs expressing podocyte markers. Thus, in a mouse model of focal segmental glomerulosclerosis typified by abrupt podocyte depletion followed by regeneration, PECs undergo two phenotypic changes once they migrate to the glomerular tuft. Initially these cells are predominantly activated CD44 expressing cells coinciding with glomerulosclerosis, and later they predominantly exhibit a podocyte phenotype, which is likely reparative.

The relation of Complementary-Alternative Medicine use with glomerular filtration rate and depression in patients with chronic kidney disease at predialysis stage.

Science.gov (United States)

Esen, Bennur; Atay, Ahmet Engin; Gokmen, Emel Saglam; Karakoc, Ayten; Sari, Hakan; Sarisakal, Samprie; Kahvecioglu, Serdar; Kayabasi, Hasan; Sit, Dede

2015-05-08

Complementary and alternative medicine is a broad field of health including all health care practices and methods; and their accompanying theories and beliefs. In the present study, we aimed to examine the frequency of complementary-alternative medicine use, and its relation with glomerular filtration rate and depression in patients with chronic kidney disease at predialysis stage. A total of 1053 predialysis patients; 518 female and 535 male, that were followed up with chronic kidney disease for at least 3 months were enrolled into the study. Demographic features, biochemical parameters and findings of physical examination were recorded. Their compliance to diet, and knowledge about disease were questioned. Beck depression inventory and questionnaire regarding to complementary-alternative medicine use were performed. The overall frequency of complementary-alternative medicine use was 40.3% . Total ratio of herbal products was 46%. Complementary-alternative medicine use was significantly more frequent in female or single patients, and patients that informed about chronic kidney disease or under strict diet (p:0.007, p:0.016, p:0.02, p:0.016; respectively). When glomerular filtration rate of participants were considered, complementary-alternative medicine use was similar in different stages of kidney disease. Depression was observed in 41.9% of patients and significantly frequent in patients with alternative method use (p:0.002). Depression score was higher as creatinine increases and glomerular filtration rate decreases (p:0.002; r: 0,093). We determined that complementary-alternative medicine use gradually increases at predialysis stage as glomerular filtration rate decreases and there is a strict relation between complementary-alternative medicine use and depression or female gender. Disorder related stressors may lead to seeking of alternative methods. This article is protected by copyright. All rights reserved.

Transcriptional profiling reveals progeroid Ercc1-/Δ mice as a model system for glomerular aging

Science.gov (United States)

2013-01-01

Background Aging-related kidney diseases are a major health concern. Currently, models to study renal aging are lacking. Due to a reduced life-span progeroid models hold the promise to facilitate aging studies and allow examination of tissue-specific changes. Defects in genome maintenance in the Ercc1-/Δ progeroid mouse model result in premature aging and typical age-related pathologies. Here, we compared the glomerular transcriptome of young and aged Ercc1-deficient mice to young and aged WT mice in order to establish a novel model for research of aging-related kidney disease. Results In a principal component analysis, age and genotype emerged as first and second principal components. Hierarchical clustering of all 521 genes differentially regulated between young and old WT and young and old Ercc1-/Δ mice showed cluster formation between young WT and Ercc1-/Δ as well as old WT and Ercc1-/Δ samples. An unexpectedly high number of 77 genes were differentially regulated in both WT and Ercc1-/Δ mice (p aging glomerulus. At the level of the transcriptome, the pattern of gene activities is similar in the progeroid Ercc1-/Δ mouse model constituting a valuable tool for future studies of aging-associated glomerular pathologies. PMID:23947592

Transcriptional profiling reveals progeroid Ercc1(-/Δ) mice as a model system for glomerular aging.

Science.gov (United States)

Schermer, Bernhard; Bartels, Valerie; Frommolt, Peter; Habermann, Bianca; Braun, Fabian; Schultze, Joachim L; Roodbergen, Marianne; Hoeijmakers, Jan Hj; Schumacher, Björn; Nürnberg, Peter; Dollé, Martijn Et; Benzing, Thomas; Müller, Roman-Ulrich; Kurschat, Christine E

2013-08-16

Aging-related kidney diseases are a major health concern. Currently, models to study renal aging are lacking. Due to a reduced life-span progeroid models hold the promise to facilitate aging studies and allow examination of tissue-specific changes. Defects in genome maintenance in the Ercc1(-/Δ) progeroid mouse model result in premature aging and typical age-related pathologies. Here, we compared the glomerular transcriptome of young and aged Ercc1-deficient mice to young and aged WT mice in order to establish a novel model for research of aging-related kidney disease. In a principal component analysis, age and genotype emerged as first and second principal components. Hierarchical clustering of all 521 genes differentially regulated between young and old WT and young and old Ercc1(-/Δ) mice showed cluster formation between young WT and Ercc1(-/Δ) as well as old WT and Ercc1(-/Δ) samples. An unexpectedly high number of 77 genes were differentially regulated in both WT and Ercc1(-/Δ) mice (p aging glomerulus. At the level of the transcriptome, the pattern of gene activities is similar in the progeroid Ercc1(-/Δ) mouse model constituting a valuable tool for future studies of aging-associated glomerular pathologies.

Monitoring renal function in children with Fabry disease: comparisons of measured and creatinine-based estimated glomerular filtration rate

NARCIS (Netherlands)

Tøndel, Camilla; Ramaswami, Uma; Aakre, Kristin Moberg; Wijburg, Frits; Bouwman, Machtelt; Svarstad, Einar

2010-01-01

Studies on renal function in children with Fabry disease have mainly been done using estimated creatinine-based glomerular filtration rate (GFR). The aim of this study was to compare estimated creatinine-based GFR (eGFR) with measured GFR (mGFR) in children with Fabry disease and normal renal

Renal scintigraphy in insulin-dependent diabetes mellitus: Early glomerular and urologic dysfunction

International Nuclear Information System (INIS)

Poirier, J.Y.; Moisan, A.; Le Cloirec, J.; Siemen, C.; Yaouanq, J.; Edan, G.; Herry, J.Y.

1990-01-01

Glomerular filtration rate (GFR) and renal plasma flow (RPF) were measured by intravenous injection of 99mTc-diethylenetriaminepentaacetic acid (DTPA) and 131I-Hippuran in 115 insulin-dependent diabetic patients with albumin excretion rates (AER) less than 200 micrograms/min, and in 45 normal subjects. Separate kidney function and urinary elimination were estimated by renography. GFR was increased in the diabetic patients (152 +/- 24 ml/min/1.73 m2 vs. 128 +/- 15) and correlated significantly with RPF (r = 0.5; p less than 10(-9)). No relationship was found between GFR and the duration of diabetes, blood glucose, HbA1c, or AER. Fifty patients were hyperfiltering with RPF and filtration fraction higher than those in the normofiltering group. Slow intrarenal or pyeloureteral elimination, either unilateral or bilateral, was observed in 3 controls and 60 diabetic subjects (24 hyperfiltering; 36 normofiltering) and did not disappear with the patient in the standing position. In these 60 patients, mean age, duration of diabetes, blood glucose, HbA1c, 24 h albumin excretion rate, and frequency of peripheral or autonomic neuropathy did not differ from patients with normal scintigraphy; GFR was lower in the group with slow elimination, but not significantly so. 99mTc-DTPA renal uptake was symmetric in all the controls; asymmetric renal uptake with asymmetric GFR was observed in 13 patients (7 hyperfiltering; 6 normofiltering) and often associated with slower elimination. No evidence for renal stenotic atheroma or parenchymatous disease was found on the angiopyleoureterography. The results suggest that incipient uropathy is a very common phenomenon that occurs irrespective of glomerular dysfunction

Renal Subcapsular Transplantation of PSC-Derived Kidney Organoids Induces Neo-vasculogenesis and Significant Glomerular and Tubular Maturation In Vivo

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Cathelijne W. van den Berg

2018-03-01

Full Text Available Summary: Human pluripotent stem cell (hPSC-derived kidney organoids may facilitate disease modeling and the generation of tissue for renal replacement. Long-term application, however, will require transferability between hPSC lines and significant improvements in organ maturation. A key question is whether time or a patent vasculature is required for ongoing morphogenesis. Here, we show that hPSC-derived kidney organoids, derived in fully defined medium conditions and in the absence of any exogenous vascular endothelial growth factor, develop host-derived vascularization. In vivo imaging of organoids under the kidney capsule confirms functional glomerular perfusion as well as connection to pre-existing vascular networks in the organoids. Wide-field electron microscopy demonstrates that transplantation results in formation of a glomerular basement membrane, fenestrated endothelial cells, and podocyte foot processes. Furthermore, compared with non-transplanted organoids, polarization and segmental specialization of tubular epithelium are observed. These data demonstrate that functional vascularization is required for progressive morphogenesis of human kidney organoids. : In this article, Van den Berg and colleagues show that PSC-derived kidney organoids contain nephron structures but remain disorganized and immature after prolonged culture. Upon transplantation, the organoids develop host-derived vascularization, functional glomerular perfusion, and connection to pre-existing vascular networks. The authors conclude that patent vasculature is required for ongoing morphogenesis and maturation of these kidney organoids. Keywords: human pluripotent stem cells, directed differentiation, kidney organoids, transplantation, intravital microscopy, vascularization, maturation

Estimating glomerular filtration rate: Cockcroft-Gault and Modification of Diet in Renal Disease formulas compared to renal inulin clearance.

NARCIS (Netherlands)

Botev, R.; Mallie, J.P.; Couchoud, C.; Schuck, O.; Fauvel, J.P.; Wetzels, J.F.M.; Lee, N.; Santo, N.G. De; Cirillo, M.

2009-01-01

BACKGROUND AND OBJECTIVES: Evaluation of renal function by estimation of the glomerular filtration rate (GFR) is very important for the diagnosis and treatment of patients with chronic kidney disease (CKD). The Cockcroft-Gault (CG) and Modification of Diet in Renal Disease (MDRD) formulas are the

MDRD or CKD-EPI for glomerular filtration rate estimation in living kidney donors

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Carla Burballa

2018-03-01

Full Text Available Introduction: The evaluation of the measured Glomerular Filtration Rate (mGFR or estimated Glomerular Filtration Rate (eGFR is key in the proper assessment of the renal function of potential kidney donors. We aim to study the correlation between glomerular filtration rate estimation equations and the measured methods for determining renal function. Material and methods: We analyzed the relationship between baseline GFR values measured by Tc-99m-DTPA (diethylene-triamine-pentaacetate and those estimated by the four-variable Modification of Diet in Renal Disease (MDRD4 and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI equations in a series of living donors at our institution. Results: We included 64 donors (70.6% females; mean age 48.3 ± 11 years. Baseline creatinine was 0.8 ± 0.1 mg/dl and it was 1.1 ± 0.2 mg/dl one year after donation. The equations underestimated GFR when measured by Tc99m-DTPA (MDRD4 – 9.4 ± 25 ml/min, P < .05, and CKD-EPI – 4.4 ± 21 ml/min. The correlation between estimation equations and the measured method was superior for CKD-EPI (r = .41; P < .004 than for MDRD4 (r = .27; P < .05. eGFR decreased to 59.6 ± 11 (MDRD4 and 66.2 ± 14 ml/min (CKD-EPI one year after donation. This means a mean eGFR reduction of 28.2 ± 16.7 ml/min (MDRD4 and 27.31 ± 14.4 ml/min (CKD-EPI at one year. Conclusions: In our experience, CKD-EPI is the equation that better correlates with mGFR-Tc99m-DTPA when assessing renal function for donor screening purposes. Resumen: Introducción: El estudio del filtrado glomerular medido (FGm o del estimado (FGe es el eje de la evaluación adecuada de la función renal en la valoración de un potencial donante vivo renal. Nos planteamos estudiar la correlación entre las fórmulas de estimación del FG y los métodos de medición para

Facile Synthesis of a Hydroxyl-Functionalized Tröger’s Base Diamine: A New Building Block for High-Performance Polyimide Gas Separation Membranes

KAUST Repository

Ma, Xiaohua; Abdul Hamid, Mahmoud; Miao, Xiaohe; Pinnau, Ingo

2017-01-01

the highest gas-pair permselectivity values of all reported OH-functionalized PIM-PIs to date. The high permselectivity of 6FDA-HTB resulted primarily from exceptional diffusion selectivity due to strong size-sieving properties caused by hydrogen bonding

Selective Loss of Podoplanin Protein Expression Accompanies Proteinuria and Precedes Alterations in Podocyte Morphology in a Spontaneous Proteinuric Rat Model

Science.gov (United States)

Koop, Klaas; Eikmans, Michael; Wehland, Markus; Baelde, Hans; Ijpelaar, Daphne; Kreutz, Reinhold; Kawachi, Hiroshi; Kerjaschki, Dontscho; de Heer, Emile; Bruijn, Jan Anthonie

2008-01-01

To evaluate changes during the development of proteinuria, podocyte morphology and protein expression were evaluated in spontaneously proteinuric, Dahl salt-sensitive (Dahl SS) rats. Dahl SS rats on a low-salt diet were compared with spontaneously hypertensive rats (SHR) at age 2, 4, 6, 8, and 10 weeks. Blood pressure, urinary protein excretion, urinary albumin excretion, and podocyte morphology were evaluated. In addition, the expression of 11 podocyte-related proteins was determined by analyzing protein and mRNA levels. In Dahl SS rats, proteinuria became evident around week 5, increasing thereafter. SHR rats remained non-proteinuric. Dahl SS rats showed widespread foot process effacement at 10 weeks. At ≤8 weeks, expression and distribution of the podocyte proteins was similar between the two strains, except for the protein podoplanin. At 4 weeks, podoplanin began decreasing in the glomeruli of Dahl SS rats in a focal and segmental fashion. Podoplanin loss increased progressively and correlated with albuminuria (r = 0.8, P < 0.001). Double labeling experiments revealed increased expression of the podocyte stress marker desmin in glomerular areas where podoplanin was lost. Dahl SS rats did not show podoplanin gene mutations or decreased mRNA expression. Thus, podocyte morphology and the expression and distribution of most podocyte-specific proteins were normal in young Dahl SS rats, despite marked proteinuria. Our study suggests that decreased expression of podoplanin plays a role in the decrease of glomerular permselectivity. PMID:18599604

Glomerular filtration and tubular secretion of MAG-3 in the rat kidney

International Nuclear Information System (INIS)

Mueller-Suur, R.M.; Mueller-Suur, C.

1989-01-01

Technetium-99m mercaptoacetyltriglycine (MAG-3) has recently been introduced as a new radiopharmaceutical for dynamic renal scintigraphy. To elucidate the mechanism of renal excretion, micropuncture experiments were performed in rat kidneys for direct measurements of glomerular filtration and tubular secretory capacity. Fluid of Bowman space was collected from superficial glomeruli and analyzed for its contents of [99mTc]MAG-3, [125I]hippurate and [3H]inulin during constant infusion of these compounds. The ratio of activity of ultrafiltrate to that of arterial plasma was 0.23 for MAG-3, 0.68 for hippurate and 1.04 for inulin which demonstrates that the filtrated amount of MAG-3 is only 23% of that of inulin, presumably because of higher plasma protein binding which was also measured in vitro and found to be 80 +/- 1.5% for MAG-3 and 32 +/- 2% for [125I]hippurate. Proximal and distal tubules were also micropunctured and their tubular fluid as well as the final urine analyzed for the activity of hippurate and MAG-3. The tubular fluid to plasma ratio values along the nephron and in the final urine were all lower for MAG-3 than for hippurate, indicating a lower secretory capacity. From measurements of whole renal clearance, GFR and plasma protein binding the filtered amount of MAG-3 was 0.26 and of hippurate 0.87 ml/min.g kidney weight (p less than 0.001) and the secreted amount 2.01 and 2.38 ml/min.g kidney weight (p less than 0.05), respectively. We conclude that MAG-3 is predominantly excreted by tubular secretion and that the lower renal clearance of MAG-3 as compared with that of hippurate is a result both of a substantially decreased glomerular filtration and of a lower tubular secretion

Interaction between alpha 2-adrenergic and angiotensin II systems in the control of glomerular hemodynamics as assessed by renal micropuncture in the rat

Science.gov (United States)

Thomson, S. C.; Gabbai, F. B.; Tucker, B. J.; Blantz, R. C.

1992-01-01

The hypothesis that renal alpha 2 adrenoceptors influence nephron filtration rate (SNGFR) via interaction with angiotensin II (AII) was tested by renal micropuncture. The physical determinants of SNGFR were assessed in adult male Munich Wistar rats 5-7 d after ipsilateral surgical renal denervation (DNX). DNX was performed to isolate inhibitory central and presynaptic alpha 2 adrenoceptors from end-organ receptors within the kidney. Two experimental protocols were employed: one to test whether prior AII receptor blockade with saralasin would alter the glomerular hemodynamic response to alpha 2 adrenoceptor stimulation with the selective agonist B-HT 933 under euvolemic conditions, and the other to test whether B-HT 933 would alter the response to exogenous AII under conditions of plasma volume expansion. In euvolemic rats, B-HT 933 caused SNGFR to decline as the result of a decrease in glomerular ultrafiltration coefficient (LpA), an effect that was blocked by saralasin. After plasma volume expansion, B-HT 933 showed no primary effect on LpA but heightened the response of arterial blood pressure, glomerular transcapillary pressure gradient, and LpA to AII. The parallel results of these converse experiments suggest a complementary interaction between renal alpha 2-adrenergic and AII systems in the control of LpA.

Glomerular filtration rate, cardiovascular risk factors and insulin resistance Filtrado glomerular, riesgo cardiovascular y resistencia a la insulina

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Martín R. Salazar

2009-10-01

Full Text Available The aim of this paper was to study the estimated glomerular filtration rate (eGFR, its changes with age, and its association with systolic blood pressure (SBP and diastolic BP (DBP, indicators of obesity, dyslipemia, insulin resistance and inflammation on a random population sample. BP, weight, size and waist circumference (WC were recorded at home. Fasting morning blood samples were analysed. The eGFR was calculated with MDRD (eGFR-MDRD, Cockroft-Gault (eGFR-CG adjusted to 1.73 m² and reciprocal of serum creatinine (100/serum cretinine. A total of 1016 individuals, 722 females (41.97 ± 0.66 years old and 294 males (42.06 ± 0.99 years old, completed the laboratory tests. The mean of 100/Scr was 115.13 ± 0.60 (dl/mg, the mean eGFR-CG was 98.48 ± 0.82 ml/min/1.73 m²; the mean eGFR-MDRD was 85.15 ± 0.58 ml/min/1.73 m². The eGFR-MDRD decreased with age and with the number of risk factors in both sexes. The eGFR-MDRD El objetivo fue evaluar en una muestra poblacional aleatoria el filtrado glomerular estimado (FGe, sus cambios con la edad y su asociación con presión arterial sistólica (PAS y diastólica (PAD, indicadores de obesidad, dislipemia, resistencia a la insulina e inflamación. En cada domicilio fueron medidos presión arterial, peso y talla y perímetro de la cintura (PC. Se analizaron muestras de sangre en ayunas y fue calculado el FGe usando las fórmulas de MDRD (FGe-MDRD y Cockroft-Gault (FGe-CG ajustado a 1.73 m², y la inversa de la creatinina sérica (100/CrS. Completaron el protocolo de laboratorio 1016 sujetos, 722 mujeres (41.97 ± 0.66 años y 294 varones (42.06 ± 0.99 años. La media de 100/Crs fue 115.13 ± 0.60 (dl/mg, la del FGe-CG 98.48 ± 0.82 ml/min/1.73 m² y la del FGe-MDRD 85.15 ± 0.58 ml/min/1.73 m² (CI 95% 84.00-86.29. El FGe-MDRD disminuyó con la edad y con el número de factores de riesgo cardiovascular en ambos sexos. La prevalecencia ajustada de FGe-MDRD < 60 ml/min/1.73 m² fue 6.2 por 100

Microencapsulation of Pancreatic Islets for Use in a Bioartificial Pancreas

Science.gov (United States)

Opara, Emmanuel C.; McQuilling, John P.; Farney, Alan C.

2013-01-01

Islet transplantation is the most exciting treatment option for individuals afflicted with Type 1 diabetes. However, the severe shortage of human pancreas and the need to use risky immunosuppressive drugs to prevent transplant rejection remain two major obstacles for the routine use of islet transplantation in diabetic patients. Successful development of a bioartificial pancreas using the approach of microencapsulation with perm-selective coating of islets with biopolymers for graft immunoisolation holds tremendous promise for diabetic patients because it has great potential to overcome these two barriers. In this chapter, we provide a detailed description of the microencapsulation process. PMID:23494435

The effects of cimetidine on creatinine excretion, glomerular filtration rate and tubular function in renal transplant recipients

DEFF Research Database (Denmark)

Olsen, N V; Ladefoged, S D; Feldt-Rasmussen, B

1989-01-01

The renal clearance of endogenous creatinine (CCr), sodium (CNa) and lithium (CLi) was determined before and after a single intravenous bolus of cimetidine in nine renal transplant recipients. The glomerular filtration rate (GFR) was measured with 125I-iothalamate clearance (CTh). The initial CCr...... tubular flow. This suggests that on-going cimetidine treatment must be taken into account when graft function is evaluated by the CCr alone....

Effects of levosimendan on glomerular filtration rate, renal blood flow, and renal oxygenation after cardiac surgery with cardiopulmonary bypass: a randomized placebo-controlled study.

Science.gov (United States)

Bragadottir, Gudrun; Redfors, Bengt; Ricksten, Sven-Erik

2013-10-01

Acute kidney injury develops in a large proportion of patients after cardiac surgery because of the low cardiac output syndrome. The inodilator levosimendan increases cardiac output after cardiac surgery with cardiopulmonary bypass, but a detailed analysis of its effects on renal perfusion, glomerular filtration, and renal oxygenation in this group of patients is lacking. We therefore evaluated the effects of levosimendan on renal blood flow, glomerular filtration rate, renal oxygen consumption, and renal oxygen demand/supply relationship, i.e., renal oxygen extraction, early after cardiac surgery with cardiopulmonary bypass. Prospective, placebo-controlled, and randomized trial. Cardiothoracic ICU of a tertiary center. Postcardiac surgery patients (n=30). The patients were randomized to receive levosimendan, 0.1 µg/kg/min after a loading dose of 12 µg/kg (n=15), or placebo (n=15). The experimental procedure started 4-6 hours after surgery in the ICU during propofol sedation and mechanical ventilation. Systemic hemodynamic were evaluated by a pulmonary artery thermodilution catheter. Renal blood flow and glomerular filtration rate were measured by the renal vein retrograde thermodilution technique and by renal extraction of Cr-EDTA, respectively. Central venous pressure was kept constant by colloid/crystalloid infusion. Compared to placebo, levosimendan increased cardiac index (22%), stroke volume index (15%), and heart rate (7%) and decreased systemic vascular resistance index (21%), whereas mean arterial pressure was not affected. Levosimendan induced significant increases in renal blood flow (12%, prenal vascular resistance (18%, prenal oxygen consumption, or renal oxygen extraction, compared to placebo. After cardiac surgery with cardiopulmonary bypass, levosimendan induces a vasodilation, preferentially of preglomerular resistance vessels, increasing both renal blood flow and glomerular filtration rate without jeopardizing renal oxygenation. Due to its

APOL1-associated glomerular disease among African-American children: a collaboration of the Chronic Kidney Disease in Children (CKiD) and Nephrotic Syndrome Study Network (NEPTUNE) cohorts.

Science.gov (United States)

Ng, Derek K; Robertson, Catherine C; Woroniecki, Robert P; Limou, Sophie; Gillies, Christopher E; Reidy, Kimberly J; Winkler, Cheryl A; Hingorani, Sangeeta; Gibson, Keisha L; Hjorten, Rebecca; Sethna, Christine B; Kopp, Jeffrey B; Moxey-Mims, Marva; Furth, Susan L; Warady, Bradley A; Kretzler, Matthias; Sedor, John R; Kaskel, Frederick J; Sampson, Matthew G

2017-06-01

Individuals of African ancestry harboring two variant alleles within apolipoprotein L1 ( APOL1 ) are classified with a high-risk (HR) genotype. Adults with an HR genotype have increased risk of focal segmental glomerulosclerosis and chronic kidney disease compared with those with a low-risk (LR) genotype (0 or 1 variants). The role of APOL1 risk genotypes in children with glomerular disease is less well known. This study characterized 104 African-American children with a glomerular disease by APOL1 genotype in two cohorts: the Chronic Kidney Disease in Children (CKiD) and Nephrotic Syndrome Study Network (NEPTUNE). Among these subjects, 46% had an HR genotype with a similar age at cohort enrollment. For APOL1 HR children, the median age of disease onset was older (CKiD: 4.5 versus 11.5 years for LR versus HR; NEPTUNE: 11 versus 14 years for LR versus HR, respectively) and preterm birth was more common [CKiD: 27 versus 4%; NEPTUNE: 26 versus 12%; combined odds ratio 4.6 (95% confidence interval: 1.4, 15.5)]. Within studies, HR children had lower initial estimated glomerular filtration rate (eGFR) (CKiD: 53 versus 69 mL/min/1.73 m 2 ; NEPTUNE: 74 versus 94 mL/min/1.73 m 2 ). Longitudinal eGFR decline was faster among HR children versus LR (CKiD: -18 versus -8% per year; NEPTUNE: -13 versus -3% per year). Children with an HR genotype in CKiD and NEPTUNE seem to have a more aggressive form of glomerular disease, in part due to a higher prevalence of focal segmental glomerulosclerosis. These consistent findings across independent cohorts suggest a common natural history for children with APOL1 -associated glomerular disease. Further study is needed to determine the generalizability of these findings. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

A comparison between cystatin C, plasma creatinine and the Cockcroft and Gault formula for the estimation of glomerular filtration rate

NARCIS (Netherlands)

Hoek, Frans J.; Kemperman, Frits A. W.; Krediet, Raymond T.

2003-01-01

BACKGROUND: In clinical practice, the glomerular filtration rate (GFR) is often estimated from plasma creatinine. Several studies have shown cystatin C (cys C) to be a better parameter for the diagnosis of impaired renal function. No data are available, however, on the performance of cys C in

WY14,643, a PPARα ligand, attenuates expression of anti-glomerular basement membrane disease

Science.gov (United States)

Archer, D C; Frkanec, J T; Cromwell, J; Clopton, P; Cunard, R

2007-01-01

Peroxisome proliferator-activated receptor alpha (PPARα) ligands are medications used to treat hyperlipidaemia and atherosclerosis. Increasing evidence suggests that these agents are immunosuppressive. In the following studies we demonstrate that WY14,643, a PPARα ligand, attenuates expression of anti-glomerular basement membrane disease (AGBMD). C57BL/6 mice were fed 0·05% WY14,643 or control food and immunized with the non-collagenous domain of the α3 chain of Type IV collagen [α3(IV) NC1] in complete Freund's adjuvant (CFA). WY14,643 reduced proteinuria and greatly improved glomerular and tubulo-interstitial lesions. However, the PPARα ligand did not alter the extent of IgG-binding to the GBM. Immunohistochemical studies revealed that the prominent tubulo-interstitial infiltrates in the control-fed mice consisted predominately of F4/80+ macrophages and WY14,643-feeding decreased significantly the number of renal macrophages. The synthetic PPARα ligand also reduced significantly expression of the chemokine, monocyte chemoattractant protein (MCP)-1/CCL2. Sera from mice immunized with AGBMD were also evaluated for antigen-specific IgGs. There was a significant increase in the IgG1 : IgG2c ratio and a decline in the intrarenal and splenocyte interferon (IFN)-γ mRNA expression in the WY14,643-fed mice, suggesting that the PPARα ligand could skew the immune response to a less inflammatory T helper 2-type of response. These studies suggest that PPARα ligands may be a novel treatment for inflammatory renal disease. PMID:17888025

WY14,643, a PPARalpha ligand, attenuates expression of anti-glomerular basement membrane disease.

Science.gov (United States)

Archer, D C; Frkanec, J T; Cromwell, J; Clopton, P; Cunard, R

2007-11-01

Peroxisome proliferator-activated receptor alpha (PPARalpha) ligands are medications used to treat hyperlipidaemia and atherosclerosis. Increasing evidence suggests that these agents are immunosuppressive. In the following studies we demonstrate that WY14,643, a PPARalpha ligand, attenuates expression of anti-glomerular basement membrane disease (AGBMD). C57BL/6 mice were fed 0.05% WY14,643 or control food and immunized with the non-collagenous domain of the alpha3 chain of Type IV collagen [alpha3(IV) NC1] in complete Freund's adjuvant (CFA). WY14,643 reduced proteinuria and greatly improved glomerular and tubulo-interstitial lesions. However, the PPARalpha ligand did not alter the extent of IgG-binding to the GBM. Immunohistochemical studies revealed that the prominent tubulo-interstitial infiltrates in the control-fed mice consisted predominately of F4/80(+) macrophages and WY14,643-feeding decreased significantly the number of renal macrophages. The synthetic PPARalpha ligand also reduced significantly expression of the chemokine, monocyte chemoattractant protein (MCP)-1/CCL2. Sera from mice immunized with AGBMD were also evaluated for antigen-specific IgGs. There was a significant increase in the IgG1 : IgG2c ratio and a decline in the intrarenal and splenocyte interferon (IFN)-gamma mRNA expression in the WY14,643-fed mice, suggesting that the PPARalpha ligand could skew the immune response to a less inflammatory T helper 2-type of response. These studies suggest that PPARalpha ligands may be a novel treatment for inflammatory renal disease.

有机/无机杂化渗透汽化优先透醇膜研究进展%Advances in organic/inorganic hybrid alcohol perm-selective pervaporation membrane

Institute of Scientific and Technical Information of China (English)

李杰; 王乃鑫; 纪树兰

2014-01-01

渗透汽化优先透醇膜分离技术可有效解决燃料乙醇和丁醇生产中发酵产率较低的瓶颈问题，受到广泛关注。膜材料的选择与改性以及膜结构的构建是提高透醇性能的关键。有机/无机杂化膜可以实现有机和无机材料的优势互补，被认为是未来分离膜领域最重要的发展方向之一。本文扼要回顾了用于优先透醇渗透汽化分离的有机无机杂化材料，结合本文作者课题组的研究工作，重点阐述了杂化粒子的结构、粒径、界面相容性、纳微分散、负载量等因素对渗透汽化传递过程的作用机制，进一步对近年来发展的成膜新方法进行了总结。在此基础上，提出今后有机/无机杂化渗透汽化优先透醇膜研究的主要方向是发展新型纳米级、超疏水并与有机聚合物具有高度界面相容性的无机粒子，以及构建高负载量的纳微结构与超亲醇表面。%Alcohol perm-selective pervaporations membrane could resolve the product inhibition problem effectively for the use of ethanol and butanol recovery from fermentation process. The selection and modification of membrane material,and the construction of membrane structure are the key issues for better pervaporation performance. Organic/inorganic hybrid membranes combine the advantages of both organic polymers and inorganic materials,forming highly promising membranes for separation. This paper reviews the advances in organic/inorganic hybrid alcohol perm-selective pervaporation membrane materials. Several issues and research priorities which will impact the pervaporation ability of hybrid membrane for biofuel recovery are identified and discussed,including particle structure,particle size,compatibility and dispersion of inorganic particles in the polymer,and particle loading. Novel preparation methods in recent years are also presented in detail. Finally,the prospect of developing novel particles with nano size

[Glomerular filtration and renal volume in type II diabetes (non-insulin-dependent): study in normal and microalbuminuria patients].

Science.gov (United States)

Signorini, A M; Tanganelli, I; Fondelli, C; Vattimo, A; Ferrari, F; Borgogni, P; Borgogni, L; Gragnoli, G

1991-08-01

In type 2 diabetes elevated glomerular filtration rate (GFR) and increased renal volume (RV), often accompanied to normo or microalbuminuria, were demonstrated. This condition is considered a pathogenetic factor for clinical nephropathy. As this topic is little studied in type 2 diabetes, we have investigated 73 type 2 diabetic patients (34 normo and 39 microalbuminuric), looking for a correlation between GFR, RV, hypertension, duration of diabetes and indexes of metabolic control. GFR was measured by a scintigraphy, after infusion of 99Tc-DTPA. Renal volume was determined by ultrasound scanning. Between the groups GFR and RV weren't different; elevated GFR was demonstrated in 3 patients; increased RV in 1 patient. In the hypertensive group GFR was lower than in normotensive group and in controls. Multivariate analysis in stepwise demonstrated that GFR presents a negative correlation to systolic blood pressure as in normo as in microalbuminuric patients. In the normotensive group GFR didn't correlate to the other variables. The present data suggest that in type 2 diabetes there is a little prevalence of glomerular hyperfiltration and increased renal volume and that hypertension plays a role on GFR of hypertensive diabetic patients.

Sprache als Barriere (Language as a Barrier)

Science.gov (United States)

Mattheier, Klaus

1974-01-01

The concept of language barrier has its derivations in the fields of dialectology, sociology and psychology. In contemporary usage however, the concept has two meanings i.e. regional-cultural barrier and socio-cultural barrier. (Text is in German.) (DS)

Interfering RNA against PKC-α Inhibits TNF-α-induced IP3R1 Expression and Improves Glomerular Filtration Rate in Rats with Fulminant Hepatic Failure.

Science.gov (United States)

Wang, Dong-Lei; Dai, Wen-Ying; Wang, Wen; Wen, Ying; Zhou, Ying; Zhao, Yi-Tong; Wu, Jian; Liu, Pei

2018-01-10

We have reported that tumor necrosis factor- (TNF-α) is critical for reduction of glomerular filtration rate (GFR) in rats with fulminant hepatic failure (FHF). The present study aims to evaluate the underlying mechanisms of decreased GFR during acute hepatic failure. Rats with FHF induced by D-galactosamine plus lipopolysaccharide (GalN/LPS) were injected intravenously with recombinant lentivirus harboring shRNA against the protein kinase C-α (PKC-α) gene (Lenti-shRNA-PKC-α). GFR, serum levels of aminotransferases, creatinine, urea nitrogen, potassium, sodium, chloride, TNF-α and endothelin-1 (ET-1), as well as type 1 inositol 1,4,5-trisphosphate receptor (IP3R1) expression in renal tissue were assessed. The effects of PKC-α silencing on TNF-α-induced IP3R1, specificity protein 1 (SP-1) and c-Jun N-terminal kinase (JNK) expression, as well as cytosolic calcium content were determined in glomerular mesangial cell (GMCs) with RNAi against PKC-α. Renal IP3R1 overexpression was abrogated by pre-treatment with Lenti-shRNA-PKC-α. The PKC- silence significantly improved the compromised GFR, reduced Cr levels, and reversed the decrease in glomerular inulin space and the increase in glomerular calcium content in GalN/LPS-exposed rats. TNF-α treatment increased expression of PKC-α, IP3R1, specificity protein 1 (SP-1), JNK and p-JNK in GMCs, and increased Ca2+ release and binding activity of SP-1 to the IP3R1 promoter. These effects were blocked by transfection of siRNA against the PKC-α gene, and the PKC-α gene silence also restored cytosolic [Ca2+]i. RNAi targeting PKC-α inhibited TNF-α-induced IP3R1 overexpression, and in turn improved compromised GFR in the development of acute kidney injury during FHF in rats.

Measurement of glomerular filtration rate in children using technetium-99m diethylenetriamine penta-acetic acid

International Nuclear Information System (INIS)

Aaronson, I.A.; Mann, M.D.

1985-01-01

During the past 5 years, we have measured the glomerular filtration rate (GFR) by the slope-clearance method using technetium-99m diethylenetriamine penta-acetic acid technetium-99m-DTPA in 130 infants and children. The results in 22 children have been compared with inulin clearance, and a very good correlation between the two methods of measurement of GFR was demonstrated (r = 0,9616; P less than 0,0001). This study provides further evidence that technetium-99m-DTPA is a satisfactory agent for the clinical measurement of GFR in children

Human glomerular epithelial cell proteoglycans

International Nuclear Information System (INIS)

Thomas, G.J.; Jenner, L.; Mason, R.M.; Davies, M.

1990-01-01

Proteoglycans synthesized by cultures of human glomerular epithelial cells have been isolated and characterized. Three types of heparan sulfate were detected. Heparan sulfate proteoglycan I (HSPG-I; Kav 6B 0.04) was found in the cell layer and medium and accounted for 12% of the total proteoglycans synthesized. HSPG-II (Kav 6B 0.25) accounted for 18% of the proteoglycans and was located in the medium and cell layer. A third population (9% of the proteoglycan population), heparan sulfate glycosaminoglycan (HS-GAG; Kav 6B 0.4-0.8), had properties consistent with single glycosaminoglycan chains or their fragments and was found only in the cell layer. HSPG-I and HSPG-II from the cell layer had hydrophobic properties; they were released from the cell layer by mild trypsin treatment. HS-GAG lacked these properties, consisted of low-molecular-mass heparan sulfate oligosaccharides, and were intracellular. HSPG-I and -II released to the medium lacked hydrophobic properties. The cells also produced three distinct types of chondroitin sulfates. The major species, chondroitin sulfate proteoglycan I (CSPG-I) eluted in the excluded volume of a Sepharose CL-6B column, accounted for 30% of the proteoglycans detected, and was found in both the cell layer and medium. Cell layer CSPG-I bound to octyl-Sepharose. It was released from the cell layer by mild trypsin treatment. CSPG-II (Kav 6B 0.1-0.23) accounted for 10% of the total 35S-labeled macromolecules and was found predominantly in the culture medium. A small amount of CS-GAG (Kav 6B 0.25-0.6) is present in the cell extract and like HS-GAG is intracellular. Pulse-chase experiments indicated that HSPG-I and -II and CSPG-I and -II are lost from the cell layer either by direct release into the medium or by internalization where they are metabolized to single glycosaminoglycan chains and subsequently to inorganic sulfate

Frequently relapsing anti-glomerular basement membrane antibody disease with changing clinical phenotype and antibody characteristics over time

OpenAIRE

Gu, Bobby; Magil, Alex B.; Barbour, Sean J.

2016-01-01

Anti-glomerular basement membrane (GBM) antibody disease is a typically monophasic autoimmune disease with severe pulmonary and renal involvement. We report an atypical case of frequently relapsing anti-GBM antibody disease with both anti-GBM antibody?positive flares with pulmonary and renal involvement, and anti-GBM antibody?negative flares that were pulmonary limited with no histologic renal disease. This is the first report of alternating disease phenotype and anti-GBM antibody status over...

Preparation and characterization of a nickel/alumina composite membrane for high temperature hydrogen separation. Application in a membrane reactor for the dry reforming of methane; De la synthese d'une membrane composite nikel/ceramique permselective a l'hydrogene au reacteur membranaire. Application au reformage du methane

Energy Technology Data Exchange (ETDEWEB)

Haag, St.

2003-11-01

The objective of this work was to develop composite inorganic membranes based on nickel or palladium supported on a porous ceramic for high temperature hydrogen separation. These membranes were used in a membrane reactor for the dry reforming of methane in order to shift the chemical equilibrium towards the production of hydrogen and carbon monoxide. The metal layers were deposited on a tubular alumina support by electroless plating. The Ni and the Pd layers are 1 micron thick. The hydrogen permeation tests were done for high temperatures. The Pd/ceramic membrane is permselective to hydrogen and the H{sub 2}/N{sub 2} separation factor (single gas) is 60 at 400 deg C with a transmembrane pressure difference of 1 bar. With a gas mixture, the H{sub 2}/N{sub 2} separation factor is 13. This membrane is not completely dense and the transport mechanism of hydrogen through the Pd layer is mixed: solution-diffusion through the metal bulk and surface diffusion through the defects of the film. However, an embrittlement of the palladium layer under hydrogen atmosphere was observed at 500 deg C. The Ni/ceramic membrane is stable until 600 deg C, its permselectivity to hydrogen increases with the temperature. The use of a sweep gas can provide a H{sub 2}/N{sub 2} separation factor (mixture) of about 25. The main diffusion mechanism is surface diffusion through the pores. Both membranes are not catalytic. Thus, some catalysts composed of nickel and cobalt supported on MgO, SiO{sub 2} or Al{sub 2}O{sub 3} were prepared. These systems allow to reach theoretical limits of conversion calculated for a conventional fixed bed reactor. In the membrane reactor, an enhancement of the methane conversion (15-20%) is observed with both membranes due the selective removal of hydrogen during the reaction. The Ni/ceramic membrane more stable, more permeable and as selective as the palladium one is a brand new material for high temperature hydrogen separation. (author)

Barrier mechanisms in the Drosophila blood-brain barrier

Directory of Open Access Journals (Sweden)

Samantha Jane Hindle

2014-12-01

Full Text Available The invertebrate blood-brain barrier field is growing at a rapid pace and, in recent years, studies have shown a physiologic and molecular complexity that has begun to rival its vertebrate counterpart. Novel mechanisms of paracellular barrier maintenance through GPCR signaling were the first demonstrations of the complex adaptive mechanisms of barrier physiology. Building upon this work, the integrity of the invertebrate blood-brain barrier has recently been shown to require coordinated function of all layers of the compound barrier structure, analogous to signaling between the layers of the vertebrate neurovascular unit. These findings strengthen the notion that many blood-brain barrier mechanisms are conserved between vertebrates and invertebrates, and suggest that novel findings in invertebrate model organisms will have a significant impact on the understanding of vertebrate BBB functions. In this vein, important roles in coordinating localized and systemic signaling to dictate organism development and growth are beginning to show how the blood-brain barrier can govern whole animal physiologies. This includes novel functions of blood-brain barrier gap junctions in orchestrating synchronized neuroblast proliferation, and of blood-brain barrier secreted antagonists of insulin receptor signaling. These advancements and others are pushing the field forward in exciting new directions. In this review, we provide a synopsis of invertebrate blood-brain barrier anatomy and physiology, with a focus on insights from the past 5 years, and highlight important areas for future study.

Glomerular filtration rate is associated with free triiodothyronine in euthyroid subjects : Comparison between various equations to estimate renal function and creatinine clearance

NARCIS (Netherlands)

Anderson, Josephine L C; Gruppen, Eke G; van Tienhoven-Wind, Lynnda; Eisenga, Michele F; de Vries, Hanne; Gansevoort, Ron T; Bakker, Stephan J L; Dullaart, Robin P F

BACKGROUND: Effects of variations in thyroid function within the euthyroid range on renal function are unclear. Cystatin C-based equations to estimate glomerular filtration rate (GFR) are currently advocated for mortality and renal risk prediction. However, the applicability of cystatin C-based

Glomerulonefritis fibrilar: Una rara forma de enfermedad glomerular por depósitos organizados Fibrillary glomerulo-nephritis: A rare form of glomerular disease with organized deposits

Directory of Open Access Journals (Sweden)

Marta B. Cabrera

2011-10-01

Full Text Available Se describe el caso de una mujer de 67 años de edad que consultó por debilidad y astenia, constatándose proteinuria de rango nefrótico y dislipemia. Se realizó punción para biopsia renal, la que se analizó por microscopia óptica, inmunofluorescencia y microscopia electrónica de transmisión. El análisis ultra-estructural reveló la existencia de depósitos fibrilares organizados, rectos, no ramificados, cuyo espesor osciló entre 15 y 20 nm. Dichas fibrillas ópticamente se veían como una expansión mesangial discretamente nodular, ligeramente PAS positiva, rojo Congo negativa y débilmente positiva para IgG. El diagnóstico fue glomerulonefritis fibrilar. Las enfermedades glomerulares por depósitos organizados pueden exhibir superposición sindrómica e histopatológica. Por tal motivo, resulta de importancia una primera separación entre aquellas rojo Congo positivas o negativas, siendo en este último caso la microscopia electrónica de transmisión la que diferencia dos entidades: la glomerulonefritis fibrilar y la glomerulonefritis inmunotactoide. Esta diferencia se apoya no sólo en las características ultraestructurales, sino en sus características clínicas. La glomerulonefritis inmunotactoide muestra una fuerte asociación con procesos linfoproliferativos, a diferencia de lo que ocurre con la glomerulonefritis fibrilar.We describe the case of a 67 year-old female who presented weakness and fatigue. Laboratory data showed nephrotic level of proteinuria and dyslipidemia. A renal biopsy was performed, and studied by light microscopy, immuno-fluorescence and electron microscopy. Ultra-structural analysis revealed the existence of organized fibrillary deposits, straight and without ramifications, the thickness of which ranged from 15 to 20 nm. These fibres were identified, by light microscopy, as slightly nodular mesangial expansions PAS positive, Congo red negative and weakly positive for IgG. Given the above findings, the

Renal Blood Flow, Glomerular Filtration Rate, and Renal Oxygenation in Early Clinical Septic Shock.

Science.gov (United States)

Skytte Larsson, Jenny; Krumbholz, Vitus; Enskog, Anders; Bragadottir, Gudrun; Redfors, Bengt; Ricksten, Sven-Erik

2018-06-01

Data on renal hemodynamics, function, and oxygenation in early clinical septic shock are lacking. We therefore measured renal blood flow, glomerular filtration rate, renal oxygen consumption, and oxygenation in patients with early septic shock. Prospective comparative study. General and cardiothoracic ICUs. Patients with norepinephrine-dependent early septic shock (n = 8) were studied within 24 hours after arrival in the ICU and compared with postcardiac surgery patients without acute kidney injury (comparator group, n = 58). None. Data on systemic hemodynamics and renal variables were obtained during two 30-minute periods. Renal blood flow was measured by the infusion clearance of para-aminohippuric acid, corrected for renal extraction of para-aminohippuric acid. Renal filtration fraction was measured by renal extraction of chromium-51 labeled EDTA. Renal oxygenation was estimated from renal oxygen extraction. Renal oxygen delivery (-24%; p = 0.037) and the renal blood flow-to-cardiac index ratio (-21%; p = 0.018) were lower, renal vascular resistance was higher (26%; p = 0.027), whereas renal blood flow tended to be lower (-19%; p = 0.068) in the septic group. Glomerular filtration rate (-32%; p = 0.006) and renal sodium reabsorption (-29%; p = 0.014) were both lower in the septic group. Neither renal filtration fraction nor renal oxygen consumption differed significantly between groups. Renal oxygen extraction was significantly higher in the septic group (28%; p = 0.022). In the septic group, markers of tubular injury were elevated. In early clinical septic shock, renal function was lower, which was accompanied by renal vasoconstriction, a lower renal oxygen delivery, impaired renal oxygenation, and tubular sodium reabsorption at a high oxygen cost compared with controls.

The Application of Digital Pathology to Improve Accuracy in Glomerular Enumeration in Renal Biopsies.

Directory of Open Access Journals (Sweden)

Avi Z Rosenberg

Full Text Available In renal biopsy reporting, quantitative measurements, such as glomerular number and percentage of globally sclerotic glomeruli, is central to diagnostic accuracy and prognosis. The aim of this study is to determine the number of glomeruli and percent globally sclerotic in renal biopsies by means of registration of serial tissue sections and manual enumeration, compared to the numbers in pathology reports from routine light microscopic assessment.We reviewed 277 biopsies from the Nephrotic Syndrome Study Network (NEPTUNE digital pathology repository, enumerating 9,379 glomeruli by means of whole slide imaging. Glomerular number and the percentage of globally sclerotic glomeruli are values routinely recorded in the official renal biopsy pathology report from the 25 participating centers. Two general trends in reporting were noted: total number per biopsy or average number per level/section. Both of these approaches were assessed for their accuracy in comparison to the analogous numbers of annotated glomeruli on WSI.The number of glomeruli annotated was consistently higher than those reported (p<0.001; this difference was proportional to the number of glomeruli. In contrast, percent globally sclerotic were similar when calculated on total glomeruli, but greater in FSGS when calculated on average number of glomeruli (p<0.01. The difference in percent globally sclerotic between annotated and those recorded in pathology reports was significant when global sclerosis is greater than 40%.Although glass slides were not available for direct comparison to whole slide image annotation, this study indicates that routine manual light microscopy assessment of number of glomeruli is inaccurate, and the magnitude of this error is proportional to the total number of glomeruli.

Basement Membrane Defects in Genetic Kidney Diseases

Directory of Open Access Journals (Sweden)

Christine Chew

2018-01-01

Full Text Available The glomerular basement membrane (GBM is a specialized structure with a significant role in maintaining the glomerular filtration barrier. This GBM is formed from the fusion of two basement membranes during development and its function in the filtration barrier is achieved by key extracellular matrix components including type IV collagen, laminins, nidogens, and heparan sulfate proteoglycans. The characteristics of specific matrix isoforms such as laminin-521 (α5β2γ1 and the α3α4α5 chain of type IV collagen are essential for the formation of a mature GBM and the restricted tissue distribution of these isoforms makes the GBM a unique structure. Detailed investigation of the GBM has been driven by the identification of inherited abnormalities in matrix proteins and the need to understand pathogenic mechanisms causing severe glomerular disease. A well-described hereditary GBM disease is Alport syndrome, associated with a progressive glomerular disease, hearing loss, and lens defects due to mutations in the genes COL4A3, COL4A4, or COL4A5. Other proteins associated with inherited diseases of the GBM include laminin β2 in Pierson syndrome and LMX1B in nail patella syndrome. The knowledge of these genetic mutations associated with GBM defects has enhanced our understanding of cell–matrix signaling pathways affected in glomerular disease. This review will address current knowledge of GBM-associated abnormalities and related signaling pathways, as well as discussing the advances toward disease-targeted therapies for patients with glomerular disease.

Current status and methodological aspects on the measurement of glomerular filtration rate

International Nuclear Information System (INIS)

Froissart, M.; Hignette, C.; Kolar, P.; Prigent, A.; Paillard, M.

1995-01-01

Determination of the glomerular filtration rate (GFR) contribute to our understanding of kidney physiology and pathophysiology . Moreover, determination of GFR is of clinical importance in assessing the diagnosis and the progression of renal disease. The purpose of this article is to review the technical performance and results of GFR measurements, including the classical inulin clearance technique and more recent alternative clearance techniques using radioisotope-labelled filtration markers, bolus infusion and spontaneous bladder emptying. Some simplified techniques avoiding urinary collection are also described. We conclude that estimation of GFR from renal and in some cases plasmatic clearances is accurate and more convenient than the classical inulin clearance technique. Such measurements of GFR should be included both in clinical practice and clinical research. (authors). 80 refs., 5 figs., 1 tab

Tubular and glomerular injury in diabetes and the impact of ACE inhibition

DEFF Research Database (Denmark)

Nielsen, Stine E; Sugaya, Takeshi; Tarnow, Lise

2009-01-01

OBJECTIVE: We studied tubular and glomerular damage in type 1 diabetic patients by measuring urinary-liver fatty acid binding protein (U-LFABP) and albuminuria. Subsequently, we evaluated the effect of ACE inhibition on U-LFABP in patients with diabetic nephropathy. RESEARCH DESIGN AND METHODS: We...... studied Caucasians with type 1 diabetes: 58 with normoalbuminuria (urinary albumin or =300 mg/24 h). A control group consisted of 57 healthy individuals. The groups were matched by sex...... and duration of diabetes. In addition, U-LFABP was measured in 48 type 1 diabetic patients with diabetic nephropathy in a randomized crossover trial consisting of 2 months of treatment with 20, 40, and 60 mg lisinopril once daily in random order. RESULTS: In the cross-sectional study, levels of U-LFABP were...

A cross-sectional study on the relationship between hematological data and quantitative morphological indices from kidney biopsies in different glomerular diseases.

Science.gov (United States)

Nigro, Michelangelo; Viggiano, Davide; Ragone, Vincenzo; Trabace, Tiziana; di Palma, Annamaria; Rossini, Michele; Capasso, Giovambattista; Gesualdo, Loreto; Gigliotti, Giuseppe

2018-03-14

The classical approach to the analysis of kidney biopsies is based on semi-quantitative scores of the amount of sclerosis, inflammatory infiltrate, fibrosis and vascular damage. However, advanced renal lesions may be accompanied by a paucity of clinical features and, conversely, important clinical abnormalities may be accompanied by minimal histopathological changes. The objective of this study is to correlate new, semiautomatic, quantitative features of kidney biopsies (e.g. fractal analysis) with clinical and hematological parameters using a cross-sectional design. Whole slide images from sixty-seven biopsies of patients diagnosed for diabetic nephropathy, hypertensive nephropathy, focal segmental glomerulosclerosis (FSGS) or IgA nephropathy have been used. The images have been semi-automatically quantified in the ImageJ environment, in order to derive the glomerular density, the tubular density, the number of tubules per glomerulus and the fractal dimension of the tubular lumen in the cortex (an index of complexity of the tubular lumen). For each patient, hemato-chemical data have been retrieved, including the uric acid level and the creatinine-based eGFR. A linear relationship between eGFR and glomerular density was observed in hypertension and FSGS, but not in diabetic nephropathy. Conversely, the eGFR correlated with the tubular density across different glomerular conditions. Moreover, the tubular density was linearly correlated with uric acid levels in different pathological conditions. The fractal dimension of tubular lumen was correlated with the eGFR but only in hypertensive patients. Finally, blood pressure was not correlated to any of the morphological indices tested. We propose the use of the fractal dimension as a new morphological descriptor of the nephron integrity.

Enfermedad de depósito glomerular: a propósito de un caso de glomerulonefritis fibrilar

OpenAIRE

Jorge de Jesús Cantillo; Rocío del Pilar López; Rafael Enrique Andrade

2009-01-01

En el diagnóstico rutinario por biopsia renal encontramos enfermedades glomerulares que tienen depósitos estructurales fibrilares en la matriz extracelular del glomérulo, visibles por microscopía electrónica. La amiloidosis es la glomerulopatía más común con depósitos de estas características ultraestructurales. Sin embargo, hay otras glomerulopatías con depósitos similares, negativas con rojo Congo, pero positivas para inmunoglobulinas. La glomerulonefritis fibrilar es una entidad diagnós...

Renal Involvement in Preeclampsia: Similarities to VEGF Ablation Therapy

Directory of Open Access Journals (Sweden)

Janina Müller-Deile

2011-01-01

Full Text Available Glomerular VEGF expression is critical for the maintenance and function of an intact filtration barrier. Alterations in glomerular VEGF bioavailability result in endothelial as well as in podocyte damage. Renal involvement in preeclampsia includes proteinuria, podocyturia, elevated blood pressure, edema, glomerular capillary endotheliosis, and thrombotic microangiopathy. At least the renal signs, symptoms, and other evidence can sufficiently be explained by reduced VEGF levels. The aim of this paper was to summarize our pathophysiological understanding of the renal involvement of preeclampsia and point out similarities to the renal side effects of VEGF-ablation therapy.

Multiple recurrences of anti-glomerular basement membrane disease with variable antibody detection: can the laboratory be trusted?

OpenAIRE

Liu, Patricia; Waheed, Sana; Boujelbane, Lamya; Maursetter, Laura J.

2016-01-01

Anti-glomerular basement membrane (GBM) disease is commonly a monophasic illness. We present the case of multiple recurrences of anti-GBM disease with varying serum anti-GBM antibody findings. A 33-year-old female tobacco user presenting with hematuria was diagnosed with anti-GBM disease by renal biopsy. Five years later, she presented with alveolar hemorrhage and positive anti-GBM antibody. She presented a third time with alveolar hemorrhage but undetectable anti-GBM antibody. With each occu...

A comparison of estimated glomerular filtration rates using Cockcroft-Gault and the Chronic Kidney Disease Epidemiology Collaboration estimating equations in HIV infection

DEFF Research Database (Denmark)

Mocroft, A; Nielsen, Lene Ryom; Reiss, P

2014-01-01

The aim of this study was to determine whether the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)- or Cockcroft-Gault (CG)-based estimated glomerular filtration rates (eGFRs) performs better in the cohort setting for predicting moderate/advanced chronic kidney disease (CKD) or end...

Zika Virus Infection of the Human Glomerular Cells: Implications for Viral Reservoirs and Renal Pathogenesis.

Science.gov (United States)

Alcendor, Donald J

2017-07-15

Zika virus (ZIKV) infection in the human renal compartment has not been reported. Several clinical reports have describe high-level persistent viral shedding in the urine of infected patients, but the associated mechanisms have not been explored until now. The current study examined cellular components of the glomerulus of the human kidney for ZIKV infectivity. I infected primary human podocytes, renal glomerular endothelial cells (GECs), and mesangial cells with ZIKV. Viral infectivity was analyzed by means of microscopy, immunofluorescence, real-time reverse-transcription polymerase chain reaction (RT-PCR), and quantitative RT-PCR (qRT-PCR), and the proinflammatory cytokines interleukin 1β, interferon β, and RANTES (regulated on activation of normal T cells expressed and secreted) were assessed using qRT-PCR. I show that glomerular podocytes, renal GECs, and mesangial cells are permissive for ZIKV infection. ZIKV infectivity was confirmed in all 3 cell types by means of immunofluorescence staining, RT-PCR, and qRT-PCR, and qRT-PCR analysis revealed increased transcriptional induction of interleukin 1β, interferon β, and RANTES in ZIKV-infected podocytes at 72 hours, compared with renal GECs and mesangial cells. The findings of this study support the notion that the glomerulus may serve as an amplification reservoir for ZIKV in the renal compartment. The impact of ZIKV infection in the human renal compartment is unknown and will require further study. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Autoregulation and tubuloglomerular feedback in juxtamedullary glomerular arterioles.

Science.gov (United States)

Casellas, D; Moore, L C

1990-03-01

Videometric measurements of changes in vessel lumen diameters were made to investigate autoregulatory and tubuloglomerular feedback (TGF) responses of early efferent arterioles (EA), mid-to-late afferent arterioles (MAA), and terminal, juxtaglomerular afferent arterioles (JAA) in rat juxtamedullary nephrons in vitro. High-contrast shadow-cast images of blood-perfused arterioles at the glomerular vascular pole were obtained with incident illumination and long-working-distance objectives fitted to a compound microscope. In response to an increase in blood perfusion pressure from 60 to 140 mmHg, strong autoregulatory vasoconstriction was observed in the MAA and JAA, with respective reductions in mean luminal diameter of 23 +/- 4 and 40 +/- 4% (mean +/- SE); EA diameter was unchanged. In response to TGF excitation by direct microinjection of Ringer solution into the cortical thick ascending limb segment near the macula densa, JAA luminal diameter decreased by 34 +/- 5%. The TGF responses were completely inhibited by the addition of 0.1 mM furosemide to the tubular injectate. Calcium channel blockade achieved by adding 1 microM nimodipine to the superfusate had no effect on early EA diameter but produced a blood pressure-dependent JAA and MAA vasodilation and complete inhibition of autoregulatory responses. These results provide direct evidence that the distal afferent arteriole in juxtamedullary nephrons is a major effector site for both renal autoregulation and tubuloglomerular feedback.

Basement membrane proteoglycans in glomerular morphogenesis: chondroitin sulfate proteoglycan is temporally and spatially restricted during development

DEFF Research Database (Denmark)

McCarthy, K J; Bynum, K; St John, P L

1993-01-01

We previously reported the presence of a basement membrane-specific chondroitin sulfate proteoglycan (BM-CSPG) in basement membranes of almost all adult tissues. However, an exception to this ubiquitous distribution was found in the kidney, where BM-CSPG was absent from the glomerular capillary......, the present study used light and electron microscopic immunohistochemistry to examine the distribution of BM-CSPG and basement membrane heparan sulfate proteoglycan (BM-HSPG) during prenatal and postnatal renal development in the rat. Our results show that the temporal and spatial pattern of expression of BM...

Tracing the origin of glomerular extracapillary lesions from parietal epithelial cells.

Science.gov (United States)

Smeets, Bart; Uhlig, Sandra; Fuss, Astrid; Mooren, Fieke; Wetzels, Jack F M; Floege, Jürgen; Moeller, Marcus J

2009-12-01

Cellular lesions form in Bowman's space in both crescentic glomerulonephritis and collapsing glomerulopathy. The pathomechanism and origin of the proliferating cells in these lesions are unknown. In this study, we examined proliferating cells by lineage tracing of either podocytes or parietal epithelial cells (PECs) in the nephrotoxic nephritis model of inflammatory crescentic glomerulonephritis. In addition, we traced the fate of genetically labeled PECs in the Thy-1.1 transgenic mouse model of collapsing glomerulopathy. In both models, cellular bridges composed of PECs were observed between Bowman's capsule and the glomerular tuft. Genetically labeled PECs also populated larger, more advanced cellular lesions. In these lesions, we detected de novo expression of CD44 in activated PECs. In contrast, we rarely identified genetically labeled podocytes within the cellular lesions of crescentic glomerulonephritis. In conclusion, PECs constitute the majority of cells that compose early extracapillary proliferative lesions in both crescentic glomerulonephritis and collapsing glomerulopathy, suggesting similar pathomechanisms in both diseases.

A “Mini-Epidemic” of anti-glomerular basement membrane disease: Clinical and epidemiological study

Directory of Open Access Journals (Sweden)

Umesh Lingaraj

2017-01-01

Full Text Available Acute glomerulonephritis due to anti-glomerular basement membrane (anti-GBM antibody disease is rare, estimated to occur in fewer than one case per million population and accounts for less than 20% of rapidly progressive glomerulonephritis. The prevalence among patients evaluated for potential glomerular disease is lower. It accounts for fewer than 3% of all kidney biopsies done with crescentic glomerulonephritis. Cases of anti-GBM disease occurring in a cluster have rarely been reported. All biopsy proven anti-GBM disease cases were collected from January 2015 to March 2015 at our Institute. All cases were analyzed for demographic and clinical profile, pathological findings, treatment received and for any common environmental antigenic source. A total of 11 new biopsy proven anti-GBM cases were seen within a span of three months. Age group varied from 17–80 years. Seven were males and four were females. All were dialysis dependent at presentation. Seven had active cellular crescents, and four had fibrocellular. Only one patient was a smoker and none had a history of exposure to any forms of hydrocarbons. The peak seen from January 2015 to March 2015 does not correlate with any of seasonal occurrence of infections in southern India. Although there was clustering of cases to southern territories of Karnataka state, no common etiological agents could be identified. No patient had any previous urological surgeries. All patients received methylprednisolone with plasmapheresis 5–7 sessions and cyclophosphamide. All 11 patients were dialysis dependent at the end of three months. We conclude anti-GBM disease cannot be regarded as a rare cause of renal failure and lung hemorrhage. The occurrence of such epidemic within a short period suggests a possible unidentified environmental factor like infection or occupational agents as inciting agents. Identification of such inciting agents could help us in instituting appropriate preventing measures.

Knockout of Na-glucose transporter SGLT2 attenuates hyperglycemia and glomerular hyperfiltration but not kidney growth or injury in diabetes mellitus

Science.gov (United States)

Rose, Michael; Gerasimova, Maria; Satriano, Joseph; Platt, Kenneth A.; Koepsell, Hermann; Cunard, Robyn; Sharma, Kumar; Thomson, Scott C.; Rieg, Timo

2013-01-01

The Na-glucose cotransporter SGLT2 mediates high-capacity glucose uptake in the early proximal tubule and SGLT2 inhibitors are developed as new antidiabetic drugs. We used gene-targeted Sglt2 knockout (Sglt2−/−) mice to elucidate the contribution of SGLT2 to blood glucose control, glomerular hyperfiltration, kidney growth, and markers of renal growth and injury at 5 wk and 4.5 mo after induction of low-dose streptozotocin (STZ) diabetes. The absence of SGLT2 did not affect renal mRNA expression of glucose transporters SGLT1, NaGLT1, GLUT1, or GLUT2 in response to STZ. Application of STZ increased blood glucose levels to a lesser extent in Sglt2−/− vs. wild-type (WT) mice (∼300 vs. 470 mg/dl) but increased glucosuria and food and fluid intake to similar levels in both genotypes. Lack of SGLT2 prevented STZ-induced glomerular hyperfiltration but not the increase in kidney weight. Knockout of SGLT2 attenuated the STZ-induced renal accumulation of p62/sequestosome, an indicator of impaired autophagy, but did not attenuate the rise in renal expression of markers of kidney growth (p27 and proliferating cell nuclear antigen), oxidative stress (NADPH oxidases 2 and 4 and heme oxygenase-1), inflammation (interleukin-6 and monocyte chemoattractant protein-1), fibrosis (fibronectin and Sirius red-sensitive tubulointerstitial collagen accumulation), or injury (renal/urinary neutrophil gelatinase-associated lipocalin). SGLT2 deficiency did not induce ascending urinary tract infection in nondiabetic or diabetic mice. The results indicate that SGLT2 is a determinant of hyperglycemia and glomerular hyperfiltration in STZ-induced diabetes mellitus but is not critical for the induction of renal growth and markers of renal injury, inflammation, and fibrosis. PMID:23152292

Local CD34-positive capillaries decrease in mouse models of kidney disease associating with the severity of glomerular and tubulointerstitial lesions.

Science.gov (United States)

Masum, Md Abdul; Ichii, Osamu; Elewa, Yaser Hosny Ali; Nakamura, Teppei; Kon, Yasuhiro

2017-09-04

The renal vasculature plays important roles in both homeostasis and pathology. In this study, we examined pathological changes in the renal microvascular in mouse models of kidney diseases. Glomerular lesions (GLs) in autoimmune disease-prone male BXSB/MpJ-Yaa (Yaa) mice and tubulointerstitial lesions (TILs) in male C57BL/6 mice subjected to unilateral ureteral obstruction (UUO) for 7 days were studied. Collected kidneys were examined using histopathological techniques. A nonparametric Mann-Whitney U test (P < 0.05) was performed to compare healthy controls and the experimental mice. The Kruskal-Wallis test was used to compare three or more groups, and multiple comparisons were performed using Scheffe's method when significant differences were observed (P < 0.05). Yaa mice developed severe autoimmune glomerulonephritis, and the number of CD34 + glomerular capillaries decreased significantly in GLs compared to that in control mice. However, UUO-treated mice showed severe TILs only, and CD34 + tubulointerstitial capillaries were decreased significantly in TILs with the progression of tubulointerstitial fibrosis compared to those in untreated control kidneys. Infiltrations of B-cells, T-cells, and macrophages increased significantly in the respective lesions of both disease models (P < 0.05). In observations of vascular corrosion casts by scanning electron microscopy and of microfil rubber-perfused thick kidney sections by fluorescence microscopy, segmental absences of capillaries were observed in the GLs and TILs of Yaa and UUO-treated mice, respectively. Further, transmission electron microscopy revealed capillary endothelial injury in the respective lesions of both models. The numbers of CD34 + glomerular and tubulointerstitial capillaries were negatively correlated with all examined parameters in GLs (P < 0.05) and TILs (P < 0.01), respectively. From the analysis of mouse models, we identified inverse pathological correlations between the number of

Smart parking barrier

KAUST Repository

Alharbi, Abdulrazaq M.

2016-05-06

Various methods and systems are provided for smart parking barriers. In one example, among others, a smart parking barrier system includes a movable parking barrier located at one end of a parking space, a barrier drive configured to control positioning of the movable parking barrier, and a parking controller configured to initiate movement of the parking barrier, via the barrier drive. The movable parking barrier can be positioned between a first position that restricts access to the parking space and a second position that allows access to the parking space. The parking controller can initiate movement of the movable parking barrier in response to a positive identification of an individual allowed to use the parking space. The parking controller can identify the individual through, e.g., a RFID tag, a mobile device (e.g., a remote control, smartphone, tablet, etc.), an access card, biometric information, or other appropriate identifier.

Estimated glomerular filtration rate, chronic kidney disease and antiretroviral drug use in HIV-positive patients

DEFF Research Database (Denmark)

Mocroft, Amanda; Kirk, Ole; Reiss, Peter

2010-01-01

with at least three serum creatinine measurements and corresponding body weight measurements from 2004 onwards. METHODS:: CKD was defined as either confirmed (two measurements >/=3 months apart) estimated glomerular filtration rate (eGFR) of 60 ml/min per 1.73 m or below for persons with baseline eGFR of above...... cumulative exposure to tenofovir [incidence rate ratio (IRR) per year 1.16, 95% CI 1.06-1.25, P ... increased rate of CKD. Consistent results were observed in wide-ranging sensitivity analyses, although of marginal statistical significance for lopinavir/r. No other antiretroviral dugs were associated with increased incidence of CKD. CONCLUSION:: In this nonrandomized large cohort, increasing exposure...

Precursors-Derived Ceramic Membranes for High-Temperature Separation of Hydrogen

OpenAIRE

Yuji, Iwamoto

2007-01-01

This review describes recent progress in the development of hydrogen-permselective ceramic membranes derived from organometallic precursors. Microstructure and gas transport property of microporous amorphous silica-based membranes are briefly described. Then, high-temperature hydrogen permselectivity, hydrothermal stability as well as hydrogen/steam selectivity of the amorphous silica-based membranes are discussed from a viewpoint of application to membrane reactors for conversion enhancement...

Chaotic correlations in barrier billiards with arbitrary barriers

International Nuclear Information System (INIS)

Osbaldestin, A H; Adamson, L N C

2013-01-01

We study autocorrelation functions in symmetric barrier billiards for golden mean trajectories with arbitrary barriers. Renormalization analysis reveals the presence of a chaotic invariant set and thus that, for a typical barrier, there are chaotic correlations. The chaotic renormalization set is the analogue of the so-called orchid that arises in a generalized Harper equation. (paper)

Comparison between a serum creatinine-and a cystatin C-based glomerular filtration rate equation in patients receiving amphotericin B.

Science.gov (United States)

Karimzadeh, Iman; Khalili, Hossein

2016-06-06

Serum cystatin C (Cys C) has a number of advantages over serum creatinine in the evaluation of kidney function. Apart from Cys C level itself, several formulas have also been introduced in different clinical settings for the estimation of glomerular filtration rate (GFR) based upon serum Cys C level. The aim of the present study was to compare a serum Cys C-based equation with Cockcroft-Gault serum creatinine-based formula, both used in the calculation of GFR, in patients receiving amphotericin B. Fifty four adult patients with no history of acute or chronic kidney injury having been planned to receive conventional amphotericin B for an anticipated duration of at least 1 week for any indication were recruited. At three time points during amphotericin B treatment, including days 0, 7, and 14, serum cystatin C as well as creatinine levels were measured. GFR at the above time points was estimated by both creatinine (Cockcroft-Gault) and serum Cys C based equations. There was significant correlation between creatinine-based and Cys C-based GFR values at days 0 (R = 0.606, P = 0.001) and 7 (R = 0.714, P creatinine-and a cystatin C-based glomerular filtration rate equation in patients receiving amphotericin B.

Reduced glomerular filtration rate and its association with clinical outcome in older patients at risk of vascular events: secondary analysis.

LENUS (Irish Health Repository)

Ford, Ian

2009-01-20

Reduced glomerular filtration rate (GFR) is associated with increased cardiovascular risk in young and middle aged individuals. Associations with cardiovascular disease and mortality in older people are less clearly established. We aimed to determine the predictive value of the GFR for mortality and morbidity using data from the 5,804 participants randomized in the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER).

Comparison of inulin, iothalamate, and /sup 99m/Tc-DTPA for measurement of glomerular filtration rate

International Nuclear Information System (INIS)

Barbour, G.L.; Crumb, C.K.; Boyd, C.M.; Reeves, R.D.; Rastogi, S.P.; Patterson, R.M.

1976-01-01

Clearances of inulin, 125 I-iothalamate, and /sup 99m/Tc-Sn-DTPA were measured simultaneously in five mongrel dogs exhibiting a wide range of glomerular filtration rates (GFR). Standard constant-infusion inulin clearance was compared to radionuclide clearances after subcutaneous injection of the emitters mixed with aqueous epinephrine. All three substances were found to have virtually identical clearances. The accuracy, accessibility, low cost, low radiation hazard, and short half-life of /sup 99m/Tc-Sn-DTPA make it an excellent substance for measuring GFR. The subcutaneous technique offers an accuracy comparable to the more difficult constant-infusion method

Assessment of glomerular filtration rate in diabetic nephropathy using the plasma clearance of 51Cr-EDTA

DEFF Research Database (Denmark)

Hansen, H P; Rossing, P; Mathiesen, E R

1998-01-01

Plasma clearance of 51Cr-EDTA is widely used to assess the glomerular filtration rate (GFR) in diabetic nephropathy. Originally, the ratio between the intravenously injected amount of tracer and the total area under the plasma concentration curve was used for the calculation of total 51Cr...... and rate of decline in GFR based upon these three methods. Bland & Altman plots were used to illustrate the range of agreement. We investigated 76 insulin-dependent diabetic (IDDM) patients with microalbuminuria or diabetic nephropathy. GFR was measured after a single intravenous injection of 3.7 MBq 51Cr...

Smart parking barrier

KAUST Repository

Alharbi, Abdulrazaq M.

2016-01-01

positioning of the movable parking barrier, and a parking controller configured to initiate movement of the parking barrier, via the barrier drive. The movable parking barrier can be positioned between a first position that restricts access to the parking

Effects of body mass index and age on N-terminal pro brain natriuretic peptide are associated with glomerular filtration rate in chronic heart failure patients

DEFF Research Database (Denmark)

Schou, Morten; Gustafsson, Finn; Kistorp, Caroline N

2007-01-01

BACKGROUND: Obesity is a state characterized by glomerular hyperfiltration and age-related decreases in glomerular filtration rate (GFR). Body mass index (BMI), age, and GFR are associated with plasma concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP) in chronic heart failure...... (CHF) patients. We hypothesized that the effects of BMI and age on plasma concentrations of NT-proBNP are associated with GFR. METHODS: We obtained clinical data and laboratory test results from 345 CHF patients at the baseline visit in our heart failure clinic and examined the hypothesis using...... estimates for BMI (P = 0.3807) and age (P = 0.7238) changed markedly and became insignificant. In another model, after adjustment for GFR estimated by the 4-component Modification of Diet in Renal Disease formula (eGFR(MDRD)), the parameter estimates for age (P = 0.0674) changed markedly and became...

Variability of glomerular filtration rate estimation equations in elderly Chinese patients with chronic kidney disease

Directory of Open Access Journals (Sweden)

Liu X

2012-10-01

Full Text Available Xun Liu,1,2,* Mu-hua Cheng,3,* Cheng-gang Shi,1 Cheng Wang,1 Cai-lian Cheng,1 Jin-xia Chen,1 Hua Tang,1 Zhu-jiang Chen,1 Zeng-chun Ye,1 Tan-qi Lou11Division of Nephrology, Department of Internal Medicine, The Third Affiliated Hospital of Sun Yet-sun University, Guangzhou, China; 2College of Biology Engineering, South China University of Technology, Guangzhou, China; 3Department of Nuclear Medicine, The Third Affiliated Hospital of Sun Yet-sun University, Guangzhou, China *These authors contributed equally to this paperBackground: Chronic kidney disease (CKD is recognized worldwide as a public health problem, and its prevalence increases as the population ages. However, the applicability of formulas for estimating the glomerular filtration rate (GFR based on serum creatinine (SC levels in elderly Chinese patients with CKD is limited.Materials and methods: Based on values obtained with the technetium-99m diethylenetriaminepentaacetic acid (99mTc-DTPA renal dynamic imaging method, 319 elderly Chinese patients with CKD were enrolled in this study. Serum creatinine was determined by the enzymatic method. The GFR was estimated using the Cockroft–Gault (CG equation, the Modification of Diet in Renal Disease (MDRD equations, the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI equation, the Jelliffe-1973 equation, and the Hull equation.Results: The median of difference ranged from −0.3–4.3 mL/min/1.73 m2. The interquartile range (IQR of differences ranged from 13.9–17.6 mL/min/1.73 m2. Accuracy with a deviation less than 15% ranged from 27.6%–32.9%. Accuracy with a deviation less than 30% ranged from 53.6%–57.7%. Accuracy with a deviation less than 50% ranged from 74.9%–81.5%. None of the equations had accuracy up to the 70% level with a deviation less than 30% from the standard glomerular filtration rate (sGFR. Bland–Altman analysis demonstrated that the mean difference ranged from −3.0–2.4 mL/min/1.73 m2. However, the

Estimating glomerular filtration rate in a population-based study

Directory of Open Access Journals (Sweden)

Anoop Shankar

2010-07-01

Full Text Available Anoop Shankar1, Kristine E Lee2, Barbara EK Klein2, Paul Muntner3, Peter C Brazy4, Karen J Cruickshanks2,5, F Javier Nieto5, Lorraine G Danforth2, Carla R Schubert2,5, Michael Y Tsai6, Ronald Klein21Department of Community Medicine, West Virginia University School of Medicine, Morgantown, WV, USA; 2Department of Ophthalmology and Visual Sciences, 4Department of Medicine, 5Department of Population Health Sciences, University of Wisconsin, School of Medicine and Public Health, Madison, WI, USA; 3Department of Community Medicine, Mount Sinai School of Medicine, NY, USA; 6Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USABackground: Glomerular filtration rate (GFR-estimating equations are used to determine the prevalence of chronic kidney disease (CKD in population-based studies. However, it has been suggested that since the commonly used GFR equations were originally developed from samples of patients with CKD, they underestimate GFR in healthy populations. Few studies have made side-by-side comparisons of the effect of various estimating equations on the prevalence estimates of CKD in a general population sample.Patients and methods: We examined a population-based sample comprising adults from Wisconsin (age, 43–86 years; 56% women. We compared the prevalence of CKD, defined as a GFR of <60 mL/min per 1.73 m2 estimated from serum creatinine, by applying various commonly used equations including the modification of diet in renal disease (MDRD equation, Cockcroft–Gault (CG equation, and the Mayo equation. We compared the performance of these equations against the CKD definition of cystatin C >1.23 mg/L.Results: We found that the prevalence of CKD varied widely among different GFR equations. Although the prevalence of CKD was 17.2% with the MDRD equation and 16.5% with the CG equation, it was only 4.8% with the Mayo equation. Only 24% of those identified to have GFR in the range of 50–59 mL/min per 1

Correlation of the glomerular filtration rate by the Gates scintigraphy method and by the creatinine purification in urine of 24 hours; Correlacion de la tasa de filtracion glomerular por el metodo gamagrafico de Gates y por la depuracion de creatinina en orina de 24 horas

Energy Technology Data Exchange (ETDEWEB)

Gomez A, E

2003-07-01

The kidney is an important organ that makes that exist equilibrium inside the organism. In it' s multiple functions, one that interests us to know is the glomerular filtration rate (GFR). To know this, exist laboratory and scintigraphy studies like the scintigraphy with technique of Gates and the creatinine purification in urine of 24 hours. The files of 44 patients were studied, which were clinically candidates to kidney donors healthy (25 women and 19 men) with ages that varied from the 18 years to the 54 years ( 35.1 years), with a weight of 43 kilograms to 94 kilograms (68.95 Kg) and with a corporal surface of 1.29 to 2.08 m{sup 2} (1.70 m{sup 2}). These patients underwent study protocols with creatinine purification and with renal scintigraphy. The glomerular filtration rate obtained by creatinine purification varied from 51.9 ml/min. to 156 ml/min. and the GFR obtained by scintigraphy varied from 3.6 ml/min. to 155.2 ml/min. Once obtained the gathering of data the test of Student was applied to compare the averages of both distributions and the analysis of lineal regression to determine the coefficients of correlation of the complete group. (Author)

Stability of barrier buckets with zero RF-barrier separations

Energy Technology Data Exchange (ETDEWEB)

Ng, K.Y.; /Fermilab

2005-03-01

A barrier bucket with very small separation between the rf barriers (relative to the barrier widths) or even zero separation has its synchrotron tune decreasing rather slowly from a large value towards the boundary of the bucket. As a result, large area at the bucket edges can become unstable under the modulation of rf voltage and/or rf phase. In addition, chaotic regions may form near the bucket center and extend outward under increasing modulation. Application is made to those barrier buckets used in the process of momentum mining at the Fermilab Recycler Ring.

Beta thalassemia major: The effect of age on glomerular filtration rate

Directory of Open Access Journals (Sweden)

Majid Malaki

2011-01-01

Full Text Available Thalassemia is a common hereditary hemoglobinopathy disorder that affects many organs in the body. Estimation of kidney function is important, as it is the vital organ that plays the major role in the elimination of accumulated iron as well as the chelating drugs that have to be used as therapy. Sixty- three patients aged 1-29 years, with a mean ± SD of 14 ± 6.7 years, affected with beta- thalassemia major in Tabriz Children′s Hospital were evaluated for their renal function on the basis of their age, serum iron, serum ferritin and serum creatinine levels along with two methods of estimating glomerular filtration rate (GFR; by Schwartz method for those under 18 years old and using Modification of Diet in Renal Disease (MDRD formula for those who were 18 years and above. Elevation of serum creatinine denoting renal dysfunction was not seen in our patients, but hyperfiltration was a common finding. An increasing GFR was observed, which corresponded to age, but no relationships were seen between serum iron, serum ferritin, regular blood transfusion, chelating therapy to GFR.

Renal extramedullary hematopoiesis: interstitial and glomerular pathology.

Science.gov (United States)

Alexander, Mariam P; Nasr, Samih H; Kurtin, Paul J; Casey, Edward T; Hernandez, Loren P Herrera; Fidler, Mary E; Sethi, Sanjeev; Cornell, Lynn D

2015-12-01

Renal extramedullary hematopoiesis is rarely recognized in the antemortem setting. We identified 14 patients with renal extramedullary hematopoiesis on antemortem specimens from 1994 to 2015. The mean age was 68 years (range 47-87 years); males predominated (M:F=9:5). All presented with renal insufficiency, including five (36%) with acute kidney injury. The mean serum creatinine at biopsy was 2.9 mg/dl (range 1.2-7.3 mg/dl). All had proteinuria (mean 7.9 g/24 h; range 0.5-28; n=13), including 9 with ≥3 g/24 h. Renal extramedullary hematopoiesis appeared histologically as an interstitial infiltrate (n=12) and/or a perirenal infiltrate (n=3) or mass-like lesion (n=1). Five were misdiagnosed as interstitial nephritis. Concurrent glomerular disease was prevalent and included fibrillary-like glomerulonephritis (n=3), chronic thrombotic microangiopathy (n=5), focal segmental glomerulosclerosis (n=6), and diabetic glomerulosclerosis (n=2). All patients had an underlying hematologic malignancy: primary myelofibrosis in 9, myeloproliferative neoplasm not otherwise specified in 1, essential thrombocythemia in 1, polycythemia vera in 1, and plasma cell myeloma in 2. Clinical follow-up was available in 12 patients, mean of 29 months (range 4-120 months). In 10 patients for whom treatment history could be obtained, 9 were treated with chemotherapy, and 1 was treated with steroids. The mean creatinine at last follow-up was 2 mg/dl (range 1.2-3.9 mg/dl) (n=9). Ten patients died in the follow-up period from their underlying hematological disease and had persistent renal disease. The two remaining patients had persistent chronic kidney disease. Renal extramedullary hematopoiesis should be considered in the differential diagnosis of interstitial infiltrates, particularly in the presence of a glomerulopathy and a hematologic malignancy.

Safety- barrier diagrams

DEFF Research Database (Denmark)

Duijm, Nijs Jan

2008-01-01

Safety-barrier diagrams and the related so-called 'bow-tie' diagrams have become popular methods in risk analysis. This paper describes the syntax and principles for constructing consistent and valid safety-barrier diagrams. The relation of safety-barrier diagrams to other methods such as fault...... trees and Bayesian networks is discussed. A simple method for quantification of safety-barrier diagrams is proposed. It is concluded that safety-barrier diagrams provide a useful framework for an electronic data structure that integrates information from risk analysis with operational safety management....

Safety-barrier diagrams

DEFF Research Database (Denmark)

Duijm, Nijs Jan

2007-01-01

Safety-barrier diagrams and the related so-called "bow-tie" diagrams have become popular methods in risk analysis. This paper describes the syntax and principles for constructing consistent and valid safety-barrier diagrams. The relation with other methods such as fault trees and Bayesian networks...... are discussed. A simple method for quantification of safety-barrier diagrams is proposed, including situations where safety barriers depend on shared common elements. It is concluded that safety-barrier diagrams provide a useful framework for an electronic data structure that integrates information from risk...... analysis with operational safety management....

Comparison of Glomerular Transcriptome Profiles of Adult-Onset Steroid Sensitive Focal Segmental Glomerulosclerosis and Minimal Change Disease.

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Jun Tong

Full Text Available To search for biomarkers to differentiate primary focal segmental glomerulosclerosis (FSGS and minimal change disease (MCD.We isolated glomeruli from kidney biopsies of 6 patients with adult-onset steroid sensitiveFSGS and 5 patients with MCD, and compared the profiles of glomerular transcriptomes between the two groups of patients using microarray analysis.Analysis of differential expressed genes (DEGs revealed that up-regulated DEGs in FSGS patients compared with MCD patients were primarily involved in spermatogenesis, gamete generation, regulation of muscle contraction, response to unfolded protein, cell proliferation and skeletal system development. The down-regulated DEGs were primarily related to metabolic process, intracellular transport, oxidation/reduction andestablishment of intracellular localization. We validated the expression of the top 6 up-regulated and top 6 down-regulated DEGs using real-time PCR. Membrane metallo-endopeptidase (MME is a down-regulated gene that was previously identified as a key gene for kidney development. Immunostaining confirmed that the protein expression of MME decreased significantly in FSGS kidneys compared with MCD kidneys.This report was the first study to examine transcriptomes in Chinese patients with various glomerular diseases. Expressions of MME both in RNA and protein level decreased significantly in glomeruli of FSGS kidneys compared with MCD kidneys. Our data suggested that MME might play a role in the normal physiological function of podocytes and a decrease in MME expression might be related to podocyte injury. We also identified genes and pathways specific for FSGS versus MCD, and our data could help identify potential new biomarkers for the differential diagnosis between these two diseases.

Rituximab for the treatment of refractory simultaneous anti-glomerular basement membrane (anti-GBM) and membranous nephropathy.

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Bandak, Ghassan; Jones, Bruce A; Li, Jian; Yee, Jerry; Umanath, Kausik

2014-02-01

Antibody-mediated anti-glomerular basement membrane (anti-GBM) disease occurs rarely in the presence of another B-cell disorder, membranous nephropathy. The coexistence of these two autoimmune disorders would be anticipated to require differing, specific therapies targeted to each disease process. We describe a case of concomitant membranous nephropathy and anti-GBM disease in which conventional therapy, including steroids, plasmapheresis and cyclophosphamide, failed to attenuate the anti-GBM disease, yet responded to an alternative treatment of rituximab. This B-cell directed, monoclonal, chimeric antibody treatment substantially reduced anti-GBM antibody titers and led to discontinuation of plasmapheresis, while maintaining the remission of membranous nephropathy and anti-GBM disease.

Lower estimated glomerular filtration rate and higher albuminuria are associated with all-cause and cardiovascular mortality. A collaborative meta-analysis of high-risk population cohorts

NARCIS (Netherlands)

van der Velde, Marije; Matsushita, Kunihiro; Coresh, Josef; Astor, Brad C.; Woodward, Mark; Levey, Andrew S.; de Jong, Paul E.; Gansevoort, Ron T.

Screening for chronic kidney disease is recommended in people at high risk, but data on the independent and combined associations of estimated glomerular filtration rate (eGFR) and albuminuria with all-cause and cardiovascular mortality are limited. To clarify this, we performed a collaborative

Vehicle barrier systems

International Nuclear Information System (INIS)

Sena, P.A.

1986-01-01

The ground vehicle is one of the most effective tools available to an adversary force. Vehicles can be used to penetrate many types of perimeter barriers, transport equipment and personnel rapidly over long distances, and deliver large amounts of explosives directly to facilities in suicide missions. The function of a vehicle barrier system is to detain or disable a defined threat vehicle at a selected distance from a protected facility. Numerous facilities are installing, or planning to install, vehicle barrier systems and many of these facilities are requesting guidance to do so adequately. Therefore, vehicle barriers are being evaluated to determine their stopping capabilities so that systems can be designed that are both balanced and capable of providing a desired degree of protection. Equally important, many of the considerations that should be taken into account when establishing a vehicle barrier system have been identified. These considerations which pertain to site preparation, barrier selection, system integration and operation, and vehicle/barrier interaction, are discussed in this paper

Expression and response to angiotensin-converting enzyme inhibition of matrix metalloproteinases 2 and 9 in renal glomerular damage in young transgenic rats with renin-dependent hypertension

NARCIS (Netherlands)

Bolbrinker, J; Markovic, S; Wehland, M; Melenhorst, WBWH; van Goor, H; Kreutz, R

Extracellular matrix expansion in the glomerular mesangium contributes to the development of glomerulosclerosis and chronic renal disease in arterial hypertension. Transforming growth factor-beta 1 (TGF-beta 1), matrix metalloproteinases (MMPs), and tissue inhibitors of MMPs (TIMPs) are involved in

Renal uptake of dimercaptosuccinic acid and glomerular filtration rate in chronic nephropathy at angiotensin converting enzyme inhibition

DEFF Research Database (Denmark)

Kamper, A L; Thomsen, H S; Nielsen, S L

1990-01-01

function. Scintigrams of the kidneys showed an unaltered distribution of DMSA during treatment. GFR estimated by 51Cr-EDTA plasma clearance fell by 14% (P less than 0.01), but renal uptake of 99mTc-DMSA increased by 10% (P less than 0.01). It is concluded that DMSA in chronic renal failure is mainly taken......Glomerular filtration rate (GFR) and renal uptake of dimercaptosuccinic acid (DMSA) were measured in 31 patients with progressive chronic nephropathy before and immediately after the start of treatment with angiotensin converting enzyme (ACE) inhibitor in order to control adverse effects on kidney...

Aging and physiological changes of the kidneys including changes in glomerular filtration rate.

Science.gov (United States)

Musso, Carlos G; Oreopoulos, Dimitrios G

2011-01-01

In addition to the structural changes in the kidney associated with aging, physiological changes in renal function are also found in older adults, such as decreased glomerular filtration rate, vascular dysautonomia, altered tubular handling of creatinine, reduction in sodium reabsorption and potassium secretion, and diminished renal reserve. These alterations make aged individuals susceptible to the development of clinical conditions in response to usual stimuli that would otherwise be compensated for in younger individuals, including acute kidney injury, volume depletion and overload, disorders of serum sodium and potassium concentration, and toxic reactions to water-soluble drugs excreted by the kidneys. Additionally, the preservation with aging of a normal urinalysis, normal serum urea and creatinine values, erythropoietin synthesis, and normal phosphorus, calcium and magnesium tubular handling distinguishes decreased GFR due to normal aging from that due to chronic kidney disease. Copyright © 2011 S. Karger AG, Basel.

Insulin's acute effects on glomerular filtration rate correlate with insulin sensitivity whereas insulin's acute effects on proximal tubular sodium reabsorption correlate with salt sensitivity in normal subjects

NARCIS (Netherlands)

ter Maaten, JC; Bakker, SJL; Serne, EH; ter Wee, PM; Gans, ROB

1999-01-01

Background. Insulin induces increasing distal tubular sodium reabsorption. Opposite effects of insulin to offset insulin-induced sodium retention are supposedly increases in glomerular filtration rate (GFR) and decreases in proximal tubular sodium reabsorption. Defects in these opposing effects

Barriers to fusion

International Nuclear Information System (INIS)

Berriman, A.C.; Butt, R.D.; Dasgupta, M.; Hinde, D.J.; Morton, C.R.; Newton, J.O.

1999-01-01

The fusion barrier is formed by the combination of the repulsive Coulomb and attractive nuclear forces. Recent research at the Australian National University has shown that when heavy nuclei collide, instead of a single fusion barrier, there is a set of fusion barriers. These arise due to intrinsic properties of the interacting nuclei such deformation, rotations and vibrations. Thus the range of barrier energies depends on the properties of both nuclei. The transfer of matter between nuclei, forming a neck, can also affect the fusion process. High precision data have been used to determine fusion barrier distributions for many nuclear reactions, leading to new insights into the fusion process

Extremal surface barriers

International Nuclear Information System (INIS)

Engelhardt, Netta; Wall, Aron C.

2014-01-01

We present a generic condition for Lorentzian manifolds to have a barrier that limits the reach of boundary-anchored extremal surfaces of arbitrary dimension. We show that any surface with nonpositive extrinsic curvature is a barrier, in the sense that extremal surfaces cannot be continuously deformed past it. Furthermore, the outermost barrier surface has nonnegative extrinsic curvature. Under certain conditions, we show that the existence of trapped surfaces implies a barrier, and conversely. In the context of AdS/CFT, these barriers imply that it is impossible to reconstruct the entire bulk using extremal surfaces. We comment on the implications for the firewall controversy

Indomethacin reduces glomerular and tubular damage markers but not renal inflammation in chronic kidney disease patients: a post-hoc analysis.

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Martin H de Borst

Full Text Available Under specific conditions non-steroidal anti-inflammatory drugs (NSAIDs may be used to lower therapy-resistant proteinuria. The potentially beneficial anti-proteinuric, tubulo-protective, and anti-inflammatory effects of NSAIDs may be offset by an increased risk of (renal side effects. We investigated the effect of indomethacin on urinary markers of glomerular and tubular damage and renal inflammation. We performed a post-hoc analysis of a prospective open-label crossover study in chronic kidney disease patients (n = 12 with mild renal function impairment and stable residual proteinuria of 4.7±4.1 g/d. After a wash-out period of six wks without any RAAS blocking agents or other therapy to lower proteinuria (untreated proteinuria (UP, patients subsequently received indomethacin 75 mg BID for 4 wks (NSAID. Healthy subjects (n = 10 screened for kidney donation served as controls. Urine and plasma levels of total IgG, IgG4, KIM-1, beta-2-microglobulin, H-FABP, MCP-1 and NGAL were determined using ELISA. Following NSAID treatment, 24 h -urinary excretion of glomerular and proximal tubular damage markers was reduced in comparison with the period without anti-proteinuric treatment (total IgG: UP 131[38-513] vs NSAID 38[17-218] mg/24 h, p<0.01; IgG4: 50[16-68] vs 10[1-38] mg/24 h, p<0.001; beta-2-microglobulin: 200[55-404] vs 50[28-110] ug/24 h, p = 0.03; KIM-1: 9[5]-[14] vs 5[2]-[9] ug/24 h, p = 0.01. Fractional excretions of these damage markers were also reduced by NSAID. The distal tubular marker H-FABP showed a trend to reduction following NSAID treatment. Surprisingly, NSAID treatment did not reduce urinary excretion of the inflammation markers MCP-1 and NGAL, but did reduce plasma MCP-1 levels, resulting in an increased fractional MCP-1 excretion. In conclusion, the anti-proteinuric effect of indomethacin is associated with reduced urinary excretion of glomerular and tubular damage markers, but not with reduced excretion of renal

Podoplanin, novel 43-kd membrane protein of glomerular epithelial cells, is down-regulated in puromycin nephrosis.

Science.gov (United States)

Breiteneder-Geleff, S.; Matsui, K.; Soleiman, A.; Meraner, P.; Poczewski, H.; Kalt, R.; Schaffner, G.; Kerjaschki, D.

1997-01-01

Puromycin aminonucleoside nephrosis (PAN), a rat model of human minimal change nephropathy, is characterized by extensive flattening of glomerular epithelial cell (podocyte) foot processes and by severe proteinuria. For comparison of expression of glomerular membrane proteins of normal and PAN rats, a membrane protein fraction of isolated rat glomeruli was prepared and monoclonal antibodies were raised against it. An IgG-secreting clone designated LF3 was selected that specifically immunolabeled podocytes of normal but not of PAN rats. The antigen of LF3 IgG was identified as a 43-kd glycoprotein. Molecular cloning of its cDNA was performed in a delta gt11 expression library prepared from mRNA of isolated rat glomeruli. The predicted amino acid sequence indicated a 166-amino-acid integral membrane protein with a single membrane-spanning domain, two potential phosphorylation sites in its short cytoplasmic tail, and six potential O-glycosylation sites in the large ectodomain. High amino acid sequence identities were found to membrane glycoproteins of rat lung and bone and mouse thymus epithelial cells as well as to a phorbol-ester-induced protein in a mouse osteoblast cell line and to a canine influenza C virus receptor. In PAN, expression of this 43-kd protein was selectively reduced to < 30%, as determined by quantitative immunogold electron microscopy, immunoblotting, and Northern blotting. These data provide evidence that transcription of the 43-kd transmembrane podocyte glycoprotein is specifically down-regulated in PAN. To indicate that this protein could be associated with transformation of arborized foot processes to flat feet (Latin, pes planus) we have called it podoplanin. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 10 Figure 12 Figure 13 Figure 14 Figure 15 PMID:9327748

A clinicopathologic study of glomerular disease: A single-center, five-year retrospective study from Northwest India

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Pankaj Beniwal

2016-01-01

Full Text Available Studies published from centers across India have reported different and contradicting patterns of glomerular disease. In this retrospective study, we report our experience from a Tertiary Care Center in Northwest India. A total of 702 renal biopsies performed between 2008 and 2013 were reviewed of which 80 were excluded from the study because of having insufficient records or if the biopsies were taken from an allograft. The study included 411 males (66.1 % and 211 females (33.9% with an age range of 12-70 years (mean 30.34 ± 7.04 years. Majority of the biopsies (93.9% showed some form of glomerulonephritis (GN, either primary (79.4% or secondary glomerular disease (SGD (14.5%. Minimal change disease (MCD was the most common type of primary GN (26.5% of primary GN, followed by membranous nephropathy (MN; 18.8% and focal and segmental glomerulosclerosis (FSGS; 13.2%. Lupus nephritis (LN was the most frequent SGD (52.2% of secondary GN. Amyloidosis was found in 41.1% and diabetic glomerulosclerosis in 4.4%. LN was also the second most common diagnosis in females after MCD, seen in 19.4% of females. MCD followed by membranoproliferative GN and diffuse proliferative GN were the most common entities in individuals <20 years of age. In the 20-39 years age group, MN was the most common pathology seen. MN was again the most common pathology seen in patients aged above 40 years followed by amyloidosis and FSGS. In this study, MCD was the most common primary GN observed overall from this part of India. MN was the most common GN in individuals above 20 years of age presenting with the nephrotic syndrome. The geographical and regional differences in the pattern of GNs point to the necessity of having a central biopsy registry.

Multilayer moisture barrier

Science.gov (United States)

Pankow, Joel W; Jorgensen, Gary J; Terwilliger, Kent M; Glick, Stephen H; Isomaki, Nora; Harkonen, Kari; Turkulainen, Tommy

2015-04-21

A moisture barrier, device or product having a moisture barrier or a method of fabricating a moisture barrier having at least a polymer layer, and interfacial layer, and a barrier layer. The polymer layer may be fabricated from any suitable polymer including, but not limited to, fluoropolymers such as polyethylene terephthalate (PET) or polyethylene naphthalate (PEN), or ethylene-tetrafluoroethylene (ETFE). The interfacial layer may be formed by atomic layer deposition (ALD). In embodiments featuring an ALD interfacial layer, the deposited interfacial substance may be, but is not limited to, Al.sub.2O.sub.3, AlSiO.sub.x, TiO.sub.2, and an Al.sub.2O.sub.3/TiO.sub.2 laminate. The barrier layer associated with the interfacial layer may be deposited by plasma enhanced chemical vapor deposition (PECVD). The barrier layer may be a SiO.sub.xN.sub.y film.

Lower estimated glomerular filtration rate and higher albuminuria are associated with mortality and end-stage renal disease. A collaborative meta-analysis of kidney disease population cohorts

DEFF Research Database (Denmark)

Astor, Brad C; Matsushita, Kunihiro; Gansevoort, Ron T

2011-01-01

We studied here the independent associations of estimated glomerular filtration rate (eGFR) and albuminuria with mortality and end-stage renal disease (ESRD) in individuals with chronic kidney disease (CKD). We performed a collaborative meta-analysis of 13 studies totaling 21,688 patients selected...

Correlation of the glomerular filtration rate by the Gates scintigraphy method and by the creatinine purification in urine of 24 hours

International Nuclear Information System (INIS)

Gomez A, E.

2003-01-01

The kidney is an important organ that makes that exist equilibrium inside the organism. In it' s multiple functions, one that interests us to know is the glomerular filtration rate (GFR). To know this, exist laboratory and scintigraphy studies like the scintigraphy with technique of Gates and the creatinine purification in urine of 24 hours. The files of 44 patients were studied, which were clinically candidates to kidney donors healthy (25 women and 19 men) with ages that varied from the 18 years to the 54 years ( 35.1 years), with a weight of 43 kilograms to 94 kilograms (68.95 Kg) and with a corporal surface of 1.29 to 2.08 m 2 (1.70 m 2 ). These patients underwent study protocols with creatinine purification and with renal scintigraphy. The glomerular filtration rate obtained by creatinine purification varied from 51.9 ml/min. to 156 ml/min. and the GFR obtained by scintigraphy varied from 3.6 ml/min. to 155.2 ml/min. Once obtained the gathering of data the test of Student was applied to compare the averages of both distributions and the analysis of lineal regression to determine the coefficients of correlation of the complete group. (Author)

Radioisotopic measurement of glomerular filtration rate in severe chronic renal failure

International Nuclear Information System (INIS)

LaFrance, N.D.; Drew, H.H.; Walser, M.

1988-01-01

In order to determine the best method for routine measurement of glomerular filtration rate (GFR) in severe renal failure, we compared simultaneously the urinary clearances of [/sup 99m/Tc] diethylenetriaminepentaacetic acid (DTPA) (UD), [ 125 I]iothalamate (UI), 24-hr creatinine clearance (UC) and plasma clearance of [/sup 99m/Tc]DTPA (PD), based on three plasma samples. In 60 studies in 22 patients with serum creatinine values of 2 to 8 mg/dl, UD and UI were almost identical: UD = 0.358 +/- 0.976 UI +/- 0.87 ml/min, r = 0.990. However, PD overestimated UD by a large and variable extent: PD = 11.3 +/- 0.843 UD +/- 5.5 ml/min, r = 0.694, and was inconsistent in sequential measurements in individual patients. UC also overestimated urinary isotope clearance: UC = 4.2 + 0.95 UI +/- 3.9 ml/min, r = 0.865. Sequential measurements of GFR in five patients with severe but stable renal failure (mean GFR 5.9 ml/min) showed an average standard deviation of only 0.83 ml/min. Thus both UD and UI appear to be reliable and precise measures of GFR in severe renal failure

125I iothalamate an ideal marker for glomerular filtration

International Nuclear Information System (INIS)

Odlind, B.; Haellgren, R.S.; Sohtell, M.; Lindstroem, B.

1985-01-01

The triiodinated angiographic contrast medium, iothalamate (usually labelled 125 I), has been used extensively as a marker for glomerular filtration. The authors have studied the renal handling of 125 I iothalamate (IOT) in vivo and in vitro in several species. In renal cortical slices from chicken, rabbit, rat, and monkey, the tissue-to-medium ratio of IOT was twice that of 51 Cr-EDTA (EDTA) at 37 degrees C; a difference that was abolished at 0 degree C and markedly reduced by added o-iodohippurate or iodipamide. In five chickens the steady-state renal clearance of IOT (CIOT) was twice that of EDTA (CEDTA) or 3 H inulin (C1); a difference that was abolished by administration of 100 mg/kg/hr of novobiocin, an organic anion transport inhibitor. CEDTA was similar to C1 before as well as after transport inhibition. Utilizing the Sperber technique the mean apparent tubular excretion fraction (ATEF) of IOT was 8%, while that of EDTA was 1%. After novobiocin coinfusion (new steady-state) ATEFIOT was significantly reduced and not different from that of EDTA (-1%). In the same animals the total urinary recovery of IOT was 84 and 57% before and after novobiocin, respectively, while corresponding values for EDTA was unchanged by the inhibitor. In seven rats the renal extraction of IOT was reduced from 29 to 17% by coinfusion of probenecid (5 mg/kg/hr). Corresponding extractions were 82 to 34% and 22% (unchanged) for PAH and EDTA, respectively

Crucial Role of Mesangial Cell-derived Connective Tissue Growth Factor in a Mouse Model of Anti-Glomerular Basement Membrane Glomerulonephritis.

Science.gov (United States)

Toda, Naohiro; Mori, Kiyoshi; Kasahara, Masato; Ishii, Akira; Koga, Kenichi; Ohno, Shoko; Mori, Keita P; Kato, Yukiko; Osaki, Keisuke; Kuwabara, Takashige; Kojima, Katsutoshi; Taura, Daisuke; Sone, Masakatsu; Matsusaka, Taiji; Nakao, Kazuwa; Mukoyama, Masashi; Yanagita, Motoko; Yokoi, Hideki

2017-02-13

Connective tissue growth factor (CTGF) coordinates the signaling of growth factors and promotes fibrosis. Neonatal death of systemic CTGF knockout (KO) mice has hampered analysis of CTGF in adult renal diseases. We established 3 types of CTGF conditional KO (cKO) mice to investigate a role and source of CTGF in anti-glomerular basement membrane (GBM) glomerulonephritis. Tamoxifen-inducible systemic CTGF (Rosa-CTGF) cKO mice exhibited reduced proteinuria with ameliorated crescent formation and mesangial expansion in anti-GBM nephritis after induction. Although CTGF is expressed by podocytes at basal levels, podocyte-specific CTGF (pod-CTGF) cKO mice showed no improvement in renal injury. In contrast, PDGFRα promoter-driven CTGF (Pdgfra-CTGF) cKO mice, which predominantly lack CTGF expression by mesangial cells, exhibited reduced proteinuria with ameliorated histological changes. Glomerular macrophage accumulation, expression of Adgre1 and Ccl2, and ratio of M1/M2 macrophages were all reduced both in Rosa-CTGF cKO and Pdgfra-CTGF cKO mice, but not in pod-CTGF cKO mice. TGF-β1-stimulated Ccl2 upregulation in mesangial cells and macrophage adhesion to activated mesangial cells were decreased by reduction of CTGF. These results reveal a novel mechanism of macrophage migration into glomeruli with nephritis mediated by CTGF derived from mesangial cells, implicating the therapeutic potential of CTGF inhibition in glomerulonephritis.

Involvement of renal corpuscle microRNA expression on epithelial-to-mesenchymal transition in maternal low protein diet in adult programmed rats.

Directory of Open Access Journals (Sweden)

Letícia de Barros Sene

Full Text Available Prior study shows that maternal protein-restricted (LP 16-wk-old offspring have pronounced reduction of nephron number and arterial hypertension associated with unchanged glomerular filtration rate, besides enhanced glomerular area, which may be related to glomerular hyperfiltration/overflow and which accounts for the glomerular filtration barrier breakdown and early glomerulosclerosis. In the current study, LP rats showed heavy proteinuria associated with podocyte simplification and foot process effacement. TGF-β1 glomerular expression was significantly enhanced in LP. Isolated LP glomeruli show a reduced level of miR-200a, miR-141, miR-429 and ZEB2 mRNA and upregulated collagen 1α1/2 mRNA expression. By western blot analyzes of whole kidney tissue, we found significant reduction of both podocin and nephrin and enhanced expression of mesenchymal protein markers such as desmin, collagen type I and fibronectin. From our present knowledge, these are the first data showing renal miRNA modulation in the protein restriction model of fetal programming. The fetal-programmed adult offspring showed pronounced structural glomerular disorders with an accentuated and advanced stage of fibrosis, which led us to state that the glomerular miR-200 family would be downregulated by TGF-β1 action inducing ZEB 2 expression that may subsequently cause glomeruli epithelial-to-mesenchymal transition.

Glomerular filtration in kidney recipients measured by plasma clearance of 169Yb-DTPA

International Nuclear Information System (INIS)

Stribrna, J.; Oppelt, A.; Jirickova, E.; Janata, V.; Kocandrle, V.; Sup, I.; Woller, P.; Franke, W.G.

1986-01-01

Values of 169 Yb-DTPA clearance (C DTPA ) calculated after a single injection were compared in 26 recipients of kidneys with renal clearance of inulin (C in ), polyfructosan S (C pf ) and creatinine (C cr ). In 21 patients the examinations were made simultaneously, in 5 patients C DTPA was measured within a short interval after the examination of renal clearance. The mean C DTPA values did not significantly differ from C cr but were significantly higher (p in and C pf (by 33% on average). Investigation of changes in C DTPA as compared with C in and C pf showed no significant difference in glomerular filtration (GF). This was measured using inulin and polyfructosan. The results showed that the differing molecular weight of inulin and polyfructosan S had no detectable effect on the GF of kidney recipients. The plasma clearance of 169 Yb-DTPA similarly to C cr overestimates the GF measured by inulin and polyfructosan clearance. (author)

Renal uptake of dimercaptosuccinic acid and glomerular filtration rate in chronic nephropathy at angiotensin converting enzyme inhibition

International Nuclear Information System (INIS)

Kamper, A.L.; Thomsen, H.S.; Nielsen, S.L.; Strandgaard, S.; Herlev Hospital

1990-01-01

Glomerular filtration rate (GFR) and renal uptake of dimercaptosuccinic acid (DMSA) were measured in 31 patients with progressive chronic nephropathy before and immediately after the start of treatment with angiotensin converting enzyme (ACE) inhibitor in order to control adverse effects on kidney function. Scintigrams of the kidneys showed an unaltered distribution of DMSA during treatment. GFR estimated by 51 Cr-EDTA plasma clearance fell by 14% (P 99m Tc-DMSA increased by 10% (P<0.01). It is concluded that DMSA in chronic renal failure is mainly taken up by the tubular cells from the peritubular capillaries since the uptake was unaffected by the acute decrease in GFR. (orig.)

Verification on the use of the Inoue method for precisely determining glomerular filtration rate in Philippine pediatrics

Science.gov (United States)

Magcase, M. J. D. J.; Duyan, A. Q.; Carpio, J.; Carbonell, C. A.; Trono, J. D.

2015-06-01

The objective of this study is to validate the Inoue method so that it would be the preferential choice in determining glomerular filtration rate (GFR) in Philippine pediatrics. The study consisted of 36 patients ranging from ages 2 months to 19 years old. The subjects used were those who were previously subjected to in-vitro method. The scintigrams of the invitro method was obtained and processed for split percentage uptake and for parameters needed to obtain Inoue GFR. The result of this paper correlates the Inoue GFR and In-vitro method (r = 0.926). Thus, Inoue method is a viable, simple, and practical technique in determining GFR in pediatric patients.

RENAL HEMODYNAMICS AND GLOMERULAR FILTRATION RATE IN MEN AND WOMEN WITH ARTERIAL HYPERTENSION AT THE AGE OF 40-60 YEARS

OpenAIRE

I. G. Fomina; A. E. Bragina; N. E. Gaydamakina; J. N. Salimzhanova

2015-01-01

Aim. To study parameters of a renal hemodynamic and the general glomerular filtration rate (GGFR) and their correlations with cardiovascular risk factors (RF) in patient with arterial hypertension (AH).Material and methods. 102 patients with AH (35 men and 67 women of 40-60 y.o.) were involved in the study. 20 persons (10 men and 10 women) with normal blood pressure (BP) were included in control group. Dynamic renal angioscintigraphy was used for an estimation of a renal hemodynamic and GGFR....

Size- and charge selectivity of glomerular filtration in Type 1 (insulin-dependent) diabetic patients with and without albuminuria

DEFF Research Database (Denmark)

Deckert, T; Kofoed-Enevoldsen, A; Vidal, P

1993-01-01

Albuminuria is the first clinical event in the development of diabetic nephropathy. We assessed glomerular charge- and size selectivity in 51 patients with Type 1 (insulin-dependent) diabetes mellitus of juvenile onset and 11 healthy individuals. Patients were allocated to five groups. The urinary...... techniques and tubular protein reabsorption by excretion of beta 2-microglobulin. Charge selectivity was estimated from the IgG/IgG4 selectivity index. Size selectivity was measured by dextran clearance. Dextran was measured by refractive index detection after fractionation (2 A fractions in the range 26...... macromolecular pathways in the development of diabetic nephropathy....

Normal values of glomerular filtration rate in geriatrics in Bandung and its correlation with serum cystatin-C levels

International Nuclear Information System (INIS)

Resnaldi, A.; Yuliani, A.; Hidayat, B.; Kartamihardja, A.H.S.

2007-01-01

Full text: Determination of the normal values of glomerular filtration rate (GFR) is an essential part of the evaluation of patient with kidney disease. GFR almost linearly decreases with age at a mean annual rate of 0.8 ml/min/1.73 m2 over the age of 30 years old. According to NHANES III mean GFR for population with age > 60 years was 80 mL/min/1.73 m2. It is recommended for each centre to determine their own normal values of GFR for different age groups particularly in geriatric population. Recently, serum cystatin-C has been proposed as a new endogenous marker of glomerular filtration rate. Aim of the study was to determination of normal values of glomerular filtration rate (GFR) in geriatrics in Bandung and its correlation with serum Cystatin-C levels. Subjects were 24 males and 36 females (mean age 66.71 ± 6.7 years; range 60-87 yrs), without any renal and/or systemic disease. Creatinine clearance was estimated by using Cockroft-Gault formula and serum cystatin-C level were determined by using particle enhanced immunonephelometric method, while GFR values were determined by external body counting methods using Tc-99m DTPA ( Gates' methods ). Pearson correlation was used to determine correlation between variables and a P value < 0.05 is considered significant. Results and Discussion. Mean total GFR was 67.57 ml/min/1.73 m2 (SD ± 16.02), range from 45 to 100 ml/min/1.73 m2. Mean total GFR for male was 69.46 ml/min/1.73 m2, and female was 66.31 ml/min/1.73 m2, the difference was statistically significant (p < 0.05). The results were lower than NHANES III values. There was a better correlation between total GFR and cystatin-C level (r = -0.522 and p < 0.001) compared to total GFR and creatinine clearance (r 0.306 and p < 0.005). Mean creatinine clearance was 57.93 ml/min and serum cystatin-C was 0.97 mg/dl, the correlation was statistically significant (r -0.414 and p < 0.005). Conclusions: The normal values of GFR in geriatric population in Bandung were 69

Thames barrier (flood protection barriers on the Thames)

International Nuclear Information System (INIS)

Ilkovic, J.

2005-01-01

In this paper the flood protection barriers on the Thames are presented. The flood protection system on the Thames in 1984 was commissioned. During two decades this barrier was used 54 times against to the high water and 34 times against storm-sewage. There is installed buttress type hydroelectric power plant

Polymerization of Phenylacetylene-Based Monodendrons with Alkoxy Peripheral Groups and Oxygen/Nitrogen Permeation Behavior of Their Membranes

Directory of Open Access Journals (Sweden)

Takashi Kaneko

2012-01-01

Full Text Available Monodendron monomers with alkoxy peripheral groups were synthesized, and the focal point of monodendrons, terminal acetylene, was polymerized with rhodium catalyst to yield corresponding polydendrons with a high molecular weight. The polydendrons were soluble in common organic solvents and readily formed membranes. Oxygen permselectivity was improved in the polydendrons with a space-persistent dendritic crowd. It was found that the well-defined dendritic and rod-like structure of the polydendrons was useful for permselective membrane.

Podocytes from the diagnostic and therapeutic point of view.

Science.gov (United States)

Müller-Deile, Janina; Schiffer, Mario

2017-08-01

The central role of podocytes in glomerular diseases makes this cell type an interesting diagnostic tool as well as a therapeutic target. In this review, we discuss the current literature on the use of podocytes and podocyte-specific markers as non-invasive diagnostic tools in different glomerulopathies. Furthermore, we highlight the direct effects of drugs currently used to treat primary glomerular diseases and describe their direct cellular effects on podocytes. A new therapeutic potential is seen in drugs targeting the podocytic actin cytoskeleton which is essential for podocyte foot process structure and function. Incubation of cultured human podocyte cell lines with sera from patients with active glomerular diseases is currently also used to identify novel circulating factors with pathophysiological relevance for the glomerular filtration barrier. In addition, treatment of detached urinary podocytes from patients with substances that restore their cytoskeleton might serve as a novel personalized tool to estimate their potential for podocyte recovery ex vivo.

Estimated Glomerular Filtration Rate; Laboratory Implementation and Current Global Status.

Science.gov (United States)

Miller, W Greg; Jones, Graham R D

2018-01-01

In 2002, the Kidney Disease Outcomes Quality Initiative guidelines for identifying and treating CKD recommended that clinical laboratories report estimated glomerular filtration rate (eGFR) with every creatinine result to assist clinical practitioners to identify people with early-stage CKD. At that time, the original Modification of Diet in Renal Disease (MDRD) Study equation based on serum creatinine measurements was recommended for calculating eGFR. Because the MDRD Study equation was developed using a nonstandardized creatinine method, a Laboratory Working Group of the National Kidney Disease Education program was formed and implemented standardized calibration traceability for all creatinine methods from global manufacturers by approximately 2010. A modified MDRD Study equation for use with standardized creatinine was developed. The Chronic Kidney Disease Epidemiology Collaboration developed a new equation in 2009 that was more accurate than the MDRD Study equation at values above 60 mL/min/1.73 m 2 . As of 2017, reporting eGFR with creatinine is almost universal in many countries. A reference system for cystatin C became available in 2010, and manufacturers are in the process to standardize cystatin C assays. Equations for eGFR based on standardized cystatin C alone and with creatinine are now available from the Chronic Kidney Disease Epidemiology Collaboration and other groups. Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Automating and estimating glomerular filtration rate for dosing medications and staging chronic kidney disease

Directory of Open Access Journals (Sweden)

Trinkley KE

2014-05-01

Full Text Available Katy E Trinkley,1 S Michelle Nikels,2 Robert L Page II,1 Melanie S Joy11Skaggs School of Pharmacy and Pharmaceutical Sciences, 2School of Medicine, University of Colorado, Aurora, CO, USA Objective: The purpose of this paper is to serve as a review for primary care providers on the bedside methods for estimating glomerular filtration rate (GFR for dosing and chronic kidney disease (CKD staging and to discuss how automated health information technologies (HIT can enhance clinical documentation of staging and reduce medication errors in patients with CKD.Methods: A nonsystematic search of PubMed (through March 2013 was conducted to determine the optimal approach to estimate GFR for dosing and CKD staging and to identify examples of how automated HITs can improve health outcomes in patients with CKD. Papers known to the authors were included, as were scientific statements. Articles were chosen based on the judgment of the authors.Results: Drug-dosing decisions should be based on the method used in the published studies and package labeling that have been determined to be safe, which is most often the Cockcroft–Gault formula unadjusted for body weight. Although Modification of Diet in Renal Disease is more commonly used in practice for staging, the CKD–Epidemiology Collaboration (CKD–EPI equation is the most accurate formula for estimating the CKD staging, especially at higher GFR values. Automated HITs offer a solution to the complexity of determining which equation to use for a given clinical scenario. HITs can educate providers on which formula to use and how to apply the formula in a given clinical situation, ultimately improving appropriate medication and medical management in CKD patients.Conclusion: Appropriate estimation of GFR is key to optimal health outcomes. HITs assist clinicians in both choosing the most appropriate GFR estimation formula and in applying the results of the GFR estimation in practice. Key limitations of the

Skin barrier function

DEFF Research Database (Denmark)

2016-01-01

Renowned experts present the latest knowledge Although a very fragile structure, the skin barrier is probably one of the most important organs of the body. Inward/out it is responsible for body integrity and outward/in for keeping microbes, chemicals, and allergens from penetrating the skin. Since...... the role of barrier integrity in atopic dermatitis and the relationship to filaggrin mutations was discovered a decade ago, research focus has been on the skin barrier, and numerous new publications have become available. This book is an interdisciplinary update offering a wide range of information...... on the subject. It covers new basic research on skin markers, including results on filaggrin and on methods for the assessment of the barrier function. Biological variation and aspects of skin barrier function restoration are discussed as well. Further sections are dedicated to clinical implications of skin...

Geophysical characterization of subsurface barriers

International Nuclear Information System (INIS)

Borns, D.J.

1995-08-01

An option for controlling contaminant migration from plumes and buried waste sites is to construct a subsurface barrier of a low-permeability material. The successful application of subsurface barriers requires processes to verify the emplacement and effectiveness of barrier and to monitor the performance of a barrier after emplacement. Non destructive and remote sensing techniques, such as geophysical methods, are possible technologies to address these needs. The changes in mechanical, hydrologic and chemical properties associated with the emplacement of an engineered barrier will affect geophysical properties such a seismic velocity, electrical conductivity, and dielectric constant. Also, the barrier, once emplaced and interacting with the in situ geologic system, may affect the paths along which electrical current flows in the subsurface. These changes in properties and processes facilitate the detection and monitoring of the barrier. The approaches to characterizing and monitoring engineered barriers can be divided between (1) methods that directly image the barrier using the contrasts in physical properties between the barrier and the host soil or rock and (2) methods that reflect flow processes around or through the barrier. For example, seismic methods that delineate the changes in density and stiffness associated with the barrier represents a direct imaging method. Electrical self potential methods and flow probes based on heat flow methods represent techniques that can delineate the flow path or flow processes around and through a barrier

Sodium bicarbonate loading limits tubular cast formation independent of glomerular injury and proteinuria in dahl salt-sensitive rats.

Science.gov (United States)

Ray, S C; Patel, B; Irsik, D L; Sun, J; Ocasio, H; Crislip, G R; Jin, C H; Chen, J K; Baban, B; Polichnowski, A J; O'Connor, P M

2018-04-12

Sodium bicarbonate (NaHCO 3 ) slows the decline in kidney function in patients with chronic kidney disease (CKD), yet the mechanisms mediating this effect remain unclear. The Dahl salt-sensitive (SS) rat develops hypertension and progressive renal injury when fed a high salt diet; however, the effect of alkali loading on kidney injury has never been investigated in this model. We hypothesized that 'NaHCO 3 protects from the development of renal injury in Dahl salt-sensitive rats via luminal alkalization which limits the formation of tubular casts, which are a prominent pathological feature in this model. To examine this hypothesis, we determined blood pressure and renal injury responses in Dahl SS rats drinking vehicle (0.1M NaCl) or NaHCO 3 (0.1M) solutions as well as in Dahl SS rats lacking the voltage gated proton channel (Hv1). We found that oral NaHCO 3 reduced tubular NH 4 + production, tubular cast formation and interstitial fibrosis in rats fed a high salt diet for 2 weeks. This effect was independent of changes in blood pressure, glomerular injury or proteinuria and did not associate with changes in renal inflammatory status. We found that null mutation of Hv1 also limited cast formation in Dahl SS rats independent of proteinuria or glomerular injury. As Hv1 is localized to the luminal membrane of TAL, our data, suggest that alkalization of the luminal fluid within this segment limits cast formation in this model. Reduced cast formation, secondary to luminal alkalization within TAL segments may mediate some of the protective effects of alkali loading observed in CKD patients. ©2018 The Author(s).

Novel subdomains of the mouse olfactory bulb defined by molecular heterogeneity in the nascent external plexiform and glomerular layers

Directory of Open Access Journals (Sweden)

Yona Golan

2007-05-01

Full Text Available Abstract Background In the mouse olfactory system, the role of the olfactory bulb in guiding olfactory sensory neuron (OSN axons to their targets is poorly understood. What cell types within the bulb are necessary for targeting is unknown. What genes are important for this process is also unknown. Although projection neurons are not required, other cell-types within the external plexiform and glomerular layers also form synapses with OSNs. We hypothesized that these cells are important for targeting, and express spatially differentially expressed guidance cues that act to guide OSN axons within the bulb. Results We used laser microdissection and microarray analysis to find genes that are differentially expressed along the dorsal-ventral, medial-lateral, and anterior-posterior axes of the bulb. The expression patterns of these genes divide the bulb into previously unrecognized subdomains. Interestingly, some genes are expressed in both the medial and lateral bulb, showing for the first time the existence of symmetric expression along this axis. We use a regeneration paradigm to show that several of these genes are altered in expression in response to deafferentation, consistent with the interpretation that they are expressed in cells that interact with OSNs. Conclusion We demonstrate that the nascent external plexiform and glomerular layers of the bulb can be divided into multiple domains based on the expression of these genes, several of which are known to function in axon guidance, synaptogenesis, and angiogenesis. These genes represent candidate guidance cues that may act to guide OSN axons within the bulb during targeting.

Information barriers

International Nuclear Information System (INIS)

Fuller, J.L.; Wolford, J.

2001-01-01

Full text: An information barrier (IB) consists of procedures and technology that prevent the release of sensitive information during a joint inspection of a sensitive nuclear item, and provides confidence that the measurement system into which it has been integrated functions exactly as designed and constructed. Work in the U.S. on radiation detection system information barriers dates back at least to 1990, even though the terminology is more recent. In January 1999 the Joint DoD-DOE Information Barrier Working Group was formed in the United States to help coordinate technical efforts related to information barrier R and D. This paper presents an overview of the efforts of this group, by its Chairs, as well as recommendations for further information barrier R and D. Progress on the demonstration of monitoring systems containing IBs is also provided. From the U.S. perspective, the basic, top-level functional requirements for the information barrier portion of an integrated radiation signature-information barrier inspection system are twofold: The host must be assured that his classified information is protected from disclosure to the inspecting party; and The inspecting party must be confident that the integrated inspection system measures, processes, and presents the radiation-signature-based measurement conclusion in an accurate and reproducible manner. It is the position of the United States that in the absence of any agreement to share classified nuclear weapons design information in the conduct of an inspection regime, the requirement to protect host country classified warhead design information is paramount and admits no tradeoff versus the confidence provided to the inspecting party in the accuracy and reproducibility of the measurements. The U.S. has reached an internal consensus on several critical design elements that define a general standard for radiation signature information barrier design. These criteria have stood the test of time under intense

Effect of template on chiral separation of phenylalanine using molecularly imprinted membrane in aqueous medium

International Nuclear Information System (INIS)

Haq, N.U.

2014-01-01

Wet phase inversion method was used to prepare L-Phenylalanine (L-Phe) and D-Phenylalanine (D-Phe) imprinted poly ((acrylonitrile)-co-(acrylic acid)) membranes for chiral separation. Ultrafiltration experiments were conducted to evaluate the chiral separation ability of the prepared membrane towards racemate aqueous solution of Phenylalanine. The continuous permselectivity was observed by novel membrane. The chiral resolution ability of L-Phe imprinted membrane was much better than that of D-Phe. It was observed that both membranes simultaneously, selectively reject, selectively adsorbed and selectively permeate solute. The achieved adsorption selectivities of L-Phe imprinted membrane (AlphaAds)L and D-Phe imprinted membrane (AlphaAds)D were 2.6 and 2.40 respectively. Permselectivity of L-Phe imprinted membrane (AlphaPerm)L was 2.56 while D-Phe imprinted membrane permselectivity (AlphaPerm)D was 2.03. The rejection selectivities of L-Phe and D-Phe imprinted membranes were (AlphaRej)L=0.32 and (AlphaRej)D =0.28 respectively. (author)

Enhancement of glomerular filtration rate and renal plasma flow by oral glucose load in well controlled insulin-dependent diabetics

DEFF Research Database (Denmark)

Sandahl Christiansen, J; Christensen, C K; Hermansen, K

1986-01-01

Glomerular filtration rate (GFR) and renal plasma flow (RPF) were measured in 27 patients with uncomplicated insulin-dependent diabetes (IDDM) before and after an oral glucose load of 1.1 g glucose/kg body wt. In the 18 patients showing near-normoglycaemia (blood glucose less than or equal to 8....... No changes in blood pressure or urinary albumin excretion rates took place in either group. The reduction in plasma protein and in plasma growth hormone concentration were similar in the two groups. No change was seen in plasma arginine vasopressin concentration. There was no difference in the qualitative...

Over-estimation of glomerular filtration rate by single injection [51Cr]EDTA plasma clearance determination in patients with ascites

DEFF Research Database (Denmark)

Henriksen, Jens Henrik Sahl; Brøchner-Mortensen, J; Malchow-Møller, A

1980-01-01

The total plasma (Clt) and the renal plasma (Clr) clearances of [51Cr]EDTA were determined simultaneously in nine patients with ascites due to liver cirrhosis. Clt (mean 78 ml/min, range 34-115 ml/min) was significantly higher than Clr (mean 52 ml/min, range 13-96 ml/min, P ... fluid-plasma activity ratio of [51Cr]EDTA increased throughout the investigation period (5h). The results suggest that [51Cr]EDTA equilibrates slowly with the peritoneal space which indicates that Clt will over-estimate the glomerular filtration rate by approximately 20 ml/min in patients with ascites...

Tritium/hydrogen barrier development

International Nuclear Information System (INIS)

Hollenberg, G.W.; Simonen, E.P.; Kalinen, G.; Terlain, A.

1994-06-01

A review of hydrogen permeation barriers that can be applied to structural metals used in fusion power plants is presented. Both implanted and chemically available hydrogen isotopes must be controlled in fusion plants. The need for permeation barriers appears strongest in Li17-Pb blanket designs, although barriers also appear necessary for other blanket and coolant systems. Barriers that provide greater than a 1000 fold reduction in the permeation of structural metals are desired. In laboratory experiments, aluminide and titanium ceramic coatings provide permeation reduction factors, PRFS, from 1000 to over 100,000 with a wide range of scatter. The rate-controlling mechanism for hydrogen permeation through these barriers may be related to the number and type of defects in the barriers. Although these barriers appear robust and resistant to liquid metal corrosion, irradiation tests which simulate blanket environments result in very low PRFs in comparison to laboratory experiments, i.e., <150. It is anticipated from fundamental research activities that the REID enhancement of hydrogen diffusion in oxides may contribute to the lower permeation reduction factors during in-reactor experiments

Barriers for realisation of energy savings in buildings; Barrierer for realisering af energibesparelser i bygninger

Energy Technology Data Exchange (ETDEWEB)

Jensen, O.M.

2004-07-01

Many years' efforts within the energy labelling area have shown large saving potentials in heating and use of electricity in buildings. At the same time it has been proved that these saving potentials, even when economically advantageous, only are cashed to a limited extent. The reason to this is ascribed to barriers that meet the individual building owner who wants to start saving energy. Most barriers are known and a lot of these have been sought overcome for some time. The questions are how many barriers still exist, have new barriers arisen and the character of these barriers. On this background the objective of this survey has been to concretize and study the barriers, which are blocking reasonable energy savings. Focus has especially been on barriers for realisation of heating savings, but through a general evaluation of energy savings of barriers other forms of energy saving methods have been taken into consideration. Special interest has been directed towards houses, typically one family houses, which are affected by the Energy Labelling Scheme. The concept barriers include all kinds of barriers, also barriers that not are acknowledged as barriers by the individual house owner, or that on closer inspection turn out to be something else than actual barriers. This note suggests an alternative inertia model, in order to create an idea of the inertness characteristic of the many house owners who understand the message but fail to act on it. (BA)

Systems study on engineered barriers: barrier performance analysis

International Nuclear Information System (INIS)

Stula, R.T.; Albert, T.E.; Kirstein, B.E.; Lester, D.H.

1980-09-01

A performance assessment model for multiple barrier packages containing unreprocessed spent fuel has been modified and applied to several package designs. The objective of the study was to develop information to be used in programmatic decision making concerning engineered barrier package design and development. The assessment model, BARIER, was developed in previous tasks of the System Study on Engineered Barriers (SSEB). The new version discussed in this report contains a refined and expanded corrosion rate data base which includes pitting, crack growth, and graphitization as well as bulk corrosion. Corrosion rates for oxic and anoxic conditions at each of the two temperature ranges are supplied. Other improvements include a rigorous treatment of radionuclide release after package failure which includes resistance of damaged barriers and backfill, refined temperature calculations that account for convection and radiation, a subroutine to calculate nuclear gamma radiation field at each barrier surface, refined stress calculations with reduced conservatism and various coding improvements to improve running time and core usage. This report also contains discussion of alternative scenarios to the assumed flooded repository as well as the impact of water exclusion backfills. The model was used to assess post repository closure performance for several designs which were all variation of basic designs from the Spent Unreprocessed Fuel (SURF) program. Many designs were found to delay the onset of leaching by at least a few hundreds of years in all geologic media. Long delay times for radionuclide release were found for packages with a few inches of sorption backfill. Release of uranium, plutonium, and americium was assessed

Systems study on engineered barriers: barrier performance analysis

Energy Technology Data Exchange (ETDEWEB)

Stula, R.T.; Albert, T.E.; Kirstein, B.E.; Lester, D.H.

1980-09-01

A performance assessment model for multiple barrier packages containing unreprocessed spent fuel has been modified and applied to several package designs. The objective of the study was to develop information to be used in programmatic decision making concerning engineered barrier package design and development. The assessment model, BARIER, was developed in previous tasks of the System Study on Engineered Barriers (SSEB). The new version discussed in this report contains a refined and expanded corrosion rate data base which includes pitting, crack growth, and graphitization as well as bulk corrosion. Corrosion rates for oxic and anoxic conditions at each of the two temperature ranges are supplied. Other improvements include a rigorous treatment of radionuclide release after package failure which includes resistance of damaged barriers and backfill, refined temperature calculations that account for convection and radiation, a subroutine to calculate nuclear gamma radiation field at each barrier surface, refined stress calculations with reduced conservatism and various coding improvements to improve running time and core usage. This report also contains discussion of alternative scenarios to the assumed flooded repository as well as the impact of water exclusion backfills. The model was used to assess post repository closure performance for several designs which were all variation of basic designs from the Spent Unreprocessed Fuel (SURF) program. Many designs were found to delay the onset of leaching by at least a few hundreds of years in all geologic media. Long delay times for radionuclide release were found for packages with a few inches of sorption backfill. Release of uranium, plutonium, and americium was assessed.

76 FR 47217 - Government-Owned Inventions; Availability for Licensing

Science.gov (United States)

2011-08-04

... filtration barrier. Podocyte damage and loss contribute to the initiation of glomerular diseases. Cyclin... markers. Furthermore, confluent CDK4-podocyte cultures show higher levels of gene expression for multiple podocyte differentiation genes compared with subconfluent or lower density culture. Development Stage...

Measurement of single-kidney glomerular filtration function from magnetic resonance perfusion renography

Energy Technology Data Exchange (ETDEWEB)

Zeng, Meiying; Cheng, Yingsheng [Department of Radiology, Shanghai Jiao Tong University Affiliated Sixth People' s Hospital, Shanghai 200233 (China); Zhao, Binghui, E-mail: binghuizhao@163.com [Department of Radiology, Shanghai Tenth People' s Hospital, Tongji University, Shanghai 200072 (China)

2015-08-15

Highlights: • MRPR monitors the transit of contrast material through nephron. • MRPR could reveal renal physiological characteristics in quality and quantity. • This review outlines the basics and future challenges of DCE MRPR. - Abstract: Glomerular filtration rate (GFR) describes the flow rate of filtered fluid through the kidney, and is considered to be the reference standard in the evaluation of renal function. There are many ways to test the GFR clinically, such as serum creatinine concentration, blood urea nitrogen and SPECT renography, however, they’re all not a good standard to evaluate the early damage of renal function. In recent years, the improvement of MRI hardware and software makes it possible to reveal physiological characteristics such as renal blood flow or GFR by dynamic contrast enhancement magnetic resonance perfusion renography (DEC MRPR). MRPR is a method used to monitor the transit of contrast material, typically a gadolinium chelate, through the renal cortex, the medulla, and the collecting system. This review outlines the basics of DCE MRPR included acquisition of dynamic MR perfusion imaging, calculation of the contrast concentration from signal intensity and compartment models, and some challenges of MRPR method faced in prospective clinical application.

Barrier penetration database

International Nuclear Information System (INIS)

Fainberg, A.; Bieber, A.M. Jr.

1978-11-01

This document is intended to supply the NRC and nuclear power plant licensees with basic data on the times required to penetrate forcibly the types of barriers commonly found in nuclear plants. These times are necessary for design and evaluation of the physical protection system required under 10CFR73.55. Each barrier listed is described in detail. Minor variations in basic barrier construction that result in the same penetration time, are also described

Alterações ultra-estruturais do glomérulo na pré-eclâmpsia Ultrastructural glomerular alterations in preeclampsia

Directory of Open Access Journals (Sweden)

Suzana Maria Pires do Rio

2004-04-01

Full Text Available OBJETIVOS: identificar as alterações ultra-estruturais glomerulares em pacientes com pré-eclâmpsia grave, assim como avaliar a evolução destas lesões e sua relação com o momento de realização da biópsia renal. MÉTODOS: dentre as 72 gestantes com síndrome hipertensiva que se submeteram à biópsia renal no puerpério, em 39 o material obtido mostrou-se adequado para exame à microscopia eletrônica de transmissão, assim distribuídas: 25 eram portadoras de pré-eclâmpsia pura e 14 tiveram diagnóstico de pré-eclâmpsia superposta à hipertensão arterial crônica. As apresentações morfológicas estiveram representadas por rim normal, edema das células endoteliais, expansão do mesângio, interposição mesangial, depósitos subendoteliais e fusão dos pés dos podócitos. RESULTADOS: as alterações mais freqüentes nos dois grupos foram os depósitos subendoteliais e a fusão dos pés dos podócitos. O edema da célula endotelial ocorreu em 84% das pacientes com pré-eclâmpsia pura e 92,9% das pacientes com pré-eclâmpsia superposta. Não foi observada associação entre a gravidade da doença e a intensidade do edema da célula endotelial. Verificou-se tendência de interposição mesangial em pacientes biopsiadas após o sétimo dia pós-parto. A fusão dos podócitos apresentou associação significativa com a proteinúria de 24 horas. CONCLUSÕES: as alterações glomerulares citadas representam espectro de lesões complexas e dinâmicas que, em conjunto, constituem as características ultra-estruturais da pré-eclâmpsia, que não deve, pois, ser identificada somente pela presença do edema da célula endotelial.PURPOSE: to investigate the glomerular alterations in patients with severe preeclampsia, as well as to evaluate the evolution of these lesions, relating them to the moment of the renal biopsy. METHODS: seventy-two pregnant women with hypertensive syndrome underwent renal biopsy in the puerperium. Appropriate

[Estimating glomerular filtration rate in 2012: which adding value for the CKD-EPI equation?].

Science.gov (United States)

Delanaye, Pierre; Mariat, Christophe; Moranne, Olivier; Cavalier, Etienne; Flamant, Martin

2012-07-01

Measuring or estimating glomerular filtration rate (GFR) is still considered as the best way to apprehend global renal function. In 2009, the new Chronic Kidney Disease Epidemiology (CKD-EPI) equation has been proposed as a better estimator of GFR than the Modification of Diet in Renal Disease (MDRD) study equation. This new equation is supposed to underestimate GFR to a lesser degree in higher GFR levels. In this review, we will present and deeply discuss the performances of this equation. Based on articles published between 2009 and 2012, this review will underline advantages, notably the better knowledge of chronic kidney disease prevalence, but also limitations of this new equation, especially in some specific populations. We eventually insist on the fact that all these equations are estimations and nephrologists should remain cautious in their interpretation. Copyright © 2012 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

Effect of diabetes on in vivo metabolism of [35S]-labeled glomerular basement membrane

International Nuclear Information System (INIS)

Cohen, M.P.; Surma, M.L.

1984-01-01

Glomerular basement membrane (GBM) was labeled in vivo by the injection of tracer amounts of [ 35 S]-sulfate into normal and streptozotocin-diabetic rats. The biosynthesis and turnover of sulfated glycosaminoglycans in the GBM was determined from the specific activity of [ 35 S] after pronase digestion of basement membranes purified from glomeruli isolated 1-7 days after injection. Peak radiolabeling of both normal and diabetic GBM occurred 24 h after injection and, when corrected for differences in serum sulfate specific activities, was less in diabetic than in normal samples. The specific activity of GBM sulfate, expressed as cpm/microgram uronic acid, progressively diminished over the ensuing period of study in both normal and diabetic samples. The rate of decrease in specific activity of [ 35 S]-labeled GBM was not significantly different in diabetic preparations compared with that in normal controls. The findings are compatible with diminished sulfation and/or production but normal turnover of glycosaminoglycans in the renal GBM in experimental diabetes

Prediction of hospital mortality by changes in the estimated glomerular filtration rate (eGFR).

LENUS (Irish Health Repository)

Berzan, E

2015-03-01

Deterioration of physiological or laboratory variables may provide important prognostic information. We have studied whether a change in estimated glomerular filtration rate (eGFR) value calculated using the (Modification of Diet in Renal Disease (MDRD) formula) over the hospital admission, would have predictive value. An analysis was performed on all emergency medical hospital episodes (N = 61964) admitted between 1 January 2002 and 31 December 2011. A stepwise logistic regression model examined the relationship between mortality and change in renal function from admission to discharge. The fully adjusted Odds Ratios (OR) for 5 classes of GFR deterioration showed a stepwise increased risk of 30-day death with OR\\'s of 1.42 (95% CI: 1.20, 1.68), 1.59 (1.27, 1.99), 2.71 (2.24, 3.27), 5.56 (4.54, 6.81) and 11.9 (9.0, 15.6) respectively. The change in eGFR during a clinical episode, following an emergency medical admission, powerfully predicts the outcome.

Design of engineered sorbent barriers

International Nuclear Information System (INIS)

Jones, E.O.; Freeman, H.D.

1988-01-01

A sorbent barrier uses sorbent material such as activated carbon or natural zeolites to prevent the migration of radionuclides from a low-level waste site to the aquifer. The sorbent barrier retards the movement of radioactive contaminants, thereby providing time for the radionuclides to decay. Sorbent barriers can be a simple, effective, and inexpensive method for reducing the migration of radionuclides to the environment. Designing a sorbent barrier consists of using soil and sorbent material properties and site conditions as input to a model which will determine the necessary sorbent barrier thickness to meet contaminant limits. The paper covers the following areas: techniques for measuring sorption properties of barrier materials and underlying soils, use of a radionuclide transport model to determine the required barrier thickness and performance under a variety of site conditions, and cost estimates for applying the barrier

Progressive IgA Nephropathy Is Associated With Low Circulating Mannan-Binding Lectin–Associated Serine Protease-3 (MASP-3 and Increased Glomerular Factor H–Related Protein-5 (FHR5 Deposition

Directory of Open Access Journals (Sweden)

Nicholas R. Medjeral-Thomas

2018-03-01

Conclusion: Our data indicate that circulating MASP-3 levels could be used as a biomarker of disease severity in IgAN and that glomerular staining for FHR5 could both indicate alternative complement pathway activation and be a tissue marker of disease severity.

Barrier Data Base user's guide

International Nuclear Information System (INIS)

Worrell, R.B.; Gould, D.J.; Wall, D.W.

1977-06-01

A special purpose data base for physical security barriers has been developed. In addition to barriers, the entities accommodated by the Barrier Data Base (BDB) include threats and references. A threat is established as a configuration of people and equipment which has been employed to penetrate (or attempt to penetrate) a barrier. References are used to cite publications pertinent to the barriers and threats in the data base. Utilization and maintenance of the Barrier Data Base is achieved with LIST, QUERY, ENTER, DELETE, and CHANGE commands which are used to manipulate the data base entities

Design of engineered sorbent barriers

International Nuclear Information System (INIS)

Jones, E.O.; Freeman, H.D.

1988-08-01

A sorbent barrier uses sorbent material such as activated carbon or natural zeolites to prevent the migration of radionuclides from a low-level waste site to the aquifer. The sorbent barrier retards the movement of radioactive contaminants, thereby providing time for the radionuclides to decay. Sorbent barriers can be a simple, effective, and inexpensive method for reducing the migration of radionuclides to the environment. Designing a sorbent barrier consists of using soil and sorbent material properties and site conditions as input to a model which will determine the necessary sorbent barrier thickness to meet contaminant limits. The paper will cover the following areas: techniques for measuring sorption properties of barrier materials and underlying soils, use of a radionuclide transport model to determine the required barrier thickness and performance under a variety of site conditions, and cost estimates for applying the barrier. 8 refs., 6 figs., 1 tab

Hanford protective barriers program: Status of asphalt barrier studies - FY 1989

International Nuclear Information System (INIS)

Freeman, H.D.; Gee, G.W.

1989-11-01

The Hanford Protective Barrier Program is evaluating alternate barriers to provide a means of meeting stringent water infiltration requirements. One type of alternate barrier being considered is an asphalt-based layer, 1.3 to 15 cm thick. Evaluations of these barriers were initiated in FY 1988, and, based on laboratory studies, two asphalt formulations were selected for further testing in small-tube lysimeters: a hot rubberized asphalt and an admixture of cationic asphalt emulsion and concrete sand containing 24 wt% residual asphalt. Eight lysimeters containing asphalt seals were installed as part of the Small Tube Lysimeter Test Facility on the Hanford Site. Two control lysimeters containing Hanford sand with a surface gravel treatment were also installed for comparison. 5 refs., 13 figs., 1 tab

Complement factor H protects mice from ischemic acute kidney injury but is not critical for controlling complement activation by glomerular IgM.

Science.gov (United States)

Goetz, Lindsey; Laskowski, Jennifer; Renner, Brandon; Pickering, Matthew C; Kulik, Liudmila; Klawitter, Jelena; Stites, Erik; Christians, Uwe; van der Vlag, Johan; Ravichandran, Kameswaran; Holers, V Michael; Thurman, Joshua M

2018-05-01

Natural IgM binds to glomerular epitopes in several progressive kidney diseases. Previous work has shown that IgM also binds within the glomerulus after ischemia/reperfusion (I/R) but does not fully activate the complement system. Factor H is a circulating complement regulatory protein, and congenital or acquired deficiency of factor H is a strong risk factor for several types of kidney disease. We hypothesized that factor H controls complement activation by IgM in the kidney after I/R, and that heterozygous factor H deficiency would permit IgM-mediated complement activation and injury at this location. We found that mice with targeted heterozygous deletion of the gene for factor H developed more severe kidney injury after I/R than wild-type controls, as expected, but that complement activation within the glomeruli remained well controlled. Furthermore, mice that are unable to generate soluble IgM were not protected from renal I/R, even in the setting of heterozygous factor H deficiency. These results demonstrate that factor H is important for limiting injury in the kidney after I/R, but it is not critical for controlling complement activation by immunoglobulin within the glomerulus in this setting. IgM binds to glomerular epitopes after I/R, but it is not a significant source of injury. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A Case Report of Adrenocorticotropic Hormone to Treat Recurrent Focal Segmental Glomerular Sclerosis Post-transplantation and Biomarker Monitoring

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Anwar eSiddiq

2015-03-01

Full Text Available Background: Recurrent focal segmental glomerular sclerosis (rFSGS in renal transplant recipients (RTR is difficult to predict and treat. Early rFSGS is likely from circulating factors and preformed antibodies. Methods: We present the case of a 23-year-old white man who presented with rFSGS and acute renal failure requiring dialysis 9-months after a 1-haplotype matched living-related transplant. We retrospectively analyzed serum samples from various clinical stages for rFSGS biomarkers: serum glomerular albumin permeability (Palb, soluble urokinase-type plasminogen activator receptor (suPAR serum level with suPAR-β3 integrin signaling on human podocytes, and angiotensin II type I receptor-antibody (AT1R-Ab titer. Results: All biomarkers were abnormal at 1-year pre-transplant prior to initiation of dialysis and at the time of transplant. After initiation of hemodialysis, β3 integrin activity on human podocytes, in response to patient serum, as well as AT1R-Ab were further elevated. At the time of biopsy-proven recurrence, all biomarkers were abnormally high. One week after therapy with aborted plasmapheresis (secondary to intolerance, and high dose steroids, the Palb and suPAR- β3 integrin activity remained significantly positive. After 12-weeks of treatment with high-dose steroids, rituximab, and galactose, the patient remained hemodialysis-dependent. Three-months after his initial presentation we commenced adrenocorticotropic hormone (ACTH, Acthar® Gel, 80 units subcutaneously twice weekly. Four-weeks later he was able to discontinue dialysis. After 8-months of maintenance ACTH therapy, his serum creatinine stabilized at 1.79 mg/dL with less than 1 gram of proteinuria. Conclusion: ACTH therapy was associated with improvement in renal function within 4 weeks. The use of rFSGS biomarkers may aid in predicting development of rFSGS.

Studies on binding and mitogenic effect of insulin and insulin-like growth factor I in glomerular mesangial cells

International Nuclear Information System (INIS)

Conti, F.G.; Striker, L.J.; Lesniak, M.A.; MacKay, K.; Roth, J.; Striker, G.E.

1988-01-01

The mesangial cells are actively involved in regulating glomerular hemodynamics. Their overlying endothelium is fenestrated; therefore, these cells are directly exposed to plasma substances, including hormones such as insulin and insulin-like growth factor I (IGF-I). These peptides may contribute to the mesangial sclerosis and cellular hyperplasia that characterize diabetic glomerulopathy. We report herein the characterization of the receptors and the mitogenic effects of IGF-I and insulin on mouse glomerular mesangial cells in culture. The IGF-I receptor was characterized on intact cells. The Kd of the IGF-I receptor was 1.47 X 10(-9) M, and the estimated number of sites was 64,000 receptors/cell. The binding was time, temperature, and pH dependent, and the receptor showed down-regulation after exposure to serum. The expression of the receptor did not change on cells at different densities. The specific binding for insulin was too low to allow characterization of the insulin receptor on intact cells. However, it was possible to identify the insulin receptor in a wheat germ agglutinin-purified preparation of solubilized mesangial cells. This receptor showed the characteristic features of the insulin receptor, including pH dependence of binding and a curvilinear Scatchard plot. The mitogenic effects of insulin and IGF-I on mesangial cells were measured by the incorporation of [3H]thymidine into DNA. IGF-I was more potent than insulin. The half-maximal response to IGF-I stimulation occurred at 1.3 X 10(-10) M, and a similar increase with insulin was observed at concentrations in the range of 10(-7) M, suggesting that this insulin action was mediated through the IGF-I receptor. These data show that the mouse microvascular smooth muscle cells of the glomerulus express a cell surface receptor for IGF-I in vitro and that this peptide is a potent mitogen for these mesangial cells

Lipid rafts are required for signal transduction by angiotensin II receptor type 1 in neonatal glomerular mesangial cells

Energy Technology Data Exchange (ETDEWEB)

Adebiyi, Adebowale, E-mail: aadebiyi@uthsc.edu; Soni, Hitesh; John, Theresa A.; Yang, Fen

2014-05-15

Angiotensin II (ANG-II) receptors (AGTRs) contribute to renal physiology and pathophysiology, but the underlying mechanisms that regulate AGTR function in glomerular mesangium are poorly understood. Here, we show that AGTR1 is the functional AGTR subtype expressed in neonatal pig glomerular mesangial cells (GMCs). Cyclodextrin (CDX)-mediated cholesterol depletion attenuated cell surface AGTR1 protein expression and ANG-II-induced intracellular Ca{sup 2+} ([Ca{sup 2+}]{sub i}) elevation in the cells. The COOH-terminus of porcine AGTR1 contains a caveolin (CAV)-binding motif. However, neonatal GMCs express CAV-1, but not CAV-2 and CAV-3. Colocalization and in situ proximity ligation assay detected an association between endogenous AGTR1 and CAV-1 in the cells. A synthetic peptide corresponding to the CAV-1 scaffolding domain (CSD) sequence also reduced ANG-II-induced [Ca{sup 2+}]{sub i} elevation in the cells. Real-time imaging of cell growth revealed that ANG-II stimulates neonatal GMC proliferation. ANG-II-induced GMC growth was attenuated by EMD 66684, an AGTR1 antagonist; BAPTA, a [Ca{sup 2+}]{sub i} chelator; KN-93, a Ca{sup 2+}/calmodulin-dependent protein kinase II inhibitor; CDX; and a CSD peptide, but not PD 123319, a selective AGTR2 antagonist. Collectively, our data demonstrate [Ca{sup 2+}]{sub i}-dependent proliferative effect of ANG-II and highlight a critical role for lipid raft microdomains in AGTR1-mediated signal transduction in neonatal GMCs. - Highlights: • AGTR1 is the functional AGTR subtype expressed in neonatal mesangial cells. • Endogenous AGTR1 associates with CAV-1 in neonatal mesangial cells. • Lipid raft disruption attenuates cell surface AGTR1 protein expression. • Lipid raft disruption reduces ANG-II-induced [Ca{sup 2+}]{sub i} elevation in neonatal mesangial cells. • Lipid raft disruption inhibits ANG-II-induced neonatal mesangial cell growth.

Anti-nucleosome antibodies complexed to nucleosomal antigens show anti-DNA reactivity and bind to rat glomerular basement membrane in vivo.

Science.gov (United States)

Kramers, C; Hylkema, M N; van Bruggen, M C; van de Lagemaat, R; Dijkman, H B; Assmann, K J; Smeenk, R J; Berden, J H

1994-01-01

Histones can mediate the binding of DNA and anti-DNA to the glomerular basement membrane (GBM). In ELISA histone/DNA/anti-DNA complexes are able to bind to heparan sulfate (HS), an intrinsic constituent of the GBM. We questioned whether histone containing immune complexes are able to bind to the GBM, and if so, whether the ligand in the GBM is HS. Monoclonal antibodies (mAbs) complexed to nucleosomal antigens and noncomplexed mAbs were isolated from culture supernatants of four IgG anti-nuclear mAbs. All noncomplexed mAbs showed strong anti-nucleosome reactivity in ELISA. One of them showed in addition anti-DNA reactivity in noncomplexed form. The other three mAbs only showed anti-DNA reactivity when they were complexed to nucleosomal antigens. After renal perfusion a fine granular binding of complexed mAbs to the glomerular capillary wall and activation of complement was observed in immunofluorescence, whereas noncomplexed mAbs did not bind. Immuno-electron microscopy showed binding of complexes to the whole width of the GBM. When HS in the GBM was removed by renal heparinase perfusion the binding of complexed mAb decreased, but did not disappear completely. We conclude that anti-nucleosome mAbs, which do not bind DNA, become DNA reactive once complexed to nucleosomal antigens. These complexed mAbs can bind to the GBM. The binding ligand in the GBM is partly, but not solely, HS. Binding to the GBM of immune complexes containing nucleosomal material might be an important event in the pathogenesis of lupus nephritis. Images PMID:8040312

Association of Microalbuminuria and Estimated Glomerular Filtration Rate With Carotid Intima-Media Thickness in Patients With Type 2 Diabetes Mellitus

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Dehdashti Shahrokh

2015-04-01

Full Text Available Background Atherosclerosis is the main cause of cardiovascular diseases, and its risk enhances in type 2 diabetes mellitus. Objectives This study aimed to evaluate Carotid Intima-Media Thickness (CIMT by carotid artery ultrasonography and assess its correlation with microalbuminuria and estimated Glomerular Filtration Rate (eGFR in the patients with type 2 diabetes mellitus. Patients and Methods This cross-sectional study was included 205 patients with Type 2 Diabetes Mellitus (T2DM. We recorded clinical and biochemical data such as FBS, lipid profile, and urinary albumin. Intima-media thickness of carotid arteries was measured in all patients by high frequency ultrasound. Results In simple correlation coefficients analysis, CIMT was significantly associated with total cholesterol (r = 0.197, P = 0.008, serum creatinine (r = 0.240, P = 0.001, and urinary albumin (r = 0.420, P = 0.000. Also, CIMT elevated significantly with the stage progression of chronic kidney disease (0.67 ± 0.15 mm in stage 1, 0.73 ± 0.22 mm in stage 2, and 0.82 ± 0.21 mm in stage 3 (P value = 0.024. In multivariate linear regression analysis, the duration of diabetes, weight, HDL, serum creatinine, urinary albumin, and estimated Glomerular Filtration Rate (eGFR were independently associated with CIMT (P value < 0.05 for all. Conclusions Our study shows a relationship between CIMT and renal parameters, including eGFR and albuminuria. This study confirms the importance of intensive examinations for early detection of atherosclerosis and treatment of risk factors.

Barrier cell sheath formation

International Nuclear Information System (INIS)

Kesner, J.

1980-04-01

The solution for electrostatic potential within a simply modeled tandem mirror thermal barrier is seen to exhibit a sheath at each edge of the cell. The formation of the sheath requires ion collisionality and the analysis assmes that the collisional trapping rate into the barrier is considerably slower than the barrier pump rate

Fluorescent and radiolabelling of pepsin-digested human glomerular basement membrane with a newly developed hydroxy-coumarin derivative (CASE)

International Nuclear Information System (INIS)

Rand-Weaver, M.; Abuknesha, R.A.; Price, R.G.

1985-01-01

The labelling of pepsin-digested human glomerular basement membrane (pHGBM) with a newly developed fluorescent iodine acceptor 7-hydroxy-coumarin-3-acetic acid N-hydroxysucciniimydyl ester (CASE) is described. The binding of a monoclonal antibody to pHGBM was assessed by radiobinding assays, and when directly iodinated pHGBM was used there was no apparent binding. When CASE was conjugated to pHGBM prior to iodination 11% binding was achieved. CASE acting as an iodine acceptor may be useful for proteins containing few or inaccessible tyrosine residues or which are destroyed by introduction of 125 I. Since CASE is fluorescent, small amounts of material can be detected during isolation prior to iodination. (orig.)

Barriers to the future

Energy Technology Data Exchange (ETDEWEB)

Massey, C T

1986-09-01

Opportunities for the British coal industry seem vast yet there are still barriers to progress. Seven areas are identified and discussed: mining mobility (for example, longwall mining systems are rigid and inflexible compared with American stall and pillar working); mine structure (many mines are more suitable to pit ponies than to large pieces of equipment); financial barriers (Government requires the industry to break even in 1987/88); personnel barriers (less specialization, better use of skills); safety barriers (increased use of remote control, ergonomics and robotics to protect workers); microelectronic management (nationalization has cushioned management from the market place; there is a need for a more multidisciplinary approach to the industry); and legal barriers (most legislation in the past has been in response to accidents; legislation external to the industry but affecting it is more fundamental).

Chemical barriers for controlling groundwater contamination

International Nuclear Information System (INIS)

Morrison, S.J.; Spangler, R.R.

1993-01-01

Chemical barriers are being explored as a low-cost means of controlling groundwater contamination. The barrier can intercept a contaminant plume and prevent migration by transferring contaminants from the groundwater to immobile solids. A chemical barrier can be emplaced in a landfill liner or in an aquifer cutoff wall or can be injected into a contaminant plume. Chemical barriers can be classified as either precipitation barriers or sorption barriers depending upon the dominant mode of contaminant extraction. In a precipitation barrier, contaminants are bound in the structures of newly formed phases; whereas, in a sorption barrier, contaminants attach to the surfaces of preexisting solids by adsorption or some other surface mechanism. Sorption of contaminants is pH dependent. A precipitation barrier can control the pH of the system, but alkaline groundwater may dominate the pH in a sorption barrier. A comparison is made of the characteristics of precipitation and sorption barriers. Experimental data on the extraction of uranium and molybdenum from simulated groundwater are used to demonstrate these concepts. 10 refs., 9 figs., 1 tab

Barrier mechanisms in the Drosophila blood-brain barrier.

Science.gov (United States)

Hindle, Samantha J; Bainton, Roland J

2014-01-01

The invertebrate blood-brain barrier (BBB) field is growing at a rapid pace and, in recent years, studies have shown a physiologic and molecular complexity that has begun to rival its vertebrate counterpart. Novel mechanisms of paracellular barrier maintenance through G-protein coupled receptor signaling were the first demonstrations of the complex adaptive mechanisms of barrier physiology. Building upon this work, the integrity of the invertebrate BBB has recently been shown to require coordinated function of all layers of the compound barrier structure, analogous to signaling between the layers of the vertebrate neurovascular unit. These findings strengthen the notion that many BBB mechanisms are conserved between vertebrates and invertebrates, and suggest that novel findings in invertebrate model organisms will have a significant impact on the understanding of vertebrate BBB functions. In this vein, important roles in coordinating localized and systemic signaling to dictate organism development and growth are beginning to show how the BBB can govern whole animal physiologies. This includes novel functions of BBB gap junctions in orchestrating synchronized neuroblast proliferation, and of BBB secreted antagonists of insulin receptor signaling. These advancements and others are pushing the field forward in exciting new directions. In this review, we provide a synopsis of invertebrate BBB anatomy and physiology, with a focus on insights from the past 5 years, and highlight important areas for future study.

Barriers against psychosocial communication: oncologists' perceptions.

Science.gov (United States)

Fagerlind, Hanna; Kettis, Åsa; Glimelius, Bengt; Ring, Lena

2013-10-20

To explore oncologists' psychosocial attitudes and beliefs and their perceptions regarding barriers against psychosocial communication. A questionnaire was distributed to oncologists in Sweden (n = 537). Questions covered demography, the Physician Psychosocial Beliefs Scale (PPBS), and barriers against psychosocial communication. Stepwise multiple regression was used to determine what factors contribute the most to the PPBS score and the total number of barriers and barriers affecting clinical practice, respectively. Spearman rank-order correlation was used to determine correlation between PPBS score and number of barriers. Questionnaire response rate was 64%. Mean PPBS value was 85.5 (range, 49 to 123; SD, 13.0). Most oncologists (93%) perceived one or more barriers in communicating psychosocial aspects with patients. On average, five different communication barriers were perceived, of which most were perceived to affect clinical practice. These barriers included insufficient consultation time, lack of resources for taking care of problems discovered, and lack of methods to evaluate patients' psychosocial health in clinical practice. There was a positive correlation (rs = 0.490; P barriers (ie, less psychosocially oriented oncologists perceived more barriers). Oncologists with supplementary education with a psychosocial focus perceived fewer barriers/barriers affecting clinical practice (P barriers affecting psychosocial communication in clinical practice. Interventions aiming to improve psychosocial communication must therefore be multifaceted and individualized to clinics and individual oncologists. It is important to minimize barriers to facilitate optimal care and treatment of patients with cancer.

Barriers to improvements in energy efficiency

Energy Technology Data Exchange (ETDEWEB)

Reddy, A.K.N.

1991-10-01

To promote energy-efficiency improvements, actions may be required at one or more levels -- from the lowest level of the consumer (residential, commercial, industrial, etc.) through the highest level of the global agencies. But barriers to the implementation of energy-efficiency improvements exist or can arise at all these levels. Taking up each one of these barriers in turn, the paper discusses specific measures that can contribute to overcoming the barriers. However, a one-barrier-one-measure approach must be avoided. Single barriers may in fact involve several sub-barriers. Also, combinations of measures are much more effective in overcoming barriers. In particular, combinations of measures that simultaneously overcome several barriers are most successful. The paper discusses the typology of barriers, explores their origin and suggests measures that by themselves or in combination with other measures, will overcome these barriers. Since most of the barriers dealt with can be found in the barriers'' literature, any originality in the paper lies in its systematic organization, synoptic view and holistic treatment of this issue. This paper is intended to initiate a comprehensive treatment of barriers, their origins and the measures that contribute to overcoming them. Hopefully, such a treatment will facilitate the implementation of energy-efficiency improvements involving a wide diversity of ever-changing energy end uses and consumer preferences.

Barriers to improvements in energy efficiency

Energy Technology Data Exchange (ETDEWEB)

Reddy, A.K.N.

1991-10-01

To promote energy-efficiency improvements, actions may be required at one or more levels -- from the lowest level of the consumer (residential, commercial, industrial, etc.) through the highest level of the global agencies. But barriers to the implementation of energy-efficiency improvements exist or can arise at all these levels. Taking up each one of these barriers in turn, the paper discusses specific measures that can contribute to overcoming the barriers. However, a one-barrier-one-measure approach must be avoided. Single barriers may in fact involve several sub-barriers. Also, combinations of measures are much more effective in overcoming barriers. In particular, combinations of measures that simultaneously overcome several barriers are most successful. The paper discusses the typology of barriers, explores their origin and suggests measures that by themselves or in combination with other measures, will overcome these barriers. Since most of the barriers dealt with can be found in the ``barriers`` literature, any originality in the paper lies in its systematic organization, synoptic view and holistic treatment of this issue. This paper is intended to initiate a comprehensive treatment of barriers, their origins and the measures that contribute to overcoming them. Hopefully, such a treatment will facilitate the implementation of energy-efficiency improvements involving a wide diversity of ever-changing energy end uses and consumer preferences.

The blood-tendon barrier: identification and characterisation of a novel tissue barrier in tendon blood vessels

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C Lehner

2016-05-01

Full Text Available Tissue barriers function as “gate keepers” between different compartments (usually blood and tissue and are formed by specialised membrane-associated proteins, localising to the apicolateral plasma membrane domain of epithelial and endothelial cells. By sealing the paracellular space, the free diffusion of solutes and molecules across epithelia and endothelia is impeded. Thereby, tissue barriers contribute to the establishment and maintenance of a distinct internal and external environment, which is crucial during organ development and allows maintenance of an organ-specific homeostatic milieu. So far, various epithelial and endothelial tissue barriers have been described, including the blood-brain barrier, the blood-retina barrier, the blood-testis barrier, the blood-placenta barrier, and the cerebrospinal fluid (CSF-brain barrier, which are vital for physiological function and any disturbance of these barriers can result in severe organ damage or even death. Here, we describe the identification of a novel barrier, located in the vascular bed of tendons, which we term the blood-tendon barrier (BTB. By using immunohistochemistry, transmission electron microscopy, and tracer studies we demonstrate the presence of a functional endothelial barrier within tendons restricting the passage of large blood-borne molecules into the surrounding tendon tissue. We further provide in vitro evidence that the BTB potentially contributes to the creation of a distinct internal tissue environment impacting upon the proliferation and differentiation of tendon-resident cells, effects which might be fundamental for the onset of tendon pathologies.

Anti-glomerular basement membrane autoantibodies in the Brown Norway rat: detection by a solid-phase radioimmunoassay

International Nuclear Information System (INIS)

Bowman, C.; Peters, D.K.; Lockwood, C.M.

1983-01-01

A solid-phase radioimmunoassay (RIA) is described for the detection of IgG autoantibodies to glomerular basement membrane (GBM) induced in the Brown Norway rat by mercuric chloride. The assay involves the adsorption of a collagenase digest of GBM to plastic microtitre plates and detection of bound antibody with affinity purified radiolabelled rabbit anti-rat IgG. Comparison with existing immunofluorescence methods for detection of anti-GBM antibody showed that the solid-phase RIA is highly sensitive, allowing detection of antibody in solutions with as low as 0.5 ng protein/ml. The assay is suitable for detection of anti-GBM antibody both in serum and in eluates from nephritic kidneys. The assay proved to be specific in competitive studies of inhibition brought about by GBM, keyhole limpet antigen and ovalbumin. This solid-phase RIA is reproducible, robust and easy to perform. (Auth.)

Beneficial Effect of Conversion to Belatacept in Kidney-Transplant Patients with a Low Glomerular-Filtration Rate

Directory of Open Access Journals (Sweden)

Julie Belliere

2014-01-01

Full Text Available Belatacept has been found to be efficient at preserving good kidney function in maintenance kidney-transplant patients. Herein, we report on the use of belatacept as a rescue therapy for two kidney-transplant patients presenting with severe adverse events after treatment with calcineurin inhibitors (CNIs and mammalian target-of-rapamycin (mTOR inhibitors. Two kidney-transplant patients developed severely impaired kidney function after receiving CNIs. The use of everolimus was associated with severe angioedema. Belatacept was then successfully used to improve kidney function in both cases, even though estimated glomerular-filtration rate before conversion was <20 mL/min. These case reports show that belatacept can be used as a rescue therapy, even if kidney function is very low in kidney-transplant patients who cannot tolerate CNIs and/or mTOR inhibitors.

Loss of the Podocyte-Expressed Transcription Factor Tcf21/Pod1 Results in Podocyte Differentiation Defects and FSGS

DEFF Research Database (Denmark)

Maezawa, Yoshiro; Onay, Tuncer; Scott, Rizaldy P

2014-01-01

Podocytes are terminally differentiated cells with an elaborate cytoskeleton and are critical components of the glomerular barrier. We identified a bHLH transcription factor, Tcf21, that is highly expressed in developing and mature podocytes. Because conventional Tcf21 knockout mice die in the pe...

Changes in ceftriaxone pharmacokinetics/pharmacodynamics during the early phase of sepsis: a prospective, experimental study in the rat

Directory of Open Access Journals (Sweden)

Valentina Selmi

2016-11-01

Full Text Available Abstract Background Sepsis is characterized by the loss of the perm-selectivity properties of the glomerular filtration barrier (GFB with consequent albuminuria. We examined whether the pharmacokinetics–pharmacodynamics (PK/PD of ceftriaxone (CTX, an extensively protein-bound 3rd generation cephalosporin, is altered during early sepsis and whether an increase in urinary loss of bound-CTX, due to GFB alteration, can occur in this condition. Methods A prospective, experimental, randomized study was carried out in adult male Sprague–Dawley rats. Sepsis was induced by cecal ligation and puncture (CLP. Rats were divided into two groups: Sham-operated and CLP. CTX (100 mg i.p., equivalent to 1 g dose in humans was administered in order to measure plasma and lung CTX concentrations at several time-points: baseline and 1, 2, 4 and 6 h after administration. CTX was measured by High Performance Liquid Chromatography (HPLC. The morphological status of the sialic components of the GFB barrier was assessed by lectin histo-chemistry. Monte Carlo simulation was performed to calculate the probability of target attainment (PTA >90% for 80 and 100% of Tfree > minimum inhibitory concentration (MIC for 80 and 100% of dosing interval. Measurements and main results After CLP, sepsis developed in rats as documented by the growth of polymicrobial flora in the peritoneal fluid (≤1 × 101 CFU in sham rats vs 5 × 104–1 × 105 CFU in CLP rats. CTX plasma concentrations were higher in CLP than in sham rats at 2 and 4 h after administration (difference at 2 h was 47.3, p = 0.012; difference at 4 h was 24.94, p = 0.004, while lung penetration tended to be lower. An increased urinary elimination of protein-bound CTX occurred (553 ± 689 vs 149 ± 128 mg/L, p  90% for 100% of the dosing interval was reached neither for sham nor CLP rats using MIC = 1 mg/L, the clinical breakpoint for Enterobacteriacee. Conclusions Sepsis causes changes in

Effect of the barrier properties on the surface part of the barrier discharge

International Nuclear Information System (INIS)

Sokolova, M.V.; Zhukov, S.V.

1998-01-01

The effect of barrier characteristics on the discharge processes in a barrier discharge was investigated, main attention being paid to the amount and distribution of the charge left on the barrier surface by the volume discharge in the main air gap. The measurements show that the main part of the gap charge is due to the volume part of the discharge. The measured values of the surface charge significantly increase with the voltage applied and with the length of the gas gap, while the dimensions of the charge spot and the distribution of charge density are determined by the barrier properties. (J.U.)

Single- versus multiple-sample method to measure glomerular filtration rate.

Science.gov (United States)

Delanaye, Pierre; Flamant, Martin; Dubourg, Laurence; Vidal-Petiot, Emmanuelle; Lemoine, Sandrine; Cavalier, Etienne; Schaeffner, Elke; Ebert, Natalie; Pottel, Hans

2018-01-08

There are many different ways to measure glomerular filtration rate (GFR) using various exogenous filtration markers, each having their own strengths and limitations. However, not only the marker, but also the methodology may vary in many ways, including the use of urinary or plasma clearance, and, in the case of plasma clearance, the number of time points used to calculate the area under the concentration-time curve, ranging from only one (Jacobsson method) to eight (or more) blood samples. We collected the results obtained from 5106 plasma clearances (iohexol or 51Cr-ethylenediaminetetraacetic acid (EDTA)) using three to four time points, allowing GFR calculation using the slope-intercept method and the Bröchner-Mortensen correction. For each time point, the Jacobsson formula was applied to obtain the single-sample GFR. We used Bland-Altman plots to determine the accuracy of the Jacobsson method at each time point. The single-sample method showed within 10% concordances with the multiple-sample method of 66.4%, 83.6%, 91.4% and 96.0% at the time points 120, 180, 240 and ≥300 min, respectively. Concordance was poorer at lower GFR levels, and this trend is in parallel with increasing age. Results were similar in males and females. Some discordance was found in the obese subjects. Single-sample GFR is highly concordant with a multiple-sample strategy, except in the low GFR range (<30 mL/min). © The Author 2018. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

A meta-analysis on diagnostic value of serum cystatin C and creatinine for the evaluation of glomerular filtration function in renal transplant patients.

Science.gov (United States)

Pan, Pan; Binjie, Hu; Min, Li; Lipei, Fan; Yanli, Ni; Junwen, Zhou; Xianghua, Shi

2014-12-01

This meta-analysis aimed to perform a systematic review on comparing the diagnostic value of serum cystatin C and creatinine for glomerular filtration rate in renal transplant patients. The data was extracted into 2×2 table after the articles were assessed by the tool of QUADAS and heterogeneity analysis. The SROC curve and meta-analysis were performed by MetaDisc1.4. Meta-analysis showed that the serum cystatin C had no heterogeneity (P=0.418, I2=2.2%, DOR=25.03), while creatinine heterogeneity was high (P=0.109, I2=37.5%, DOR=9.11). The values of SEN, SPE and SAUC were calculated as 0.86, 0.70 and 0.9015 for cystatin C, and 0.78, 0.73 and 0.8285 for creatinine individually. This study utilized GFR detection and subgroups analysis by cutoff. The PLR was 6.13 and the NLR was 0.12 for cystatin C, compared to SCr (3.72, 0.32). There was homogeneity among these studies using PENIA testing for cystatin C (χ2=2.61, P=0.4560, I2=0.0%. There were significant correlations among cystatin C , creatinine and glomerular filtration rate (GFR). Cystatin C had more sensitivity but less specificity than creatinine for evaluation of GFR. Cystatin C had strong ability in diagnosing renal function after renal transplant and ruling out diagnostic efficacy.

Measurement of glomerular filtration rate in the conscious rat.

Science.gov (United States)

Pestel, Sabine; Krzykalla, Volker; Weckesser, Gerhard

2007-01-01

Glomerular filtration rate (GFR) is an important parameter for studying drug-induced impairments on renal function in rats. The GFR is calculated from the concentration of creatinine and blood urea nitrogen (BUN) in serum and in urine, respectively. Following current protocols serum and urine samples must be taken from the same animal. Thus, in order to determine time-dependent effects it is necessary to use for each time point one separated group of animals. We developed a statistical test which allows analyzing the GFR from two different groups of animals: one used for repeated serum and the other one used for repeated urine analysis. Serum and urine samples were taken from two different sets of rats which were otherwise treated identically, i.e. drug doses, routes of administration (per os or per inhalation) and tap water loading. For each dose group GFR mean, standard deviation and statistical analysis to identify differences between the dose groups were determined. After determination of the optimal time points for measurements, the effect on GFR of the three reference compounds, furosemide, hydrochlorothiazide and formoterol, was calculated. The results showed that the diuretic drugs furosemide and hydrochlorothiazide decreased the GFR and the antidiuretic drug formoterol increased the GFR, as counter regulation on urine loss or urine retention, respectively. A mathematical model and the corresponding algorithm were developed, which can be used to calculate the GFR, and to test for differences between groups from two separated sets of rats, one used for urine, and the other one for serum analysis. This new method has the potential to reduce the number of animals needed and to improve the quality of data generated from various groups of animals in renal function studies.

Transport barriers in plasmas

International Nuclear Information System (INIS)

Caldas, I L; Szezech, J D Jr; Kroetz, T; Marcus, F A; Roberto, M; Viana, R L; Lopes, S R

2012-01-01

We discuss the creation of transport barriers in magnetically confined plasmas with non monotonic equilibrium radial profiles. These barriers reduce the transport in the shearless region (i.e., where the twist condition does not hold). For the chaotic motion of particles in an equilibrium electric field with a nonmonotonic radial profile, perturbed by electrostatic waves, we show that a nontwist transport barrier can be created in the plasma by modifying the electric field radial profile. We also show non twist barriers in chaotic magnetic field line transport in the plasma near to the tokamak wall with resonant modes due to electric currents in external coils.

Glomerular filtration rate and renal recovery of [14C]-allantoin in Bali and Zebu cattle of Indonesia

International Nuclear Information System (INIS)

Prasitkusol, P.; Chen, X.B.; Orskov, E.R.; Kyle, D.J.; Yusiati, L.M.

2004-01-01

The urinary recovery of [ 14 C]-allantoin injected into the blood of Bali Cattle (Bos banteng) and Zebu cattle (Bos indicus), and the glomerular filtration rate (GFR) of these animals, were determined. The cattle were fed with king grass at 95% of ad libitum intake. The recovery of [ 14 C]-allantoin in the urine was significantly higher for Bali (83 ± SE 0.94 %) than for Zebu Cattle (74 ± SE 0.79 %). There were no significant differences in GFR between Bali and Zebu cattle (302 ± SE23.8 and 285 ± SE18.7 L/d). Within each species, there was no significant effect of GFR on the [ 14 C]-allantoin recovery. It remains to be investigated whether the differences in [ 14 C]-allantoin recovery between species is affected by GFR. (author)

Escaping the correction for body surface area when calculating glomerular filtration rate in children

International Nuclear Information System (INIS)

Piepsz, Amy; Tondeur, Marianne; Ham, Hamphrey

2008-01-01

51 Cr ethylene diamine tetraacetic acid ( 51 Cr EDTA) clearance is nowadays considered as an accurate and reproducible method for measuring glomerular filtration rate (GFR) in children. Normal values in function of age, corrected for body surface area, have been recently updated. However, much criticism has been expressed about the validity of body surface area correction. The aim of the present paper was to present the normal GFR values, not corrected for body surface area, with the associated percentile curves. For that purpose, the same patients as in the previous paper were selected, namely those with no recent urinary tract infection, having a normal left to right 99m Tc MAG3 uptake ratio and a normal kidney morphology on the early parenchymal images. A single blood sample method was used for 51 Cr EDTA clearance measurement. Clearance values, not corrected for body surface area, increased progressively up to the adolescence. The percentile curves were determined and allow, for a single patient, to estimate accurately the level of non-corrected clearance and the evolution with time, whatever the age. (orig.)

Protective effects of antioxidants on high Glucose-induced malfunctions in human glomerular mesangial cells

Directory of Open Access Journals (Sweden)

Hosseini R

2000-08-01

Full Text Available Altered functions of mesangial cells induced by high glucose concentrations are thought to play an important role in the pathogenesis of diabetic nephropathy. We therefore investigated the effect of high glucose (39.2 mM alone and in combination with taurine (500 µM or vitamin E (100 µM in serum free medium (RPMI 1640 on the proliferative growth response and turnover of type IV collagen by human glomerular mesangial cells (GMC. The results showed that the high glucose level decreases the proliferation of the GMC which is reversed by taurine and vitamin E. In order to control the osmotic effects of high glucose, the GMC were also cultured in the presence of manitol. Manitol had no effect on the proliferation of GMC. Furthermore, the results showed that addition of vitamin E or taurine to media containing high glucose could reverse and normalize the collagen turn-over by the cultured mesangial cells. These results suggest that taurie and vitamin E may function as endogenous agents in the kidney to limit the development of glomerulosclerosis in diabetic renal disease.

Proenkephalin, Neutrophil Gelatinase-Associated Lipocalin, and Estimated Glomerular Filtration Rates in Patients With Sepsis.

Science.gov (United States)

Kim, Hanah; Hur, Mina; Lee, Seungho; Marino, Rossella; Magrini, Laura; Cardelli, Patrizia; Struck, Joachim; Bergmann, Andreas; Hartmann, Oliver; Di Somma, Salvatore

2017-09-01

Proenkephalin (PENK) has been suggested as a novel biomarker for kidney function. We investigated the diagnostic and prognostic utility of plasma PENK in comparison with neutrophil gelatinase-associated lipocalin (NGAL) and estimated glomerular filtration rates (eGFR) in septic patients. A total of 167 septic patients were enrolled: 99 with sepsis, 37 with septic shock, and 31 with suspected sepsis. PENK and NGAL concentrations were measured and GFR was estimated by using the isotope dilution mass spectrometry traceable-Modification of Diet in Renal Disease (MDRD) Study and three Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations: CKD-EPI(Cr), CDK-EPI(CysC), and CKD-EPI(Cr-CysC). The PENK, NGAL, and eGFR results were compared according to sepsis severity, presence or absence of acute kidney injury (AKI), and clinical outcomes. The PENK, NGAL, and eGFR results were significantly associated with sepsis severity and differed significantly between patients with and without AKI only in the sepsis group (all Psepsis. © The Korean Society for Laboratory Medicine

Devices for overcoming biological barriers: the use of physical forces to disrupt the barriers.

Science.gov (United States)

Mitragotri, Samir

2013-01-01

Overcoming biological barriers including skin, mucosal membranes, blood brain barrier as well as cell and nuclear membrane constitutes a key hurdle in the field of drug delivery. While these barriers serve the natural protective function in the body, they limit delivery of drugs into the body. A variety of methods have been developed to overcome these barriers including formulations, targeting peptides and device-based technologies. This review focuses on the use of physical methods including acoustic devices, electric devices, high-pressure devices, microneedles and optical devices for disrupting various barriers in the body including skin and other membranes. A summary of the working principles of these devices and their ability to enhance drug delivery is presented. Copyright © 2012. Published by Elsevier B.V.

Differential associations between glomerular filtration rate and duration of obesity depending on the presence or absence of left ventricular diastolic dysfunction.

Science.gov (United States)

Ybarra, Juan; Sánchez-Hernández, Joan; Vilallonga, Ramon; Romeo, June H

2016-07-01

A robust and consistent association between increasing body mass index (BMI) and chronic kidney disease (CKD) has been reported in several observational studies. Obesity remains the main preventable risk factor for CKD because it largely mediates diabetes and hypertension, the 2 most common etiologies for end-stage kidney disease (ESKD). Obesity is associated weakly with early stages of kidney disease but strongly with kidney progression to ESKD, even after adjustment for hypertension and diabetes. To assess the relationship between estimated glomerular filtration rate (eGFR) and trans-thoracic echocardiography left ventricular function parameters in a cohort of patients with obesity. Cross-sectional study involving 324 obese (BMI=44.0±2.2Kg/m(2)) apparently healthy asymptomatic patients with an eGFR >60ml/min/1.73m(2). Each patient underwent transthoracic echocardiography and a blood testing. The eGFR was addressed by the CKD-EPI formula. All patients had a normal systolic function whereas 24.5% disclosed diastolic dysfunction (DD). Hypertension and type 2 diabetes mellitus prevalence were 34.5% and 4.5% (respectively). All patients disclosed an eGFR >60ml/min while none of them disclosed hyperfiltration (eGFR >120ml/min). eGFR correlated inversely with BMI and the duration of obesity and positively with diastolic function parameters (Pobesity (PObesity and its duration are likely to impose hemodynamic changes affecting simultaneously both heart (diastolic dysfunction) and kidney (decreased glomerular filtration rate). Larger prospective studies are warranted. Copyright © 2016 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Blood pressure influences end-stage renal disease of Cd151 knockout mice

NARCIS (Netherlands)

Sachs, Norman; Claessen, Nike; Aten, Jan; Kreft, Maaike; Teske, Gwendoline J. D.; Koeman, Anneke; Zuurbier, Coert J.; Janssen, Hans; Sonnenberg, Arnoud

2012-01-01

Podocytes of the kidney adhere tightly to the underlying glomerular basement membrane (GBM) in order to maintain a functional filtration barrier. The clinical importance of podocyte binding to the GBM via an integrin-laminin-actin axis has been illustrated in models with altered function of alpha 3

Recombinant human erythropoietin in humans down-regulates proximal renal tubular reabsorption and causes a fall in glomerular filtration rate

DEFF Research Database (Denmark)

Olsen, Niels Vidiendal; Aachmann-Andersen, Niels Jacob; Oturai, Peter

2010-01-01

HuEPO for 28 days in doses raising the hematocrit to 48.3 (4.1) %. Renal clearance studies with urine collections (N = 8) were done at baseline and at days 4, 11, 29, and 42. Glomerular filtration rate (GFR) was measured by (51)Cr-EDTA. Renal clearance of lithium (C(Li)) was used as an index of proximal...... tubular outflow and to assess segmental renal tubular handling of sodium and water. rHuEPO-induced increases in hematocrit occurred from day 10 onwards and was caused by both an increase in red cell volume and a fall in plasma volume. Well before that (from day 2 and throughout the treatment time), r...... and water (APR = GFR - C(Li), P

Performing a local barrier operation

Science.gov (United States)

Archer, Charles J; Blocksome, Michael A; Ratterman, Joseph D; Smith, Brian E

2014-03-04

Performing a local barrier operation with parallel tasks executing on a compute node including, for each task: retrieving a present value of a counter; calculating, in dependence upon the present value of the counter and a total number of tasks performing the local barrier operation, a base value, the base value representing the counter's value prior to any task joining the local barrier; calculating, in dependence upon the base value and the total number of tasks performing the local barrier operation, a target value of the counter, the target value representing the counter's value when all tasks have joined the local barrier; joining the local barrier, including atomically incrementing the value of the counter; and repetitively, until the present value of the counter is no less than the target value of the counter: retrieving the present value of the counter and determining whether the present value equals the target value.

Glomerular epithelial foot processes in normal man and rats. Distribution of true width and its intra- and inter-individual variation.

Science.gov (United States)

Gundersen, H J; Seefeldt, T; Osterby, R

1980-01-01

The width of individual glomerular epithelial foot processes appears very different on electron micrographs. A method for obtainining distributions of the true width of foot processes from that of their apparent width on electron micrographs has been developed based on geometric probability theory pertaining to a specific geometric model. Analyses of foot process width in humans and rats show a remarkable interindividual invariance implying rigid control and therefore great biological significance of foot process width or a derivative thereof. The very low inter-individual variation of the true width, shown in the present paper, makes it possible to demonstrate slight changes in rather small groups of patients or experimental animals.

Glomerular filtration rate and functional decline in an acute geriatric unit

Directory of Open Access Journals (Sweden)

Ocampo Chaparro, José Mauricio

2018-01-01

Full Text Available Introduction: Low estimated Glomerular filtration rate (eGFR is associated with functional decline. Little is known on that association in hospitalized elderly. Objective: Determine if low eGFR is associated with functional decline. Methods: Prospective cohort study that included 1826 patients 60 years and older hospitalized in a Geriatric Acute Unit, admitted between January 2012 and August 2015. The outcome was functional status assessed four times by the Barthel Index (BI. Kidney function was estimated by MDRD-4 IDMS and was grouped into four categories according to eGFR (normal ≥90, mild 60-89, moderate 59-30, severe <30. Multivariate logistic regression models and GLIMMIX procedure for longitudinal analyzes were used. Results: Mean age was 82.3±7.2 years, 51 % were women. In multivariate logistic regression, a BI≤60 at admission was associated with age ≥80, female gender, high comorbidity, social deterioration, hypoalbuminemia, anemia, MMSE<19, while the presence of mild or moderate renal failure reduced this risk. In the longitudinal analysis, lower total BI at follow-up was associated with age ≥80, female gender, social deterioration, hospital stay ≥15 days, high comorbidity, hypoalbuminemia, MMSE<19. The presence of mild, moderate or severe renal impairment was associated with higher BI over time. Conclusions: A low eGFR was associated with lower risk for functional decline at admission and overtime. These findings differ from previous reports in the literature.

Intraglomerular inhibition shapes the strength and temporal structure of glomerular output.

Science.gov (United States)

Shao, Zuoyi; Puche, Adam C; Liu, Shaolin; Shipley, Michael T

2012-08-01

Odor signals are transmitted to the olfactory bulb by olfactory nerve (ON) synapses onto mitral/tufted cells (MCs) and external tufted cells (ETCs). ETCs, in turn, provide feedforward excitatory input to MCs. MC and ETCs are also regulated by inhibition: intraglomerular and interglomerular inhibitory circuits act at MC and ETC apical dendrites; granule cells (GCs) inhibit MC lateral dendrites via the MC→GC→MC circuit. We investigated the contribution of intraglomerular inhibition to MC and ETCs responses to ON input. ON input evokes initial excitation followed by early, strongly summating inhibitory postsynaptic currents (IPSCs) in MCs; this is followed by prolonged, intermittent IPSCs. The N-methyl-d-aspartate receptor antagonist dl-amino-5-phosphovaleric acid, known to suppress GABA release by GCs, reduced late IPSCs but had no effect on early IPSCs. In contrast, selective intraglomerular block of GABA(A) receptors eliminated all early IPSCs and caused a 5-fold increase in ON-evoked MC spiking and a 10-fold increase in response duration. ETCs also receive intraglomerular inhibition; blockade of inhibition doubled ETC spike responses. By reducing ETC excitatory drive and directly inhibiting MCs, intraglomerular inhibition is a key factor shaping the strength and temporal structure of MC responses to sensory input. Sensory input generates an intraglomerular excitation-inhibition sequence that limits MC spike output to a brief temporal window. Glomerular circuits may dynamically regulate this input-output window to optimize MC encoding across sniff-sampled inputs.

Barrier island facies models and recognition criteria

Science.gov (United States)

Mulhern, J.; Johnson, C. L.

2017-12-01

Barrier island outcrops record transgressive shoreline motion at geologic timescales, providing integral clues to understanding how coastlines respond to rising sea levels. However, barrier island deposits are difficult to recognize. While significant progress has been made in understanding the modern coastal morphodynamics, this insight is not fully leveraged in existing barrier island facies models. Excellent outcrop exposures of the paralic Upper Cretaceous Straight Cliffs Formation of southern Utah provide an opportunity to revise facies models and recognition criteria for barrier island deposits. Preserved barrier islands are composed of three main architectural elements (shorefaces, tidal inlets, and tidal channels) which occur independently or in combination to create larger-scale barrier island deposits. Barrier island shorefaces record progradation, while barrier island tidal inlets record lateral migration, and barrier island tidal channels record aggradation within the tidal inlet. Four facies associations are used to describe and characterize these barrier island architectural elements. Barrier islands occur in association with backarrier fill and internally contain lower and upper shoreface, high-energy upper shoreface, and tidal channel facies. Barrier islands bound lagoons or estuaries, and are distinguished from other shoreface deposits by their internal facies and geometry, association with backbarrier facies, and position within transgressive successions. Tidal processes, in particular tidal inlet migration and reworking of the upper shoreface, also distinguish barrier island deposits. Existing barrier island models highlight the short term heterogeneous and dynamic nature of barrier island systems, yet overlook processes tied to geologic time scales, such as multi-directional motion, erosion, and reworking, and their expressions in preserved barrier island strata. This study uses characteristic outcrop expressions of barrier island successions to

Enershield : energy saving air barriers

Energy Technology Data Exchange (ETDEWEB)

Hallihan, D. [Enershield Industries Ltd., Edmonton, AB (Canada)

2008-07-01

Enershield Industries is a leader in air barrier technology and provides solution for the Canadian climate. This presentation described the advantages of air barriers and the impact of rising energy costs. An air barrier is used to separate areas of differing environments and makes existing building systems more efficient. This presentation discussed how an air barrier works. It also identified how Enershield Industries calculates energy savings. It described air barrier applications and those who use barrier technology. These include the commercial and industrial sector as well as the personnel and retail sector. Barrier technology can be used for cold storage; vehicle and equipment washes; food processing; and environmental separation. Features and benefits such as the ability to create seal, acoustic insulation, and long term durability were also discussed. Last, the presentation addressed model selection and design criteria issues. Design criteria that were presented included a discussion of acoustic installation, articulating nozzles, scroll cased fans, and structural frame. Other design criteria presented were galvanized frames, telescopic sliders, and off the shelf parts. It was concluded that the ability to reduce energy consumption and enhance employee/client comfort is beneficial to the employer as well as to the employee. figs.

Engineered barriers: current status

International Nuclear Information System (INIS)

Atkinson, A.; Marsh, G.P.

1988-01-01

This report summarises the current state of research relevant to assessing the performance of engineered barriers made of steel and concrete in radioactive waste repositories. The objective of these barriers is to contain the radionuclides within them by providing both physical and chemical impediment to their release. The physical barriers are of most value for highly soluble isotopes with relatively short half-lives (eg 137 Cs), since they can provide containment until a large fraction of the activity has decayed. In addition they can facilitate retrievability for some period after disposal. The chemical barriers operate by beneficial conditioning of the near field groundwater and providing sites for sorption of radionuclides. Both of these reduce the aqueous concentration of radionuclides in the near field. (author)

Material Barriers to Diffusive Mixing

Science.gov (United States)

Haller, George; Karrasch, Daniel

2017-11-01

Transport barriers, as zero-flux surfaces, are ill-defined in purely advective mixing in which the flux of any passive scalar is zero through all material surfaces. For this reason, Lagrangian Coherent Structures (LCSs) have been argued to play the role of mixing barriers as most repelling, attracting or shearing material lines. These three kinematic concepts, however, can also be defined in different ways, both within rigorous mathematical treatments and within the realm of heuristic diagnostics. This has lead to a an ever-growing number of different LCS methods, each generally identifying different objects as transport barriers. In this talk, we examine which of these methods have actual relevance for diffusive transport barriers. The latter barriers are arguably the practically relevant inhibitors in the mixing of physically relevant tracers, such as temperature, salinity, vorticity or potential vorticity. We demonstrate the role of the most effective diffusion barriers in analytical examples and observational data. Supported in part by the DFG Priority Program on Turbulent Superstructures.

Process for the production of high purity deuterium

International Nuclear Information System (INIS)

Arrathoon, R.

1977-01-01

A process for the electrolysis of heavy water which results in the production of high purity deuterium without periodic replenishment of the electrolyte with additional deuterated compounds is defined. Electrolysis is effected through the use of an inexpensive cation-action permselective membrane which is essentially a solid polymer electrolyte and which is capable of automatically separating the evolved deuterium and oxygen gas. This cation-active permselective membrane does not introduce any intrinsic impurities or tritium contamination in the generated deuterium gas, does not require periodic revitalization with deuterated compounds or other chemical compounds, and is characterized by an unusually high electrical efficiency

Novel Materials for High Efficiency Direct Methanol Fuel Cells

Energy Technology Data Exchange (ETDEWEB)

Carson, Stephen [Arkema Inc.; Mountz, David [Arkema Inc.; He, Wensheng [Arkema Inc.; Zhang, Tao [Arkema Inc.

2013-12-31

Direct methanol fuel cell membranes were developed using blends of different polyelectrolytes with PVDF. The membranes showed complex relationships between polyelectrolyte chemistry, morphology, and processing. Although the PVDF grade was found to have little effect on the membrane permselectivity, it does impact membrane conductivity and methanol permeation values. Other factors, such as varying the polyelectrolyte polarity, using varying crosslinking agents, and adjusting the equivalent weight of the membranes impacted methanol permeation, permselectivity, and areal resistance. We now understand, within the scope of the project work completed, how these inter-related performance properties can be tailored to achieve a balance of performance.

Diabetes and diet : managing dietary barriers

NARCIS (Netherlands)

Friele, R.D.

1989-01-01

This thesis reports on the barriers diabetic patients experience with their diet, and the ways they cope with these barriers. A dietary barrier is a hinderance to a person's well-being, induced by being advised a diet. First inventories were made of possible dietary barriers and ways of

Barriers to healthcare for transgender individuals.

Science.gov (United States)

Safer, Joshua D; Coleman, Eli; Feldman, Jamie; Garofalo, Robert; Hembree, Wylie; Radix, Asa; Sevelius, Jae

2016-04-01

Transgender persons suffer significant health disparities and may require medical intervention as part of their care. The purpose of this manuscript is to briefly review the literature characterizing barriers to healthcare for transgender individuals and to propose research priorities to understand mechanisms of those barriers and interventions to overcome them. Current research emphasizes sexual minorities' self-report of barriers, rather than using direct methods. The biggest barrier to healthcare reported by transgender individuals is lack of access because of lack of providers who are sufficiently knowledgeable on the topic. Other barriers include: financial barriers, discrimination, lack of cultural competence by providers, health systems barriers, and socioeconomic barriers. National research priorities should include rigorous determination of the capacity of the US healthcare system to provide adequate care for transgender individuals. Studies should determine knowledge and biases of the medical workforce across the spectrum of medical training with regard to transgender medical care; adequacy of sufficient providers for the care required, larger social structural barriers, and status of a framework to pay for appropriate care. As well, studies should propose and validate potential solutions to address identified gaps.

24 CFR 574.645 - Coastal barriers.

Science.gov (United States)

2010-04-01

... 24 Housing and Urban Development 3 2010-04-01 2010-04-01 false Coastal barriers. 574.645 Section....645 Coastal barriers. In accordance with the Coastal Barrier Resources Act, 16 U.S.C. 3501, no financial assistance under this part may be made available within the Coastal Barrier Resources System. ...

Comparison of methods for estimating glomerular filtration rate in head and neck cancer patients treated with cisplatin

DEFF Research Database (Denmark)

Lindberg, Lotte; Brødbæk, Kasper; Hägerström, Erik G

2017-01-01

Cisplatin is a chemotherapeutic agent widely used in the treatment of various solid tumors. Cisplatin induces nephrotoxicity and may lead to long-term reduction of kidney function. Consequently, determination of glomerular filtration rate (GFR) is used to monitor potential kidney damage. This study...... aimed to compare two commonly used algorithms for estimating GFR (eGFR) from plasma creatinine (PCr) with 51Cr-EDTA clearance (CrCl) as a reference method. This was a retrospective single center study of 94 head and neck cancer patients treated with cisplatin. CrCl was performed once before, during......, and after treatment, and PCr was measured concurrently. eGFR was assessed from PCr applying the Cockcroft-Gault (CG) and the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equations. Agreement was assessed applying the statistical methods of Bland and Altman. A predefined limit of clinically...

Sphingosine-1-phosphate (S1P) enhances glomerular endothelial cells activation mediated by anti-myeloperoxidase antibody-positive IgG.

Science.gov (United States)

Sun, Xiao-Jing; Chen, Min; Zhao, Ming-Hui

2018-03-01

Cumulating evidences suggested an important role of sphingosine-1-phosphate (S1P) and its receptors in regulating endothelial barrier integrity. Our previous study revealed that the circulating S1P levels and renal expression of S1PRs correlated with disease activity and renal damage in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). This study investigated the role of S1P and its receptors in myeloperoxidase (MPO)-ANCA-positive IgG-mediated glomerular endothelial cell (GEnC) activation. The effect of S1P on morphological alteration of GEnCs in the presence of MPO-ANCA-positive IgG was observed. Permeability assay was performed to determine endothelial monolayer activation in quantity. Both membrane-bound and soluble ICAM-1 and VCAM-1 levels were measured. Furthermore, antagonists and/or agonists of various S1PRs were employed to determine the role of different S1PRs. S1P enhanced MPO-ANCA-positive IgG-induced disruption of tight junction and disorganization of cytoskeleton in GEnCs. S1P induced further increase in monolayer permeability of GEnC monolayers in the presence of MPO-ANCA-positive IgG. S1P enhanced MPO-ANCA-positive IgG-induced membrane-bound and soluble ICAM-1/VCAM-1 up-regulation of GEnCs. Soluble ICAM-1 levels in the supernatants of GEnCs stimulated by S1P and MPO-ANCA-positive IgG increased upon pre-incubation of S1PR1 antagonist, while pre-incubation of GEnCs with the S1PR1 agonist down-regulated sICAM-1 level. Blocking S1PR2-4 reduced sICAM-1 levels in the supernatants of GEnCs stimulated by S1P and MPO-ANCA-positive IgG. Pre-incubation with S1PR5 agonist could increase sICAM-1 level in the supernatants of GEnC stimulated by S1P and MPO-ANCA-positive IgG. S1P can enhance MPO-ANCA-positive IgG-mediated GEnC activation through S1PR2-5. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

A comparison of freeway median crash frequency, severity, and barrier strike outcomes by median barrier type.

Science.gov (United States)

Russo, Brendan J; Savolainen, Peter T

2018-08-01

Median-crossover crashes are among the most hazardous events that can occur on freeways, often resulting in severe or fatal injuries. The primary countermeasure to reduce the occurrence of such crashes is the installation of a median barrier. When installation of a median barrier is warranted, transportation agencies are faced with the decision among various alternatives including concrete barriers, beam guardrail, or high-tension cable barriers. Each barrier type differs in terms of its deflection characteristics upon impact, the required installation and maintenance costs, and the roadway characteristics (e.g., median width) where installation would be feasible. This study involved an investigation of barrier performance through an in-depth analysis of crash frequency and severity data from freeway segments where high-tension cable, thrie-beam, and concrete median barriers were installed. A comprehensive manual review of crash reports was conducted to identify crashes in which a vehicle left the roadway and encroached into the median. This review also involved an examination of crash outcomes when a barrier strike occurred, which included vehicle containment, penetration, or re-direction onto the travel lanes. The manual review of crash reports provided critical supplementary information through narratives and diagrams not normally available through standard fields on police crash report forms. Statistical models were estimated to identify factors that affect the frequency, severity, and outcomes of median-related crashes, with particular emphases on differences between segments with varying median barrier types. Several roadway-, traffic-, and environmental-related characteristics were found to affect these metrics, with results varying across the different barrier types. The results of this study provide transportation agencies with important guidance as to the in-service performance of various types of median barrier. Copyright © 2018 Elsevier Ltd. All rights

Protective barrier development: Overview

International Nuclear Information System (INIS)

Wing, N.R.; Gee, G.W.

1990-01-01

Protective barrier and warning marker systems are being developed to isolate wastes disposed of near the earth's surface at the Hanford Site. The barrier is designed to function in an arid to semiarid climate, to limit infiltration and percolation of water through the waste zone to near-zero, to be maintenance free, and to last up to 10,000 yr. Natural materials (e.g., fine soil, sand, gravel, riprap, clay, asphalt) have been selected to optimize barrier performance and longevity and to create an integrated structure with redundant features. These materials isolate wastes by limiting water drainage; reducing the likelihood of plant, animal, and human intrusion; controlling emission of noxious gases; and minimizing erosion. Westinghouse Hanford Company and Pacific Northwest Laboratory efforts to assess the performance of various barrier and marker designs will be discussed

Detection of Chronic Kidney Disease by Using Different Equations of Glomerular Filtration Rate in Patients with Type 2 Diabetes Mellitus: A Cross-Sectional Analysis

OpenAIRE

Zaman, Sojib Bin

2017-01-01

Introduction Chronic kidney disease (CKD) is a global threat due to its high mortality. It is essential to know the actual magnitude of diabetic CKD to design a specific management program. However, there is limited knowledge regarding the most suitable equation to measure CKD in patients with Type 2 diabetes mellitus (T2DM). This paper aimed to analyze estimated glomerular filtration rate (eGFR) based on different equations to detect the CKD among T2DM.? Methods A hospital-based cross-sectio...

The Evolving Complexity of the Podocyte Cytoskeleton.

Science.gov (United States)

Schell, Christoph; Huber, Tobias B

2017-11-01

Podocytes exhibit a unique cytoskeletal architecture that is fundamentally linked to their function in maintaining the kidney filtration barrier. The cytoskeleton regulates podocyte shape, structure, stability, slit diaphragm insertion, adhesion, plasticity, and dynamic response to environmental stimuli. Genetic mutations demonstrate that even slight impairment of the podocyte cytoskeletal apparatus results in proteinuria and glomerular disease. Moreover, mechanisms underpinning all acquired glomerular pathologies converge on disruption of the cytoskeleton, suggesting that this subcellular structure could be targeted for therapeutic purposes. This review summarizes our current understanding of the function of the cytoskeleton in podocytes and the associated implications for pathophysiology. Copyright © 2017 by the American Society of Nephrology.

Anti-glomerular basement membrane glomerulonephritis in an HIV positive patient: case report

Directory of Open Access Journals (Sweden)

Eduardo José Bellotto Monteiro

Full Text Available We report on a case of a patient with HIV infection, diagnosed 18 months prior to the development of an anti-glomerular basement membrane (anti-GBM rapidly progressive glomerulonephritis; this is probably the first report of such an association. A 30-year-old white man presented with elevation of serum creatinine (1.3 - 13.5 mg/dL within one month. At admission, the urinalysis showed proteinuria of 7.2 g/L and 8,000,000 erythrocytes/mL. Renal biopsy corresponded to a crescentic diffuse proliferative glomerulonephritis mediated by anti-GBM, and serum testing for anti-GBM antibodies was positive; antinuclear antibodies (ANA and anti-neutrophilic cytoplasmic antibodies (ANCA were also positive. The patient underwent hemodyalisis and was treated with plasmapheresis, cyclophosphamide and prednisone. The association described here is not casual, as crescentic glomerulonephritis is not common in HIV-positive patients, anti-GBM glomerulonephritis is rare and anti-GBM antibodies are frequently observed in HIV-positive subjects when compared to the overall population. Based on the current case and on the elevated frequency of the positivity for such antibodies in this group of patients, it is advisable to be aware of the eventual association between these two conditions and to promote an active search for anti-GBM antibodies and early diagnosis of eventual urinary abnormalities in HIV-positive subjects, considering the severity of anti-GBM glomerulonephritis.

Fusion barriers in heavy ion collisions

International Nuclear Information System (INIS)

Zhu Long; Su Jun; Xie Wenjie; Guo Chenchen; Zhang Donghong; Zhang Fengshou

2014-01-01

Study of fusion barrier is very important for people to better understand fusion reactions. In this paper the Improved Isospin-dependent Quantum Molecular Dynamics (ImIQMD) model is introduced firstly. Then the shell correction effects, energy dependence, isospin effects and orientation effects of fusion barrier are studied. The fusion barriers for the fusion reactions "4"0Ca + "4"0Ca, "4"8Ca + "2"0"8Pb, "4"8Ca + "2"0"4Pb and "1"6O + "1"5"4Sm are extracted. The negative shell correction energies lower potential barriers of a certain reaction. A complex phenomenon of energy dependence is observed. It is also found that incident energy dependence of the barrier radius and barrier height shows opposite behaviors. The Coulomb potential shows weak energy dependence when distance of two colliding nuclei is lower than the touching distance. The isospin effects of the potential barrier are investigated. The orientation effects of the potential barrier are also discussed for the system "1"6O + "1"5"4Sm. (authors)

Determination of the best method to estimate glomerular filtration rate from serum creatinine in adult patients with sickle cell disease: a prospective observational cohort study

Directory of Open Access Journals (Sweden)

Arlet Jean-Benoît

2012-08-01

Full Text Available Abstract Background Sickle cell disease (SCD leads to tissue hypoxia resulting in chronic organ dysfunction including SCD associated nephropathy. The goal of our study was to determine the best equation to estimate glomerular filtration rate (GFR in SCD adult patients. Methods We conducted a prospective observational cohort study. Since 2007, all adult SCD patients in steady state, followed in two medical departments, have had their GFR measured using iohexol plasma clearance (gold standard. The Cockcroft-Gault, MDRD-v4, CKP-EPI and finally, MDRD and CKD-EPI equations without adjustment for ethnicity were tested to estimate GFR from serum creatinine. Estimated GFRs were compared to measured GFRs according to the graphical Bland and Altman method. Results Sixty-four SCD patients (16 men, median age 27.5 years [range 18.0-67.5], 41 with SS-genotype were studied. They were Sub-Saharan Africa and French West Indies natives and predominantly lean (median body mass index: 22 kg/m2 [16-33]. Hyperfiltration (defined as measured GFR >110 mL/min/1.73 m2 was detected in 53.1% of patients. Urinary albumin/creatinine ratio was higher in patients with hyperfiltration than in patients with normal GFR (4.05 mg/mmol [0.14-60] versus 0.4 mg/mmol [0.7-81], p = 0.01. The CKD-EPI equation without adjustment for ethnicity had both the lowest bias and the greatest precision. Differences between estimated GFRs using the CKP-EPI equation and measured GFRs decreased with increasing GFR values, whereas it increased with the Cockcroft-Gault and MDRD-v4 equations. Conclusions We confirm that SCD patients have a high rate of glomerular hyperfiltration, which is frequently associated with microalbuminuria or macroalbuminuria. In non-Afro-American SCD patients, the best method for estimating GFR from serum creatinine is the CKD-EPI equation without adjustment for ethnicity. This equation is particularly accurate to estimate high GFR values, including glomerular

Predictors of estimated glomerular filtration rate progression, stabilization or improvement after chronic renal impairment in HIV-positive individuals

DEFF Research Database (Denmark)

Ryom, Lene; Mocroft, Amanda; Kirk, Ole

2017-01-01

OBJECTIVES: The objectives of this analysis were to investigate predictors of progression, stabilization or improvement in estimated glomerular filtration rate (eGFR) after development of chronic renal impairment (CRI) in HIV-positive individuals. DESIGN: Prospective observational study. METHODS......: The Data Collection on Adverse events of Anti-HIV Drugs (D:A:D) study participants progressing to CRI defined as confirmed, at least 3 months apart, and eGFR 70 ml/min per 1.73 m or less were included in the analysis. The median of all eGFRs measured 24-36 months post-CRI was compared with the median e......GFR defining CRI, and changes were grouped into improvement (>+10 ml/min per 1.73 m), stabilization (-10 to +10 ml/min per 1.73 m) and progression (

Economic alternatives for containment barriers

International Nuclear Information System (INIS)

Nicholson, P.J.; Jasperse, B.H.; Fisher, M.J.

1997-01-01

Fixation, barriers, and containment of existing landfills and other disposal areas are often performed by insitu auger type soil mixing and jet grouting. Cement or other chemical reagents are mixed with soil to form both vertical and horizontal barriers. Immobilization of contaminants can be economically achieved by mixing soil and the contaminants with reagents that solidify or stabilize the contaminated area. Developed in Japan, and relatively new to the United States, the first large scale application was for a vertical barrier at the Jackson Lake Dam project in 1986. This technology has grown in both the civil and environmental field since. The paper describes current United States practice for Deep Soil Mixing (over 12 meters in depth), and Shallow Soil Mixing for vertical barriers and stabilization/solidification, and Jet Grouting for horizontal and vertical barriers. Creating very low permeability barriers at depth with minimal surface return often makes these techniques economical when compared to slurry trenches. The paper will discuss equipment, materials, soil and strength parameters, and quality control

Progress on Incorporating Zeolites in Matrimid®5218 Mixed Matrix Membranes towards Gas Separation

Directory of Open Access Journals (Sweden)

Roberto Castro-Muñoz

2018-06-01

Full Text Available Membranes, as perm-selective barriers, have been widely applied for gas separation applications. Since some time ago, pure polymers have been used mainly for the preparation of membranes, considering different kinds of polymers for such preparation. At this point, polyimides (e.g., Matrimid®5218 are probably one of the most considered polymers for this purpose. However, the limitation on the performance relationship of polymeric membranes has promoted their enhancement through the incorporation of different inorganic materials (e.g., zeolites into their matrix. Therefore, the aim of this work is to provide an overview about the progress of zeolite embedding in Matrimid®5218, aiming at the preparation of mixed matrix membranes for gas separation. Particular attention is paid to the relevant experimental results and current findings. Finally, we describe the prospects and future trends in the field.

Adjustment of Serum HE4 to reduced Glomerular filtration and its use in Biomarker-based prediction of deep Myometrial invasion in endometrial cancer

DEFF Research Database (Denmark)

Chovanec, Josef; Selingerova, Iveta; Greplova, Kristina

2017-01-01

Background: We investigated the efficacy of circulating biomarkers together with histological grade and age to predict deep myometrial invasion (dMI) in endometrial cancer patients. Methods: HE4ren was developed adjusting HE4 serum levels towards decreased glomerular filtration rate as quantified...... levels to reduced eGFR that enables quantification of time-dependent changes in HE4 production and elimination irrespective of age and renal function in women. Utilizing HE4ren improves performance of biomarker-based models for prediction of dMI in endometrial cancer patients....

Synthesis of alkyl-ether glycerophospholipids in rat glomerular mesangial cells: evidence for alkyldihydroxyacetone phosphate synthase activity

International Nuclear Information System (INIS)

Zanglis, A.; Lianos, E.A.

1987-01-01

We studied the ability of rat glomerular mesangial cells and their microsomal fractions to incorporate 1-[ 14 C]hexadecanol to glycerophospholipids via an O-alkyl ether linkage and assessed the presence and activity of the required enzyme: alkyl-dihydroxy acetone phosphate synthase. Suspensions of cultured mesangial cells incorporated 1-[ 14 C]hexadecanol to the phosphatidyl ethanolamine and phosphatidyl choline lipid pools, via a bond resistant to acid and base hydrolysis. When cell homogenates or microsomal fractions were incubated with palmitoyl-DHAP and 1-[ 14 C]hexadecanol, alkyl-DHAP and 1-O-alkyl glycerol were formed (alkyl:hexadecyl). The activity of the enzyme responsible for the O-alkyl product formation was calculated to be 2.5 +/- 0.3 and 544 +/- 50 pmoles/min/mg protein for mesangial cell homogenates and mesangial cell microsomes, respectively. These observations provide evidence that mesangial cells may elaborate either linked lipid precursors de novo for the biosynthesis of O-alkyl glycerophospholipids

Converse Barrier Certificate Theorem

DEFF Research Database (Denmark)

Wisniewski, Rafael; Sloth, Christoffer

2013-01-01

This paper presents a converse barrier certificate theorem for a generic dynamical system.We show that a barrier certificate exists for any safe dynamical system defined on a compact manifold. Other authors have developed a related result, by assuming that the dynamical system has no singular...... points in the considered subset of the state space. In this paper, we redefine the standard notion of safety to comply with generic dynamical systems with multiple singularities. Afterwards, we prove the converse barrier certificate theorem and illustrate the differences between ours and previous work...

Tunnel superpenetrability of potential barriers

International Nuclear Information System (INIS)

Zakhariev, B N.

1982-01-01

The transmission of two particles through the same barrier is considered. The limiting cases are compared when the particles are joined together in a single particle with double mass-energy and potential and when they pass the barrier independently. As an intermediate case a pair of particles bound in a quasideuteron of a finite size is considered. It is shown that long-range collective correlations of particles (of the superfluidity type and others) simplify very much for them passing through high potential barriers. This happens due to the transfer of the additional energy from the particles outside the barriers to those inside it

Barrier rf systems in synchrotrons

International Nuclear Information System (INIS)

Bhat, Chandra M.

2004-01-01

Recently, many interesting applications of the barrier RF system in hadron synchrotrons have been realized. A remarkable example of this is the development of longitudinal momentum mining and implementation at the Fermilab Recycler for extraction of low emittance pbars for the Tevatron shots. At Fermilab, we have barrier RF systems in four different rings. In the case of Recycler Ring, all of the rf manipulations are carried out using a barrier RF system. Here, the author reviews various uses of barrier rf systems in particle accelerators including some new schemes for producing intense proton beam and possible new applications

Subsurface barrier verification technologies, informal report

International Nuclear Information System (INIS)

Heiser, J.H.

1994-06-01

One of the more promising remediation options available to the DOE waste management community is subsurface barriers. Some of the uses of subsurface barriers include surrounding and/or containing buried waste, as secondary confinement of underground storage tanks, to direct or contain subsurface contaminant plumes and to restrict remediation methods, such as vacuum extraction, to a limited area. To be most effective the barriers should be continuous and depending on use, have few or no breaches. A breach may be formed through numerous pathways including: discontinuous grout application, from joints between panels and from cracking due to grout curing or wet-dry cycling. The ability to verify barrier integrity is valuable to the DOE, EPA, and commercial sector and will be required to gain full public acceptance of subsurface barriers as either primary or secondary confinement at waste sites. It is recognized that no suitable method exists for the verification of an emplaced barrier's integrity. The large size and deep placement of subsurface barriers makes detection of leaks challenging. This becomes magnified if the permissible leakage from the site is low. Detection of small cracks (fractions of an inch) at depths of 100 feet or more has not been possible using existing surface geophysical techniques. Compounding the problem of locating flaws in a barrier is the fact that no placement technology can guarantee the completeness or integrity of the emplaced barrier. This report summarizes several commonly used or promising technologies that have been or may be applied to in-situ barrier continuity verification

Escaping the correction for body surface area when calculating glomerular filtration rate in children

Energy Technology Data Exchange (ETDEWEB)

Piepsz, Amy; Tondeur, Marianne [CHU St. Pierre, Department of Radioisotopes, Brussels (Belgium); Ham, Hamphrey [University Hospital Ghent, Department of Nuclear Medicine, Ghent (Belgium)

2008-09-15

{sup 51}Cr ethylene diamine tetraacetic acid ({sup 51}Cr EDTA) clearance is nowadays considered as an accurate and reproducible method for measuring glomerular filtration rate (GFR) in children. Normal values in function of age, corrected for body surface area, have been recently updated. However, much criticism has been expressed about the validity of body surface area correction. The aim of the present paper was to present the normal GFR values, not corrected for body surface area, with the associated percentile curves. For that purpose, the same patients as in the previous paper were selected, namely those with no recent urinary tract infection, having a normal left to right {sup 99m}Tc MAG3 uptake ratio and a normal kidney morphology on the early parenchymal images. A single blood sample method was used for {sup 51}Cr EDTA clearance measurement. Clearance values, not corrected for body surface area, increased progressively up to the adolescence. The percentile curves were determined and allow, for a single patient, to estimate accurately the level of non-corrected clearance and the evolution with time, whatever the age. (orig.)

Fluctuations in Schottky barrier heights

International Nuclear Information System (INIS)

Mahan, G.D.

1984-01-01

A double Schottky barrier is often formed at the grain boundary in polycrystalline semiconductors. The barrier height is shown to fluctuate in value due to the random nature of the impurity positions. The magnitude of the fluctuations is 0.1 eV, and the fluctuations cause the barrier height measured by capacitance to differ from the one measured by electrical conductivity

Albumin-induced apoptosis of glomerular parietal epithelial cells is modulated by extracellular signal-regulated kinase 1/2

Science.gov (United States)

Ohse, Takamoto; Krofft, Ron D.; Wu, Jimmy S.; Eddy, Allison A.; Pippin, Jeffrey W.; Shankland, Stuart J.

2012-01-01

Background. The biological role(s) of glomerular parietal epithelial cells (PECs) is not fully understood in health or disease. Given its location, PECs are constantly exposed to low levels of filtered albumin, which is increased in nephrotic states. We tested the hypothesis that PECs internalize albumin and increased uptake results in apoptosis. Methods. Confocal microscopy of immunofluorescent staining and immunohistochemistry were used to demonstrate albumin internalization in PECs and to quantitate albumin uptake in normal mice and rats as well as experimental models of membranous nephropathy, minimal change disease/focal segmental glomerulosclerosis and protein overload nephropathy. Fluorescence-activated cell sorting analysis was performed on immortalized cultured PECs exposed to fluorescein isothiocyanate (FITC)-labeled albumin in the presence of an endosomal inhibitor or vehicle. Apoptosis was measured by Hoechst staining in cultured PECs exposed to bovine serum albumin. Levels of phosphorylated extracellular signal-regulated kinase 1 and 2 (p-ERK1/2) were restored by retroviral infection of mitogen-activated protein kinase (MEK) 1/2 and reduced by U0126 in PECs exposed to high albumin levels in culture and apoptosis measured by Hoechst staining. Results. PECs internalized albumin normally, and this was markedly increased in all of the experimental disease models (P PECs also internalize FITC-labeled albumin, which was reduced by endosomal inhibition. A consequence of increased albumin internalization was PEC apoptosis in vitro and in vivo. Candidate signaling pathways underlying these events were examined. Data showed markedly reduced levels of phosphorylated extracellular signal-regulated kinase 1 and 2 (ERK1/2) in PECs exposed to high albumin levels in nephropathy and in culture. A role for ERK1/2 in limiting albumin-induced apoptosis was shown by restoring p-ERK1/2 by retroviral infection, which reduced apoptosis in cultured PECs, while a forced

Converse Barrier Certificate Theorems

DEFF Research Database (Denmark)

Wisniewski, Rafael; Sloth, Christoffer

2016-01-01

This paper shows that a barrier certificate exists for any safe dynamical system. Specifically, we prove converse barrier certificate theorems for a class of structurally stable dynamical systems. Other authors have developed a related result by assuming that the dynamical system has neither...

Barrier inhomogeneities limited current and 1/f noise transport in GaN based nanoscale Schottky barrier diodes

Science.gov (United States)

Kumar, Ashutosh; Heilmann, M.; Latzel, Michael; Kapoor, Raman; Sharma, Intu; Göbelt, M.; Christiansen, Silke H.; Kumar, Vikram; Singh, Rajendra

2016-01-01

The electrical behaviour of Schottky barrier diodes realized on vertically standing individual GaN nanorods and array of nanorods is investigated. The Schottky diodes on individual nanorod show highest barrier height in comparison with large area diodes on nanorods array and epitaxial film which is in contrast with previously published work. The discrepancy between the electrical behaviour of nanoscale Schottky diodes and large area diodes is explained using cathodoluminescence measurements, surface potential analysis using Kelvin probe force microscopy and 1ow frequency noise measurements. The noise measurements on large area diodes on nanorods array and epitaxial film suggest the presence of barrier inhomogeneities at the metal/semiconductor interface which deviate the noise spectra from Lorentzian to 1/f type. These barrier inhomogeneities in large area diodes resulted in reduced barrier height whereas due to the limited role of barrier inhomogeneities in individual nanorod based Schottky diode, a higher barrier height is obtained. PMID:27282258

Richards Barrier LA Reference Design Feature Evaluation

International Nuclear Information System (INIS)

N.E. Kramer

1999-01-01

The Richards Barrier is one of the design features of the repository to be considered for the License Application (LA), Richards was a soil scientist who first described the diversion of moisture between two materials with different hydrologic properties. In this report, a Richards Barrier is a special type of backfill with a fine-grained material (such as sand) overlaying a coarse-grained material (such as gravel). Water that enters an emplacement drift will first encounter the fine-grained material and be transported around the coarse-grained material covering the waste package, thus protecting the waste package from contact with most of the groundwater. The objective of this report is to discuss the benefits and liabilities to the repository by the inclusion of a Richards Barrier type backfill in emplacement drifts. The Richards Barrier can act as a barrier to water flow, can reduce the waste package material dissolution rate, limit mobilization of the radionuclides, and can provide structural protection for the waste package. The scope of this report is to: (1) Analyze the behavior of barrier materials following the intrusion of groundwater for influxes of 1 to 300 mm per year. The report will demonstrate diversion of groundwater intrusions into the barrier over an extended time period when seismic activity and consolidation may cause the potential for liquefaction and settlement of the Richards Barrier. (2) Review the thermal effects of the Richards Barrier on material behavior. (3) Analyze the effect of rockfall on the performance of the Richards Barrier and the depth of the barrier required to protect waste packages under the barrier. (4) Review radiological and heating conditions on placement of multiple layers of the barrier. Subsurface Nuclear Safety personnel will perform calculations to determine the radiation reduction-time relationship and shielding capacity of the barrier. (5) Evaluate the effects of ventilation on cooling of emplacement drifts and

Skin barrier composition

International Nuclear Information System (INIS)

Osburn, F.G.

1985-01-01

A skin barrier composition comprises a mixture of a copolymer resin of ethylene and vinyl acetate (EVA), and a water-insoluble dry tack-providing elastomer such as polyisobutylene. The composition after mixing and molding, is subjected to ionizing irradiation to form cross-linked polymer networks of the EVA. The compositions have exceptional properties for use as barrier sheets, rings, or strips in ostomy, wound drainage, and incontinence devices. (author)

Skin barrier composition

Energy Technology Data Exchange (ETDEWEB)

Osburn, F G

1985-06-12

A skin barrier composition comprises a mixture of a copolymer resin of ethylene and vinyl acetate (EVA), and a water-insoluble dry tack-providing elastomer such as polyisobutylene. The composition after mixing and molding, is subjected to ionizing irradiation to form cross-linked polymer networks of the EVA. The compositions have exceptional properties for use as barrier sheets, rings, or strips in ostomy, wound drainage, and incontinence devices.

Barriers for recess physical activity

DEFF Research Database (Denmark)

Pawlowski, Charlotte Skau; Tjørnhøj-Thomsen, Tine; Schipperijn, Jasper

2014-01-01

BACKGROUND: Many children, in particular girls, do not reach the recommended amount of daily physical activity. School recess provides an opportunity for both boys and girls to be physically active, but barriers to recess physical activity are not well understood. This study explores gender...... differences in children's perceptions of barriers to recess physical activity. Based on the socio-ecological model four types of environmental barriers were distinguished: natural, social, physical and organizational environment. METHODS: Data were collected through 17 focus groups (at 17 different schools...... this study, we recommend promoting recess physical activity through a combination of actions, addressing barriers within the natural, social, physical and organizational environment....

Validation of estimated glomerular filtration rate equations for Japanese children.

Science.gov (United States)

Gotoh, Yoshimitsu; Uemura, Osamu; Ishikura, Kenji; Sakai, Tomoyuki; Hamasaki, Yuko; Araki, Yoshinori; Hamda, Riku; Honda, Masataka

2018-01-25

The gold standard for evaluation of kidney function is renal inulin clearance (Cin). However, the methodology for Cin is complicated and difficult, especially for younger children and/or patients with bladder dysfunction. Therefore, we developed a simple and easier method for obtaining the estimated glomerular filtration rate (eGFR) using equations and values for several biomarkers, i.e., serum creatinine (Cr), serum cystatin C (cystC), serum beta-2 microglobulin (β 2 MG), and creatinine clearance (Ccr). The purpose of the present study was to validate these equations with a new data set. To validate each equation, we used data of 140 patients with CKD with clinical need for Cin, using the measured GFR (mGFR). We compared the results for each eGFR equation with the mGFR using mean error (ME), root mean square error (RMSE), P 30 , and Bland-Altman analysis. The ME of Cr, cystC, β 2 MG, and Ccr based on eGFR was 15.8 ± 13.0, 17.2 ± 16.5, 15.4 ± 14.3, and 10.6 ± 13.0 ml/min/1.73 m 2 , respectively. The RMSE was 29.5, 23.8, 20.9, and 16.7, respectively. The P 30 was 79.4, 71.1, 69.5, and 92.9%, respectively. The Bland-Altman bias analysis showed values of 4.0 ± 18.6, 5.3 ± 16.8, 12.7 ± 17.0, and 2.5 ± 17.2 ml/min/1.73 m 2 , respectively, for these parameters. The bias of each eGFR equation was not large. Therefore, each eGFR equation could be used.

Sub-barrier fusion and near-barrier quasi-elastic scattering

International Nuclear Information System (INIS)

Kolata, J.J.; Tighe, R.J.

1990-01-01

Elastic scattering of 32 S on 58,64 Ni and fusion of 32 S+ 58,64 Ni and 34 S+ 64 Ni have been measured at energies near the Coulomb barrier. Our results differ in several important respects from previous measurements on these systems. Coupled-channels calculations which explicitly allow for inelastic excitation and single-nucleon transfer reproduce the main features of the new data. Near-barrier elastic scattering of 48 Ca on 40 Ca has also been measured. These data provide evidence for the effect of strong coupling to positive Q-value channels other than single-nucleon transfer. 18 refs., 3 figs

Self-regulation of turbulence bursts and transport barriers

International Nuclear Information System (INIS)

Floriani, E; Ciraolo, G; Ghendrih, Ph; Sarazin, Y; Lima, R

2013-01-01

The interplay between turbulent bursts and transport barriers is analyzed with a simplified model of interchange turbulence in magnetically confined plasmas. The turbulent bursts spread into the transport barriers and, depending on the competing magnitude of the burst and stopping capability of the barrier, can burn through. Simulations of two models of transport barriers are presented: a hard barrier where interchange turbulence modes are stable in a prescribed region and a soft barrier with external plasma biasing. The response of the transport barriers to the non-linear perturbations of the turbulent bursts, addressed in a predator–prey approach, indicates that the barriers monitor an amplification factor of the turbulent bursts, with amplification smaller than one for most bursts and, in some cases, amplification factors that can significantly exceed unity. The weak barriers in corrugated profiles and magnetic structures, as well as the standard barriers, are characterized by these transmission properties, which then regulate the turbulent burst transport properties. The interplays of barriers and turbulent bursts are modeled as competing stochastic processes. For different classes of the probability density function (PDF) of these processes, one can predict the heavy tail properties of the bursts downstream from the barrier, either exponential for a leaky barrier, or with power laws for a tight barrier. The intrinsic probing of the transport barriers by the turbulent bursts thus gives access to the properties of the barriers. The main stochastic variables are the barrier width and the spreading distance of the turbulent bursts within the barrier, together with their level of correlation. One finds that in the case of a barrier with volumetric losses, such as radiation or particle losses as addressed in our present simulations, the stochastic model predicts a leaky behavior with an exponential PDF of escaping turbulent bursts in agreement with the simulation

Identifying barriers to emergency care services.

Science.gov (United States)

Cannoodt, Luk; Mock, Charles; Bucagu, Maurice

2012-01-01

This paper aims to present a review of published evidence of barriers to emergency care, with attention towards both financial and other barriers. With the keywords (financial) accessibility, barriers and emergency care services, citations in PubMed were searched and further selected in the context of the objective of this article. Forty articles, published over a period of 15 years, showed evidence of significant barriers to emergency care. These barriers often tend to persist, despite the fact that the evidence was published many years ago. Several publications stressed the importance of the financial barriers in foregoing or delaying potentially life-saving emergency services, both in poor and rich countries. Other publications report non-financial barriers that prevent patients in need of emergency care (pre-hospital and in-patient care) from seeking care, from arriving in the proper emergency department without undue delay or from receiving proper treatment when they do arrive in these departments. It is clear that timely access to life-saving and disability-preventing emergency care is problematic in many settings. Yet, low-cost measures can likely be taken to significantly reduce these barriers. It is time to make an inventory of these measures and to implement the most cost-effective ones worldwide. Copyright © 2011 John Wiley & Sons, Ltd.

Cryogenic Barrier Demonstration Project. Final report

Energy Technology Data Exchange (ETDEWEB)

Johnson, L.A.; Yarmak, E.; Long, E.L.

2000-03-01

A long-term frozen soil barrier was implemented at the HRE (Homogeneous Reactor Experiment) Pond facility at the Oak Ridge National Laboratory in 1997. This was performed to verify the technical feasibility and costs of deploying a frozen barrier at a radiologically contaminated site. Work began in September 1996 and progressed through to December 1999. The frozen barrier has been operational since November 1997. Verification of the barrier integrity was performed independently by the EPA's SITE Program. This project showed frozen barriers offer a proven technology to retain below grade hazardous substances at relatively low costs with minimal effect on the environment.

Fuzzy barrier distributions

International Nuclear Information System (INIS)

Piasecki, E.

2009-01-01

Heavy-ion collisions often produce a fusion barrier distribution with structures displaying a fingerprint of couplings to highly collective excitations [1]. Basically the same distribution can be obtained from large-angle quasi-elastic scattering, though here the role of the many weak direct-reaction channels is unclear. For 2 0N e + 9 0Z r we have observed the barrier structures expected for the highly deformed neon projectile, but for 2 0N e + 9 2Z r we find completely smooth distribution (see Fig.1). We find that transfer channels in these systems are of similar strength but single particle excitations are significantly stronger in the latter case. They apparently reduce the 'resolving power' of the quasi-elastic channel, what leads to smeared out, or 'fuzzy' barrier distribution. This is the first case when such a phenomenon has been observed.(author)

Barriers to evidence-based medicine: a systematic review.

Science.gov (United States)

Sadeghi-Bazargani, Homayoun; Tabrizi, Jafar Sadegh; Azami-Aghdash, Saber

2014-12-01

Evidence-based medicine (EBM) has emerged as an effective strategy to improve health care quality. The aim of this study was to systematically review and carry out an analysis on the barriers to EBM. Different database searching methods and also manual search were employed in this study using the search words ('evidence-based' or 'evidence-based medicine' or 'evidence-based practice' or 'evidence-based guidelines' or 'research utilization') and (barrier* or challenge or hinder) in the following databases: PubMed, Scopus, Web of Knowledge, Cochrane library, Pro Quest, Magiran, SID. Out of 2592 articles, 106 articles were finally identified for study. Research barriers, lack of resources, lack of time, inadequate skills, and inadequate access, lack of knowledge and financial barriers were found to be the most common barriers to EBM. Examples of these barriers were found in primary care, hospital/specialist care, rehabilitation care, medical education, management and decision making. The most common barriers to research utilization were research barriers, cooperation barriers and changing barriers. Lack of resources was the most common barrier to implementation of guidelines. The result of this study shows that there are many barriers to the implementation and use of EBM. Identifying barriers is just the first step to removing barriers to the use of EBM. Extra resources will be needed if these barriers are to be tackled. © 2014 John Wiley & Sons, Ltd.

Market and Policy Barriers to Energy Storage Deployment

Energy Technology Data Exchange (ETDEWEB)

Bhatnagar, Dhruv [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Currier, Aileen [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Hernandez, Jacquelynne [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Ma, Ookie [Dept. of Energy (DOE), Washington DC (United States) Office of Energy Efficiency and Renewable Energy; Kirby, Brendan [Consultant

2013-09-01

Electric energy storage technologies can provide numerous grid services; there are a number of factors that restrict their current deployment. The most significant barrier to deployment is high capital costs, though several recent deployments indicate that capital costs are decreasing and energy storage may be the preferred economic alternative in certain situations. However, a number of other market and regulatory barriers persist, limiting further deployment. These barriers can be categorized into regulatory barriers, market (economic) barriers, utility and developer business model barriers, cross-cutting barriers and technology barriers.

Information barriers and authentication

International Nuclear Information System (INIS)

MacArthur, D.W.; Wolford, J.K.

2001-01-01

Acceptance of nuclear materials into a monitoring regime is complicated if the materials are in classified shapes or have classified composition. An attribute measurement system with an information barrier can be emplo,yed to generate an unclassified display from classified measurements. This information barrier must meet two criteria: (1) classified information cannot be released to the monitoring party, and (2) the monitoring party must be convinced that the unclassified output accurately represents the classified input. Criterion 1 is critical to the host country to protect the classified information. Criterion 2 is critical to the monitoring party and is often termed the 'authentication problem.' Thus, the necessity for authentication of a measurement system with an information barrier stems directly from the description of a useful information barrier. Authentication issues must be continually addressed during the entire development lifecycle of the measurement system as opposed to being applied only after the system is built.

Fusion barrier characteristics of actinides

Science.gov (United States)

Manjunatha, H. C.; Sridhar, K. N.

2018-03-01

We have studied fusion barrier characteristics of actinide compound nuclei with atomic number range 89 ≤ Z ≤ 103 for all projectile target combinations. After the calculation of fusion barrier heights and positions, we have searched for their parameterization. We have achieved the empirical formula for fusion barrier heights (VB), positions (RB), curvature of the inverted parabola (ħω) of actinide compound nuclei with atomic number range 89 ≤ Z ≤ 103 for all projectile target combinations (6 projectile target combinations. The values produced by the present formula are also compared with experiments. The present pocket formula produces fusion barrier characteristics of actinides with the simple inputs of mass number (A) and atomic number (Z) of projectile-targets.

Congenital nephrotic syndrome.

Science.gov (United States)

Hamed, Radi Ma

2003-01-01

The congenital nephrotic syndrome (CNS) is an uncommon disorder with onset of the nephrotic syndrome usually in the first three months of life. Several different diseases may cause the syndrome. These may be inherited, sporadic, acquired or part of a general malformation syndrome. The clinical course is marked by failure to thrive, recurrent life threatening bacterial infections, and early death from sepsis and/or uremia. A characteristic phenotype may be seen in children with CNS. The majority of reported cases of CNS are of the Finnish type (CNF). Although the role of the glomerular basement membrane has been emphasized as the barrier for retaining plasma proteins, recent studies have clearly shown that the slit diaphragm is the structure most likely to be the barrier in the glomerular capillary wall. The gene (NPHS1) was shown to encode a novel protein that was termed nephrin, due to its specific location in the kidney filter barrier, where it seems to form a highly organized filter structure. Nephrin is a transmembrane protein that probably forms the main building block of an isoporous zipper-like slit diaphragm filter structure. Defects in nephrin lead to the abnormal or absent slit diaphragm resulting in massive proteinuria and renal failure.

Prediction of cardiovascular outcome by estimated glomerular filtration rate and estimated creatinine clearance in the high-risk hypertension population of the VALUE trial.

Science.gov (United States)

Ruilope, Luis M; Zanchetti, Alberto; Julius, Stevo; McInnes, Gordon T; Segura, Julian; Stolt, Pelle; Hua, Tsushung A; Weber, Michael A; Jamerson, Ken

2007-07-01

Reduced renal function is predictive of poor cardiovascular outcomes but the predictive value of different measures of renal function is uncertain. We compared the value of estimated creatinine clearance, using the Cockcroft-Gault formula, with that of estimated glomerular filtration rate (GFR), using the Modification of Diet in Renal Disease (MDRD) formula, as predictors of cardiovascular outcome in 15 245 high-risk hypertensive participants in the Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial. For the primary end-point, the three secondary end-points and for all-cause death, outcomes were compared for individuals with baseline estimated creatinine clearance and estimated GFR or = 60 ml/min using hazard ratios and 95% confidence intervals. Coronary heart disease, left ventricular hypertrophy, age, sex and treatment effects were included as covariates in the model. For each end-point considered, the risk in individuals with poor renal function at baseline was greater than in those with better renal function. Estimated creatinine clearance (Cockcroft-Gault) was significantly predictive only of all-cause death [hazard ratio = 1.223, 95% confidence interval (CI) = 1.076-1.390; P = 0.0021] whereas estimated GFR was predictive of all outcomes except stroke. Hazard ratios (95% CIs) for estimated GFR were: primary cardiac end-point, 1.497 (1.332-1.682), P cause death, 1.231 (1.098-1.380), P = 0.0004. These results indicate that estimated glomerular filtration rate calculated with the MDRD formula is more informative than estimated creatinine clearance (Cockcroft-Gault) in the prediction of cardiovascular outcomes.

ER stress and basement membrane defects combine to cause glomerular and tubular renal disease resulting from Col4a1 mutations in mice

Directory of Open Access Journals (Sweden)

Frances E. Jones

2016-02-01

Full Text Available Collagen IV is a major component of basement membranes, and mutations in COL4A1, which encodes collagen IV alpha chain 1, cause a multisystemic disease encompassing cerebrovascular, eye and kidney defects. However, COL4A1 renal disease remains poorly characterized and its pathomolecular mechanisms are unknown. We show that Col4a1 mutations in mice cause hypotension and renal disease, including proteinuria and defects in Bowman's capsule and the glomerular basement membrane, indicating a role for Col4a1 in glomerular filtration. Impaired sodium reabsorption in the loop of Henle and distal nephron despite elevated aldosterone levels indicates that tubular defects contribute to the hypotension, highlighting a novel role for the basement membrane in vascular homeostasis by modulation of the tubular response to aldosterone. Col4a1 mutations also cause diabetes insipidus, whereby the tubular defects lead to polyuria associated with medullary atrophy and a subsequent reduction in the ability to upregulate aquaporin 2 and concentrate urine. Moreover, haematuria, haemorrhage and vascular basement membrane defects confirm an important vascular component. Interestingly, although structural and compositional basement membrane defects occurred in the glomerulus and Bowman's capsule, no tubular basement membrane defects were detected. By contrast, medullary atrophy was associated with chronic ER stress, providing evidence for cell-type-dependent molecular mechanisms of Col4a1 mutations. These data show that both basement membrane defects and ER stress contribute to Col4a1 renal disease, which has important implications for the development of treatment strategies for collagenopathies.

Programmer's description of the Barrier Data Base

International Nuclear Information System (INIS)

Wall, D.W.; Jones, R.E.; Worrell, R.B.

1976-12-01

The Barrier Data Base is a body of information concerning different kinds of barriers that are used in safeguarding nuclear materials and installations. The two programs written for creating, updating, and manipulating the Barrier Data Base are discussed. The BARRIER program is used to add, delete, modify, display, or search for specific data in the data base. A utility program named NUMBER is used to compress and renumber the barrier and threat tables

Permanent isolation surface barrier development plan

International Nuclear Information System (INIS)

Wing, N.R.

1994-01-01

The exhumation and treatment of wastes may not always be the preferred alternative in the remediation of a waste site. In-place disposal alternatives, under certain circumstances, may be the most desirable alternatives to use in the protection of human health and the environment. The implementation of an in-place disposal alternative will likely require some type of protective covering that will provide long-term isolation of the wastes from the accessible environment. Even if the wastes are exhumed and treated, a long-term barrier may still be needed to adequately dispose of the treated wastes or any remaining waste residuals. Currently, no open-quotes provenclose quotes long-term barrier is available. The Hanford Site Permanent Isolation Surface Barrier Development Program (BDP) was organized to develop the technology needed to provide a long-term surface barrier capability for the Hanford Site. The permanent isolation barrier technology also could be used at other sites. Permanent isolation barriers use engineered layers of natural materials to create an integrated structure with redundant protective features. Drawings of conceptual permanent isolation surface barriers are shown. The natural construction materials (e.g., fine soil, sand, gravel, riprap, asphalt) have been selected to optimize barrier performance and longevity. The objective of current designs is to use natural materials to develop a maintenance-free permanent isolation surface barrier that isolates wastes for a minimum of 1,000 years by limiting water drainage to near-zero amounts; reducing the likelihood of plant, animal, and human intrusion; controlling the exhalation of noxious gases; and minimizing erosion-related problems

Permanent isolation surface barrier development plan

Energy Technology Data Exchange (ETDEWEB)

Wing, N.R.

1994-01-01

The exhumation and treatment of wastes may not always be the preferred alternative in the remediation of a waste site. In-place disposal alternatives, under certain circumstances, may be the most desirable alternatives to use in the protection of human health and the environment. The implementation of an in-place disposal alternative will likely require some type of protective covering that will provide long-term isolation of the wastes from the accessible environment. Even if the wastes are exhumed and treated, a long-term barrier may still be needed to adequately dispose of the treated wastes or any remaining waste residuals. Currently, no {open_quotes}proven{close_quotes} long-term barrier is available. The Hanford Site Permanent Isolation Surface Barrier Development Program (BDP) was organized to develop the technology needed to provide a long-term surface barrier capability for the Hanford Site. The permanent isolation barrier technology also could be used at other sites. Permanent isolation barriers use engineered layers of natural materials to create an integrated structure with redundant protective features. Drawings of conceptual permanent isolation surface barriers are shown. The natural construction materials (e.g., fine soil, sand, gravel, riprap, asphalt) have been selected to optimize barrier performance and longevity. The objective of current designs is to use natural materials to develop a maintenance-free permanent isolation surface barrier that isolates wastes for a minimum of 1,000 years by limiting water drainage to near-zero amounts; reducing the likelihood of plant, animal, and human intrusion; controlling the exhalation of noxious gases; and minimizing erosion-related problems.

Paraffin-based immunohistochemistry in the evaluation of glomerular diseases in renal biopsies

International Nuclear Information System (INIS)

Rathore, M.U.; Khadim, M.T.; Atique, M.

2012-01-01

Objective: To determine sensitivity and specificity of paraffin-based immunohistochemistry in the evaluation of glomerular diseases in renal biopsies using immunofluorescence as gold standard. Study Design: Cross-sectional analytical study. Place and Duration of Study: Department of Histopathology, Armed Forces Institute of Pathology, Rawalpindi, from August 2008 to August 2009. Methodology: Seventy renal biopsy specimens fulfilling the inclusion criteria for light microscopy and immuno-fluorescence during the study period were evaluated. Antibodies to immunoglobulins (IgG, IgA, and IgM) and components of complement system (C3) were applied on 70 formalin-fixed paraffin-embedded renal biopsy specimens previously classified by means of light microscopy and immunofluorescence (IF). Staining for these antibodies was recorded as positive and negative for immunohistochemistry (IHC) and IF in paired proportions presuming IF as gold standard test. The sensitivity, specificity, positive predictive value and negative predictive value of individual antibody were calculated. Results: Of 70 patients, mean age was 33 +- 18 years ranging from 2 to 80 years. Forty five (64%) were males and 25 (36%) were females. The sensitivity, specificity and predictive values of individual antibodies to IgG, IgA, IgM and C3 were very low and generally in the range of 40 - 60%. Conclusion: The sensitivity, specificity and predictive values of immunohistochemistry on formalin-fixed paraffin-embedded renal biopsy specimens were very low and therefore, not suitable for evaluation of renal biopsies in current circumstances. (author)

Tunnelling through a Gaussian random barrier

International Nuclear Information System (INIS)

Bezak, Viktor

2008-01-01

A thorough analysis of the tunnelling of electrons through a laterally inhomogeneous rectangular barrier is presented. The barrier height is defined as a statistically homogeneous Gaussian random function. In order to simplify calculations, we assume that the electron energy is low enough in comparison with the mean value of the barrier height. The randomness of the barrier height is defined vertically by a constant variance and horizontally by a finite correlation length. We present detailed calculations of the angular probability density for the tunnelled electrons (i.e. for the scattering forwards). The tunnelling manifests a remarkably diffusive character if the wavelength of the electrons is comparable with the correlation length of the barrier

Prototype Hanford Surface Barrier: Design basis document

International Nuclear Information System (INIS)

Myers, D.R.; Duranceau, D.A.

1994-11-01

The Hanford Site Surface Barrier Development Program (BDP) was organized in 1985 to develop the technology needed to provide a long-term surface barrier capability for the Hanford Site and other arid sites. This document provides the basis of the prototype barrier. Engineers and scientists have momentarily frozen evolving barrier designs and incorporated the latest findings from BDP tasks. The design and construction of the prototype barrier has required that all of the various components of the barrier be brought together into an integrated system. This integration is particularly important because some of the components of the protective barreir have been developed independently of other barreir components. This document serves as the baseline by which future modifications or other barrier designs can be compared. Also, this document contains the minutes of meeting convened during the definitive design process in which critical decisions affecting the prototype barrier's design were made and the construction drawings

Market barriers to welfare product innovations

NARCIS (Netherlands)

Binnekamp, M.H.A.; Ingenbleek, P.T.M.

2006-01-01

New products that are based on higher animal welfare standards encounter several barriers on the road to market acceptance. The authors focus on the Dutch poultry sector and distinguish between retailer and consumer barriers. Retailer barriers include the powerful position of retailers, the price

Deployment Efficiency and Barrier Effectiveness Testing of a Temporary Anti-Personnel (TAP) Barrier System.

Energy Technology Data Exchange (ETDEWEB)

Allen, David James [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Hedrick, Charles D. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Martinez, Ruben [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

2017-02-01

This report documents tests conducted by Sandia National Laboratories (SNL) on behalf of the U.S. Department of State to evaluate a temporary anti-personnel (TAP) barrier system developed by Mitigation Technologies. For this, the SNL Denial and Structural Assessment department developed a test protocol for the evaluation of the TAP barrier system on the basis of deployment efficiency and barrier effectiveness against a riotous/mob attack threat. The test protocol was then executed by SNL personnel and the results of the testing are documented.

Effects of barrier composition and electroplating chemistry on adhesion and voiding in copper/dielectric diffusion barrier films

Energy Technology Data Exchange (ETDEWEB)

Birringer, Ryan P.; Dauskardt, Reinhold H. [Department of Materials Science and Engineering, Stanford University, Durand Building, Stanford, California 94305-4034 (United States); Shaviv, Roey [Novellus Systems Inc., 4000 North First Street, San Jose, California 95134 (United States); Geiss, Roy H.; Read, David T. [National Institute of Standards and Technology, 325 Broadway, Boulder, Colorado 80305 (United States)

2011-08-15

The effects of electroplating chemistry and dielectric diffusion barrier composition on copper voiding and barrier adhesion are reported. Adhesion was quantified using the four-point bend thin film adhesion technique, and voiding in the Cu films was quantified using scanning electron microscopy. A total of 12 different film stacks were investigated, including three different Cu electroplating chemistries and four different barrier materials (SiN, N-doped SiC, O-doped SiC, and dual-layer SiC). Both plating chemistry and barrier composition have a large effect on interface adhesion and voiding in the Cu film. X-ray photoelectron spectroscopy was used to investigate the segregation of Cu electroplating impurities, such as S and Cl, to the Cu/barrier interface. Secondary ion mass spectrometry was used to quantify oxygen content at the Cu/barrier interface in a subset of samples. This interface oxygen content is correlated with measured adhesion values.

Adjustment of serum HE4 to reduced glomerular filtration and its use in biomarker-based prediction of deep myometrial invasion in endometrial cancer

DEFF Research Database (Denmark)

Chovanec, Josef; Selingerova, Iveta; Greplova, Kristina

2017-01-01

based on single-institution data from 120 EC patients and validated against multicentric data from 379 EC patients. Results: In non-cancer individuals, serum HE4 levels increase log-linearly with reduced glomerular filtration of eGFR = 90 ml/min/1.73 m2. HE4ren, adjusting HE4 serum levels to decreased e...... levels to reduced eGFR that enables quantification of time-dependent changes in HE4 production and elimination irrespective of age and renal function in women. Utilizing HE4ren improves performance of biomarker-based models for prediction of dMI in endometrial cancer patients....

Measuring solvent barrier properties of paper

International Nuclear Information System (INIS)

Bollström, Roger; Saarinen, Jarkko J; Toivakka, Martti; Räty, Jukka

2012-01-01

New methods for measuring barrier properties against solvents, acids and bases on dispersion coated paper were developed and investigated. Usability, reliability and repeatability were compared both between the new methods and with the standardized method for measuring barrier properties against water vapor. Barrier properties could be measured with all methods and the results obtained by the different methods were in correlation with each other. A qualitative method based on a trace color provided an indicative result, whereas further developed methods also took into account the durability. The effective barrier lifetime could be measured by measuring the conductivity through the substrate as a function of time, or by utilizing a glass prism where the change in refractive index caused by penetrated liquid was monitored, also as a function of time. Barrier properties against water and humidity were also measured and were found not to be predictors for barrier properties against either solvents, or acids or bases, which supports the need to develop new methods

Radon barrier: Method of testing airtightness

DEFF Research Database (Denmark)

Rasmussen, Torben Valdbjørn; Buch-Hansen, Thomas Cornelius

2017-01-01

The test method NBI 167/02 Radon membrane: Test of airtightness can be used for determining the airtightness of a radon barrier as a system solution. The test determines the air infiltration through the radon barrier for a number of levels of air pressure differences. The airflow through versus...... of the barrier with the low air pressure, through a well-defined opening, as a modification of the test method in general. Results, obtained using the improved test method, are shown for a number of radon barriers tested....

Associations of blood lead, cadmium, and mercury with estimated glomerular filtration rate in the Korean general population: Analysis of 2008-2010 Korean National Health and Nutrition Examination Survey data

Energy Technology Data Exchange (ETDEWEB)

Kim, Yangho [Department of Occupational and Environmental Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan (Korea, Republic of); Lee, Byung-Kook, E-mail: bklee@sch.ac.kr [Institute of Environmental and Occupational Medicine, Soonchunhyang University 646 Eupnae-ri, Shinchang-myun, Asan-si, Choongnam 336-745 (Korea, Republic of)

2012-10-15

Introduction: The objective of this study was to evaluate associations between blood lead, cadmium, and mercury levels with estimated glomerular filtration rate in a general population of South Korean adults. Methods: This was a cross-sectional study based on data obtained in the Korean National Health and Nutrition Examination Survey (KNHANES) (2008-2010). The final analytical sample consisted of 5924 participants. Estimated glomerular filtration rate (eGFR) was calculated using the MDRD Study equation as an indicator of glomerular function. Results: In multiple linear regression analysis of log2-transformed blood lead as a continuous variable on eGFR, after adjusting for covariates including cadmium and mercury, the difference in eGFR levels associated with doubling of blood lead were -2.624 mL/min per 1.73 m Superscript-Two (95% CI: -3.803 to -1.445). In multiple linear regression analysis using quartiles of blood lead as the independent variable, the difference in eGFR levels comparing participants in the highest versus the lowest quartiles of blood lead was -3.835 mL/min per 1.73 m Superscript-Two (95% CI: -5.730 to -1.939). In a multiple linear regression analysis using blood cadmium and mercury, as continuous or categorical variables, as independent variables, neither metal was a significant predictor of eGFR. Odds ratios (ORs) and 95% CI values for reduced eGFR calculated for log2-transformed blood metals and quartiles of the three metals showed similar trends after adjustment for covariates. Discussion: In this large, representative sample of South Korean adults, elevated blood lead level was consistently associated with lower eGFR levels and with the prevalence of reduced eGFR even in blood lead levels below 10 {mu}g/dL. In conclusion, elevated blood lead level was associated with lower eGFR in a Korean general population, supporting the role of lead as a risk factor for chronic kidney disease.

Reliability of single kidney glomerular filtration rate measured by a 99mTc-DTPA gamma camera technique

International Nuclear Information System (INIS)

Rehling, M.; Moller, M.L.; Jensen, J.J.; Thamdrup, B.; Lund, J.O.; Trap-Jensen, J.

1986-01-01

The reliability of a previously published method for determination of single kidney glomerular filtration rate (SKGFR) by means of technetium-99m-diethylenetriaminepenta-acetate (99mTc-DTPA) gamma camera renography was evaluated. The day-to-day variation in the calculated SKGFR values was earlier found to be 8.8%. The technique was compared to the simultaneously measured renal clearance of inulin in 19 unilaterally nephrectomized patients with GFR varying from 11 to 76 ml/min. The regression line (y = 1.04 X -2.5) did not differ significantly from the line of identity. The standard error of estimate was 4.3 ml/min. In 17 patients the inter- and intraobserver variation of the calculated SKGFR values was 1.2 ml/min and 1.3 ml/min, respectively. In 21 of 25 healthy subjects studied (age range 27-29 years), total GFR calculated from the renograms was within an established age-dependent normal range of GFR

Rac1 in podocytes promotes glomerular repair and limits the formation of sclerosis.

Science.gov (United States)

Asao, Rin; Seki, Takuto; Takagi, Miyuki; Yamada, Hiroyuki; Kodama, Fumiko; Hosoe-Nagai, Yoshiko; Tanaka, Eriko; Trejo, Juan Alejandro Oliva; Yamamoto-Nonaka, Kanae; Sasaki, Yu; Hidaka, Teruo; Ueno, Takashi; Yanagita, Motoko; Suzuki, Yusuke; Tomino, Yasuhiko; Asanuma, Katsuhiko

2018-03-22

Rac1, a Rho family member, is ubiquitously expressed and participates in various biological processes. Rac1 expression is induced early in podocyte injury, but its role in repair is unclear. To investigate the role of Rac1 expression in podocytes under pathological conditions, we used podocyte-specific Rac1 conditional knock-out (cKO) mice administered adriamycin (ADR), which causes nephrosis and glomerulosclerosis. Larger areas of detached podocytes, more adhesion of the GBM to Bowman's capsule, and a higher ratio of sclerotic glomeruli were observed in Rac1 cKO mice than in control mice, whereas no differences were observed in glomerular podocyte numbers in both groups after ADR treatment. The mammalian target of rapamycin (mTOR) pathway, which regulates the cell size, was more strongly suppressed in the podocytes of Rac1 cKO mice than in those of control mice under pathological conditions. In accordance with this result, the volumes of podocytes in Rac1 cKO mice were significantly reduced compared with those of control mice. Experiments using in vitro ADR-administered Rac1 knockdown podocytes also supported that a reduction in Rac1 suppressed mTOR activity in injured podocytes. Taken together, these data indicate that Rac1-associated mTOR activation in podocytes plays an important role in preventing the kidneys from developing glomerulosclerosis.

The ADF/Cofilin-Pathway and Actin Dynamics in Podocyte Injury

Directory of Open Access Journals (Sweden)

Beina Teng

2012-01-01

Full Text Available ADF/cofilins are the major regulators of actin dynamics in mammalian cells. The activation of ADF/cofilins is controlled by a variety of regulatory mechanisms. Dysregulation of ADF/cofilin may result in loss of a precisely organized actin cytoskeletal architecture and can reduce podocyte migration and motility. Recent studies suggest that cofilin-1 can be regulated through several extracellular signals and slit diaphragm proteins. Cofilin knockdown and knockout animal models show dysfunction of glomerular barrier and filtration with foot process effacement and loss of secondary foot processes. This indicates that cofilin-1 is necessary for modulating actin dynamics in podocytes. Podocyte alterations in actin architecture may initiate or aid the progression of a large variety of glomerular diseases, and cofilin activity is required for reorganization of an intact filtration barrier. Since almost all proteinuric diseases result from a similar phenotype with effacement of the foot processes, we propose that cofilin-1 is at the centre stage of the development of proteinuria and thus may be an attractive drug target for antiproteinuric treatment strategies.

Kidney-specific Sonoporation-mediated Gene Transfer.

Science.gov (United States)

Ishida, Ryo; Kami, Daisuke; Kusaba, Tetsuro; Kirita, Yuhei; Kishida, Tsunao; Mazda, Osam; Adachi, Takaomi; Gojo, Satoshi

2016-02-01

Sonoporation can deliver agents to target local organs by systemic administration, while decreasing the associated risk of adverse effects. Sonoporation has been used for a variety of materials and in a variety of organs. Herein, we demonstrated that local sonoporation to the kidney can offer highly efficient transfer of oligonucleotides, which were systemically administrated to the tubular epithelium with high specificity. Ultrasonic wave irradiation to the kidney collapsed the microbubbles and transiently affected the glomerular filtration barrier and increased glomerular permeability. Oligonucleotides were passed through the barrier all at once and were absorbed throughout the tubular epithelium. Tumor necrosis factor alpha (TNFα), which plays a central role in renal ischemia-reperfusion injury, was targeted using small interfering RNA (siRNA) with renal sonoporation in a murine model. The reduction of TNFα expression after single gene transfer significantly inhibited the expression of kidney injury markers, suggesting that systemic administration of siRNA under temporary and local sonoporation could be applicable in the clinical setting of ischemic acute kidney injury.

Insight into podocyte differentiation from the study of human genetic disease: nail-patella syndrome and transcriptional regulation in podocytes.

Science.gov (United States)

Morello, Roy; Lee, Brendan

2002-05-01

In recent years, our understanding of the molecular basis of kidney development has benefited from the study of rare genetic diseases affecting renal function. This has especially been the case with the differentiation of the highly specialized podocyte in the pathogenesis of human disorders and mouse phenotypes affecting the renal filtration barrier. This filtration barrier represents the end product of a complex series of signaling events that produce a tripartite structure consisting of interdigitating podocyte foot processes with intervening slit diaphragms, the glomerular basement membrane, and the fenestrated endothelial cell. Dysregulation of unique cytoskeletal and extracellular matrix proteins in genetic forms of nephrotic syndrome has shown how specific structural proteins contribute to podocyte function and differentiation. However, much less is known about the transcriptional determinants that both specify and maintain this differentiated cell. Our studies of a skeletal malformation syndrome, nail-patella syndrome, have shown how the LIM homeodomain transcription factor, Lmx1b, contributes to transcriptional regulation of glomerular basement membrane collagen expression by podocytes. Moreover, they raise intriguing questions about more global transcriptional regulation of podocyte morphogenesis.

Double barrier system for an in situ conversion process

Science.gov (United States)

McKinzie, Billy John [Houston, TX; Vinegar, Harold J [Bellaire, TX; Cowan, Kenneth Michael [Sugar land, TX; Deeg, Wolfgang Friedrich Johann [Houston, TX; Wong, Sau-Wai [Rijswijk, NL

2009-05-05

A barrier system for a subsurface treatment area is described. The barrier system includes a first barrier formed around at least a portion of the subsurface treatment area. The first barrier is configured to inhibit fluid from exiting or entering the subsurface treatment area. A second barrier is formed around at least a portion of the first barrier. A separation space exists between the first barrier and the second barrier.

Engineered barriers: current status 1989

International Nuclear Information System (INIS)

Atkinson, A.; Marsh, G.B.

1989-06-01

This report summarises the current state of research relevant to assessing the performance of engineered barriers made of steel and concrete in radioactive waste repositories. The objective of these barriers is to contain substantially the radionuclides within them by providing both physical and chemical impediment to their release. The physical barriers are of most value for highly soluble isotopes with relatively short half-lives (eg 137 Cs), since they can provide a measure of containment until a large fraction of the activity has decayed. In addition they can facilitate retrievability for some period after disposal. The chemical barriers operate by beneficial conditioning of the near field groundwater and providing sites for sorption of radionuclides. Both of these reduce the aqueous concentration of radionuclides in the near field. (author)

Transport barrier in Helical system

International Nuclear Information System (INIS)

Ida, Katsumi

1998-01-01

Experiments on the transport barrier in Helical plasmas are reviewed. There are two mechanisms of transport improvement, that results in the formation of the transport barrier. One is the improvement of neoclassical transport by reducing the ripple loss with radial electric field, which exist only in helical plasma. The other is the improvement of anomalous transport due to the suppression of fluctuations associated with a radial electric field shear both in tokamak and helical plasma. The formation of the transport barrier can be triggered by the radial electric field shear associated with the transition of the radial electric field (L/H transition or ion-electron root transition) or the peaked density or the optimization of magnetic field shear. The mechanisms of transport barrier formation are also discussed. (author). 60 refs

Glomerular Filtration Rate in Patients with Multiple Sclerosis Undergoing Stem Cell Transplantation and Treated With Cyclophosphamide.

Science.gov (United States)

Ruiz-Argüelles, Alejandro; Gastélum-Cano, Jose M; Méndez-Huerta, Mariana A; Rodríguez-Gallegos, Alma B; Ruiz-Argüelles, Guillermo J

2018-06-15

Glomerular filtration rate (GFR) is partially impaired in patients with multiple sclerosis (MS). When given chemotherapy before receiving hematopoietic stem-cell transplantation, GFR might be further deteriorated. To measure the effect of cyclophosphamide on GFR in patients with MS who undergo chemotherapy. We estimated GFR based on creatinine and cystatin C plasma concentrations in patients undergoing autologous hematopoietic stem-cell transplantation to treat their MS. Baseline GFR values were lower in the 28 patients with MS than in the 20 healthy individuals. Also, according to the Chronic Kidney Disease-Epidemiology Collaborative Group (CKD-EPI) 2012 Creat-CysC equation criteria, 4 of 28 patients were classified as having chronic kidney disease (CKD) before receiving the chemotherapy drugs. After receiving 4 × 50 mg per kg body weight cyclophosphamide, abnormal GFR results were recorded in 12 of 28 patients. Renal function must be monitored in patients with MS undergoing autologous stem-cell transplantation. Also, chemotherapy should be constrained as much as possible to prevent further deterioration of renal function.

Influence of Acute High Glucose on Protein Abundance Changes in Murine Glomerular Mesangial Cells

Directory of Open Access Journals (Sweden)

Michelle T. Barati

2016-01-01

Full Text Available The effects of acute exposure to high glucose levels as experienced by glomerular mesangial cells in postprandial conditions and states such as in prediabetes were investigated using proteomic methods. Two-dimensional gel electrophoresis and matrix assisted laser desorption ionization time of flight mass spectrometry methods were used to identify protein expression patterns in immortalized rat mesangial cells altered by 2 h high glucose (HG growth conditions as compared to isoosmotic/normal glucose control (NG⁎ conditions. Unique protein expression changes at 2 h HG treatment were measured for 51 protein spots. These proteins could be broadly grouped into two categories: (1 proteins involved in cell survival/cell signaling and (2 proteins involved in stress response. Immunoblot experiments for a protein belonging to both categories, prohibitin (PHB, supported a trend for increased total expression as well as significant increases in an acidic PHB isoform. Additional studies confirmed the regulation of proteasomal subunit alpha-type 2 and the endoplasmic reticulum chaperone and oxidoreductase PDI (protein disulfide isomerase, suggesting altered ER protein folding capacity and proteasomal function in response to acute HG. We conclude that short term high glucose induces subtle changes in protein abundances suggesting posttranslational modifications and regulation of pathways involved in proteostasis.

Mediated Intercultural Communication Barrier in No Drama Zone! Group

OpenAIRE

Lizal, Valentino

2015-01-01

This research study aimed to describe the mediated intercultural communication barriers in the No Drama Zone! group. This study is a qualitative descriptive type of research, with case study method. By doing in depth interview and observation, researcher found two barriers that generates other barriers in the group's mediated intercultural communication. The two big barriers were: language and physical barriers. Language barriers in this group generated two barriers, emotional barrier and pe...

Design of a bioartificial pancreas

Science.gov (United States)

Pareta, Rajesh A; Farney, Alan C; Opara, Emmanuel C

2013-01-01

Summary Islet transplantation has been shown to be a viable treatment option for patients afflicted with Type 1 diabetes. However, the severe shortage of human pancreas and the need to use risky immunosuppressive drugs to prevent transplant rejection remain two major obstacles to routine use of islet transplantation in diabetic patients. Successful development of a bioartificial pancreas using the approach of microencapsulation with perm-selective coating of islets in hydrogels for graft immunoisolation holds tremendous promise for diabetic patients because it has great potential to overcome these two barriers. In this review article, we will discuss the need for bioartificial pancreas, provide a detailed description of the microencapsulation process, and review the status of the technology in clinical development. We will also critically review the various factors that need to be taken into consideration in order to achieve the ultimate goal of routine clinical application. PMID:23652283

Article Including Environmental Barrier Coating System

Science.gov (United States)

Lee, Kang N. (Inventor)

2015-01-01

An enhanced environmental barrier coating for a silicon containing substrate. The enhanced barrier coating may include a bond coat doped with at least one of an alkali metal oxide and an alkali earth metal oxide. The enhanced barrier coating may include a composite mullite bond coat including BSAS and another distinct second phase oxide applied over said surface.

Psychological Barriers to Behavior Change: How to indentify the barriers that inhibit change

OpenAIRE

Olson, James M.

1992-01-01

Adopting a healthy lifestyle often requires changing patterns of behavior. This article describes three categories of psychological barriers to behavior change: those that prevent the admission of a problem, those that interfere with initial attempts to change behavior, and those that make long-term change difficult. Strategies are identified that family physicians can use to overcome the barriers.

Development and modification of glass membranes for aggressive gas separations

Energy Technology Data Exchange (ETDEWEB)

Lindbraaten, Arne

2004-07-01

important s factor as the perm-selectivities. To evaluate this, both short- and long-term aggressive gas exposures are performed using a special designed durability chamber. From the combination of the perm-selectivities and the durability tests, the following conclusions may be drawn (evaluated at 30 Deg C and 1 bar): Firstly, the pure glasses have a relatively poor stability (for chlorine gas) and the perm-selectivity is too low (for both separations in question). Secondly, the C8 and C12 modified glass membranes have a relatively satisfactory perm-selectivity for chlorine separation, but the durability in chlorine is poor. Thirdly, the long-chained C 18 modified glass membrane has a relatively satisfactory perm-selectivity but a fair to low chlorine stability. If the C 18 membrane is applied in the hydrogen chlorine separation the perm-selectivity is a bit low, but the stability is sufficient. However, this membrane is the best choice for a low temperature HC1 selective membrane. Finally, to improve the chlorine stability, a perfluorinated version of a C 10 modification is tried out. This membrane has excellent chlorine stability, and the perm-selectivity is fair. This membrane is the best choice for a chlorine selective membrane. The stability of the fibres is comparable to that found for the pure glass tubes. However, the permeabilities in the glass fibres are several orders of magnitude lower than for the glass tubes. The pore size in the fibre is so narrow that separation occurs according to a molecular sieving mechanism. The mounting of the fibres into a lab-sized module is tricky and the permeabilities are at the border of detection, so the results obtained here should only serve as trends. (Author)

Electrical characteristics of schottky barriers on 4H-SiC: The effects of barrier height nonuniformity

Science.gov (United States)

Skromme, B. J.; Luckowski, E.; Moore, K.; Bhatnagar, M.; Weitzel, C. E.; Gehoski, T.; Ganser, D.

2000-03-01

Electrical properties, including current-voltage (I-V) and capacitance-voltage (C-V) characteristics, have been measured on a large number of Ti, Ni, and Pt-based Schottky barrier diodes on 4H-SiC epilayers. Various nonideal behaviors are frequently observed, including ideality factors greater than one, anomalously low I-V barrier heights, and excess leakage currents at low forward bias and in reverse bias. The nonidealities are highly nonuniform across individual wafers and from wafer to wafer. We find a pronounced linear correlation between I-V barrier height and ideality factor for each metal, while C-V barrier heights remain constant. Electron beam induced current (EBIC) imaging strongly suggests that the nonidealities result from localized low barrier height patches. These patches are related to discrete crystal defects, which become visible as recombination centers in the EBIC images. Alternative explanations involving generation-recombination current, uniform interfacial layers, and effects related to the periphery are ruled out.

Air barrier systems: Construction applications

Energy Technology Data Exchange (ETDEWEB)

Perrault, J.C

1989-01-01

An examination is presented of how ordinary building materials can be used in an innovative manner to design, detail, and construct effective air barrier systems for common types of walls. For residential construction, the air drywall approach uses the interior gypsum board as the main component of the wall air barrier system. Joints between the gypsum board and adjacent materials or assemblies are sealed by gaskets. In commercial construction, two different techniques are employed for using gypsum board as air barrier material: the accessible drywall and non-accessible drywall approaches. The former is similar to the air drywall approach except that high performance sealants are used instead of gaskets. In the latter approach, exterior drywall sheathing is the main component of the air barrier system; joints between boards are taped and joints between boards and other components are sealed using elastomeric membrane strips. For various types of commercial and institutional buildings, metal air barrier systems are widely used and include pre-engineered curtain walls or sheet metal walls. Masonry wall systems are regarded as still the most durable, fireproof, and soundproof wall type available but an effective air barrier system has typically been difficult to implement. Factory-made elastomeric membranes offer the potential to provide airtightness to masonry walls. These membranes are applied on the entire masonry wall surface and are used to make airtight connections with other building components. Two types of product are available: thermofusible and peel-and-stick membranes. 5 figs.

Podocyte Pathology and Nephropathy

Directory of Open Access Journals (Sweden)

Sandra eMerscher

2014-07-01

Full Text Available Sphingolipids are components of the lipid rafts in plasma membranes, which are important for proper function of podocytes, a key element of the glomerular filtration barrier. Research revealed an essential role of sphingolipids and sphingolipid metabolites in glomerular disorders of genetic and non-genetic origin. The discovery that glucocerebrosides accumulate in Gaucher disease in glomerular cells and are associated with clinical proteinuria initiated intensive research into the function of other sphingolipids in glomerular disorders. The accumulation of sphingolipids in other genetic diseases including Tay-Sachs, Sandhoff, Fabry, hereditary inclusion body myopathy 2, Niemann-Pick and nephrotic syndrome of the Finnish type and its implications with respect to glomerular pathology will be discussed. Similarily, sphingolipid accumulation occurs in glomerular diseases of non-genetic origin including diabetic kidney disease (DKD, HIV-associated nephropathy, focal segmental glomerulosclerosis (FSGS and lupus nephritis. Sphingomyelin metabolites, such as ceramide, sphingosine and sphingosine-1-phosphate have also gained tremendous interest. We recently described that sphingomyelin phosphodiesterase acid-like 3b (SMPDL3b is expressed in podocytes where it modulates acid sphingomyelinase (ASMase activity and acts as a master modulator of danger signaling. Decreased SMPDL3b expression in post-reperfusion kidney biopsies from transplant recipients with idiopathic FSGS correlates with the recurrence of proteinuria in patients and in experimental models of xenotransplantation. Increased SMPDL3b expression is associated with DKD. The consequences of differential SMPDL3b expression in podocytes in these diseases with respect to their pathogenesis will be discussed. Finally, the role of sphingolipids in the formation of lipid rafts in podocytes and their contribution to the maintenance of a functional slit diaphragm in the glomerulus will be discussed.

Effects of topical application of aqueous solutions of hexoses on epidermal permeability barrier recovery rate after barrier disruption.

Science.gov (United States)

Denda, Mitsuhiro

2011-11-01

Previous studies have suggested that hexose molecules influence the stability of phospholipid bilayers. Therefore, the effects of topical application of all 12 stereoisomers of dextro-hexose on the epidermal barrier recovery rate after barrier disruption were evaluated. Immediately after tape stripping, 0.1 m aqueous solution of each hexose was applied on hairless mouse skin. Among the eight dextro-aldohexoses, topical application of altose, idose, mannose and talose accelerated the barrier recovery, while allose, galactose, glucose and gulose had no effect. Among the four dextro-ketohexoses, psicose, fructose, sorbose and tagatose all accelerated the barrier recovery. As the effects of hexoses on the barrier recovery rate appeared within 1 h, the mechanism is unlikely to be genomic. Instead, these hexoses may influence phase transition of the lipid bilayers of lamellar bodies and cell membrane, a crucial step in epidermal permeability barrier homeostasis. © 2011 John Wiley & Sons A/S.

Advanced house air-barrier systems

Energy Technology Data Exchange (ETDEWEB)

Lee, R.K. [Natural Resources Canada, Ottawa, ON (Canada)

1996-08-01

Air barrier systems used in modern Canadian airtight homes were discussed. The Advanced Houses Program sets its airtightness requirements at 1.5 air changes per hour at 50 Pascals pressure difference (ACH{sub 5}0). In recent tests of 10 houses, it was suggested that a better airtightness level was attainable with average airtightness of about 1.0 ACH{sub 5}0. Six of the homes tested did not use the traditional polyethylene approach. Two of the houses used the airtight drywall approach, one used a foam system, and three used exterior air barriers. The advantages and disadvantages of each system was described, including cost effectiveness, cost reduction, performance and installation advantages. The confusion between an air barrier and a vapour diffusion retarder was explained. Exterior air barriers showed the greatest potential for meeting airtightness requirements at reasonable cost. 5 refs., 3 tabs.

Podocytes [version 1; referees: 2 approved

Directory of Open Access Journals (Sweden)

Jochen Reiser

2016-01-01

Full Text Available Podocytes are highly specialized cells of the kidney glomerulus that wrap around capillaries and that neighbor cells of the Bowman’s capsule. When it comes to glomerular filtration, podocytes play an active role in preventing plasma proteins from entering the urinary ultrafiltrate by providing a barrier comprising filtration slits between foot processes, which in aggregate represent a dynamic network of cellular extensions. Foot processes interdigitate with foot processes from adjacent podocytes and form a network of narrow and rather uniform gaps. The fenestrated endothelial cells retain blood cells but permit passage of small solutes and an overlying basement membrane less permeable to macromolecules, in particular to albumin. The cytoskeletal dynamics and structural plasticity of podocytes as well as the signaling between each of these distinct layers are essential for an efficient glomerular filtration and thus for proper renal function. The genetic or acquired impairment of podocytes may lead to foot process effacement (podocyte fusion or retraction, a morphological hallmark of proteinuric renal diseases. Here, we briefly discuss aspects of a contemporary view of podocytes in glomerular filtration, the patterns of structural changes in podocytes associated with common glomerular diseases, and the current state of basic and clinical research.

Large magnetocurrents in double-barrier tunneling transistors

International Nuclear Information System (INIS)

Lee, J.H.; Jun, K.-I.; Shin, K.-H.; Park, S.Y.; Hong, J.K.; Rhie, K.; Lee, B.C.

2005-01-01

Magnetic tunneling transistors (MTT) with double tunneling barriers are fabricated. The structure of the transistor is AFM/FM/I/FM/I/FM/AFM, and ferromagnetic layers serve as the emitter, base and collector. This double-barrier tunneling transistor (DBTT) has an advantage of controlling the potential between the base and collector, compared to the Schottky-barrier-based base and collector of MTT. We found that the collector current density of DBTT is at least 10 3 times larger than that of conventional MTT, since tunneling through AlO x barrier provides much larger current density than that through Schottky barrier

Potential barrier classification by short-time measurement

International Nuclear Information System (INIS)

Granot, Er'el; Marchewka, Avi

2006-01-01

We investigate the short-time dynamics of a delta-function potential barrier on an initially confined wave packet. There are mainly two conclusions: (A) At short times the probability density of the first particles that passed through the barrier is unaffected by it. (B) When the barrier is absorptive (i.e., its potential is imaginary) it affects the transmitted wave function at shorter times than a real potential barrier. Therefore, it is possible to distinguish between an imaginary and a real potential barrier by measuring its effect at short times only on the transmitting wave function

Potential barrier classification by short-time measurement

Science.gov (United States)

Granot, Er'El; Marchewka, Avi

2006-03-01

We investigate the short-time dynamics of a delta-function potential barrier on an initially confined wave packet. There are mainly two conclusions: (A) At short times the probability density of the first particles that passed through the barrier is unaffected by it. (B) When the barrier is absorptive (i.e., its potential is imaginary) it affects the transmitted wave function at shorter times than a real potential barrier. Therefore, it is possible to distinguish between an imaginary and a real potential barrier by measuring its effect at short times only on the transmitting wave function.

Penetration through the Skin Barrier

DEFF Research Database (Denmark)

Nielsen, Jesper Bo; Benfeldt, Eva; Holmgaard, Rikke

2016-01-01

The skin is a strong and flexible organ with barrier properties essential for maintaining homeostasis and thereby human life. Characterizing this barrier is the ability to prevent some chemicals from crossing the barrier while allowing others, including medicinal products, to pass at varying rates......-through diffusion cells) as well as in vivo methods (microdialysis and microperfusion). Then follows a discussion with examples of how different characteristics of the skin (age, site and integrity) and of the penetrants (size, solubility, ionization, logPow and vehicles) affect the kinetics of percutaneous...

Big Data as Information Barrier

Directory of Open Access Journals (Sweden)

Victor Ya. Tsvetkov

2014-07-01

Full Text Available The article covers analysis of ‘Big Data’ which has been discussed over last 10 years. The reasons and factors for the issue are revealed. It has proved that the factors creating ‘Big Data’ issue has existed for quite a long time, and from time to time, would cause the informational barriers. Such barriers were successfully overcome through the science and technologies. The conducted analysis refers the “Big Data” issue to a form of informative barrier. This issue may be solved correctly and encourages development of scientific and calculating methods.

Associations of blood lead, cadmium, and mercury with estimated glomerular filtration rate in the Korean general population: Analysis of 2008–2010 Korean National Health and Nutrition Examination Survey data

International Nuclear Information System (INIS)

Kim, Yangho; Lee, Byung-Kook

2012-01-01

Introduction: The objective of this study was to evaluate associations between blood lead, cadmium, and mercury levels with estimated glomerular filtration rate in a general population of South Korean adults. Methods: This was a cross-sectional study based on data obtained in the Korean National Health and Nutrition Examination Survey (KNHANES) (2008–2010). The final analytical sample consisted of 5924 participants. Estimated glomerular filtration rate (eGFR) was calculated using the MDRD Study equation as an indicator of glomerular function. Results: In multiple linear regression analysis of log2-transformed blood lead as a continuous variable on eGFR, after adjusting for covariates including cadmium and mercury, the difference in eGFR levels associated with doubling of blood lead were −2.624 mL/min per 1.73 m² (95% CI: −3.803 to −1.445). In multiple linear regression analysis using quartiles of blood lead as the independent variable, the difference in eGFR levels comparing participants in the highest versus the lowest quartiles of blood lead was −3.835 mL/min per 1.73 m² (95% CI: −5.730 to −1.939). In a multiple linear regression analysis using blood cadmium and mercury, as continuous or categorical variables, as independent variables, neither metal was a significant predictor of eGFR. Odds ratios (ORs) and 95% CI values for reduced eGFR calculated for log2-transformed blood metals and quartiles of the three metals showed similar trends after adjustment for covariates. Discussion: In this large, representative sample of South Korean adults, elevated blood lead level was consistently associated with lower eGFR levels and with the prevalence of reduced eGFR even in blood lead levels below 10 μg/dL. In conclusion, elevated blood lead level was associated with lower eGFR in a Korean general population, supporting the role of lead as a risk factor for chronic kidney disease.

Late complications following total-body irradiation and bone marrow rescue in mice: predominance of glomerular nephropathy and hemolytic anemia

International Nuclear Information System (INIS)

Down, J.D.; Berman, A.J.; Mauch, P.; Warhol, M.

1990-01-01

Late mortality and pathology were assessed in various mouse strains following total-body irradiation (TBI) and bone marrow transplantation. Long-term survival data revealed both radiation dose- and strain-dependent onset of mortality between 1 and 2 years post-treatment. Renal damage appeared to have contributed to the late mortality in most treatment groups as shown by glomerular lesions, elevated blood urea nitrogen and an accompanying fall in hematocrit. Hemolysis was deduced to be the major cause of anemia, as concluded from results of 51 Cr-labeled erythrocyte survival. No decrease in erythropoiesis was evident as seen from spleen and bone marrow 59 Fe uptake. These findings are together consistent with the manifestation of a hemolytic uremic syndrome (HUS) with kidney glomeruli representing the principal sites of injury responsible for both renal dysfunction and microangiopathic hemolysis. (author)

Late complications following total-body irradiation and bone marrow rescue in mice: predominance of glomerular nephropathy and hemolytic anemia

Energy Technology Data Exchange (ETDEWEB)

Down, J.D.; Berman, A.J.; Mauch, P. (Harvard Medical School, Boston, MA (USA)); Warhol, M. (Pennsylvania Hospital, Philadelphia, PA (USA). Dept. of Pathology); Yeap, B. (Dana Farber Cancer Inst., Boston, MA (USA))

1990-03-01

Late mortality and pathology were assessed in various mouse strains following total-body irradiation (TBI) and bone marrow transplantation. Long-term survival data revealed both radiation dose- and strain-dependent onset of mortality between 1 and 2 years post-treatment. Renal damage appeared to have contributed to the late mortality in most treatment groups as shown by glomerular lesions, elevated blood urea nitrogen and an accompanying fall in hematocrit. Hemolysis was deduced to be the major cause of anemia, as concluded from results of {sup 51}Cr-labeled erythrocyte survival. No decrease in erythropoiesis was evident as seen from spleen and bone marrow {sup 59}Fe uptake. These findings are together consistent with the manifestation of a hemolytic uremic syndrome (HUS) with kidney glomeruli representing the principal sites of injury responsible for both renal dysfunction and microangiopathic hemolysis. (author).

Physician variation in perceived barriers to personal health

Directory of Open Access Journals (Sweden)

Rubenfire M

2012-01-01

Full Text Available Adam RB Kosteva1, Brian M Salata1, Sangeetha Mahadevan Krishnan2, Michael Howe3, Alissa Weber3, Melvyn Rubenfire2,3, Elizabeth A Jackson2,31Michigan Cardiovascular Research and Reporting Program, 2Division of Cardiovascular Medicine, 3Department of Internal Medicine, University of Michigan Health System, Ann Arbor, MI, USAObjective: Physicians’ personal health habits are associated with their counseling habits regarding physical activity. We sought to examine physicians’ own barriers to a healthy lifestyle by level of training and gender.Methods: Physicians at a major teaching hospital were surveyed regarding their lifestyle habits and barriers to healthy habits. The frequency of reported barriers was examined by years in practice (trainees vs staff physicians and gender.Results: 183 total responses were received. Over 20% of respondents were overweight. Work schedule was cited as the greatest barrier to regular exercise in 70.5% of respondents. Trainees were more likely to cite time constraints or cost as a barrier to a healthy diet compared to staff physicians. Staff physicians were more likely to report the time to prepare healthy foods as a barrier. For both trainees and staff physicians, time was a barrier to regular exercise. For trainees work schedule was a barrier, while both work schedule and family commitments were top barriers cited by staff physicians. Women were more likely to report family commitments as a barrier than men. Respondents suggested healthier options in vending machines and the hospital cafeteria, healthy recipes, and time and/or facilities for exercise at work as options to help overcome these barriers.Conclusion: Work schedules and family commitments are frequently reported by providers as barriers to healthy lifestyle. Efforts to reduce such barriers may lead to improved health habits among providers.Keywords: diet, exercise, counseling, prevention, gender, barriers, health

Permselectivity of the liver blood-lymph (ascitic fluid) barrier to macromolecules in decompensated cirrhosis: relation to calculated pore-size

DEFF Research Database (Denmark)

Henriksen, Jens Henrik Sahl

1983-01-01

in plasma and ascitic fluid from 13 cirrhotic patients. As previously substantiated in patients with cirrhosis, the ascitic fluid/plasma concentration ratio (R) of a protein is proportional to the transport rate from blood to lymph (ascitic fluid). Mean Ralb = 0.28 and RIgG = 0.29 were identical......, but significantly higher than, RIgM = 0.18 (P less than 0.01). Ralb was directly correlated to RIgG (r = 0.97, P less than 0.001) and to RIgM (r = 0.78, P less than 0.005). Mean RIgG/Ralb = 1.03, which expresses the relative flux rates between IgG and albumin, was significantly above the ratio between the free...... diffusion coefficients (DIgG/Dalb = 0.64, P less than 0.01). Mean RIgM/Ralb = 0.61 was significantly above DIgM/Dalb = 0.39 (P less than 0.05) and significantly below unity (P less than 0.01). The results are best explained by filtration as the dominant mechanism of the liver blood-lymph (ascitic fluid...