Tubule urate and PAH transport: sensitivity and specificity of serum protein inhibition

International Nuclear Information System (INIS)

Grantham, J.J.; Kennedy, J.; Cowley, B.

1987-01-01

Macromolecules in rabbit serum inhibit the cellular uptake and transepithelial secretion of [ 14 C]urate and p-[ 3 H]aminohippurate ([ 3 H]PAH) in rabbit S 2 proximal tubule segments. To understand better the potential role these inhibitors may have in the regulation of renal organic anion excretion, the authors examined the specificity and relative inhibitory effects on tubule urate and PAH transport of albumin and γ-globulin, the major inhibitory proteins in rabbit serum. Native rabbit serum markedly inhibited the cellular accumulation or urate and PAH by isolated nonperfused segments. Urate and PAH transport was also inhibited by bovine serum, human serum, Cohn-fractionated rabbit albumin, and rabbit γ-globulin, but not by Cohn-fractionated bovine serum albumin. α-Lactalbumin and β-lactoglobulin, derived from milk, also inhibited urate and PAH transport, but to a lesser extent than albumin and γ-globulin. The transport inhibitory effects of proteins were independent of their binding to urate and PAH. Unidirectional influx and the steady-state intracellular accumulation of urate and PAH in suspensions of proximal tubules were decreased by rabbit serum proteins, suggesting that these inhibitors act on the external face of the cells to diminish the uptake of the organic anions. These studies indicate that the principal plasma proteins (albumin and γ-globulin) significantly inhibit urate and PAH transporters in the basolateral membranes of S 2 proximal tubules. They suggest that circulating plasma proteins that can penetrate the basement membrane of proximal tubules may directly modulate the renal excretion of urate and PAH

Role of calcium in the dopaminergic effect on the proximal convoluted tubule of rat kidney

International Nuclear Information System (INIS)

Chan, Y.L.; Chatsudthipong, V.; Su-Tsai, S.M.; von Riotte, A.

1986-01-01

Microperfusion studies have shown that dopamine inhibits fluid and bicarbonate absorption in the rate proximal tubule. These studies are designed to examine the cellular mechanism underlying the proximal cellular response to dopamine action. In the isolated proximal cells, dopamine, in the concentration of 10 -6 M or less, had no effect on cAMP production. However, dopamine could increase cytosolic calcium concentration (from 90 nM to 210 nM) as measured by fluorospectrometry with fura-2 as a calcium indicator. Ca-45 flux studies have shown that dopamine could increase initial influx but not the steady state uptake of Ca. Dopamine could also increase efflux of Ca. In situ microperfusion of proximal tubule and peritubular capillaries has demonstrated that Ca ionophore, A23187 (10 -6 M), could simulate the inhibitory effects of dopamine on fluid and biocarbonate absorption. There was no additive effect observed when both agents were added together in the capillary perfusate. Removal of calcium from the perfusate could partially blunt the effect of dopamine. These results suggest that intracellular calcium plays a crucial role in the dopaminergic regulation of proximal tubular transport

Proximal tubule-specific glutamine synthetase deletion alters basal and acidosis-stimulated ammonia metabolism

NARCIS (Netherlands)

Lee, Hyun-Wook; Osis, Gunars; Handlogten, Mary E.; Lamers, Wouter H.; Chaudhry, Farrukh A.; Verlander, Jill W.; Weiner, I. David

2016-01-01

Glutamine synthetase (GS) catalyzes the recycling of NH4 (+) with glutamate to form glutamine. GS is highly expressed in the renal proximal tubule (PT), suggesting ammonia recycling via GS could decrease net ammoniagenesis and thereby limit ammonia available for net acid excretion. The purpose of

Data on Na,K-ATPase in primary cultures of renal proximal tubule cells treated with catecholamines

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Mary Taub

2016-03-01

Full Text Available This data article is concerned with chronic regulation of Na,K-ATPase by catecholamines. After a chronic treatment, inhibition of Na,K-ATPase activity was observed in cultures with dopamine, while a stimulation was observed in cultures treated with norepinephrine. Following a chronic incubation with guanabenz, an α adrenergic agonist, an increase in Na,K-ATPase α and β subunit mRNAs was observed. This data supports the research article entitled, “Renal proximal tubule Na, K-ATPase is controlled by CREB regulated transcriptional coactivators as well as salt inducible kinase 1” (Taub et al. 2015 [1]. Keywords: Catecholamines, Kidney, Proximal tubule, Na,K-ATPase, Chronic

A telomerase immortalized human proximal tubule cell line with a truncation mutation (Q4004X in polycystin-1.

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Brittney-Shea Herbert

Full Text Available Autosomal dominant polycystic kidney disease (ADPKD is associated with a variety of cellular phenotypes in renal epithelial cells. Cystic epithelia are secretory as opposed to absorptive, have higher proliferation rates in cell culture and have some characteristics of epithelial to mesenchymal transitions. In this communication we describe a telomerase immortalized cell line that expresses proximal tubule markers and is derived from renal cysts of an ADPKD kidney. These cells have a single detectable truncating mutation (Q4004X in polycystin-1. These cells make normal appearing but shorter cilia and fail to assemble polycystin-1 in the cilia, and less uncleaved polycystin-1 in membrane fractions. This cell line has been maintained in continuous passage for over 35 passages without going into senescence. Nephron segment specific markers suggest a proximal tubule origin for these cells and the cell line will be useful to study mechanistic details of cyst formation in proximal tubule cells.

Thiazolidinediones enhance sodium-coupled bicarbonate absorption from renal proximal tubules via PPARγ-dependent nongenomic signaling.

Science.gov (United States)

Endo, Yoko; Suzuki, Masashi; Yamada, Hideomi; Horita, Shoko; Kunimi, Motoei; Yamazaki, Osamu; Shirai, Ayumi; Nakamura, Motonobu; Iso-O, Naoyuki; Li, Yuehong; Hara, Masumi; Tsukamoto, Kazuhisa; Moriyama, Nobuo; Kudo, Akihiko; Kawakami, Hayato; Yamauchi, Toshimasa; Kubota, Naoto; Kadowaki, Takashi; Kume, Haruki; Enomoto, Yutaka; Homma, Yukio; Seki, George; Fujita, Toshiro

2011-05-04

Thiazolidinediones (TZDs) improve insulin resistance by activating a nuclear hormone receptor, peroxisome proliferator-activated receptor γ (PPARγ). However, the use of TZDs is associated with plasma volume expansion through a mechanism that remains to be clarified. Here we showed that TZDs rapidly stimulate sodium-coupled bicarbonate absorption from the renal proximal tubule in vitro and in vivo. TZD-induced transport stimulation is dependent on PPARγ-Src-EGFR-ERK and observed in rat, rabbit and human, but not in mouse proximal tubules where Src-EGFR is constitutively activated. The existence of PPARγ-Src-dependent nongenomic signaling, which requires the ligand-binding ability, but not the transcriptional activity of PPARγ, is confirmed in mouse embryonic fibroblast cells. The enhancement of the association between PPARγ and Src by TZDs supports an indispensable role of Src in this signaling. These results suggest that the PPARγ-dependent nongenomic stimulation of renal proximal transport is also involved in TZD-induced volume expansion. Copyright © 2011 Elsevier Inc. All rights reserved.

The Leptospira outer membrane protein LipL32 induces tubulointerstitial nephritis-mediated gene expression in mouse proximal tubule cells.

Science.gov (United States)

Yang, Chih-Wei; Wu, Mai-Szu; Pan, Ming-Jeng; Hsieh, Wang-Ju; Vandewalle, Alain; Huang, Chiu-Ching

2002-08-01

Tubulointerstitial nephritis is a main renal manifestation caused by pathogenic leptospira that accumulate mostly in the proximal tubules, thereby inducing tubular injury and tubulointerstitial nephritis. To elucidate the role of leptospira outer membrane proteins in tubulointerstitial nephritis, outer membrane proteins from pathogenic Leptospira shermani and nonpathogenic Leptospira patoc extracted by Triton X-114 were administered to cultured mouse proximal tubule cells. A dose-dependent increase of monocyte chemoattractant protein-1 (MCP-1), RANTES, nitrite, and tumor necrosis factor-alpha (TNF-alpha) in the culture supernatant was observed 48 h after incubating Leptospira shermani outer membrane proteins with mouse proximal tubule cells. RT competitive-PCR experiments showed that Leptospira shermani outer membrane proteins (0.2 microg/ml) increased the expression of MCP-1, nitric oxide synthase (iNOS), RANTES, and TNF-alpha mRNA by 3.0-, 9.4-, 2.5-, and 2.5-fold, respectively, when compared with untreated cells. Outer membrane proteins extract from avirulent Leptospira patoc did not induce significant effects. The pathogenic outer membrane proteins extract contain a major component of a 32-kD lipoprotein (LipL32), which is absent in the nonpathogenic leptospira outer membrane. An antibody raised against LipL32 prevented the stimulatory effect of Leptospira shermani outer membrane proteins extract on MCP-1 and iNOS mRNA expression in cultured proximal tubule cells, whereas recombinant LipL32 significantly stimulated the expression of MCP-1 and iNOS mRNAs and augmented nuclear binding of nuclear factor-kappaB (NF-kappaB) and AP-1 transcription factors in proximal tubule cells. An antibody raised against LipL32 also blunted the effects induced by the recombinant LipL32. This study demonstrates that LipL32 is a major component of pathogenic leptospira outer membrane proteins involved in the pathogenesis of tubulointerstitial nephritis.

Mechanism of cisplatin proximal tubule toxicity revealed by integrating transcriptomics, proteomics, metabolomics and biokinetics

NARCIS (Netherlands)

Wilmes, Anja; Bielow, Chris; Ranninger, Christina; Bellwon, Patricia; Aschauer, Lydia; Limonciel, Alice; Chassaigne, Hubert; Kristl, Theresa; Aiche, Stephan; Huber, Christian G; Guillou, Claude; Hewitt, Philipp; Leonard, Martin O; Dekant, Wolfgang; Bois, Frederic Y; Jennings, Paul

2015-01-01

Cisplatin is one of the most widely used chemotherapeutic agents for the treatment of solid tumours. The major dose-limiting factor is nephrotoxicity, in particular in the proximal tubule. Here, we use an integrated omics approach, including transcriptomics, proteomics and metabolomics coupled to

NMR-based urine analysis in rats: prediction of proximal tubule kidney toxicity and phospholipidosis.

Science.gov (United States)

Lienemann, Kai; Plötz, Thomas; Pestel, Sabine

2008-01-01

The aim of safety pharmacology is early detection of compound-induced side-effects. NMR-based urine analysis followed by multivariate data analysis (metabonomics) identifies efficiently differences between toxic and non-toxic compounds; but in most cases multiple administrations of the test compound are necessary. We tested the feasibility of detecting proximal tubule kidney toxicity and phospholipidosis with metabonomics techniques after single compound administration as an early safety pharmacology approach. Rats were treated orally, intravenously, inhalatively or intraperitoneally with different test compounds. Urine was collected at 0-8 h and 8-24 h after compound administration, and (1)H NMR-patterns were recorded from the samples. Variation of post-processing and feature extraction methods led to different views on the data. Support Vector Machines were trained on these different data sets and then aggregated as experts in an Ensemble. Finally, validity was monitored with a cross-validation study using a training, validation, and test data set. Proximal tubule kidney toxicity could be predicted with reasonable total classification accuracy (85%), specificity (88%) and sensitivity (78%). In comparison to alternative histological studies, results were obtained quicker, compound need was reduced, and very importantly fewer animals were needed. In contrast, the induction of phospholipidosis by the test compounds could not be predicted using NMR-based urine analysis or the previously published biomarker PAG. NMR-based urine analysis was shown to effectively predict proximal tubule kidney toxicity after single compound administration in rats. Thus, this experimental design allows early detection of toxicity risks with relatively low amounts of compound in a reasonably short period of time.

The role of renal proximal tubule P450 enzymes in chloroform-induced nephrotoxicity: Utility of renal specific P450 reductase knockout mouse models

International Nuclear Information System (INIS)

Liu, Senyan; Yao, Yunyi; Lu, Shijun; Aldous, Kenneth; Ding, Xinxin; Mei, Changlin; Gu, Jun

2013-01-01

The kidney is a primary target for numerous toxic compounds. Cytochrome P450 enzymes (P450) are responsible for the metabolic activation of various chemical compounds, and in the kidney are predominantly expressed in proximal tubules. The aim of this study was to test the hypothesis that renal proximal tubular P450s are critical for nephrotoxicity caused by chemicals such as chloroform. We developed two new mouse models, one having proximal tubule-specific deletion of the cytochrome P450 reductase (Cpr) gene (the enzyme required for all microsomal P450 activities), designated proximal tubule-Cpr-null (PTCN), and the other having proximal tubule-specific rescue of CPR activity with the global suppression of CPR activity in all extra-proximal tubular tissues, designated extra-proximal tubule-Cpr-low (XPT-CL). The PTCN, XPT-CL, Cpr-low (CL), and wild-type (WT) mice were treated with a single oral dose of chloroform at 200 mg/kg. Blood, liver and kidney samples were obtained at 24 h after the treatment. Renal toxicity was assessed by measuring BUN and creatinine levels, and by pathological examination. The blood and tissue levels of chloroform were determined. The severity of toxicity was less in PTCN and CL mice, compared with that of WT and XPT-CL mice. There were no significant differences in chloroform levels in the blood, liver, or kidney, between PTCN and WT mice, or between XPT-CL and CL mice. These findings indicate that local P450-dependent activities play an important role in the nephrotoxicity induced by chloroform. Our results also demonstrate the usefulness of these novel mouse models for studies of chemical-induced kidney toxicity. - Highlights: • New mouse models were developed with varying P450 activities in the proximal tubule. • These mouse models were treated with chloroform, a nephrotoxicant. • Studies showed the importance of local P450s in chloroform-induced nephrotoxicity

Subcellular distribution of folate and folate binding protein in renal proximal tubules

International Nuclear Information System (INIS)

Sharkey, C.; Hjelle, J.T.; Selhub, J.

1986-01-01

High affinity folate binding protein (FBP) found in brush border membranes derived from renal cortices is thought to be involved in the renal conservation of folate. To examine the mechanisms of folate recovery, the subcellular distribution of FBP and 3 H-folate in rabbit renal proximal tubules (PT) was examined using analytical cell fractionation techniques. Tubules contain 3.41 +/- 0.32 picomoles FBP/mg protein (X +/- S.D.; n = 5). Postnuclear supernates (PNS) of PT were layered atop Percoll-sucrose gradients, centrifuged, fractions collected and assayed for various marker enzymes and FBP. Pooled fractions from such gradients were subsequently treated with digitonin and centrifuged in a stoichiometric manner with the activity of the microvillar enzyme, alanylaminopeptidase (AAP); excess FBP distributed with more buoyant particles. Infusion of 3 H-folate into rabbit kidneys followed by tubule isolation and fractionation revealed a time dependent shift in distribution of radiolabel from the AAP-rich gradient fractions to a region containing more buoyant particles; radiolevel was not associated with lysosomal markers. EM-radioautography revealed grains over intracellular vesicles. These results are consistent with the hypothesis that folate is recovered by a process involving receptor-mediated endocytosis or transcytosis

Renal compensation to chronic hypoxic hypercapnia: downregulation of pendrin and adaptation of the proximal tubule.

NARCIS (Netherlands)

Seigneux, S. de; Malte, H.; Dimke, H.; Frokiaer, J.; Nielsen, S.; Frische, S.

2007-01-01

The molecular basis for the renal compensation to respiratory acidosis and specifically the role of pendrin in this condition are unclear. Therefore, we studied the adaptation of the proximal tubule and the collecting duct to respiratory acidosis. Male Wistar-Hannover rats were exposed to either

P-glycoprotein-deficient mice have proximal tubule dysfunction but are protected against ischemic renal injury

NARCIS (Netherlands)

Huls, M.; Kramers, C.; Levtchenko, E.N.; Wilmer, M.J.G.; Dijkman, H.B.P.M.; Kluijtmans, L.A.J.; Hoorn, J.W.A. van der; Russel, F.G.M.; Masereeuw, R.

2007-01-01

The multidrug resistance gene 1 product, P-glycoprotein (P-gp), is expressed in several excretory organs, including the apical membrane of proximal tubules. After inducing acute renal failure, P-gp expression is upregulated and this might be a protective function by pumping out toxicants and harmful

Substrate modulation of fatty acid effects on energization and respiration of kidney proximal tubules during hypoxia/reoxygenation.

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Anja Bienholz

Full Text Available Kidney proximal tubules subjected to hypoxia/reoxygenation develop a nonesterified fatty acid-induced energetic deficit characterized by persistent partial mitochondrial deenergization that can be prevented and reversed by citric acid cycle substrates. To further assess the role of competition between fatty acids and substrates on inner membrane substrate carriers in the deenergization and the contribution to deenergization of fatty acid effects on respiratory function, digitonin-permeabilized rabbit and mouse tubules were studied using either addition of exogenous oleate after control normoxic incubation or increases of endogenous fatty acids produced by hypoxia/reoxygenation. The results demonstrated major effects of matrix oxaloacetate accumulation on succinate-supported energization and respiration and their modification by fatty acids. Improvements of energization in the presence of fatty acids by glutamate were shown to result predominantly from lowering matrix oxaloacetate rather than from amelioration of transmembrane cycling of fatty acids and uncoupling. Mouse tubules had 2.5 fold higher rates of succinate utilization, which resulted in stronger effects of oxaloacetate accumulation than rabbit tubules. Hypoxia/reoxygenation induced respiratory inhibition that was more severe for complex I-dependent substrates. Fatty acids themselves did not acutely contribute to this respiratory inhibition, but lowering them during 60 min. reoxygenation to allow recovery of ATP during that period alleviated it. These data clarify the basis for the nonesterified fatty acid-induced mitochondrial energetic deficit in kidney proximal tubules that impairs structural and functional recovery and provide insight into interactions that need to be considered in the design of substrate-based interventions to improve mitochondrial function.

Passive permeability of salicylic acid in renal proximal S2 and S3 tubules

International Nuclear Information System (INIS)

Chatton, J.Y.; Roch-Ramel, F.

1991-01-01

The role of nonionic diffusion in the transport of salicylic acid across rabbit proximal S2 and S3 segments was investigated using the in vitro isolated perfused tubule technique. The [ 14 C] salicylic acid apparent reabsorptive permeability (P'I-b, 10(-5) cm/s) was measured at 19 degrees C with luminal solutions kept at different pH and bath maintained at pH 7.4. In S2 tubules, P'I-b was 25.0 +/- 3.5 when luminal pH was 6.0; P'I-b decreased to 8.1 +/- 1.4 and to 4.4 +/- 1.2 at a luminal pH of 6.5 and 7.0, respectively. In S3 tubules, P'I-b was 17.6 +/- 2.4, 5.3 +/- 1.1 and 3.4 +/- 1.1 at a luminal pH of 6.0, 6.5 and 7.0, respectively. There was a close correlation between P'I-b and the calculated proportion of nonionized salicylic acid present at each pH, indicating that only the nonionized molecule could diffuse in our conditions. We calculated the apparent permeability of nonionic salicylic acid and found 0.248 +/- 0.032 cm/s for S2 and 0.176 +/- 0.022 cm/s for S3 tubules. These calculated permeabilities were independent of pH

Reversible effects of acute hypertension on proximal tubule sodium transporters

DEFF Research Database (Denmark)

Zhang, Y; Magyar, C E; Norian, J M

1998-01-01

Acute hypertension provokes a rapid decrease in proximal tubule sodium reabsorption with a decrease in basolateral membrane sodium-potassium-ATPase activity and an increase in the density of membranes containing apical membrane sodium/hydrogen exchangers (NHE3) [Y. Zhang, A. K. Mircheff, C. B....... Renal cortex lysate was fractionated on sorbitol gradients. Basolateral membrane sodium-potassium-ATPase activity (but not subunit immunoreactivity) decreased one-third to one-half after BP was elevated and recovered after BP was normalized. After BP was elevated, 55% of the apical NHE3 immunoreactivity......, smaller fractions of sodium-phosphate cotransporter immunoreactivity, and apical alkaline phosphatase and dipeptidyl-peptidase redistributed to membranes of higher density enriched in markers of the intermicrovillar cleft (megalin) and endosomes (Rab 4 and Rab 5), whereas density distributions...

Proximal Tubule Cell Hypothesis for Cardiorenal Syndrome in Diabetes

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Akihiko Saito

2011-01-01

Full Text Available Incidence of cardiovascular disease (CVD is remarkably high among patients with chronic kidney disease (CKD, even in the early microalbuminuric stages with normal glomerular filtration rates. Proximal tubule cells (PTCs mediate metabolism and urinary excretion of vasculotoxic substances via apical and basolateral receptors and transporters. These cells also retrieve vasculoprotective substances from circulation or synthesize them for release into the circulation. PTCs are also involved in the uptake of sodium and phosphate, which are critical for hemodynamic regulation and maintaining the mineral balance, respectively. Dysregulation of PTC functions in CKD is likely to be associated with the development of CVD and is linked to the progression to end-stage renal disease. In particular, PTC dysfunction occurs early in diabetic nephropathy, a leading cause of CKD. It is therefore important to elucidate the mechanisms of PTC dysfunction to develop therapeutic strategies for treating cardiorenal syndrome in diabetes.

Effects of phospho- and calciotropic hormones on electrolyte transport in the proximal tubule

DEFF Research Database (Denmark)

Lee, Justin J; Plain, Allein; Beggs, Megan R

2017-01-01

), active vitamin D 3, and fibroblast growth factor 23 (FGF23). The organs central to this are the kidneys, intestine, and bone. In the kidney, the proximal tubule reabsorbs the majority of filtered calcium and phosphate, which amounts to more than 60% and 90%, respectively. The basic molecular mechanisms......Calcium and phosphate are critical for a myriad of physiological and cellular processes within the organism. Consequently, plasma levels of calcium and phosphate are tightly regulated. This occurs through the combined effects of the phospho- and calciotropic hormones, parathyroid hormone (PTH...... as their regulation of active vitamin D 3 synthesis in this nephron segment. The integrative effects of both phospho- and calciotropic hormones on proximal tubular solute transport and subsequently whole body calcium-phosphate balance thus have been further complicated. Here, we first review the molecular mechanisms...

Adaptive regulation of taurine and beta-alanine uptake in a human kidney cell line from the proximal tubule

DEFF Research Database (Denmark)

Jessen, H; Jacobsen, Christian

1997-01-01

1. The underlying mechanisms involved in the adaptive regulation of beta-amino acid uptake in the human proximal tubule were examined by use of an immortalized human embryonic kidney epithelial cell line (IHKE). 2. The results indicated that the adaptive response to maintain whole-body taurine...

Effects of phospho- and calciotropic hormones on electrolyte transport in the proximal tubule [version 1; referees: 2 approved

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Justin J. Lee

2017-10-01

Full Text Available Calcium and phosphate are critical for a myriad of physiological and cellular processes within the organism. Consequently, plasma levels of calcium and phosphate are tightly regulated. This occurs through the combined effects of the phospho- and calciotropic hormones, parathyroid hormone (PTH, active vitamin D3, and fibroblast growth factor 23 (FGF23. The organs central to this are the kidneys, intestine, and bone. In the kidney, the proximal tubule reabsorbs the majority of filtered calcium and phosphate, which amounts to more than 60% and 90%, respectively. The basic molecular mechanisms responsible for phosphate reclamation are well described, and emerging work is delineating the molecular identity of the paracellular shunt wherein calcium permeates the proximal tubular epithelium. Significant experimental work has delineated the molecular effects of PTH and FGF23 on these processes as well as their regulation of active vitamin D3 synthesis in this nephron segment. The integrative effects of both phospho- and calciotropic hormones on proximal tubular solute transport and subsequently whole body calcium-phosphate balance thus have been further complicated. Here, we first review the molecular mechanisms of calcium and phosphate reabsorption from the proximal tubule and how they are influenced by the phospho- and calciotropic hormones acting on this segment and then consider the implications on both renal calcium and phosphate handling as well as whole body mineral balance.

A microfluidic renal proximal tubule with active reabsorptive function.

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Else M Vedula

Full Text Available In the kidney, the renal proximal tubule (PT reabsorbs solutes into the peritubular capillaries through active transport. Here, we replicate this reabsorptive function in vitro by engineering a microfluidic PT. The microfluidic PT architecture comprises a porous membrane with user-defined submicron surface topography separating two microchannels representing a PT filtrate lumen and a peritubular capillary lumen. Human PT epithelial cells and microvascular endothelial cells in respective microchannels created a PT-like reabsorptive barrier. Co-culturing epithelial and endothelial cells in the microfluidic architecture enhanced viability, metabolic activity, and compactness of the epithelial layer. The resulting tissue expressed tight junctions, kidney-specific morphology, and polarized expression of kidney markers. The microfluidic PT actively performed sodium-coupled glucose transport, which could be modulated by administration of a sodium-transport inhibiting drug. The microfluidic PT reproduces human physiology at the cellular and tissue levels, and measurable tissue function which can quantify kidney pharmaceutical efficacy and toxicity.

Effects of angiotensin II and ionomycin on fluid and bicarbonate absorption in the rat proximal tubule

International Nuclear Information System (INIS)

Chatsudthipong, V.; Chan, Y.L.

1986-01-01

Microperfusion of proximal convoluted tubule(PCT) and peritubular capillaries was performed to examine the effects of angiotensin II(Ang II) and ionomycin on fluid and bicarbonate absorption. Bicarbonate was determined by microcalorimetry and C-14 inulin was used as a volume marker. The rates of bicarbonate absorption (JHCO 3 ) was 143 peq/min x mm and fluid absorption(Jv) was 2.70 nl/min x mm, when PCT and capillary perfusate contained normal Ringer solution. Addition of Ang II (10 -6 M) to the capillary perfusate caused reductions of JHCO 3 and Jv by 35%. A similar effect was observed when ionomycin was added to the capillary perfusate. Ang II antagonist, (Sar 1 , Ile 8 )-Angiotensin II(10 -6 M), completely blocked the inhibitory effect of Ang II on Jv and JHCO 3 . Removal of calcium from both luminal and capillary perfusate did not change the effect of Ang II on Jv and JHCO 3 . Our results indicate that Ang II inhibits the sodium-hydrogen exchanger in the proximal tubule via interacting with angiotensin receptor. The mechanism of Ang II action may involve mobilization of intracellular calcium

Effects of lead intoxication on intercellular junctions and biochemical alterations of the renal proximal tubule cells.

Science.gov (United States)

Navarro-Moreno, L G; Quintanar-Escorza, M A; González, S; Mondragón, R; Cerbón-Solorzáno, J; Valdés, J; Calderón-Salinas, J V

2009-10-01

Lead intoxication is a worldwide health problem which frequently affects the kidney. In this work, we studied the effects of chronic lead intoxication (500 ppm of Pb in drinking water during seven months) on the structure, function and biochemical properties of rat proximal tubule cells. Lead-exposed animals showed increased lead concentration in kidney, reduction of calcium and amino acids uptake, oxidative damage and glucosuria, proteinuria, hematuria and reduced urinary pH. These biochemical and physiological alterations were related to striking morphological modifications in the structure of tubule epithelial cells and in the morphology of their mitochondria, nuclei, lysosomes, basal and apical membranes. Interestingly, in addition to the nuclei, inclusion bodies were found in the cytoplasm and in mitochondria. The epithelial cell structure modifications included an early loss of the apical microvillae, followed by a decrement of the luminal space and the respective apposition and proximity of apical membranes, resulting in the formation of atypical intercellular contacts and adhesion structures. Similar but less marked alterations were observed in subacute lead intoxication as well. Our work contributes in the understanding of the physiopathology of lead intoxication on the structure of renal tubular epithelial cell-cell contacts in vivo.

N-domain angiotensin-I converting enzyme is expressed in immortalized mesangial, proximal tubule and collecting duct cells.

Science.gov (United States)

Mei Wang, Pamella Huey; Andrade, Maria Claudina; Quinto, Beata Marie Redublo; Di Marco, Giovana; Mortara, Renato Arruda; Vio, Carlos P; Casarini, Dulce Elena

2015-01-01

Somatic ACE (sACE) is found in glomerulus, proximal tubule and excreted in urine. We hypothesized that N-domain ACE can also be found at these sites. ACE profile was analyzed in mesangial (IMC), proximal (LLC-PK1), distal tubule (MDCK) and collecting duct (IMCD) cells. Cell lysate and culture medium were submitted to gel filtration chromatography, which separated two peaks with ACE activity from cells and medium, except from distal tubule. The first had a high molecular weight and the second, a lower one (65 kDa; N-domain ACE). We focused on N-domain ACE purification and characterization from LLC-PK1. Total LLC-PK1 N-domain ACE purification was achieved by ion-exchange chromatography, which presented only one peak with ACE activity, denominated ACE(int2A). ACE(int2A) activity was influenced by pH, NaCl and temperature. The purified enzyme was inhibited by Captopril and hydrolyzed AngI, Ang1-7 and AcSDKP. Its ability to hydrolyze AcSDKP characterized it as an N-domain ACE. ACE(int2A) also presented high amino acid sequence homology with the N-terminal part of sACE from mouse, rat, human and rabbit. The presence of secreted and intracellular N-domain ACE and sACE in IMC, LLC-PK1 and IMCD cells confirmed our studies along the nephron. We identified, purified and characterized N-domain ACE from LLC-PK1. Copyright © 2014 Elsevier B.V. All rights reserved.

Phosphorylation of rat kidney Na-K pump at Ser938 is required for rapid angiotensin II-dependent stimulation of activity and trafficking in proximal tubule cells.

Science.gov (United States)

Massey, Katherine J; Li, Quanwen; Rossi, Noreen F; Keezer, Susan M; Mattingly, Raymond R; Yingst, Douglas R

2016-02-01

How angiotensin (ANG) II acutely stimulates the Na-K pump in proximal tubules is only partially understood, limiting insight into how ANG II increases blood pressure. First, we tested whether ANG II increases the number of pumps in plasma membranes of native rat proximal tubules under conditions of rapid activation. We found that exposure to 100 pM ANG II for 2 min, which was previously shown to increase affinity of the Na-K pump for Na and stimulate activity threefold, increased the amount of the Na-K pump in plasma membranes of native tubules by 33%. Second, we tested whether previously observed increases in phosphorylation of the Na-K pump at Ser(938) were part of the stimulatory mechanism. These experiments were carried out in opossum kidney cells, cultured proximal tubules stably coexpressing the ANG type 1 (AT1) receptor, and either wild-type or a S938A mutant of rat kidney Na-K pump under conditions found by others to stimulate activity. We found that 10 min of incubation in 10 pM ANG II stimulated activity of wild-type pumps from 2.3 to 3.5 nmol K · mg protein(-1) · min(-1) and increased the amount of the pump in the plasma membrane by 80% but had no effect on cells expressing the S938A mutant. We conclude that acute stimulation of Na-K pump activity in native rat proximal tubules includes increased trafficking to the plasma membrane and that phosphorylation at Ser(938) is part of the mechanism by which ANG II directly stimulates activity and trafficking of the rat kidney Na-K pump in opossum kidney cells.

Antioxidant Protection against Pathological Mycotoxins Alterations on Proximal Tubules in Rat Kidney

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Susan Abdu

2011-04-01

Full Text Available Background: Ochratoxin A (OTA was one of the mycotoxins and received attention worldwide because of the hazard it posed to human and animal health, where the kidney was the primary target organ for OTA toxicity. In the other hand, dates served as a good source of natural antioxidants and could potentially be considered as a functional food.Methods: The study was performed in the department of biology in King Abdulaziz University. Animals were gavage administrated and divided into four groups: first group received (sodium bicarbonate, second group received (289 µg OTA /kg B.W. /day, third group received (1mg Ajwa/kg B.W. / day and fourth group received (289 µg OTA /kg B.W./day+ 1mg Ajwa /kg B.W. / day. Serum (creatinine - urea levels were measured in each group at the time of tissue collection , some biopsies were fixed in 10% buffered formalin solution for light microscopy processing stained with Haematoxylin and Eosin (H& E., Periodic Acid-Schiff (PAS and Masson´s Trichrome (M.T..Other biopsies were immediately collected into electron microscopy processing. Results: After 28 days, a significant decrease in body weight, kidney weight and relative weight was detected in OTA treated group. Also, Serum (creatinine - urea level were elevated .The normal cyto-architecture of proximal tubules were lost exhibiting damaged bruch border, degenerated, binucleated and karyomegalic cells. The most destructed ultra-structure was the mitochondria which severely swollen with disintegrated membranes. In Ajwa Date extract-group the proximal tubules were normal, whereas in Ajwa date extract + OTA -group the severity of the lesions was significantly reduced. Conclusion: The present results indicated that, Ajwa date have protective effects and ameliorated the lesions of Ochratoxin nepherotoxicity which might lead to kidney failure.

Receptor-mediated endocytosis of lysozyme in renal proximal tubules of the frog Rana temporaria

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E.V. Seliverstova

2015-04-01

Full Text Available The mechanism of protein reabsorption in the kidney of lower vertebrates remains insufficiently investigated in spite of raising interest to the amphibian and fish kidneys as a useful model for physiological and pathophysiological examinations. In the present study, we examined the renal tubular uptake and the internalization rote of lysozyme after its intravenous injection in the wintering frog Rana temporaria using immunohisto- and immunocytochemistry and specific markers for some endocytic compartments. The distinct expression of megalin and cubilin in the proximal tubule cells of lysozyme-injected frogs was revealed whereas kidney tissue of control animals showed no positive immunoreactivity. Lysozyme was detected in the apical endocytic compartment of the tubular cells and colocalized with clathrin 10 min after injection. After 20 min, lysozyme was located in the subapical compartment negative to clathrin (endosomes, and intracellular trafficking of lysozyme was coincided with the distribution of megalin and cubilin. However, internalized protein was retained in the endosomes and did not reach lysosomes within 30 min after treatment that may indicate the inhibition of intracellular trafficking in hibernating frogs. For the first time, we provided the evidence that lysozyme is filtered through the glomeruli and absorbed by receptor-mediated clathrin-dependent endocytosis in the frog proximal tubule cells. Thus, the protein uptake in the amphibian mesonephros is mediated by megalin and cubilin that confirms a critical role of endocytic receptors in the renal reabsorption of proteins in amphibians as in mammals.

De novo expression of sodium-glucose cotransporter SGLT2 in Bowman's capsule coincides with replacement of parietal epithelial cell layer with proximal tubule-like epithelium.

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Tabatabai, Niloofar M; North, Paula E; Regner, Kevin R; Kumar, Suresh N; Duris, Christine B; Blodgett, Amy B

2014-08-01

In kidney nephron, parietal epithelial cells line the Bowman's capsule and function as a permeability barrier for the glomerular filtrate. Bowman's capsule cells with proximal tubule epithelial morphology have been found. However, the effects of tubular metaplasia in Bowman's capsule on kidney function remain poorly understood. Sodium-glucose cotransporter 2 (SGLT2) plays a major role in reabsorption of glucose in the kidney and is expressed on brush border membrane (BBM) of epithelial cells in the early segment of the proximal tubule. We hypothesized that SGLT2 is expressed in tubularized Bowman's capsule and used our novel antibody to test this hypothesis. Immunohistochemical analysis was performed with our SGLT2 antibody on C57BL/6 mouse kidney prone to have tubularized Bowman's capsules. Cell membrane was examined with periodic acid-Schiff (PAS) stain. The results showed that SGLT2 was localized on BBM of the proximal tubules in young and adult mice. Bowman's capsules were lined mostly with normal brush border-less parietal epithelial cells in young mice, while they were almost completely covered with proximal tubule-like cells in adult mice. Regardless of age, SGLT2 was expressed on BBM of the tubularized Bowman's capsule but did not co-localize with nephrin in the glomerulus. SGLT2-expressing tubular cells expanded from the urinary pole toward the vascular pole of the Bowman's capsule. This study identified the localization of SGLT2 in the Bowman's capsule. Bowman's capsules with tubular metaplasia may acquire roles in reabsorption of filtered glucose and sodium.

The effect of L-cysteine on the portion-selective uptake of cadmium in the renal proximal tubule

International Nuclear Information System (INIS)

Murakami, Masataka; Sano, Kenichi; Webb, M.

1987-01-01

Cadmium (Cd), co-administered with an excess of L-cysteine, accumulates rapidly in the kidneys of the rat. After subcutaneous (s.c.) injection of 3 μmol CdCl 2 /kg body wt the concentrations of Cd in the blood and kidneys increase with the dose of cysteine over the range 0.06-5.0 mmol/kg body wt. At cysteine doses of less than 1.5 mmol/kg body wt the ratio of the concentrations of Cd in the outer medulla and cortex of the kidney remains the same as that after the injection of Cd alone. This ratio, however, is more than doubled at dose levels of 5-10 mmol cysteine/kg body wt. Hepatic uptake of Cd is unaffected by doses of cysteine below 1.5 mmol/kg body wt but decreases markedly at higher doses. In animals that are dosed simultaneously with 5 mmol cysteine/kg body wt, renal uptake of 109 Cd is known to occur in the straight segments of the proximal tubules. At a dose level of less than 1.5 mmol cysteine/kg body wt the present autoradiographical studies show that 109 Cd is taken up predominantly by the proximal convoluted tubules of the kidney cortex. At the critical dose level (1.5 mmol/kg body wt), cysteine decreases the retention of Cd at the s.c. injection site, but probably has little effect on the distribution of Cd between protein and other carrier molecules in the blood. This distribution, however, is altered at higher cysteine dose levels. It is suggested that, under the latter conditions, stable Cd-cysteine complexes are formed in the blood and are filtered readily through the glomeruli. These complexes are taken up in the kidney at the sites of cysteine reabsorption which, by studies with L-[ 35 S]-cysteine, are identified as the straight segments of the proximal tubules. (orig.)

The proximal straight tubule (PST) basolateral cell membrane water channel: selectivity characteristics.

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Gutiérrez, A M; González, E; Echevarría, M; Hernández, C S; Whittembury, G

1995-02-01

Proximal straight tubules (PST) were dissected from rabbit kidneys, held by crimping pipettes in a chamber and bathed in a buffered isosmotic (295 mOsm/kg) solution containing 200 mM mannitol (MBS). Changes in tubule diameter were monitored on line with an inverted microscope, TV camera and image processor. The PST were then challenged for 20 sec with MBS made 35 mOsm/kg hyperosmotic by addition of either NaCl, KCl, mannitol (M), glycerol (G), ethylene glycol (E), glycine (g), urea (U), acetamide (A) or formamide (F). With NaCl, KCl, M, G, E, g, U, and A, tubules shrunk osmometrically within 0.5 sec and remained shrunk for as long as 20 sec without recovering their original volume (sometimes A showed some recovery). PST barely shrunk with F and quickly recovered their original volume. The permeability coefficients were 0 microns/sec (NaCl, M, g, E and U), 1 micron/sec (A), 84 microns/sec (F) and 0.02 micron/sec (G). The reflection coefficients sigma = 1.0 (NaCl, KCl, M, G, E, g and U), 0.95 (A) and 0.62 (F). Similar sigma values were obtained by substituting 200 mOsm/kg M in MBS by either NaCl, KCl, G, E, g, U, a or F. The olive oil/water partition coefficients are 5 (M), 15 (U), 85 (A) and 75 (F) (all x 10(-5)). Thus, part of F permeates the cell membrane through the lipid bilayer. The probing molecules van der Waals diameters are 7.4 x 8.2 x 12.0 (M), 3.6 x 5.2 x 5.4 (U), 3.8 x 5.2 x 5.4 (A) and (3.4 x 4.5 x 5.4 (F) A.(ABSTRACT TRUNCATED AT 250 WORDS)

Diglycolic acid is the nephrotoxic metabolite in diethylene glycol poisoning inducing necrosis in human proximal tubule cells in vitro.

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Landry, Greg M; Martin, Sarah; McMartin, Kenneth E

2011-11-01

Diethylene glycol (DEG), a solvent and chemical intermediate, can produce an acute toxic syndrome, the hallmark of which is acute renal failure due to cortical tubular degeneration and proximal tubular necrosis. DEG is metabolized to two primary metabolites, 2-hydroxyethoxyacetic acid (2-HEAA) and diglycolic acid (DGA), which are believed to be the proximate toxicants. The precise mechanism of toxicity has yet to be elucidated, so these studies were designed to determine which metabolite was responsible for the proximal tubule cell death. Human proximal tubule (HPT) cells in culture, obtained from normal cortical tissue and passaged 3-6 times, were incubated with increasing concentrations of DEG, 2-HEAA, or DGA separately and in combination for 48 h at pH 6 or 7.4, and various parameters of necrotic and apoptotic cell death were measured. DEG and 2-HEAA did not produce any cell death. DGA produced dose-dependent necrosis at concentrations above 25 mmol/l. DGA did not affect caspase-3 activity and increased annexin V staining only in propidium iodide-stained cells. Hence, DGA induced necrosis, not apoptosis, as corroborated by severe depletion of cellular adenosine triphosphate levels. DGA is structurally similar to citric acid cycle intermediates that are taken up by specific transporters in kidney cells. HPT cells, incubated with N-(p-amylcinnamoyl)anthranilic acid, a sodium dicarboxylate-1 transporter inhibitor showed significantly decreased cell death compared with DGA alone. These studies demonstrate that DGA is the toxic metabolite responsible for DEG-induced proximal tubular necrosis and suggest a possible transporter-mediated uptake of DGA leading to toxic accumulation and cellular dysfunction.

Secretory NaCl and volume flow in renal tubules.

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Beyenbach, K W

1986-05-01

This review attempts to give a retrospective survey of the available evidence concerning the secretion of NaCl and fluid in renal tubules of the vertebrate kidney. In the absence of glomerular filtration, epithelial secretory mechanisms, which to this date have not been elucidated, are responsible for the renal excretion of NaCl and water in aglomerular fish. However, proximal tubules isolated from glomerular fish kidneys of the flounder, killifish, and the shark also have the capacity to secrete NaCl and fluid. In shark proximal tubules, fluid secretion appears to be driven via secondary active transport of Cl. In another marine vertebrate, the sea snake, secretion of Na (presumably NaCl) and fluid is observed in freshwater-adapted and water-loaded animals. Proximal tubules of mammals can be made to secrete NaCl in vitro together with secretion of aryl acids. An epithelial cell line derived from dog kidney exhibits secondary active secretion of Cl when stimulated with catecholamines. Tubular secretion of NaCl and fluid may serve a variety of renal functions, all of which are considered here. The occurrence of NaCl and fluid secretion in glomerular proximal tubules of teleosts, elasmobranchs, and reptiles and in mammalian renal tissue cultures suggests that the genetic potential for NaCl secretion is present in every vertebrate kidney.

Effect of alphatocopherol on diameter of proximal convoluted tubules of kidney in diabetic mice

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Rashid, S.

2014-01-01

Objective: To evaluate the effects of alphatocopherol supplement on proximal convoluted tubular diameter of kidney in diabetic mice. Methods: The randomised controlled trials was conducted partly at the National Institute of Health (NIH), Islamabad, and partly in Army Medical College, Rawalpindi, from November 2009 to November 2010. Thirty adult female mice BALB/C were randomly divided into three equal groups. Group A served as the control group. Group B was made diabetic by the intraperitoneal injection of streptozotocin. Group C received injection streptozotocin and was fed with alphatocopherol (vitamin E) supplemented diet. After 12 weeks, the animals were sacrificed and their kidneys were removed for histomorphological study. Results: Diabetes caused significant changes in the diameter of proximal tubule of Experimental Group B (diabetic) compared to the controls in Group A, but these changes were prevented in alphatocopherol treated Group C. Tubular diameter in Group B was significantly reduced compared to the Control Group A (p 0.05). Conclusion: Significant difference in proximal tubular diameter of kidneys between diabetic and alphatocopherol treated diabetic mice confirm that vitamin E does extend a protective role in improving diabetic nephropathy. (author)

Proximal tubule proteins are significantly elevated in bladder urine of patients with ureteropelvic junction obstruction and may represent novel biomarkers: A pilot study.

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Gerber, Claire; Harel, Miriam; Lynch, Miranda L; Herbst, Katherine W; Ferrer, Fernando A; Shapiro, Linda H

2016-04-01

Ureteropelvic junction obstruction (UPJO) is the major cause of hydronephrosis in children and may lead to renal injury and early renal dysfunction. However, diagnosis of the degree of obstruction and severity of renal injury relies on invasive and often inconclusive renal scans. Biomarkers from voided urine that detect early renal injury are highly desirable because of their noninvasive collection and their potential to assist in earlier and more reliable diagnosis of the severity of obstruction. Early in response to UPJO, increased intrarenal pressure directly impacts the proximal tubule brush border. We hypothesize that single-pass, apically expressed proximal tubule brush border proteins will be shed into the urine early and rapidly and will be reliable noninvasive urinary biomarkers, providing the tools for a more reliable stratification of UPJO patients. We performed a prospective cohort study at Connecticut Children's Medical Center. Bladder urine samples from 12 UPJO patients were obtained prior to surgical intervention. Control urine samples were collected from healthy pediatric patients presenting with primary nocturnal enuresis. We determined levels of NGAL, KIM-1 (previously identified biomarkers), CD10, CD13, and CD26 (potentially novel biomarkers) by ELISA in control and experimental urine samples. Urinary creatinine levels were used to normalize the urinary protein levels measured by ELISA. Each of the proximal tubule proteins outperformed the previously published biomarkers. No differences in urinary NGAL and KIM-1 levels were observed between control and obstructed patients (p = 0.932 and p = 0.799, respectively). However, levels of CD10, CD13, and CD26 were significantly higher in the voided urine of obstructed individuals when compared with controls (p = 0.002, p = 0.024, and p = 0.007, respectively) (Figure). Targeted identification of reliable, noninvasive biomarkers of renal injury is critical to aid in diagnosing patients at risk, guiding

Acute hypotension induced by aortic clamp vs. PTH provokes distinct proximal tubule Na+ transporter redistribution patterns

DEFF Research Database (Denmark)

Leong, Patrick K K; Yang, Li E; Lin, Harrison W

2004-01-01

. This study aimed to determine the effects of acute hypotension, induced by aortic clamp or by high-dose PTH (100 microg PTH/kg), on renal hemodynamics and proximal tubule Na/H exchanger isoform 3 (NHE3) and type IIa Na-P(i) cotransporter protein (NaPi2) distribution. Subcellular distribution was analyzed...... clearance. There was, however, no significant change in glomerular filtration rate (GFR) or subcellular distribution of NHE3 and NaPi2. In contrast, high-dose PTH rapidly (

Numerical variation of cell lysosomes of the proximal convoluted tubules of mice Kidneys submitted to different X-ray doses

International Nuclear Information System (INIS)

Silva Lapa, R. de C.R. da; Pacheco, I.P.; Segreto, C.

1984-01-01

The number of cell lysosomes of the proximal convoluted tubules of mice Kidneys (Mus musculus) before and after whole-body irradiation with different X-ray doses is confronted. The mice were sacrificed after 72 hours and the cortex fragments were conduct to electron microscopy. A statistically significant numerical reduction of the lysosomas was observed in 72 hours. (M.A.C.) [pt

Luminal and basolateral uptake of insulin in isolated perfused, proximal tubules

International Nuclear Information System (INIS)

Nielsen, S.; Nielsen, J.T.; Christensen, E.I.

1987-01-01

The present study was performed to quantitate compare the luminal and the peritubular uptake of 125 I-insulin in isolated, perfused, proximal tubules from rabbit kidneys. 125 I-insulin was added in physiological concentrations to either the perfusate or the bath fluid for 30 min. The luminal uptake in 30 min averaged 0.76 pg/mm at physiological concentrations and 18.0 pg/mm at high insulin concentrations. About 15-41% of the absorbed insulin was digested and 125 I-insulin at physiological and high concentrations in the bath was 0.136 and 0.318 pg, respectively. The data indicates that insulin is bound/absorbed at the basolateral membranes both by a saturable specific mechanism and a nonspecific, nonsaturable mechanism. The basolateral absorption constituted 15.2 and 1.8% of the total tubular extraction of insulin at physiological and high insulin concentrations, respectively. Electron microscope autoradiography showed that, after luminal as well as basolateral endocytosis, insulin was exclusively accumulated in endocytic vacuoles and lysosomes

Differential patterns of injury to the proximal tubule of renal cortical slices following in vitro exposure to mercuric chloride, potassium dichromate, or hypoxic conditions.

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Ruegg, C E; Gandolfi, A J; Nagle, R B; Brendel, K

1987-09-15

The innate susceptibility of renal cell types to these agents was investigated using precision-cut rabbit renal cortical slices made perpendicular to the cortical-papillary axis. Slices were incubated in DME/F12 medium containing 10 microM, 100 microM, or 1 mM concentrations of either metal for 12 hr or in Krebs-Hepes buffer gassed with nitrogen (100%) for 0.75 to 5 hr of hypoxic exposure. To simulate postischemic reperfusion, some slices were transferred to vessels gassed with oxygen after an initial hypoxic period. Mercuric chloride (100 microM) exposure resulted in damage to the straight regions of proximal tubules by 12 hr leaving convoluted regions unaffected. Hypoxia (2.25 hr) and potassium dichromate (100 microM for 12 hr) both caused injury to the convoluted proximal tubules without affecting straight proximal tubular regions. Mercury concentrations of 10 microM and 1 mM had no effect or injured all cell types within the slice, respectively. Similar results were observed for hypoxic periods less than 1.5 hr or greater than 3 hr of exposure. Potassium dichromate had no measurable affect at 10 microM, but at 1 mM focal lesions were observed after 4 hr of exposure, and by 12 hr all cell types within the slice were affected. Intracellular potassium content normalized to DNA correlated well, but always preceded the pathological lesions observed. These results demonstrate that injury to specific regions of the proximal tubule by these agents relates to an innate susceptibility of the intoxicated cell type independent of physiologic feedback or blood delivery patterns proposed as mechanisms of selective injury from in vivo studies.

Human kidney proximal tubule cells are vulnerable to the effects of Rauwolfia serpentina.

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Mossoba, Miriam E; Flynn, Thomas J; Vohra, Sanah; Wiesenfeld, Paddy L; Sprando, Robert L

2015-12-01

Rauwolfia serpentina (or Snake root plant) is a botanical dietary supplement marketed in the USA for maintaining blood pressure. Very few studies have addressed the safety of this herb, despite its wide availability to consumers. Its reported pleiotropic effects underscore the necessity for evaluating its safety. We used a human kidney cell line to investigate the possible negative effects of R. serpentina on the renal system in vitro, with a specific focus on the renal proximal tubules. We evaluated cellular and mitochondrial toxicity, along with a variety of other kidney-specific toxicology biomarkers. We found that R. serpentina was capable of producing highly detrimental effects in our in vitro renal cell system. These results suggest more studies are needed to investigate the safety of this dietary supplement in both kidney and other target organ systems.

Mechanism of cisplatin proximal tubule toxicity revealed by integrating transcriptomics, proteomics, metabolomics and biokinetics.

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Wilmes, Anja; Bielow, Chris; Ranninger, Christina; Bellwon, Patricia; Aschauer, Lydia; Limonciel, Alice; Chassaigne, Hubert; Kristl, Theresa; Aiche, Stephan; Huber, Christian G; Guillou, Claude; Hewitt, Philipp; Leonard, Martin O; Dekant, Wolfgang; Bois, Frederic; Jennings, Paul

2015-12-25

Cisplatin is one of the most widely used chemotherapeutic agents for the treatment of solid tumours. The major dose-limiting factor is nephrotoxicity, in particular in the proximal tubule. Here, we use an integrated omics approach, including transcriptomics, proteomics and metabolomics coupled to biokinetics to identify cell stress response pathways induced by cisplatin. The human renal proximal tubular cell line RPTEC/TERT1 was treated with sub-cytotoxic concentrations of cisplatin (0.5 and 2 μM) in a daily repeat dose treating regime for up to 14 days. Biokinetic analysis showed that cisplatin was taken up from the basolateral compartment, transported to the apical compartment, and accumulated in cells over time. This is in line with basolateral uptake of cisplatin via organic cation transporter 2 and bioactivation via gamma-glutamyl transpeptidase located on the apical side of proximal tubular cells. Cisplatin affected several pathways including, p53 signalling, Nrf2 mediated oxidative stress response, mitochondrial processes, mTOR and AMPK signalling. In addition, we identified novel pathways changed by cisplatin, including eIF2 signalling, actin nucleation via the ARP/WASP complex and regulation of cell polarization. In conclusion, using an integrated omic approach together with biokinetics we have identified both novel and established mechanisms of cisplatin toxicity. Copyright © 2014 Elsevier Ltd. All rights reserved.

'Special K' and a Loss of Cell-To-Cell Adhesion in Proximal Tubule-Derived Epithelial Cells: Modulation of the Adherens Junction Complex by Ketamine

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Hills, Claire E.; Jin, Tianrong; Siamantouras, Eleftherios; Liu, Issac K-K; Jefferson, Kieran P.; Squires, Paul E.

2013-01-01

Ketamine, a mild hallucinogenic class C drug, is the fastest growing ‘party drug’ used by 16–24 year olds in the UK. As the recreational use of Ketamine increases we are beginning to see the signs of major renal and bladder complications. To date however, we know nothing of a role for Ketamine in modulating both structure and function of the human renal proximal tubule. In the current study we have used an established model cell line for human epithelial cells of the proximal tubule (HK2) to demonstrate that Ketamine evokes early changes in expression of proteins central to the adherens junction complex. Furthermore we use AFM single-cell force spectroscopy to assess if these changes functionally uncouple cells of the proximal tubule ahead of any overt loss in epithelial cell function. Our data suggests that Ketamine (24–48 hrs) produces gross changes in cell morphology and cytoskeletal architecture towards a fibrotic phenotype. These physical changes matched the concentration-dependent (0.1–1 mg/mL) cytotoxic effect of Ketamine and reflect a loss in expression of the key adherens junction proteins epithelial (E)- and neural (N)-cadherin and β-catenin. Down-regulation of protein expression does not involve the pro-fibrotic cytokine TGFβ, nor is it regulated by the usual increase in expression of Slug or Snail, the transcriptional regulators for E-cadherin. However, the loss in E-cadherin can be partially rescued pharmacologically by blocking p38 MAPK using SB203580. These data provide compelling evidence that Ketamine alters epithelial cell-to-cell adhesion and cell-coupling in the proximal kidney via a non-classical pro-fibrotic mechanism and the data provides the first indication that this illicit substance can have major implications on renal function. Understanding Ketamine-induced renal pathology may identify targets for future therapeutic intervention. PMID:24009666

Cationic uremic toxins affect human renal proximal tubule cell functioning through interaction with the organic cation transporter.

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Schophuizen, Carolien M S; Wilmer, Martijn J; Jansen, Jitske; Gustavsson, Lena; Hilgendorf, Constanze; Hoenderop, Joost G J; van den Heuvel, Lambert P; Masereeuw, Rosalinde

2013-12-01

Several organic cations, such as guanidino compounds and polyamines, have been found to accumulate in plasma of patients with kidney failure due to inadequate renal clearance. Here, we studied the interaction of cationic uremic toxins with renal organic cation transport in a conditionally immortalized human proximal tubule epithelial cell line (ciPTEC). Transporter activity was measured and validated in cell suspensions by studying uptake of the fluorescent substrate 4-(4-(dimethylamino)styryl)-N-methylpyridinium-iodide (ASP(+)). Subsequently, the inhibitory potencies of the cationic uremic toxins, cadaverine, putrescine, spermine and spermidine (polyamines), acrolein (polyamine breakdown product), guanidine, and methylguanidine (guanidino compounds) were determined. Concentration-dependent inhibition of ASP(+) uptake by TPA, cimetidine, quinidine, and metformin confirmed functional endogenous organic cation transporter 2 (OCT2) expression in ciPTEC. All uremic toxins tested inhibited ASP(+) uptake, of which acrolein required the lowest concentration to provoke a half-maximal inhibition (IC50 = 44 ± 2 μM). A Dixon plot was constructed for acrolein using three independent inhibition curves with 10, 20, or 30 μM ASP(+), which demonstrated competitive or mixed type of interaction (K i = 93 ± 16 μM). Exposing the cells to a mixture of cationic uremic toxins resulted in a more potent and biphasic inhibitory response curve, indicating complex interactions between the toxins and ASP(+) uptake. In conclusion, ciPTEC proves a suitable model to study cationic xenobiotic interactions. Inhibition of cellular uptake transport was demonstrated for several uremic toxins, which might indicate a possible role in kidney disease progression during uremia.

Organic anion and cation SLC22 "drug" transporter (Oat1, Oat3, and Oct1 regulation during development and maturation of the kidney proximal tubule.

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Thomas F Gallegos

Full Text Available Proper physiological function in the pre- and post-natal proximal tubule of the kidney depends upon the acquisition of selective permeability, apical-basolateral epithelial polarity and the expression of key transporters, including those involved in metabolite, toxin and drug handling. Particularly important are the SLC22 family of transporters, including the organic anion transporters Oat1 (originally identified as NKT and Oat3 as well as the organic cation transporter Oct1. In ex vivo cultures of metanephric mesenchyme (MM; the embryonic progenitor tissue of the nephron Oat function was evident before completion of nephron segmentation and corresponded with the maturation of tight junctions as measured biochemically by detergent extractability of the tight junction protein, ZO-1. Examination of available time series microarray data sets in the context of development and differentiation of the proximal tubule (derived from both in vivo and in vitro/ex vivo developing nephrons allowed for correlation of gene expression data to biochemically and functionally defined states of development. This bioinformatic analysis yielded a network of genes with connectivity biased toward Hnf4α (but including Hnf1α, hyaluronic acid-CD44, and notch pathways. Intriguingly, the Oat1 and Oat3 genes were found to have strong temporal co-expression with Hnf4α in the cultured MM supporting the notion of some connection between the transporters and this transcription factor. Taken together with the ChIP-qPCR finding that Hnf4α occupies Oat1, Oat3, and Oct1 proximal promoters in the in vivo differentiating rat kidney, the data suggest a network of genes with Hnf4α at its center plays a role in regulating the terminal differentiation and capacity for drug and toxin handling by the nascent proximal tubule of the kidney.

Hypoxia inducible factor 1-alpha (HIF-1 alpha is induced during reperfusion after renal ischemia and is critical for proximal tubule cell survival.

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Elisa Conde

Full Text Available Acute tubular necrosis (ATN caused by ischemia/reperfusion (I/R during renal transplantation delays allograft function. Identification of factors that mediate protection and/or epithelium recovery could help to improve graft outcome. We studied the expression, regulation and role of hypoxia inducible factor 1-alpha (HIF-1 α, using in vitro and in vivo experimental models of I/R as well as human post-transplant renal biopsies. We found that HIF-1 α is stabilized in proximal tubule cells during ischemia and unexpectedly in late reperfusion, when oxygen tension is normal. Both inductions lead to gene expression in vitro and in vivo. In vitro interference of HIF-1 α promoted cell death and in vivo interference exacerbated tissue damage and renal dysfunction. In pos-transplant human biopsies, HIF-1 α was expressed only in proximal tubules which exhibited normal renal structure with a significant negative correlation with ATN grade. In summary, using experimental models and human biopsies, we identified a novel HIF-1 α induction during reperfusion with a potential critical role in renal transplant.

Effects of mercury on lysosomal protein digestion in the kidney proximal tubule

International Nuclear Information System (INIS)

Madsen, K.M.; Christensen, E.I.

1978-01-01

The effect of mercury on renal lysosomal protein digestion was studied after administration of mercury in vitro and in vivo. Mercuric chloride or methylmercury chloride was added in vitro to lysosomal enzymes isolated from normal rats, and subsequently, digestion experiments were carried out using 125 I-labeled lysozyme or cytochrome c as substrate proteins. Both mercury compounds produced a concentration-dependent inhibition of the degradation of the proteins, mercuric chloride being the strongest inhibitor. Mercuric chloride was also administered to rats in vivo for 5 to 8 months. Renal lysosomal enzymes from these animals also had a decreased ability to digest the two substrate proteins. Furthermore, the digestion of lysozyme intravenously injected into mercury-intoxicated rats was decreased in renal cortical slices incubated in vitro. Electron microscope autoradiography showed that intravenously injected labeled lysozyme was located primarily over lysosomes in proximal tubule cells 1 hour after injection in both control animals and mercury-intoxicated rats. These results suggest a decreased catabolism of low molecular weight proteins in the kidney during chronic mercury intoxication

Antenatal glucocorticoid treatment alters Na+ uptake in renal proximal tubule cells from adult offspring in a sex-specific manner

OpenAIRE

Su, Yixin; Bi, Jianli; Pulgar, Victor M.; Figueroa, Jorge; Chappell, Mark; Rose, James C.

2015-01-01

We have shown a sex-specific effect of fetal programming on Na+ excretion in adult sheep. The site of this effect in the kidney is unknown. Therefore, we tested the hypothesis that renal proximal tubule cells (RPTCs) from adult male sheep exposed to betamethasone (Beta) before birth have greater Na+ uptake than do RPTCs from vehicle-exposed male sheep and that RPTCs from female sheep similarly exposed are not influenced by antenatal Beta. In isolated RPTCs from 1- to 1.5-yr-old male and femal...

Proximal tubule Na transporter responses are the same during acute and chronic hypertension

DEFF Research Database (Denmark)

Magyar, C E; Zhang, Y; Holstein-Rathlou, N H

2000-01-01

Acute hypertension in Sprague-Dawley rats (SD) provokes a decrease in renal proximal tubule (PT) salt and fluid reabsorption, redistribution of apical Na/H exchanger isoform 3 (NHE3) and Na-P(i) cotransporter type 2 (NaPi2) out of the brush border into higher density membranes, and inhibition...... to persistent adaptive changes in NHE3 and NaPi2 distribution and/or NKA activity. Renal cortex Na transporter protein density distributions and activities were compared by subcellular fractionation in 1) adult SHR with an acute increase or decrease in arterial pressure and 2) young SD (YSD) and young SHR (YSHR......) vs. adult SD and SHR. In adult hypertensive SHR NHE3 was shifted to membranes of higher densities, analogous to SD with acute hypertension, and there were no further changes with a further increase or decrease in arterial pressure. There was no change in total pool size of NHE3 in cortex in YSHR vs...

Effects of advanced glycation end products on ezrin-dependent functions in LLC-PK1 proximal tubule cells.

Science.gov (United States)

Bach, Leon A; Gallicchio, Marisa A; McRobert, E Anne; Tikoo, Anjali; Cooper, Mark E

2005-06-01

We have recently shown that advanced glycation products (AGEs) bind to the ERM (ezrin, radixin, moesin) family of proteins. ERM proteins act as cross-linkers between cell membrane proteins and the actin cytoskeleton. They are also involved in signal transduction pathways. They therefore have a critical role in normal cell processes, including modulation of cell shape, adhesion, and motility. We postulate that AGEs may contribute to diabetic complications by disrupting ERM function. In support of this hypothesis, AGEs inhibit ezrin-dependent tubulogenesis of proximal tubule cells. Phosphorylation is an important activating mechanism for ERM proteins, and AGEs inhibit ezrin phosphorylation mediated by the epidermal growth factor receptor.

Proximal Tubules Have the Capacity to Regulate Uptake of Albumin.

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Wagner, Mark C; Campos-Bilderback, Silvia B; Chowdhury, Mahboob; Flores, Brittany; Lai, Xianyin; Myslinski, Jered; Pandit, Sweekar; Sandoval, Ruben M; Wean, Sarah E; Wei, Yuan; Satlin, Lisa M; Wiggins, Roger C; Witzmann, Frank A; Molitoris, Bruce A

2016-02-01

Evidence from multiple studies supports the concept that both glomerular filtration and proximal tubule (PT) reclamation affect urinary albumin excretion rate. To better understand these roles of glomerular filtration and PT uptake, we investigated these processes in two distinct animal models. In a rat model of acute exogenous albumin overload, we quantified glomerular sieving coefficients (GSC) and PT uptake of Texas Red-labeled rat serum albumin using two-photon intravital microscopy. No change in GSC was observed, but a significant decrease in PT albumin uptake was quantified. In a second model, loss of endogenous albumin was induced in rats by podocyte-specific transgenic expression of diphtheria toxin receptor. In these albumin-deficient rats, exposure to diphtheria toxin induced an increase in albumin GSC and albumin filtration, resulting in increased exposure of the PTs to endogenous albumin. In this case, PT albumin reabsorption was markedly increased. Analysis of known albumin receptors and assessment of cortical protein expression in the albumin overload model, conducted to identify potential proteins and pathways affected by acute protein overload, revealed changes in the expression levels of calreticulin, disabled homolog 2, NRF2, angiopoietin-2, and proteins involved in ATP synthesis. Taken together, these results suggest that a regulated PT cell albumin uptake system can respond rapidly to different physiologic conditions to minimize alterations in serum albumin level. Copyright © 2016 by the American Society of Nephrology.

Pathophyisiology analysis overload nephron protein in the proximal tubule damage in the nephrolithiasis size stones of 0.6-1.0 sm

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Yu. Ye. Rohovyi

2017-07-01

Full Text Available Nephrolithiasis as the most common urological disorder characterized by frequent early relapses, acquires a social character, because these patients are 30 to 45% of all urological patients, while in Europe the disease is diagnosed in 2% of the population. The study included 40 patients with nephrolithiasis, 10 patients constituted the control group. Set the “hidden” damage to the proximal nephron in the presence of renal stones with a size of 0.6-1.0 cm in the upper third of the ureter, the upper and middle sections of the calyx, which is confirmed by the inhibition of enzymatic fibrinolytic activity of urine, the presence of tubular proteinuria in the absence of inhibition of proximal reabsorption of sodium ions. The link “hidden” damage to the proximal tubule of the degree of overload of the proximal nephron is a protein graphics multicorrelation dependence between the protein concentration of urine, standardized excretion protein and excretion, which are becoming more significant disharmony form towards control in the following sequence: the upper third of the ureter, medium cup, top cup.

Atgl gene deletion predisposes to proximal tubule damage by impairing the fatty acid metabolism

International Nuclear Information System (INIS)

Chen, Wen; Zhang, Qiong; Cheng, Shiwu; Huang, Jie; Diao, Ge; Han, Jian

2017-01-01

Fibrosis is the final common pathway of chronic kidney disease (CKD). Normal lipid metabolism is integral to renal physiology, and disturbances of renal lipid metabolism are increasingly being linked with CKD, including the fibrosis. Adipose triglyceride lipase (ATGL) is the rate-limiting enzyme of lipolysis. In the present study, we used Atgl −/− mice to investigate whether ATGL played a role in the regulation of proximal convoluted tubule (PCT) lipid metabolism and renal fibrosis development. ATGL deficiency led to lipid vacuolation of PCT and tubulointerstitial fibrosis, accompanied by massive albuminuria and decreased creatinine clearance rate (Ccr). In vitro experiments indicated that inhibition of ATGL in proximal tubular cell line HK-2 promoted intracellular lipid deposition, reactive oxygen species (ROS) accumulation and cell apoptosis. Both in vitro and in vivo experiments showed that ATGL inhibition decreased the renal peroxisome proliferator-activated receptorα(PPARα) expression, which implied the suppressed lipid metabolism. The antioxidant N-acetylcysteine (NAC) could partially reverse the effect of ROS accumulation and cell apoptosis, but could not restore the PPARαdecrease. These data raise the possibility that ATGL deficiency could impair the renal fatty acid metabolism though inhibiting PPARαexpression, which may lead to lipid deposition and cell apoptosis of PCT, and finally contribute to the renal fibrosis and dysfunction. - Highlights: • Atgl −/− mice develop tubulointerstitial damage and renal dysfunction. • ATGL deficiency results in lipid accumulation and apoptosis of proximal tubular cells. • ROS scavenger alleviates the ATGL-knockdown mediated lipid accumulation and apoptosis. • PPARαdown-regulation is the reason of ROS elevating in ATGL-knockdown HK-2 cells.

Novel Hg2+-Induced Nephropathy in Rats and Mice Lacking Mrp2: Evidence of Axial Heterogeneity in the Handling of Hg2+ Along the Proximal Tubule

Science.gov (United States)

Zalups, Rudolfs K.; Joshee, Lucy; Bridges, Christy C.

2014-01-01

The role of the multi-resistance protein 2 (Mrp2) in the nephropathy induced by inorganic mercuric mercury (Hg2+) was studied in rats (TR−) and mice (Mrp2−/−), which lack functional Mrp2, and control animals. Animals were exposed to nephrotoxic doses of HgCl2. Forty-eight or 24 hours after exposure, tissues were harvested and analyzed for Hg content and markers of injury. Histological analyses revealed that the proximal tubular segments affected pathologically by Hg2+ were significantly different between Mrp2-deficient animals and controls. In the absence of Mrp2, cellular injury localized almost exclusively in proximal tubular segments in the subcapsular (S1) to midcortical regions (early S2) of the kidney. In control animals, cellular death occurred mainly in the proximal tubular segments in the inner cortex (late S2) and outer stripe of the outer medulla (S3). These differences in renal pathology indicate that axial heterogeneity exists along the proximal tubule with respect to how mercuric ions are handled. Total renal and hepatic accumulation of mercury was also greater in animals lacking Mrp2 than in controls, indicating that Mrp2 normally plays a significant role in eliminating mercuric ions from within proximal tubular cells and hepatocytes. Analyses of plasma creatinine, BUN, and renal expression of Kim-1 and Ngal tend to support the severity of the nephropathies detected histologically. Collectively, our findings indicate that a fraction of mercuric ions is normally secreted by Mrp2 in early portions of proximal tubules into the lumen and then is absorbed downstream in straight portions, where mercuric species typically induce toxic effects. PMID:25145654

Role of diacylglycerol in adrenergic-stimulated sup 86 Rb uptake by proximal tubules

Energy Technology Data Exchange (ETDEWEB)

Baines, A.D.; Drangova, R.; Ho, P. (Univ. of Toronto, Ontario (Canada))

1990-05-01

We used rat proximal tubule fragments purified by Percoll centrifugation to examine the role of diacylglycerol (DAG) in noradrenergic-stimulated Na+ reabsorption. Tubular DAG concentration and ouabain-inhibitable 86Rb uptake increased within 30 s after adding norepinephrine (NE) and remained elevated for at least 5 min. NE (1 microM) increased DAG content 17% and ouabain-inhibitable 86Rb uptake 23%. Cirazoline-stimulated 86Rb uptake was not inhibited by BaCl, quinidine, or bumetanide (1-10 microM) or by the omission of HCO3- or Cl- from the medium, but it was completely inhibited by ouabain and furosemide. Oleoyl-acetyl glycerol, L-alpha-1,2-dioctanoylglycerol, and L-alpha-1,2-dioleoylglycerol (DOG) increased total 86Rb uptake 8-11%. 12-O-tetradecanoylphorbol-13-acetate (TPA) (5 nM) increased uptake by only 4%. Staurosporine at 5 nM inhibited DOG stimulation completely, whereas 50 nM staurosporine was required to inhibit NE stimulation completely. Sphingosine inhibited DOG stimulation by 66% but did not inhibit NE stimulation. Amiloride (1 mM) completely blocked DOG stimulation. Monensin increased 86Rb uptake 31% and completely blocked the DOG effect but reduced the NE effect by only 26% (P = 0.08). In tubules from salt-loaded rats, NE did not increase DAG concentration, but NE-stimulated 86Rb uptake was reduced by only 23% (P = 0.15). Thus DAG released by NE may stimulate Na+ entry through Na(+)-H+ exchange. NE predominantly stimulates Na(+)-K(+)-adenosinetriphosphatase (ATPase) by activating a protein kinase that is insensitive to DAG and TPA and is inhibited by staurosporine but not by sphingosine. NE may also stimulate K+ efflux through a BaCl-insensitive K+ channel that is inhibited by millimolar furosemide.

Detailed investigations of proximal tubular function in Imerslund-Grasbeck syndrome

DEFF Research Database (Denmark)

Storm, Tina; Zeitz, Christina; Cases, Olivier

2013-01-01

expressed in the small intestine as well as the proximal tubules of the kidney and exhibit an interdependent relationship for post-translational processing and trafficking. In the proximal tubules cubilin is involved in the reabsorption of several filtered plasma proteins including vitamin carriers...

Characterization of rPEPT2-mediated Gly-Sar transport parameters in the rat kidney proximal tubule cell line SKPT-0193 cl.2 cultured in basic growth media

DEFF Research Database (Denmark)

Bravo, Silvina A; Nielsen, Carsten Uhd; Frokjaer, Sven

2005-01-01

The rat proximal kidney tubule cell line SKPT-0193 cl.2 (SKPT) expresses the di-/tripeptide transporter PEPT2 (rPEPT2) and has been used to study PEPT2-mediated transport. Traditionally, SKPT cells have been cultured in growth media supplemented with epidermal growth factor (EGF), apotransferrin,...

Development of a living membrane comprising a functional human renal proximal tubule cell monolayer on polyethersulfone polymeric membrane.

Science.gov (United States)

Schophuizen, Carolien M S; De Napoli, Ilaria E; Jansen, Jitske; Teixeira, Sandra; Wilmer, Martijn J; Hoenderop, Joost G J; Van den Heuvel, Lambert P W; Masereeuw, Rosalinde; Stamatialis, Dimitrios

2015-03-01

The need for improved renal replacement therapies has stimulated innovative research for the development of a cell-based renal assist device. A key requirement for such a device is the formation of a "living membrane", consisting of a tight kidney cell monolayer with preserved functional organic ion transporters on a suitable artificial membrane surface. In this work, we applied a unique conditionally immortalized proximal tubule epithelial cell (ciPTEC) line with an optimized coating strategy on polyethersulfone (PES) membranes to develop a living membrane with a functional proximal tubule epithelial cell layer. PES membranes were coated with combinations of 3,4-dihydroxy-l-phenylalanine and human collagen IV (Coll IV). The optimal coating time and concentrations were determined to achieve retention of vital blood components while preserving high water transport and optimal ciPTEC adhesion. The ciPTEC monolayers obtained were examined through immunocytochemistry to detect zona occludens 1 tight junction proteins. Reproducible monolayers were formed when using a combination of 2 mg ml(-1) 3,4-dihydroxy-l-phenylalanine (4 min coating, 1h dissolution) and 25 μg ml(-1) Coll IV (4 min coating). The successful transport of (14)C-creatinine through the developed living membrane system was used as an indication for organic cation transporter functionality. The addition of metformin or cimetidine significantly reduced the creatinine transepithelial flux, indicating active creatinine uptake in ciPTECs, most likely mediated by the organic cation transporter, OCT2 (SLC22A2). In conclusion, this study shows the successful development of a living membrane consisting of a reproducible ciPTEC monolayer on PES membranes, an important step towards the development of a bioartificial kidney. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Effect of acute acid-base disturbances on ErbB1/2 tyrosine phosphorylation in rabbit renal proximal tubules.

Science.gov (United States)

Skelton, Lara A; Boron, Walter F

2013-12-15

The renal proximal tubule (PT) is a major site for maintaining whole body pH homeostasis and is responsible for reabsorbing ∼80% of filtered HCO3(-), the major plasma buffer, into the blood. The PT adapts its rate of HCO3(-) reabsorption (JHCO3(-)) in response to acute acid-base disturbances. Our laboratory previously showed that single isolated perfused PTs adapt JHCO3(-) in response to isolated changes in basolateral (i.e., blood side) CO2 and HCO3(-) concentrations but, surprisingly, not to pH. The response to CO2 concentration can be blocked by the ErbB family tyrosine kinase inhibitor PD-168393. In the present study, we exposed enriched rabbit PT suspensions to five acute acid-base disturbances for 5 and 20 min using a panel of phosphotyrosine (pY)-specific antibodies to determine the influence of each disturbance on pan-pY, ErbB1-specific pY (four sites), and ErbB2-specific pY (two sites). We found that each acid-base treatment generated a distinct temporal pY pattern. For example, the summated responses of the individual ErbB1/2-pY sites to each disturbance showed that metabolic acidosis (normal CO2 concentration and reduced HCO3(-) concentration) produced a transient summated pY decrease (5 vs. 20 min), whereas metabolic alkalosis produced a transient increase. Respiratory acidosis (normal HCO3(-) concentration and elevated CO2 concentration) had little effect on summated pY at 5 min but produced an elevation at 20 min, whereas respiratory alkalosis produced a reduction at 20 min. Our data show that ErbB1 and ErbB2 in the PT respond to acute acid-base disturbances, consistent with the hypothesis that they are part of the signaling cascade.

Stimulation of Na+-alanine cotransport activates a voltage-dependent conductance in single proximal tubule cells isolated from frog kidney

Science.gov (United States)

Robson, L; Hunter, M

1999-01-01

The swelling induced by Na+-alanine cotransport in proximal tubule cells of the frog kidney is followed by regulatory volume decrease (RVD). This RVD is inhibited by gadolinium (Gd3+), an inhibitor of stretch-activated channels, but is independent of extracellular Ca2+. In this study, the whole cell patch clamp technique was utilized to examine the effect of Na+-alanine cotransport on two previously identified volume- and Gd3+-sensitive conductances. One conductance is voltage dependent and anion selective (GVD) whilst the other is voltage independent and cation selective (GVI). Addition of 5 mM L-alanine to the bathing solution increased the whole cell conductance and gave a positive (depolarizing) shift in the reversal potential (Vrev, equivalent to the membrane potential in current-clamped cells) consistent with activation of Na+-alanine cotransport. Vrev shifted from -36 ± 4·9 to +12·9 ± 4·2 mV (n= 15). In the presence of alanine, the total whole cell conductance had several components including the cotransporter conductance and GVD and GVI. These conductances were separated using Gd3+, which inhibits both GVD and GVI, and the time dependency of GVD. Of these two volume-sensitive conductances, L-alanine elicited a specific increase in GVD, whereas GVI was unaffected. The L-alanine-induced activation of GVD was significantly reduced when cells were incubated in a hypertonic bathing solution. In summary, in single proximal tubule cells isolated from frog kidney, on stimulation of Na+-alanine cotransport GVD is activated, while GVI is unaffected. Taken with other evidence, this suggests that GVD is activated by cell swelling, consequent upon alanine entry, and may play a role as an anion efflux pathway during alanine-induced volume regulation. PMID:10226159

Visfatin Reduces Gap Junction Mediated Cell-to-Cell Communication in Proximal Tubule-Derived Epithelial Cells

Directory of Open Access Journals (Sweden)

Claire E. Hills

2013-11-01

Full Text Available Background/Aims: In the current study we examined if the adipocytokine, visfatin, alters connexin-mediated intercellular communication in proximal tubule-derived epithelial cells. Methods: The effects of visfatin (10-200ng/mL on cell viability and cytotoxicity in HK2-cells were assessed by MTT, crystal violet and lactate dehydrogenase assays. Western blot analysis was used to confirm expression of Cx26, Cx40 and Cx43. The effect of visfatin (10-200ng/mL on TGF-β1 secretion was confirmed by ELISA, and the effects of both TGF-β1 (2-10ng/mL and visfatin (10-200ng/mL on connexin expression were assessed by western blot. Functional intercellular communication was determined using transfer of Lucifer Yellow and paired-whole cell patch clamp electrophysiology. Results: In low glucose (5mM, visfatin (10-200ng/mL did not affect membrane integrity, cytotoxicity or cell viability at 48hrs, but did evoke a concentration-dependent reduction in Cx26 and Cx43 expression. The expression of Cx40 was unaffected. At 48hrs, visfatin (10-200ng/mL increased the secretion of TGF-β1 and the visfatin-evoked changes in connexin expression were mimicked by exogenous application of the pro-fibrotic cytokine (2-10ng/ml. Visfatin reduced dye transfer between coupled cells and decreased functional conductance, with levels falling by 63% as compared to control. Although input resistance was increased following visfatin treatment by 166%, the change was not significant as compared to control. The effects of visfatin on Cx-expression and cell-coupling were blocked in the presence of a TGF-β1 specific neutralizing antibody. Conclusions: The adipocytokine visfatin selectively evoked a non-toxic reduction in connexin expression in HK2-cells. The loss in gap-junction associated proteins was mirrored by a loss in functional conductance between coupled cells. Visfatin increased TGF-β secretion and the pattern of change for connexins expression was mimicked by exogenous

A pharmacologically-based array to identify targets of cyclosporine A-induced toxicity in cultured renal proximal tubule cells

International Nuclear Information System (INIS)

Sarró, Eduard; Jacobs-Cachá, Conxita; Itarte, Emilio; Meseguer, Anna

2012-01-01

Mechanisms of cyclosporine A (CsA)-induced nephrotoxicity were generally thought to be hemodynamic in origin; however, there is now accumulating evidence of a direct tubular effect. Although genomic and proteomic experiments by our group and others provided overall information on genes and proteins up- or down-regulated by CsA in proximal tubule cells (PTC), a comprehensive view of events occurring after CsA exposure remains to be described. For this purpose, we applied a pharmacologic approach based on the use of known activities of a large panel of potentially protective compounds and evaluated their efficacy in preventing CsA toxicity in cultured mouse PTC. Our results show that compounds that blocked protein synthesis and apoptosis, together with the CK2 inhibitor DMAT and the PI3K inhibitor apigenin, were the most efficient in preventing CsA toxicity. We also identified GSK3, MMPs and PKC pathways as potential targets to prevent CsA damage. Additionally, heparinase-I and MAPK inhibitors afforded partial but significant protection. Interestingly, antioxidants and calcium metabolism-related compounds were unable to ameliorate CsA-induced cytotoxicity. Subsequent experiments allowed us to clarify the hierarchical relationship of targeted pathways after CsA treatment, with ER stress identified as an early effector of CsA toxicity, which leads to ROS generation, phenotypical changes and cell death. In summary, this work presents a novel experimental approach to characterizing cellular responses to cytotoxics while pointing to new targets to prevent CsA-induced toxicity in proximal tubule cells. Highlights: ► We used a novel pharmacological approach to elucidate cyclosporine (CsA) toxicity. ► The ability of a broad range of compounds to prevent CsA toxicity was evaluated. ► CsA toxicity was monitored using LDH release assay and PARP cleavage. ► Protein synthesis, PI3K, GSK3, MMP, PKC and caspase inhibitors prevented CsA toxicity. ► We also identified ER

A pharmacologically-based array to identify targets of cyclosporine A-induced toxicity in cultured renal proximal tubule cells

Energy Technology Data Exchange (ETDEWEB)

Sarró, Eduard, E-mail: eduard.sarro@vhir.org [Departament de Bioquímica i Biologia Molecular, Unitat de Bioquímica de Biociències, Universitat Autònoma de Barcelona, 08193 Bellaterra (Barcelona) (Spain); Renal Physiopathology, CIBBIM-Nanomedicine, Vall d' Hebron Research Institute (VHIR), 08035 Barcelona (Spain); Jacobs-Cachá, Conxita, E-mail: conxita.jacobs@vhir.org [Renal Physiopathology, CIBBIM-Nanomedicine, Vall d' Hebron Research Institute (VHIR), 08035 Barcelona (Spain); Itarte, Emilio, E-mail: emili.itarte@uab.es [Departament de Bioquímica i Biologia Molecular, Unitat de Bioquímica de Biociències, Universitat Autònoma de Barcelona, 08193 Bellaterra (Barcelona) (Spain); Meseguer, Anna, E-mail: ana.meseguer@vhir.org [Renal Physiopathology, CIBBIM-Nanomedicine, Vall d' Hebron Research Institute (VHIR), 08035 Barcelona (Spain); Departament de Bioquimica i Biologia Molecular, Facultat de Medicina, Universitat Autònoma de Barcelona, 08193 Bellaterra (Barcelona) (Spain)

2012-01-15

Mechanisms of cyclosporine A (CsA)-induced nephrotoxicity were generally thought to be hemodynamic in origin; however, there is now accumulating evidence of a direct tubular effect. Although genomic and proteomic experiments by our group and others provided overall information on genes and proteins up- or down-regulated by CsA in proximal tubule cells (PTC), a comprehensive view of events occurring after CsA exposure remains to be described. For this purpose, we applied a pharmacologic approach based on the use of known activities of a large panel of potentially protective compounds and evaluated their efficacy in preventing CsA toxicity in cultured mouse PTC. Our results show that compounds that blocked protein synthesis and apoptosis, together with the CK2 inhibitor DMAT and the PI3K inhibitor apigenin, were the most efficient in preventing CsA toxicity. We also identified GSK3, MMPs and PKC pathways as potential targets to prevent CsA damage. Additionally, heparinase-I and MAPK inhibitors afforded partial but significant protection. Interestingly, antioxidants and calcium metabolism-related compounds were unable to ameliorate CsA-induced cytotoxicity. Subsequent experiments allowed us to clarify the hierarchical relationship of targeted pathways after CsA treatment, with ER stress identified as an early effector of CsA toxicity, which leads to ROS generation, phenotypical changes and cell death. In summary, this work presents a novel experimental approach to characterizing cellular responses to cytotoxics while pointing to new targets to prevent CsA-induced toxicity in proximal tubule cells. Highlights: ► We used a novel pharmacological approach to elucidate cyclosporine (CsA) toxicity. ► The ability of a broad range of compounds to prevent CsA toxicity was evaluated. ► CsA toxicity was monitored using LDH release assay and PARP cleavage. ► Protein synthesis, PI3K, GSK3, MMP, PKC and caspase inhibitors prevented CsA toxicity. ► We also identified ER

Transport of salicylate in proximal tubule (S2 segment) isolated from rabbit kidney

International Nuclear Information System (INIS)

Schild, L.; Roch-Ramel, F.

1988-01-01

The secretory and the reabsorptive transport of salicylate was studied in the isolated and perfused rabbit proximal tubule (S 2 segment). Salicylate secretion (J sal b→l ) fulfilled the criteria for a carrier-mediated transport system: J sal b→l was saturable, was reversibly inhibited by probenecid, and occurred against a concentration gradient. The K m and V max for this secretory transport were 80 μM and 3,200 fmol·min -1 ·mm -1 , respectively. At luminal pH of 7.4 and 6.6, salicylate reabsorption (J sal l→b ) was low. J sal l→b was stimulated by increasing the bath Pco 2 or by removing basolateral HCO 3 - ; J sal l→b was inhibited by ethoxyzolamide and by SITS in the bath. The results indicate that salicylate reabsorption depends on H + secretion, consistent with reabsorption by simple nonionic diffusion. When salicylate was present in the lumen only, J sal l→b increased after inhibition of the secretory transport by adding ouabain or probenecid in the bath or by lowering the bath temperature. These results are compatible with luminal recycling of salicylate, and suggest the presence of a mediated secretory transporter located at the luminal membrane

Proximal tubule-specific glutamine synthetase deletion alters basal and acidosis-stimulated ammonia metabolism

Science.gov (United States)

Lee, Hyun-Wook; Osis, Gunars; Handlogten, Mary E.; Lamers, Wouter H.; Chaudhry, Farrukh A.; Verlander, Jill W.

2016-01-01

Glutamine synthetase (GS) catalyzes the recycling of NH4+ with glutamate to form glutamine. GS is highly expressed in the renal proximal tubule (PT), suggesting ammonia recycling via GS could decrease net ammoniagenesis and thereby limit ammonia available for net acid excretion. The purpose of the present study was to determine the role of PT GS in ammonia metabolism under basal conditions and during metabolic acidosis. We generated mice with PT-specific GS deletion (PT-GS-KO) using Cre-loxP techniques. Under basal conditions, PT-GS-KO increased urinary ammonia excretion significantly. Increased ammonia excretion occurred despite decreased expression of key proteins involved in renal ammonia generation. After the induction of metabolic acidosis, the ability to increase ammonia excretion was impaired significantly by PT-GS-KO. The blunted increase in ammonia excretion occurred despite greater expression of multiple components of ammonia generation, including SN1 (Slc38a3), phosphate-dependent glutaminase, phosphoenolpyruvate carboxykinase, and Na+-coupled electrogenic bicarbonate cotransporter. We conclude that 1) GS-mediated ammonia recycling in the PT contributes to both basal and acidosis-stimulated ammonia metabolism and 2) adaptive changes in other proteins involved in ammonia metabolism occur in response to PT-GS-KO and cause an underestimation of the role of PT GS expression. PMID:27009341

Paracellular transport and energy utilization in the renal tubule.

Science.gov (United States)

Yu, Alan S L

2017-09-01

Paracellular transport across the tight junction is a general mechanism for transepithelial transport of solutes in epithelia, including the renal tubule. However, why paracellular transport evolved, given the existence of a highly versatile system for transcellular transport, is unknown. Recent studies have identified the paracellular channel, claudin-2, that is responsible for paracellular reabsorption of sodium in the proximal renal tubule. Knockout of claudin-2 in mice impairs proximal sodium and fluid reabsorption but is compensated by upregulation of sodium reabsorption in the loop of Henle. This occurs at the expense of increased renal oxygen consumption, hypoxia of the outer medulla and increased susceptibility to ischemic kidney injury. Paracellular transport can be viewed as a mechanism to exploit the potential energy in existing electrochemical gradients to drive passive transepithelial transport without consuming additional energy. In this way, it enhances the efficiency of energy utilization by transporting epithelia.

Distinct mechanisms underlie adaptation of proximal tubule Na+/H+ exchanger isoform 3 in response to chronic metabolic and respiratory acidosis.

Science.gov (United States)

Silva, Pedro Henrique Imenez; Girardi, Adriana Castello Costa; Neri, Elida Adalgisa; Rebouças, Nancy Amaral

2012-04-01

The Na(+/)H(+) exchanger isoform 3 (NHE3) is essential for HCO(3)(-) reabsorption in renal proximal tubules. The expression and function of NHE3 must adapt to acid-base conditions. The goal of this study was to elucidate the mechanisms responsible for higher proton secretion in proximal tubules during acidosis and to evaluate whether there are differences between metabolic and respiratory acidosis with regard to NHE3 modulation and, if so, to identify the relevant parameters that may trigger these distinct adaptive responses. We achieved metabolic acidosis by lowering HCO(3)(-) concentration in the cell culture medium and respiratory acidosis by increasing CO(2) tension in the incubator chamber. We found that cell-surface NHE3 expression was increased in response to both forms of acidosis. Mild (pH 7.21 ± 0.02) and severe (6.95 ± 0.07) metabolic acidosis increased mRNA levels, at least in part due to up-regulation of transcription, whilst mild (7.11 ± 0.03) and severe (6.86 ± 0.01) respiratory acidosis did not up-regulate NHE3 expression. Analyses of the Nhe3 promoter region suggested that the regulatory elements sensitive to metabolic acidosis are located between -466 and -153 bp, where two consensus binding sites for SP1, a transcription factor up-regulated in metabolic acidosis, were localised. We conclude that metabolic acidosis induces Nhe3 promoter activation, which results in higher mRNA and total protein level. At the plasma membrane surface, NHE3 expression was increased in metabolic and respiratory acidosis alike, suggesting that low pH is responsible for NHE3 displacement to the cell surface.

Experimental type II diabetes and related models of impaired glucose metabolism differentially regulate glucose transporters at the proximal tubule brush border membrane.

Science.gov (United States)

Chichger, Havovi; Cleasby, Mark E; Srai, Surjit K; Unwin, Robert J; Debnam, Edward S; Marks, Joanne

2016-06-01

What is the central question of this study? Although SGLT2 inhibitors represent a promising treatment for patients suffering from diabetic nephropathy, the influence of metabolic disruption on the expression and function of glucose transporters is largely unknown. What is the main finding and its importance? In vivo models of metabolic disruption (Goto-Kakizaki type II diabetic rat and junk-food diet) demonstrate increased expression of SGLT1, SGLT2 and GLUT2 in the proximal tubule brush border. In the type II diabetic model, this is accompanied by increased SGLT- and GLUT-mediated glucose uptake. A fasted model of metabolic disruption (high-fat diet) demonstrated increased GLUT2 expression only. The differential alterations of glucose transporters in response to varying metabolic stress offer insight into the therapeutic value of inhibitors. SGLT2 inhibitors are now in clinical use to reduce hyperglycaemia in type II diabetes. However, renal glucose reabsorption across the brush border membrane (BBM) is not completely understood in diabetes. Increased consumption of a Western diet is strongly linked to type II diabetes. This study aimed to investigate the adaptations that occur in renal glucose transporters in response to experimental models of diet-induced insulin resistance. The study used Goto-Kakizaki type II diabetic rats and normal rats rendered insulin resistant using junk-food or high-fat diets. Levels of protein kinase C-βI (PKC-βI), GLUT2, SGLT1 and SGLT2 were determined by Western blotting of purified renal BBM. GLUT- and SGLT-mediated d-[(3) H]glucose uptake by BBM vesicles was measured in the presence and absence of the SGLT inhibitor phlorizin. GLUT- and SGLT-mediated glucose transport was elevated in type II diabetic rats, accompanied by increased expression of GLUT2, its upstream regulator PKC-βI and SGLT1 protein. Junk-food and high-fat diet feeding also caused higher membrane expression of GLUT2 and its upstream regulator PKC

De novo expression of sodium-glucose cotransporter SGLT2 in Bowman’s capsule coincides with replacement of parietal epithelial cell layer with proximal tubule-like epithelium

OpenAIRE

Tabatabai, Niloofar M.; North, Paula E.; Regner, Kevin R.; Kumar, Suresh N.; Duris, Christine B.; Blodgett, Amy B.

2014-01-01

In kidney nephron, parietal epithelial cells line the Bowman’s capsule and function as a permeability barrier for the glomerular filtrate. Bowman’s capsule cells with proximal tubule epithelial morphology have been found. However, the effects of tubular metaplasia in Bowman’s capsule on kidney function remain poorly understood. Sodium-glucose cotransporter 2 (SGLT2) plays a major role in reabsorption of glucose in the kidney and is expressed on brush border membrane of epithelial cells in the...

Epidermal growth factor decreases PEPT2 transport capacity and expression in the rat kidney proximal tubule cell line SKPT0193 cl.2

DEFF Research Database (Denmark)

Bravo, Silvina A; Nielsen, Carsten Uhd; Amstrup, Jan

2004-01-01

by studies of apical uptake of [14C]glycylsarcosine, rPepT2 mRNA levels, and immunostaining of SKPT cells with a rPEPT2-specific antibody. On the contrary, apical uptake of glucose and lysine was increased in EGF-treated cells, indicating that EGF was not acting generally to decrease apical nutrient uptake...... mechanisms in the proximal tubule cells. Our findings indicate that EGF decreases rPEPT2 expression by lowering transcription of the rat PepT2 gene or by decreasing rat PepT2 mRNA stability. Previous investigators routinely used SKPT cell culture media with a high (10 ng/ml) EGF concentration. Our study...

Antenatal betamethasone attenuates the angiotensin-(1-7)-Mas receptor-nitric oxide axis in isolated proximal tubule cells.

Science.gov (United States)

Su, Yixin; Bi, Jianli; Pulgar, Victor M; Chappell, Mark C; Rose, James C

2017-06-01

We previously reported a sex-specific effect of antenatal treatment with betamethasone (Beta) on sodium (Na + ) excretion in adult sheep whereby treated males but not females had an attenuated natriuretic response to angiotensin-(1-7) [Ang-(1-7)]. The present study determined the Na + uptake and nitric oxide (NO) response to low-dose Ang-(1-7) (1 pM) in renal proximal tubule cells (RPTC) from adult male and female sheep antenatally exposed to Beta or vehicle. Data were expressed as percentage of basal uptake or area under the curve for Na + or percentage of control for NO. Male Beta RPTC exhibited greater Na + uptake than male vehicle cells (433 ± 28 vs. 330 ± 26%; P 0.05). Ang-(1-7) significantly inhibited Na + uptake in RPTC from vehicle male (214 ± 11%) and from both vehicle (190 ± 14%) and Beta (209 ± 11%) females but failed to attenuate Na + uptake in Beta male cells. Beta exposure also abolished stimulation of NO by Ang-(1-7) in male but not female RPTC. Both the Na + and NO responses to Ang-(1-7) were blocked by Mas receptor antagonist d-Ala 7 -Ang-(1-7). We conclude that the tubular Ang-(1-7)-Mas-NO pathway is attenuated in males and not females by antenatal Beta exposure. Moreover, since primary cultures of RPTC retain both the sex and Beta-induced phenotype of the adult kidney in vivo they appear to be an appropriate cell model to examine the effects of fetal programming on Na + handling by the renal tubules. Copyright © 2017 the American Physiological Society.

Locally formed dopamine inhibits Na+-K+-ATPase activity in rat renal cortical tubule cells

International Nuclear Information System (INIS)

Seri, I.; Kone, B.C.; Gullans, S.R.; Aperia, A.; Brenner, B.M.; Ballermann, B.J.

1988-01-01

Dopamine, generated locally from L-dopa, inhibits Na + -K + -ATPase in permeabilized rat proximal tubules under maximum transport rate conditions for sodium. To determine whether locally formed dopamine inhibits Na + -K + -ATPase activity in intact cortical tubule cells we studied the effect of L-dopa on ouabain-sensitive oxygen consumption rate (Qo 2 ) and 86 Rb uptake in renal cortical tubule cell suspensions. L-Dopa did not affect ouabain-insensitive Qo 2 or mitochondrial respiration. However, L-dopa inhibited ouabain-sensitive Qo 2 in a concentration-dependent manner, with half-maximal inhibition (K 0.5 ) of 5 x 10 -7 M and a maximal inhibition of 14.1 ± 1.5% at 10 -4 M. L-Dopa also blunted the nystatin-stimulated Qo 2 in a concentration-dependent manner, indicating the L-dopa directly inhibits Na + -K + -ATPase activity and not sodium entry. Ouabain-sensitive 86 Rb uptake was also inhibited by L-dopa. Carbidopa, an inhibitor of the conversion of L-dopa to dopamine, eliminated the effect of L-dopa on ouabain-sensitive Qo 2 and 86 Rb uptake, indicating that dopamine rather than L-dopa was the active agent. The finding that the L-dopa concentration-response curve was shifted to the left by one order of magnitude in the presence of nystatin suggests that the inhibitory effect is enhanced when the intracellular sodium concentration is increased. By studying the effect of L-dopa on ouabain-sensitive Qo 2 at increasing extracellular sodium concentrations in the presence of nystatin, the authors demonstrated that the inhibitory effect of locally formed dopamine on the Na + -K + -ATPase is indeed dependent on the sodium available for the enzyme and occurs in an uncompetitive manner

The transcriptome of the Didelphis virginiana opossum kidney OK proximal tubule cell line.

Science.gov (United States)

Eshbach, Megan L; Sethi, Rahil; Avula, Raghunandan; Lamb, Janette; Hollingshead, Deborah J; Finegold, David N; Locker, Joseph D; Chandran, Uma R; Weisz, Ora A

2017-09-01

The OK cell line derived from the kidney of a female opossum Didelphis virginiana has proven to be a useful model in which to investigate the unique regulation of ion transport and membrane trafficking mechanisms in the proximal tubule (PT). Sequence data and comparison of the transcriptome of this cell line to eutherian mammal PTs would further broaden the utility of this culture model. However, the genomic sequence for D. virginiana is not available and although a draft genome sequence for the opossum Monodelphis domestica (sequenced in 2012 by the Broad Institute) exists, transcripts sequenced from both species show significant divergence. The M. domestica sequence is not highly annotated, and the majority of transcripts are predicted rather than experimentally validated. Using deep RNA sequencing of the D. virginiana OK cell line, we characterized its transcriptome via de novo transcriptome assembly and alignment to the M. domestica genome. The quality of the de novo assembled transcriptome was assessed by the extent of homology to sequences in nucleotide and protein databases. Gene expression levels in the OK cell line, from both the de novo transcriptome and genes aligned to the M. domestica genome, were compared with publicly available rat kidney nephron segment expression data. Our studies demonstrate the expression in OK cells of numerous PT-specific ion transporters and other key proteins relevant for rodent and human PT function. Additionally, the sequence and expression data reported here provide an important resource for genetic manipulation and other studies on PT cell function using these cells. Copyright © 2017 the American Physiological Society.

Proximal Tubular Injury in Medullary Rays Is an Early Sign of Acute Tacrolimus Nephrotoxicity

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Diane Cosner

2015-01-01

Full Text Available Tacrolimus (FK506 is one of the principal immunosuppressive agents used after solid organ transplantations to prevent allograft rejection. Chronic renal injury induced by tacrolimus is characterized by linear fibrosis in the medullary rays; however, the early morphologic findings of acute tacrolimus nephrotoxicity are not well characterized. Kidney injury molecule-1 (KIM-1 is a specific injury biomarker that has been proven to be useful in the diagnosis of mild to severe acute tubular injury on renal biopsies. This study was motivated by a patient with acute kidney injury associated with elevated serum tacrolimus levels in whom KIM-1 staining was present only in proximal tubules located in the medullary rays in the setting of otherwise normal light, immunofluorescent, and electron microscopy. We subsequently evaluated KIM-1 expression in 45 protocol and 39 indicated renal transplant biopsies to determine whether higher serum levels of tacrolimus were associated with acute segment specific injury to the proximal tubule, as reflected by KIM-1 staining in the proximal tubules of the cortical medullary rays. The data suggest that tacrolimus toxicity preferentially affects proximal tubules in medullary rays and that this targeted injury is a precursor lesion for the linear fibrosis seen in chronic tacrolimus toxicity.

Dual Regulation of Gluconeogenesis by Insulin and Glucose in the Proximal Tubules of the Kidney.

Science.gov (United States)

Sasaki, Motohiro; Sasako, Takayoshi; Kubota, Naoto; Sakurai, Yoshitaka; Takamoto, Iseki; Kubota, Tetsuya; Inagi, Reiko; Seki, George; Goto, Moritaka; Ueki, Kohjiro; Nangaku, Masaomi; Jomori, Takahito; Kadowaki, Takashi

2017-09-01

Growing attention has been focused on the roles of the proximal tubules (PTs) of the kidney in glucose metabolism, including the mechanism of regulation of gluconeogenesis. In this study, we found that PT-specific insulin receptor substrate 1/2 double-knockout mice, established by using the newly generated sodium-glucose cotransporter 2 (SGLT2)-Cre transgenic mice, exhibited impaired insulin signaling and upregulated gluconeogenic gene expression and renal gluconeogenesis, resulting in systemic insulin resistance. In contrast, in streptozotocin-treated mice, although insulin action was impaired in the PTs, the gluconeogenic gene expression was unexpectedly downregulated in the renal cortex, which was restored by administration of an SGLT1/2 inhibitor. In the HK-2 cells, the gluconeogenic gene expression was suppressed by insulin, accompanied by phosphorylation and inactivation of forkhead box transcription factor 1 (FoxO1). In contrast, glucose deacetylated peroxisome proliferator-activated receptor γ coactivator 1-α (PGC1α), a coactivator of FoxO1, via sirtuin 1, suppressing the gluconeogenic gene expression, which was reversed by inhibition of glucose reabsorption. These data suggest that both insulin signaling and glucose reabsorption suppress the gluconeogenic gene expression by inactivation of FoxO1 and PGC1α, respectively, providing insight into novel mechanisms underlying the regulation of gluconeogenesis in the PTs. © 2017 by the American Diabetes Association.

Interactive toxicity of inorganic mercury and trichloroethylene in rat and human proximal tubules: Effects on apoptosis, necrosis, and glutathione status

International Nuclear Information System (INIS)

Lash, Lawrence H.; Putt, David A.; Hueni, Sarah E.; Payton, Scott G.; Zwickl, Joshua

2007-01-01

Simultaneous or prior exposure to one chemical may alter the concurrent or subsequent response to another chemical, often in unexpected ways. This is particularly true when the two chemicals share common mechanisms of action. The present study uses the paradigm of prior exposure to study the interactive toxicity between inorganic mercury (Hg 2+ ) and trichloroethylene (TRI) or its metabolite S-(1,2-dichlorovinyl)-L-cysteine (DCVC) in rat and human proximal tubule. Pretreatment of rats with a subtoxic dose of Hg 2+ increased expression of glutathione S-transferase-α1 (GSTα1) but decreased expression of GSTα2, increased activities of several GSH-dependent enzymes, and increased GSH conjugation of TRI. Primary cultures of rat proximal tubular (rPT) cells exhibited both necrosis and apoptosis after incubation with Hg 2+ . Pretreatment of human proximal tubular (hPT) cells with Hg 2+ caused little or no changes in GST expression or activities of GSH-dependent enzymes, decreased apoptosis induced by TRI or DCVC, but increased necrosis induced by DCVC. In contrast, pretreatment of hPT cells with TRI or DCVC protected from Hg 2+ by decreasing necrosis and increasing apoptosis. Thus, whereas pretreatment of hPT cells with Hg 2+ exacerbated cellular injury due to TRI or DCVC by shifting the response from apoptosis to necrosis, pretreatment of hPT cells with either TRI or DCVC protected from Hg 2+ -induced cytotoxicity by shifting the response from necrosis to apoptosis. These results demonstrate that by altering processes related to GSH status, susceptibilities of rPT and hPT cells to acute injury from Hg 2+ , TRI, or DCVC are markedly altered by prior exposures

Transport of water in proximal kidney tubules from whole tubules to single channels: length and section of the selectivity filter of aquaporin-1.

Science.gov (United States)

Whittembury, G; González, E; Hernández, C S; Gutiérrez, A M; Echevarría, M

1997-06-27

Proximal straight tubule (PST) were dissected from rabbit kidneys, held with crimping pipettes in a chamber bathed in a buffered mannitol isosmotic solution (MBS, 295 mOsm/kg). Tubule cell volume changes with time (dV/Adt) after steps in MBS osmolality (delta Cs) were monitored on line with an inverted microscope, a TV camera and an image processor. Reflection coefficients sigma and osmotic permeability coefficients, Pos, for several solutes were measured using two methods. Method 1: sigma was calculated from the delta Csiso of impermeant and permeant solutes at which (dV/Adt)t-->0 = 0 (i.e., by a null point method). It is denoted as sigma 1. sigma 1 = 1.00 for mannitol (M), raffinose (R), sucrose (S), glycerol (G), acetamide (A) and urea (U). With formamide (F), sigma 1, Formamide = 0.62 +/- 0.05. These findings confirm our previous value of dp = 4.5 A for the diameter of the selectivity filter of the basolateral PST cell membrane water channel AQP1. Method 2: PST were exposed for 20 s to MBS made hyperosmotic by addition of a delta Cs of 35 mOsm/kg of R, S, M, G, A and U. Cells shrunk within 500 ms of t = 0 to their osmometric volume and remained shrunk for the 20 s of the osmotic challenge. Pos was measured from the shrinking curves. P(os) = 3000 +/- 25 microns/s with R, S, M, G, A and U. Method 2 also allowed to calculate sigma, denoted as sigma 2. sigma 2 = 1.00 for R, S, M, G, A and U. By contrast, the shrinking curve produced by a delta Cs of 35 mOsm/kg F was 1/5th to 1/6th slower and smaller (i.e., subosmometric) than that produced by a delta Cs of 35 mOsm/kg R, S, M, G, A and U. Furthermore, with F cells did not remain shrunk but recovered their original volume within 3 s. P(os) (measured with F) is denoted as P(os)*, P(os)* = 480 +/- 30 microns/s. sigma 2, Formamide = 0.16 +/- 0.01. Use of sigma 1, sigma 2 and P(os)* values in Hill's equations for the bimodal theory of osmosis leads to n = 2-9. Where n is the number of water molecules single filling

Induction of apoptosis in cultured human proximal tubule cells by fumonisins and fumonisin metabolites

International Nuclear Information System (INIS)

Seefelder, W.; Humpf, H.-U.; Schwerdt, G.; Freudinger, R.; Gekle, M.

2003-01-01

Fumonisin B 1 (FB 1 ) causes apoptosis in a variety of cell types and tissues but the apoptotic potential of other fumonisins and fumonisin metabolites has not been determined and the underlying mechanisms are not completely understood. In our studies we exposed human proximal tubule-derived cells (IHKE cells) to FB 1 , fumonisin B 2 (FB 2 ), fumonisin B 3 (FB 3 ), hydrolyzed fumonisin B 1 (HFB 1 ) and N-palmitoyl-hydrolyzed fumonisin B 1 (N-Pal-HFB 1 ) and investigated caspase-3 activation, chromatin condensation and DNA fragmentation. Exposure to 10 μmol/L FB 1 for 24 h led to a significant increase in caspase-3 activity, chromatin condensation and to DNA fragmentation. All other tested compounds did not show any significant activation of caspase-3 activity nor chromatin condensation and DNA-fragmentation. Furthermore, we examined if a sphinganine accumulation is correlated with an induction of apoptosis in IHKE cells. Therefore we used a liquid chromatography/electrospray ionization-mass spectrometry(LC/ESI-MS)-method using phytosphingosine as an internal standard to determine sphinganine and sphingosine concentrations in IHKE cells. Whereas a significant increase of sphinganine (up to 7000% compared to control cells) was observed with all fumonisin-derivates, sphingosine levels nearly remained unchanged indicating that all substrates inhibited ceramide synthase effectively. These results demonstrate that all compounds let to increased sphinganine levels in IHKE cells but only FB 1 was able to induce apoptosis. We conclude that the inhibition of the ceramide synthase is not per se a predictor whether or not fumonisins induce apoptosis

Urinary Excretion of Tetrodotoxin Modeled in a Porcine Renal Proximal Tubule Epithelial Cell Line, LLC-PK1

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Takuya Matsumoto

2017-07-01

Full Text Available This study examined the urinary excretion of tetrodotoxin (TTX modeled in a porcine renal proximal tubule epithelial cell line, LLC-PK1. Time course profiles of TTX excretion and reabsorption across the cell monolayers at 37 °C showed that the amount of TTX transported increased linearly for 60 min. However, at 4 °C, the amount of TTX transported was approximately 20% of the value at 37 °C. These results indicate that TTX transport is both a transcellular and carrier-mediated process. Using a transport inhibition assay in which cell monolayers were incubated with 50 µM TTX and 5 mM of a transport inhibitor at 37 °C for 30 min, urinary excretion was significantly reduced by probenecid, tetraethylammonium (TEA, l-carnitine, and cimetidine, slightly reduced by p-aminohippuric acid (PAH, and unaffected by 1-methyl-4-phenylpyridinium (MPP+, oxaliplatin, and cefalexin. Renal reabsorption was significantly reduced by PAH, but was unaffected by probenecid, TEA and l-carnitine. These findings indicate that TTX is primarily excreted by organic cation transporters (OCTs and organic cation/carnitine transporters (OCTNs, partially transported by organic anion transporters (OATs and multidrug resistance-associated proteins (MRPs, and negligibly transported by multidrug and toxic compound extrusion transporters (MATEs.

Active lithium transport by rat renal proximal tubule: a micropuncture study

DEFF Research Database (Denmark)

Leyssac, P P; Frederiksen, O; Holstein-Rathlou, N H

1994-01-01

We tested the hypothesis that proximal tubular Li+ reabsorption is due to passive transport. Clearances of [14C]inulin (CIn) and Li+ (CLi), proximal transepithelial electrical potential difference (PD), and tubular fluid-to-plasma Li+ concentration ratios [(TF/P)Li] were measured in anesthetized ...

Induction of apoptosis in cultured human proximal tubule cells by fumonisins and fumonisin metabolites

Energy Technology Data Exchange (ETDEWEB)

Seefelder, W; Humpf, H -U; Schwerdt, G; Freudinger, R; Gekle, M

2003-10-15

Fumonisin B{sub 1} (FB{sub 1}) causes apoptosis in a variety of cell types and tissues but the apoptotic potential of other fumonisins and fumonisin metabolites has not been determined and the underlying mechanisms are not completely understood. In our studies we exposed human proximal tubule-derived cells (IHKE cells) to FB{sub 1}, fumonisin B{sub 2} (FB{sub 2}), fumonisin B{sub 3} (FB{sub 3}), hydrolyzed fumonisin B{sub 1} (HFB{sub 1}) and N-palmitoyl-hydrolyzed fumonisin B{sub 1} (N-Pal-HFB{sub 1}) and investigated caspase-3 activation, chromatin condensation and DNA fragmentation. Exposure to 10 {mu}mol/L FB{sub 1} for 24 h led to a significant increase in caspase-3 activity, chromatin condensation and to DNA fragmentation. All other tested compounds did not show any significant activation of caspase-3 activity nor chromatin condensation and DNA-fragmentation. Furthermore, we examined if a sphinganine accumulation is correlated with an induction of apoptosis in IHKE cells. Therefore we used a liquid chromatography/electrospray ionization-mass spectrometry(LC/ESI-MS)-method using phytosphingosine as an internal standard to determine sphinganine and sphingosine concentrations in IHKE cells. Whereas a significant increase of sphinganine (up to 7000% compared to control cells) was observed with all fumonisin-derivates, sphingosine levels nearly remained unchanged indicating that all substrates inhibited ceramide synthase effectively. These results demonstrate that all compounds let to increased sphinganine levels in IHKE cells but only FB{sub 1} was able to induce apoptosis. We conclude that the inhibition of the ceramide synthase is not per se a predictor whether or not fumonisins induce apoptosis.

Locally formed dopamine inhibits Na sup + -K sup + -ATPase activity in rat renal cortical tubule cells

Energy Technology Data Exchange (ETDEWEB)

Seri, I.; Kone, B.C.; Gullans, S.R.; Aperia, A.; Brenner, B.M.; Ballermann, B.J. (Harvard Medical School, Boston, MA (USA) Karolinska Institute, Stockholm (Sweden))

1988-10-01

Dopamine, generated locally from L-dopa, inhibits Na{sup +}-K{sup +}-ATPase in permeabilized rat proximal tubules under maximum transport rate conditions for sodium. To determine whether locally formed dopamine inhibits Na{sup +}-K{sup +}-ATPase activity in intact cortical tubule cells we studied the effect of L-dopa on ouabain-sensitive oxygen consumption rate ({dot Q}o{sub 2}) and {sup 86}Rb uptake in renal cortical tubule cell suspensions. L-Dopa did not affect ouabain-insensitive {dot Q}o{sub 2} or mitochondrial respiration. However, L-dopa inhibited ouabain-sensitive {dot Q}o{sub 2} in a concentration-dependent manner, with half-maximal inhibition (K{sub 0.5}) of 5 {times} 10{sup {minus}7} M and a maximal inhibition of 14.1 {plus minus} 1.5% at 10{sup {minus}4}M. L-Dopa also blunted the nystatin-stimulated {dot Q}o{sub 2} in a concentration-dependent manner, indicating the L-dopa directly inhibits Na{sup +}-K{sup +}-ATPase activity and not sodium entry. Ouabain-sensitive {sup 86}Rb uptake was also inhibited by L-dopa. Carbidopa, an inhibitor of the conversion of L-dopa to dopamine, eliminated the effect of L-dopa on ouabain-sensitive {dot Q}o{sub 2} and {sup 86}Rb uptake, indicating that dopamine rather than L-dopa was the active agent. The finding that the L-dopa concentration-response curve was shifted to the left by one order of magnitude in the presence of nystatin suggests that the inhibitory effect is enhanced when the intracellular sodium concentration is increased. By studying the effect of L-dopa on ouabain-sensitive {dot Q}o{sub 2} at increasing extracellular sodium concentrations in the presence of nystatin, the authors demonstrated that the inhibitory effect of locally formed dopamine on the Na{sup +}-K{sup +}-ATPase is indeed dependent on the sodium available for the enzyme and occurs in an uncompetitive manner.

Sodium pumps in the Malpighian tubule of Rhodnius sp.

Directory of Open Access Journals (Sweden)

CARUSO-NEVES CELSO

2000-01-01

Full Text Available Malpighian tubule of Rhodnius sp. express two sodium pumps: the classical ouabain-sensitive (Na+ + K+ATPase and an ouabain-insensitive, furosemide-sensitive Na+-ATPase. In insects, 5-hydroxitryptamine is a diuretic hormone released during meals. It inhibits the (Na+ + K+ATPase and Na+ -ATPase activities indicating that these enzymes are involved in fluid secretion. Furthermore, in Rhodnius neglectus, proximal cells of Malpighian tubule exposed to hyperosmotic medium, regulate their volume through a mechanism called regulatory volume increase. This regulatory response involves inhibition of the (Na+ + K+ATPase activity that could lead to accumulation of active osmotic solute inside the cell, influx of water and return to the normal cell volume. Adenosine, a compound produced in stress conditions, also inhibits the (Na+ + K+ATPase activity. Taken together these data indicate that (Na+ + K+ATPase is a target of the regulatory mechanisms of water and ions transport responsible for homeostasis in Rhodnius sp.

Chloride secretagogues stimulate inositol phosphate formation in shark rectal gland tubules cultured in suspension

International Nuclear Information System (INIS)

Ecay, T.W.; Valentich, J.D.

1991-01-01

Neuroendocrine activation of transepithelial chloride secretion by shark rectal gland cells is associated with increases in cellular cAMP, cGMP, and free calcium concentrations. We report here on the effects of several chloride secretagogues on inositol phosphate formation in cultured rectal gland tubules. Vasoactive intestinal peptide (VIP), atriopeptin (AP), and ionomycin increase the total inositol phosphate levels of cultured tubules, as measured by ion exchange chromatography. Forskolin, a potent chloride secretagogue, has no effect on inositol phosphate formation. The uptake of 3 H-myo-inositol into phospholipids is very slow, preventing the detection of increased levels of inositol trisphosphate. However, significant increases in inositol monophosphate (IP1) and inositol biphosphate (IP2) were measured. The time course of VIP- and AP-stimulated IP1 and IP2 formation is similar to the effects of these agents on the short-circuit current responses of rectal gland monolayer cultures. In addition, aluminum fluoride, an artificial activator of guanine nucleotide-binding proteins, stimulates IP1 and IP2 formation. We conclude that rectal gland cells contain VIP and AP receptors coupled to the activation of phospholipase C. Coupling may be mediated by G-proteins. Receptor-stimulated increases in inositol phospholipid metabolism is one mechanism leading to increased intracellular free calcium concentrations, an important regulatory event in the activation of transepithelial chloride secretion by shark rectal gland epithelial cells

A micropuncture study of proximal tubular transport of lithium during osmotic diuresis

DEFF Research Database (Denmark)

Leyssac, P P; Holstein-Rathlou, N H; Skøtt, P

1990-01-01

Lithium and sodium are normally reabsorbed in parallel with water by the renal proximal tubule whereby their tubular fluid-to-plasma concentration ratios (TF/P) remain close to unity throughout the proximal convoluted segment. During osmotic diuresis, the late proximal (TF/P)Na is known to decrease....... The present experiments were undertaken to study whether the late proximal TF/P for Li decreases like that of Na during osmotic diuresis. Data were obtained in a control period (C) and in two successive periods during mannitol diuresis (P1, P2). Glomerular filtration rate decreased gradually during osmotic...

Proximal Tubular Cannabinoid-1 Receptor Regulates Obesity-Induced CKD.

Science.gov (United States)

Udi, Shiran; Hinden, Liad; Earley, Brian; Drori, Adi; Reuveni, Noa; Hadar, Rivka; Cinar, Resat; Nemirovski, Alina; Tam, Joseph

2017-12-01

Obesity-related structural and functional changes in the kidney develop early in the course of obesity and occur independently of hypertension, diabetes, and dyslipidemia. Activating the renal cannabinoid-1 receptor (CB 1 R) induces nephropathy, whereas CB 1 R blockade improves kidney function. Whether these effects are mediated via a specific cell type within the kidney remains unknown. Here, we show that specific deletion of CB 1 R in the renal proximal tubule cells did not protect the mice from obesity, but markedly attenuated the obesity-induced lipid accumulation in the kidney and renal dysfunction, injury, inflammation, and fibrosis. These effects associated with increased activation of liver kinase B1 and the energy sensor AMP-activated protein kinase, as well as enhanced fatty acid β -oxidation. Collectively, these findings indicate that renal proximal tubule cell CB 1 R contributes to the pathogenesis of obesity-induced renal lipotoxicity and nephropathy by regulating the liver kinase B1/AMP-activated protein kinase signaling pathway. Copyright © 2017 by the American Society of Nephrology.

HK2 Proximal Tubule Epithelial Cells Synthesize and Secrete Plasma Proteins Predominantly Through the Apical Surface.

Science.gov (United States)

Zhao, Ke-Wei; Murray, Elsa J Brochmann; Murray, Samuel S

2017-04-01

Renal proximal tubule epithelial cells (PTECs) are known to reabsorb salts and small plasma proteins filtered through Bowman's capsule. Following acute kidney injury, PTECs assume some characteristics of hepatocytes in producing various plasma proteins. We now demonstrate that even at a resting state, a PTEC cell line, HK2 expresses mRNAs for and synthesizes and secretes plasma proteins in a complex with complement C3, an α 2 -macroglobulin family chaperone, including albumin, transferrin, α 1 -antitrypsin, α 1 -antichymotrypsin, α 2 -HS-glycoprotein, ceruloplasmin, haptoglobin, C1-inhibitor, secreted phosphoprotein-24, and insulin-like growth factor-1. When grown on transwell inserts, HK2 cells predominantly secrete (∼90%) plasma proteins into the apical side and a smaller fraction into the basolateral side as determined by ELISA assays. When cultured in the presence of exogenous cytokines such as IL1β, IL6, TNFα, BMP2, or TGFβ1, HK2 cell mRNA expressions for plasma proteins were variably affected whereas basolateral secretions were elevated to or in excess of those of the apical level. In addition, HK2 cells produce proTGFβ1 with its intact N-terminal latency associated peptide and latent-TGF-β-binding proteins. The complex cannot be dissociated under conditions of SDS, heating, and electrophoresis. Moreover, HK2 cells maintain their ability to quickly uptake exogenously added serum proteins from the culture medium, as if they are recognized differently by the endocytic receptors. These results provide new insight into the hepatization of PTECs. In addition to their unique uptake of plasma proteins and salts from the filtrate, they are a source of urinary proteins under normal conditions as wells as in chronic and acute kidney diseases. J. Cell. Biochem. 118: 924-933, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Transport and activation of S-(1,2-dichlorovinyl)-L-cysteine and N-acetyl-S-(1,2-dichlorovinyl)-L-cysteine in rat kidney proximal tubules

International Nuclear Information System (INIS)

Zhang, G.H.; Stevens, J.L.

1989-01-01

An important step in understanding the mechanism underlying the tubular specificity of the nephrotoxicity of toxic cysteine conjugates is to identify the rate-limiting steps in their activation. The rate-limiting steps in the activation of toxic cysteine conjugates were characterized using isolated proximal tubules from the rat and 35S-labeled S-(1,2-dichlorovinyl)-L-cysteine (DCVC) and N-acetyl-S-(1,2-dichlorovinyl)-L-cysteine (NAC-DCVC) as model compounds. The accumulation by tubules of 35S radiolabel from both DCVC and NAC-DCVC was time and temperature dependent and was mediated by both Na+-dependent and independent processes. Kinetic studies with DCVC in the presence of sodium revealed the presence of two components with apparent Km and Vmax values of (1) 46 microM and 0.21 nmol/mg min and (2) 2080 microM and 7.3 nmol/mg.min. NAC-DVVC uptake was via a single system with apparent Km and Vmax values of 157 microM and 0.65 nmol/mg.min, respectively. Probenecid, an inhibitor of the renal organic anion transport system, inhibited accumulation of radiolabel from NAC-DCVC, but not from DCVC. The covalent binding of 35S label to cellular macromolecules was much greater from [35S]DCVC than from NAC-[35S]DCVC. Analysis of metabolites showed that a substantial amount of the cellular NAC-[35S]DCVC was unmetabolized while [35S]DCVC was rapidly metabolized to bound 35S-labeled material and unidentified products. The data suggest that DCVC is rapidly metabolized following transport, but that activation of NAC-DCVC depends on a slower rate of deacetylation. The results are discussed with regard to the segment specificity of cysteine conjugate toxicity and the role of disposition in vivo in the nephrotoxicity of glutathione conjugates

Cadmium induces Wnt signaling to upregulate proliferation and survival genes in sub-confluent kidney proximal tubule cells

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Wolff Natascha A

2010-05-01

Full Text Available Abstract Background The class 1 carcinogen cadmium (Cd2+ disrupts the E-cadherin/β-catenin complex of epithelial adherens junctions (AJs and causes renal cancer. Deregulation of E-cadherin adhesion and changes in Wnt/β-catenin signaling are known to contribute to carcinogenesis. Results We investigated Wnt signaling after Cd2+-induced E-cadherin disruption in sub-confluent cultured kidney proximal tubule cells (PTC. Cd2+ (25 μM, 3-9 h caused nuclear translocation of β-catenin and triggered a Wnt response measured by TOPflash reporter assays. Cd2+ reduced the interaction of β-catenin with AJ components (E-cadherin, α-catenin and increased binding to the transcription factor TCF4 of the Wnt pathway, which was upregulated and translocated to the nucleus. While Wnt target genes (c-Myc, cyclin D1 and ABCB1 were up-regulated by Cd2+, electromobility shift assays showed increased TCF4 binding to cyclin D1 and ABCB1 promoter sequences with Cd2+. Overexpression of wild-type and mutant TCF4 confirmed Cd2+-induced Wnt signaling. Wnt signaling elicited by Cd2+ was not observed in confluent non-proliferating cells, which showed increased E-cadherin expression. Overexpression of E-cadherin reduced Wnt signaling, PTC proliferation and Cd2+ toxicity. Cd2+ also induced reactive oxygen species dependent expression of the pro-apoptotic ER stress marker and Wnt suppressor CHOP/GADD153 which, however, did not abolish Wnt response and cell viability. Conclusions Cd2+ induces Wnt signaling in PTC. Hence, Cd2+ may facilitate carcinogenesis of PTC by promoting Wnt pathway-mediated proliferation and survival of pre-neoplastic cells.

Characterization of biotransformation enzyme activities in primary rat proximal tubular cells

NARCIS (Netherlands)

Schaaf, G.; de Groene, E.M.; Maas, R.; Commandeur, J.N.M.; Fink-Gremmels, J.

2001-01-01

The proximal tubule is a frequent target for nephrotoxic compounds due to it's ability to transport and accumulate xenobiotics and their metabolites, as well as by the presence of an organ-selective set of biotransformation enzymes. The aim of the present study was to characterize the activities of

Megalin-mediated specific uptake of chitosan/siRNA nanoparticles in mouse kidney proximal tubule epithelial cells enables AQP1 gene silencing.

Science.gov (United States)

Gao, Shan; Hein, San; Dagnæs-Hansen, Frederik; Weyer, Kathrin; Yang, Chuanxu; Nielsen, Rikke; Christensen, Erik I; Fenton, Robert A; Kjems, Jørgen

2014-01-01

RNAi-based strategies provide a great therapeutic potential for treatment of various human diseases including kidney disorders, but face the challenge of in vivo delivery and specific targeting. The chitosan delivery system has previously been shown to target siRNA specifically to the kidneys in mice when administered intravenously. Here we confirm by 2D and 3D bioimaging that chitosan formulated siRNA is retained in the kidney for more than 48 hours where it accumulates in proximal tubule epithelial cells (PTECs), a process that was strongly dependent on the molecular weight of chitosan. Chitosan/siRNA nanoparticles, administered to chimeric mice with conditional knockout of the megalin gene, distributed almost exclusively in cells that expressed megalin, implying that the chitosan/siRNA particle uptake was mediated by a megalin-dependent endocytotic pathway. Knockdown of the water channel aquaporin 1 (AQP1) by up to 50% in PTECs was achieved utilizing the systemic i.v. delivery of chitosan/AQP1 siRNA in mice. In conclusion, specific targeting PTECs with the chitosan nanoparticle system may prove to be a useful strategy for knockdown of specific genes in PTECs, and provides a potential therapeutic strategy for treating various kidney diseases.

Distribution of IGF receptors in the plasma membrane of proximal tubular cells

International Nuclear Information System (INIS)

Hammerman, M.R.; Rogers, S.

1987-01-01

To characterize the distribution of receptors for insulin-like growth factors I and II (IGF I and II) in the plasma membrane of the renal proximal tubular cell, the authors measured binding of 125 I-labeled IGF I and 125 I-labeled IGF II to proximal tubular basolateral and brush-border membranes and characterized IGF I-stimulated phosphorylation of detergent-solubilized membranes. 125 I-IGF bound primarily to a 135,000 relative molecular weight (M r ) protein and IGF II to a 260,000 M r protein in isolated membranes. Binding of 125 I-IGF I was severalfold greater in basolateral than in brush-border membranes. IGF I-stimulated phosphorylation of the 92,000 M r β-subunit of its receptors could be demonstrated only in basolateral membranes. These findings are consistent with an asymmetrical distribution of receptors for IGF I in the plasma membrane of the renal proximal tubular cell, localization being primary on the basolateral side. In contrast, binding of 125 I-IGF II to isolated basolateral and brush-border membranes was equivalent, suggesting that receptors for this peptide are distributed more symmetrically in the plasma membrane. The findings suggest that the action of IGF I in proximal tubule are mediated via interaction of circulating peptide with specific receptors in the basolateral membrane. However, the findings established the potential for actions of IGF II to be exerted in proximal tubule via interaction with both basolateral and/or brush-border membrane receptors

Sorting Tubules Regulate Blood-Brain Barrier Transcytosis

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Roberto Villaseñor

2017-12-01

Full Text Available Transcytosis across the blood-brain barrier (BBB regulates key processes of the brain, but the intracellular sorting mechanisms that determine successful receptor-mediated transcytosis in brain endothelial cells (BECs remain unidentified. Here, we used Transferrin receptor-based Brain Shuttle constructs to investigate intracellular transport in BECs, and we uncovered a pathway for the regulation of receptor-mediated transcytosis. By combining live-cell imaging and mathematical modeling in vitro with super-resolution microscopy of the BBB, we show that intracellular tubules promote transcytosis across the BBB. A monovalent construct (sFab sorted for transcytosis was localized to intracellular tubules, whereas a bivalent construct (dFab sorted for degradation formed clusters with impaired transport along tubules. Manipulating tubule biogenesis by overexpressing the small GTPase Rab17 increased dFab transport into tubules and induced its transcytosis in BECs. We propose that sorting tubules regulate transcytosis in BECs and may be a general mechanism for receptor-mediated transport across the BBB.

Magnetic properties of permalloy-coated organic tubules

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Krebs, J. J.; Rubinstein, M.; Lubitz, P.; Harford, M. Z.; Baral, S.; Shashidar, R.; Ho, Y. S.; Chow, G. M.; Qadri, S.

1991-11-01

An initial investigation is presented of the ferromagnetic properties of a novel type of magnetic composite, viz., permalloy-coated submicron diameter hollow cylinders or tubules. The tubules form spontaneously from an organic material, a diacetylenic phosopholipid, and were used as templates on which the ferromagnetic material was deposited by electroless deposition. The permalloy-coated tubules were dispersed in an epoxy matrix to measure the magnetization and ferromagnetic resonance (FMR) properties of individual tubules. The nature of the magnetic anisotropy and the FMR spectra observed confirmed that the tubules are well aligned by a magnetic field during the epoxy curing. The FMR spectra are interpreted in terms of a powder pattern distribution of thin-film spectra consistent with the large diameter-to-thickness ratio.

Dentinal tubules revealed with X-ray tensor tomography.

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Jud, Christoph; Schaff, Florian; Zanette, Irene; Wolf, Johannes; Fehringer, Andreas; Pfeiffer, Franz

2016-09-01

Dentin is a mineralized material making up most of the tooth bulk. A system of microtubules, so called dentinal tubules, transverses it radially from the pulp chamber to the outside. This highly oriented structure leads to anisotropic mechanical properties directly connected to the tubules orientation and density: the ultimate tensile strength as well as the fracture toughness and the shear strength are largest perpendicular to dentinal tubules. Consequently, the fatigue strength depends on the direction of dentinal tubules, too. However, none of the existing techniques used to investigate teeth provide access to orientation and density of dentinal tubules for an entire specimen in a non-destructive way. In this paper, we measure a third molar human tooth both with conventional micro-CT and X-ray tensor tomography (XTT). While the achievable resolution in micro-CT is too low to directly resolve the dentinal tubules, we provide strong evidence that the direction and density of dentinal tubules can be indirectly measured by XTT, which exploits small-angle X-ray scattering to retrieve a 3D map of scattering tensors. We show that the mean directions of scattering structures correlate to the orientation of dentinal tubules and that the mean effective scattering strength provides an estimation of the relative density of dentinal tubules. Thus, this method could be applied to investigate the connection between tubule orientation and fatigue or tensile properties of teeth for a full sample without cutting one, non-representative peace of tooth out of the full sample. Copyright © 2016 The Academy of Dental Materials. All rights reserved.

A bioartificial renal tubule device embedding human renal stem/progenitor cells.

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Anna Giovanna Sciancalepore

Full Text Available We present a bio-inspired renal microdevice that resembles the in vivo structure of a kidney proximal tubule. For the first time, a population of tubular adult renal stem/progenitor cells (ARPCs was embedded into a microsystem to create a bioengineered renal tubule. These cells have both multipotent differentiation abilities and an extraordinary capacity for injured renal cell regeneration. Therefore, ARPCs may be considered a promising tool for promoting regenerative processes in the kidney to treat acute and chronic renal injury. Here ARPCs were grown to confluence and exposed to a laminar fluid shear stress into the chip, in order to induce a functional cell polarization. Exposing ARPCs to fluid shear stress in the chip led the aquaporin-2 transporter to localize at their apical region and the Na(+K(+ATPase pump at their basolateral portion, in contrast to statically cultured ARPCs. A recovery of urea and creatinine of (20±5% and (13±5%, respectively, was obtained by the device. The microengineered biochip here-proposed might be an innovative "lab-on-a-chip" platform to investigate in vitro ARPCs behaviour or to test drugs for therapeutic and toxicological responses.

[Effect of tail-suspension on the reproduction of adult male rats].

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Zhou, Dang-xia; Qiu, Shu-dong; Wang, Zhi-yong; Zhang, Jie

2006-04-01

To study the effects on the male reproduction in adult male rats and its mechanisms through simulated weightlessness using tail-suspension, in order to do a basic works of exploring the effects on human being's reproduction in outer space. Forty Spraque-Dawley adult male rats were randomly divided into four groups, two experimental groups and two control groups. Rats in the two experimental groups were tail-suspended for 14 d and 28 d respectively, then we examined the weight and morphology of testis, the quality and amount of sperm, also tested the serum hormone by radioimmunoassay and analyzed apoptosis rate of testicular cells by TUNEL in the experimental rats and control rats. After tail-suspension, the weight of testis, the sperm count and sperm motility significantly decreased (P 0.05). These changes were not significant between two experimental groups (P > 0.05). In addition, the seminiferous tubules became atrophy with the reduction of the layers of seminiferous epithelium, and sperm amount in lumens of seminiferous tubules decreased in experimental groups. The above were more remarkable in the 28 d experimental group. Simulating weightlessness has a harmful effect on reproduction of adult male rats. These may be caused by inducing apoptosis. The blocking apoptosis of testicular cells may be useful in improving the harmful effect.

Solo and keratin filaments regulate epithelial tubule morphology.

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Nishimura, Ryosuke; Kato, Kagayaki; Fujiwara, Sachiko; Ohashi, Kazumasa; Mizuno, Kensaku

2018-04-28

Epithelial tubules, consisting of the epithelial cell sheet with a central lumen, are the basic structure of many organs. Mechanical forces play an important role in epithelial tubulogenesis; however, little is known about the mechanisms controlling the mechanical forces during epithelial tubule morphogenesis. Solo (also known as ARHGEF40) is a RhoA-targeting guanine-nucleotide exchange factor that is involved in mechanical force-induced RhoA activation and stress fiber formation. Solo binds to keratin-8/keratin-18 (K8/K18) filaments, and this interaction plays a crucial role in mechanotransduction. In this study, we examined the roles of Solo and K8/K18 filaments in epithelial tubulogenesis using MDCK cells cultured in 3D collagen gels. Knockdown of either Solo or K18 resulted in rounder tubules with increased lumen size, indicating that Solo and K8/K18 filaments play critical roles in forming the elongated morphology of epithelial tubules. Moreover, knockdown of Solo or K18 decreased the level of diphosphorylated myosin light chain (a marker of contractile force) at the luminal and outer surfaces of tubules, suggesting that Solo and K8/K18 filaments are involved in the generation of the myosin II-mediated contractile force during epithelial tubule morphogenesis. In addition, K18 filaments were normally oriented along the long axis of the tubule, but knockdown of Solo perturbed their orientation. These results suggest that Solo plays crucial roles in forming the elongated morphology of epithelial tubules and in regulating myosin II activity and K18 filament organization during epithelial tubule formation.

Malpighian Tubules as Novel Targets for Mosquito Control

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Peter M. Piermarini

2017-01-01

Full Text Available The Malpighian tubules and hindgut are the renal excretory tissues of mosquitoes; they are essential to maintaining hemolymph water and solute homeostasis. Moreover, they make important contributions to detoxifying metabolic wastes and xenobiotics in the hemolymph. We have focused on elucidating the molecular mechanisms of Malpighian tubule function in adult female mosquitoes and developing chemical tools as prototypes for next-generation mosquitocides that would act via a novel mechanism of action (i.e., renal failure. To date, we have targeted inward rectifier potassium (Kir channels expressed in the Malpighian tubules of the yellow fever mosquito Aedes aegypti and malaria mosquito Anopheles gambiae. Inhibition of these channels with small molecules inhibits transepithelial K+ and fluid secretion in Malpighian tubules, leading to a disruption of hemolymph K+ and fluid homeostasis in adult female mosquitoes. In addition, we have used next-generation sequencing to characterize the transcriptome of Malpighian tubules in the Asian tiger mosquito Aedes albopictus, before and after blood meals, to reveal new molecular targets for potentially disrupting Malpighian tubule function. Within 24 h after a blood meal, the Malpighian tubules enhance the mRNA expression of genes encoding mechanisms involved with the detoxification of metabolic wastes produced during blood digestion (e.g., heme, NH3, reactive oxygen species. The development of chemical tools targeting these molecular mechanisms in Malpighian tubules may offer a promising avenue for the development of mosquitocides that are highly-selective against hematophagous females, which are the only life stage that transmits pathogens.

Study of the permeability of the various parts of the tubules to sodium and potassium ions

International Nuclear Information System (INIS)

Morel, F.; Falbriard, A.

1959-01-01

The method of stop flow analysis has been used in rabbits together with radioactive sodium and potassium injected in the middle of a six minutes period of arrest of urine flow during an osmotic diuresis. Urine was subsequently collected in 60 ta 80 mg samples. The specific activities of sodium and potassium suggest that both ions pass directly from the renal interstitial tissue into the urine at different and distinct areas in the tubules. The whole distal segment, including the area of active reabsorption of this ion, is impermeable to sodium in the direction interstitial tissue to lumen. The adjacent, more proximal tubule is, however, extremely permeable. The distal tubular impermeability to potassium is more limited. The specific activity already having reached a maximum at the level of active sodium reabsorption. Reprint of a paper published in 'Revue Francaise d'Etudes Cliniques et Biologiques', n. 5, vol IV, p. 471-474 [fr

Unique role of NADPH oxidase 5 in oxidative stress in human renal proximal tubule cells

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Peiying Yu

2014-01-01

Full Text Available NADPH oxidases are the major sources of reactive oxygen species in cardiovascular, neural, and kidney cells. The NADPH oxidase 5 (NOX5 gene is present in humans but not rodents. Because Nox isoforms in renal proximal tubules (RPTs are involved in the pathogenesis of hypertension, we tested the hypothesis that NOX5 is differentially expressed in RPT cells from normotensive (NT and hypertensive subjects (HT. We found that NOX5 mRNA, total NOX5 protein, and apical membrane NOX5 protein were 4.2±0.7-fold, 5.2±0.7-fold, and 2.8±0.5-fold greater in HT than NT. Basal total NADPH oxidase activity was 4.5±0.2-fold and basal NOX5 activity in NOX5 immunoprecipitates was 6.2±0.2-fold greater in HT than NT (P=<0.001, n=6–14/group. Ionomycin increased total NOX and NOX5 activities in RPT cells from HT (P<0.01, n=4, ANOVA, effects that were abrogated by pre-treatment of the RPT cells with diphenylene-iodonium or superoxide dismutase. Silencing NOX5 using NOX5-siRNA decreased NADPH oxidase activity (−45.1±3.2% vs. mock-siRNA, n=6–8 in HT. D1-like receptor stimulation decreased NADPH oxidase activity to a greater extent in NT (−32.5±1.8% than HT (−14.8±1.8. In contrast to the marked increase in expression and activity of NOX5 in HT, NOX1 mRNA and protein were minimally increased in HT, relative to NT; total NOX2 and NOX4 proteins were not different between HT and NT, while the increase in apical RPT cell membrane NOX1, NOX2, and NOX4 proteins in HT, relative to NT, was much less than those observed with NOX5. Thus, we demonstrate, for the first time, that NOX5 is expressed in human RPT cells and to greater extent than the other Nox isoforms in HT than NT. We suggest that the increased expression of NOX5, which may be responsible for the increased oxidative stress in RPT cells in human essential hypertension, is caused, in part, by a defective renal dopaminergic system.

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

Effect of dental materials on gluconeogenesis in rat kidney tubules

Energy Technology Data Exchange (ETDEWEB)

Reichl, F.X.; Durner, J.; Mueckter, H.; Elsenhans, B.; Forth, W. [Muenchen Univ. (Germany). Walter-Straub-Institut fuer Pharmakologie und Toxikologie; Kunzelmann, K.H.; Hickel, R. [Department of Operative/Restorative Dentistry, Periodontology and Pedodontics, Ludwig-Maximilians-University of Munich (Germany); Spahl, W. [Institute of Organic Chemistry, Ludwig-Maximilians-University of Munich (Germany); Hume, W.R. [Dental Research Institute, Univ. of California, Los Angeles, CA (United States); Moes, G.W. [TNO Prins-Maurits-Laboratorium, Rijswijk (Netherlands)

1999-09-01

The effect of dental composite components triethyleneglycoldimethacrylate (TEGDMA) and hydroxyethylmethacrylate (HEMA) as well as mercuric chloride (HgCl{sub 2}) and methylmercury chloride (MeHgCl) on gluconeogenesis was investigated in isolated rat kidney tubules. From starved rats kidney tubules were prepared and isolated by digestion with collagenase. Every 10 min up to 60 min 1-ml samples were drawn from the cell suspension for quantitating the glucose content. Glucose formation in controls was 3.3 {+-} 0.2 nmol/mg . per min (mean {+-} SEM, n=21). Relative rates of glucose formation were obtained by expressing individual rates as a percentage of the corresponding control. X-Y concentration curves (effective concentration, EC) of the substances were calculated by fitting a four-parametric sigmoid function to the relative rates of glucose formation at various test concentrations. At the end of the incubation period cell viability was assessed by trypan blue exclusion. Cell viability decreased within the 60 min interval from 90 to approx. 80% (controls), <25 (HEMA), <20 (TEGDMA), <10 (MeHgCl), and <10% (HgCl{sub 2}). Values of 50% effective concentration (EC{sub 50}) were calculated from fitted curves. EC{sub 50} values were (mmol; mean {+-} SEM; n=4): HEMA, 17.7 {+-} 2.9; TEGDMA, 1.8 {+-} 0.2; MeHgCl, 0.018 {+-} 0.0005; and HgCl{sub 2}, 0.0016 {+-} 0.0005. The toxic effect of HgCl{sub 2} was {proportional{underscore}to}1000 or 10 000 higher than that of the dental composite components TEGDMA or HEMA, respectively. (orig.)

Cyclophilin B interacts with sodium-potassium ATPase and is required for pump activity in proximal tubule cells of the kidney.

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Suñé, Guillermo; Sarró, Eduard; Puigmulé, Marta; López-Hellín, Joan; Zufferey, Madeleine; Pertel, Thomas; Luban, Jeremy; Meseguer, Anna

2010-11-10

Cyclophilins (Cyps), the intracellular receptors for Cyclosporine A (CsA), are responsible for peptidyl-prolyl cis-trans isomerisation and for chaperoning several membrane proteins. Those functions are inhibited upon CsA binding. Albeit its great benefits as immunosuppressant, the use of CsA has been limited by undesirable nephrotoxic effects, including sodium retention, hypertension, hyperkalemia, interstial fibrosis and progressive renal failure in transplant recipients. In this report, we focused on the identification of novel CypB-interacting proteins to understand the role of CypB in kidney function and, in turn, to gain further insight into the molecular mechanisms of CsA-induced toxicity. By means of yeast two-hybrid screens with human kidney cDNA, we discovered a novel interaction between CypB and the membrane Na/K-ATPase β1 subunit protein (Na/K-β1) that was confirmed by pull-down, co-immunoprecipitation and confocal microscopy, in proximal tubule-derived HK-2 cells. The Na/K-ATPase pump, a key plasma membrane transporter, is responsible for maintenance of electrical Na+ and K+ gradients across the membrane. We showed that CypB silencing produced similar effects on Na/K-ATPase activity than CsA treatment in HK-2 cells. It was also observed an enrichment of both alpha and beta subunits in the ER, what suggested a possible failure on the maturation and routing of the pump from this compartment towards the plasma membrane. These data indicate that CypB through its interaction with Na/K-β1 might regulate maturation and trafficking of the pump through the secretory pathway, offering new insights into the relationship between cyclophilins and the nephrotoxic effects of CsA.

Accelerated recovery of renal mitochondrial and tubule homeostasis with SIRT1/PGC-1α activation following ischemia–reperfusion injury

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Funk, Jason A., E-mail: funkj@musc.edu [Center for Cell Death, Injury, and Regeneration, Department of Drug Discovery and Biomedical Sciences, Medical University of South Carolina, Charleston, SC 29425 (United States); Schnellmann, Rick G., E-mail: schnell@musc.edu [Center for Cell Death, Injury, and Regeneration, Department of Drug Discovery and Biomedical Sciences, Medical University of South Carolina, Charleston, SC 29425 (United States); Ralph H. Johnson VA Medical Center, Charleston, SC 29401 (United States)

2013-12-01

Kidney ischemia–reperfusion (I/R) injury elicits cellular injury in the proximal tubule, and mitochondrial dysfunction is a pathological consequence of I/R. Promoting mitochondrial biogenesis (MB) as a repair mechanism after injury may offer a unique strategy to restore both mitochondrial and organ function. Rats subjected to bilateral renal pedicle ligation for 22 min were treated once daily with the SIRT1 activator SRT1720 (5 mg/kg) starting 24 h after reperfusion until 72 h–144 h. SIRT1 expression was elevated in the renal cortex of rats after I/R + vehicle treatment (IRV), but was associated with less nuclear localization. SIRT1 expression was even further augmented and nuclear localization was restored in the kidneys of rats after I/R + SRT1720 treatment (IRS). PGC-1α was elevated at 72 h–144 h in IRV and IRS kidneys; however, SRT1720 treatment induced deacetylation of PGC-1α, a marker of activation. Mitochondrial proteins ATP synthase β, COX I, and NDUFB8, as well as mitochondrial respiration, were diminished 24 h–144 h in IRV rats, but were partially or fully restored in IRS rats. Urinary kidney injury molecule-1 (KIM-1) was persistently elevated in both IRV and IRS rats; however, KIM-1 tissue expression was attenuated in IRS rats. Additionally, sustained loss of Na{sup +},K{sup +}–ATPase expression and basolateral localization and elevated vimentin in IRV rats was normalized in IRS rats, suggesting restoration of a differentiated, polarized tubule epithelium. The results suggest that SRT1720 treatment expedited recovery of mitochondrial protein expression and function by enhancing MB, which was associated with faster proximal tubule repair. Targeting MB may offer unique therapeutic strategy following ischemic injury. - Highlights: • We examined recovery of mitochondrial and renal function after ischemia–reperfusion. • SRT1720 treatment after I/R induced mitochondrial biogenesis via SIRT1/PGC-1α. • Recovery of mitochondrial function was

Cyclophilin B interacts with sodium-potassium ATPase and is required for pump activity in proximal tubule cells of the kidney.

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Guillermo Suñé

Full Text Available Cyclophilins (Cyps, the intracellular receptors for Cyclosporine A (CsA, are responsible for peptidyl-prolyl cis-trans isomerisation and for chaperoning several membrane proteins. Those functions are inhibited upon CsA binding. Albeit its great benefits as immunosuppressant, the use of CsA has been limited by undesirable nephrotoxic effects, including sodium retention, hypertension, hyperkalemia, interstial fibrosis and progressive renal failure in transplant recipients. In this report, we focused on the identification of novel CypB-interacting proteins to understand the role of CypB in kidney function and, in turn, to gain further insight into the molecular mechanisms of CsA-induced toxicity. By means of yeast two-hybrid screens with human kidney cDNA, we discovered a novel interaction between CypB and the membrane Na/K-ATPase β1 subunit protein (Na/K-β1 that was confirmed by pull-down, co-immunoprecipitation and confocal microscopy, in proximal tubule-derived HK-2 cells. The Na/K-ATPase pump, a key plasma membrane transporter, is responsible for maintenance of electrical Na+ and K+ gradients across the membrane. We showed that CypB silencing produced similar effects on Na/K-ATPase activity than CsA treatment in HK-2 cells. It was also observed an enrichment of both alpha and beta subunits in the ER, what suggested a possible failure on the maturation and routing of the pump from this compartment towards the plasma membrane. These data indicate that CypB through its interaction with Na/K-β1 might regulate maturation and trafficking of the pump through the secretory pathway, offering new insights into the relationship between cyclophilins and the nephrotoxic effects of CsA.

Renal protein synthesis in diabetes mellitus: effects of insulin and insulin-like growth factor I

International Nuclear Information System (INIS)

Barac-Nieto, M.; Lui, S.M.; Spitzer, A.

1991-01-01

Is increased synthesis of proteins responsible for the hypertrophy of kidney cells in diabetes mellitus? Does the lack of insulin, and/or the effect of insulin-like growth factor I (IGFI) on renal tubule protein synthesis play a role in diabetic renal hypertrophy? To answer these questions, we determined the rates of 3H-valine incorporation into tubule proteins and the valine-tRNA specific activity, in the presence or absence of insulin and/or IGFI, in proximal tubule suspension isolated from kidneys of streptozotocin diabetic and control rats. The rate of protein synthesis increased, while the stimulatory effects of insulin and IGFI on tubule protein synthesis were reduced, early (96 hours) after induction of experimental diabetes. Thus, hypertrophy of the kidneys in experimental diabetes mellitus is associated with increases in protein synthesis, rather than with decreases in protein degradation. Factor(s) other than the lack of insulin, or the effects of IGFI, must be responsible for the high rate of protein synthesis present in the hypertrophying tubules of diabetic rats

Use of poly (amidoamine dendrimer for dentinal tubule occlusion: a preliminary study.

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Tianda Wang

Full Text Available The occlusion of dentinal tubules is an effective method to alleviate the symptoms caused by dentin hypersensitivity, a significant health problem in dentistry and daily life. The in situ mineralization within dentinal tubules is a promising treatment for dentin hypersensitivity as it induces the formation of mineral on the sensitive regions and occludes the dentinal tubules. This study was carried out to evaluate the in vitro effect of a whole generation poly(amidoamine (PAMAM dendrimer (G3.0 on dentinal tubule occlusion by inducing mineralization within dentinal tubules. Dentin discs were treated with PAMAM dendrimers using two methods, followed by the in vitro characterization using Attenuated total reflection Fourier-transform infrared spectroscopy (ATR-FTIR, X-ray diffraction (XRD, Field emission scanning electron microscopy (FE-SEM and Energy-Dispersive X-ray Spectroscopy (EDS. These results showed that G3.0 PAMAM dendrimers coated on dentin surface and infiltrated in dentinal tubules could induce hydroxyapatite formation and resulted in effective dentinal tubule occlusion. Moreover, crosslinked PAMAM dendrimers could induce the remineralization of demineralized dentin and thus had the potential in dentinal tubule occlusion. In this in vitro study, dentinal tubules occlusion could be achieved by using PAMAM dendrimers. This could lead to the development of a new therapeutic technique for the treatment of dentin hypersensitivity.

Species diversity regarding the presence of proximal tubular progenitor cells of the kidney

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J. Hansson

2016-02-01

Full Text Available The cellular source for tubular regeneration following kidney injury is a matter of dispute, with reports suggesting a stem or progenitor cells as the regeneration source while linage tracing studies in mice seemingly favor the classical theory, where regeneration is performed by randomly surviving cells. We, and others have previously described a scattered cell population localized to the tubules of human kidney, which increases in number following injury. Here we have characterized the species distribution of these proximal tubular progenitor cells (PTPCs in kidney tissue from chimpanzee, pig, rat and mouse using a set of human PTPC markers. We detected PTPCs in chimpanzee and pig kidneys, but not in mouse tissue. Also, subjecting mice to the unilateral urethral obstruction model, caused clear signs of tubular injury, but failed to induce the PTPC phenotype in renal tubules.

Specific estrogen-induced cell proliferation of cultured Syrian hamster renal proximal tubular cells in serum-free chemically defined media

International Nuclear Information System (INIS)

Oberley, T.D.; Lauchner, L.J.; Pugh, T.D.; Gonzalez, A.; Goldfarb, S.; Li, S.A.; Li, J.J.

1989-01-01

It has long been recognized that the renal proximal tubular epithelium of the hamster is a bona fide estrogen target tissue. The effect of estrogens on the growth of proximal tubule cell explants and dissociated single cells derived from these explant outgrowths has been studied in culture. Renal tubular cells were grown on a PF-HR-9 basement membrane under serum-free chemically defined culture conditions. At 7-14 days in culture, cell number was enhanced 3-fold in the presence of either 17β-estradiol or diethylstilbestrol. A similar 3-fold increase in cell number was also seen at 1 nM 17β-estradiol in subcultured dissociated single tubular cells derived from hamster renal tubular explant outgrowths at 21 days in culture. Concomitant exposure of tamoxifen at 3-fold molar excess in culture completely abolished the increase in cell number seen with 17β-estradiol. The proliferation effect of estrogens on proximal tubular cell growth appears to be species specific since 17β-estradiol did not alter the growth of either rat or guinea pig proximal tubules in culture. In addition, at 7-10 days in culture in the presence of 17β-estradiol, [ 3 H]thymidine labeling of hamster tubular cells was enhanced 3-fold. These results clearly indicate that estrogens can directly induce primary epithelial cell proliferation at physiologic concentrations and provide strong additional evidence for an important hormonal role in the neoplastic transformation of the hamster kidney

Cystogenesis and elongated primary cilia in Tsc1-deficient distal convoluted tubules.

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Armour, Eric A; Carson, Robert P; Ess, Kevin C

2012-08-15

Tuberous sclerosis complex (TSC) is a multiorgan hamartomatous disease caused by loss of function mutations of either the TSC1 or TSC2 genes. Neurological symptoms of TSC predominate in younger patients, but renal pathologies are a serious aspect of the disease in older children and adults. To study TSC pathogenesis in the kidney, we inactivated the mouse Tsc1 gene in the distal convoluted tubules (DCT). At young ages, Tsc1 conditional knockout (CKO) mice have enlarged kidneys and mild cystogenesis with increased mammalian target of rapamycin complex (mTORC)1 but decreased mTORC2 signaling. Treatment with the mTORC1 inhibitor rapamycin reduces kidney size and cystogenesis. Rapamycin withdrawal led to massive cystogenesis involving both distal as well as proximal tubules. To assess the contribution of decreased mTORC2 signaling in kidney pathogenesis, we also generated Rictor CKO mice. These animals did not have any detectable kidney pathology. Finally, we examined primary cilia in the DCT. Cilia were longer in Tsc1 CKO mice, and rapamycin treatment returned cilia length to normal. Rictor CKO mice had normal cilia in the DCT. Overall, our findings suggest that loss of the Tsc1 gene in the DCT is sufficient for renal cystogenesis. This cytogenesis appears to be mTORC1 but not mTORC2 dependent. Intriguingly, the mechanism may be cell autonomous as well as non-cell autonomous and possibly involves the length and function of primary cilia.

Cystogenesis and elongated primary cilia in Tsc1-deficient distal convoluted tubules

Science.gov (United States)

Armour, Eric A.; Carson, Robert P.

2012-01-01

Tuberous sclerosis complex (TSC) is a multiorgan hamartomatous disease caused by loss of function mutations of either the TSC1 or TSC2 genes. Neurological symptoms of TSC predominate in younger patients, but renal pathologies are a serious aspect of the disease in older children and adults. To study TSC pathogenesis in the kidney, we inactivated the mouse Tsc1 gene in the distal convoluted tubules (DCT). At young ages, Tsc1 conditional knockout (CKO) mice have enlarged kidneys and mild cystogenesis with increased mammalian target of rapamycin complex (mTORC)1 but decreased mTORC2 signaling. Treatment with the mTORC1 inhibitor rapamycin reduces kidney size and cystogenesis. Rapamycin withdrawal led to massive cystogenesis involving both distal as well as proximal tubules. To assess the contribution of decreased mTORC2 signaling in kidney pathogenesis, we also generated Rictor CKO mice. These animals did not have any detectable kidney pathology. Finally, we examined primary cilia in the DCT. Cilia were longer in Tsc1 CKO mice, and rapamycin treatment returned cilia length to normal. Rictor CKO mice had normal cilia in the DCT. Overall, our findings suggest that loss of the Tsc1 gene in the DCT is sufficient for renal cystogenesis. This cytogenesis appears to be mTORC1 but not mTORC2 dependent. Intriguingly, the mechanism may be cell autonomous as well as non-cell autonomous and possibly involves the length and function of primary cilia. PMID:22674026

Uptake of [3H]PAH and [14C]urate into isolated proximal tubular segments of the pig kidney

International Nuclear Information System (INIS)

Schali, C.; Roch-Ramel, F.

1981-01-01

Segments of proximal convoluted (PCT) and proximal straight (PST) tubules of minipigs and normal-sized pigs were microdissected (without collagenase treatment) and incubated (30 min, 37 0 C, pH 7.4) in Ringer solution (under O 2 ) containing [ 3 H]PAH (3.10 -5 M) or [ 14 C]urate (9.10 -5 M) and, in inhibitor studies, probenecid, pyrazinoic acid (PZA), urate, or PAH, all at 1 mM. In both strains the uptake of [ 3 H]PAH expressed as mean T/M ratio (cpm per ml tissue water/cpm per ml incubation medium) was significantly higher (P 14 C]urate. In eight minipigs the T/M was 4.9 +/- 0.5 in 24 PCT and 2 +/- 0.2 in 25 PST. In normal-sized pigs the T/M was 3.8 +/- 0.3 in 35 PCT (five pigs) and 1.9 +/- 0.4 in eight PST (two pigs). In inhibitor studies urate significantly depressed the uptake of [ 3 H]PAH, and unlabeled PAH depressed the uptake of [ 14 C]urate. PZA significantly inhibited the uptake of [ 14 C]urate but not that of [ 3 H]PAH, whereas probenecid had a strong inhibitory efect on the uptake of both compounds. These results suggest that [ 14 C]urate and [ 3 H]PAH are transported by a transport system located mainly in the proximal convoluted tubule. These findings are in contrast in the findings are in contrast to the findings obtained in rabbits in which the transport system of PAH and urate is mainly located in the proximal part of the pars recta

Smad mediated regulation of inhibitor of DNA binding 2 and its role in phenotypic maintenance of human renal proximal tubule epithelial cells.

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Mangalakumar Veerasamy

Full Text Available The basic-Helix-Loop-Helix family (bHLH of transcriptional factors plays a major role in regulating cellular proliferation, differentiation and phenotype maintenance. The downregulation of one of the members of bHLH family protein, inhibitor of DNA binding 2 (Id2 has been shown to induce de-differentiation of epithelial cells. Opposing regulators of epithelial/mesenchymal phenotype in renal proximal tubule epithelial cells (PTEC, TGFβ1 and BMP7 also have counter-regulatory effects in models of renal fibrosis. We investigated the regulation of Id2 by these growth factors in human PTECs and its implication in the expression of markers of epithelial versus myofibroblastic phenotype. Cellular Id2 levels were reduced by TGFβ1 treatment; this was prevented by co-incubation with BMP7. BMP7 alone increased cellular levels of Id2. TGFβ1 and BMP7 regulated Id2 through Smad2/3 and Smad1/5 dependent mechanisms respectively. TGFβ1 mediated Id2 suppression was essential for α-SMA induction in PTECs. Although Id2 over-expression prevented α-SMA induction, it did not prevent E-cadherin loss under the influence of TGFβ1. This suggests that the loss of gate keeper function of E-cadherin alone may not necessarily result in complete EMT and further transcriptional re-programming is essential to attain mesenchymal phenotype. Although BMP7 abolished TGFβ1 mediated α-SMA expression by restoring Id2 levels, the loss of Id2 was not sufficient to induce α-SMA expression even in the context of reduced E-cadherin expression. Hence, a reduction in Id2 is critical for TGFβ1-induced α-SMA expression in this model of human PTECs but is not sufficient in it self to induce α-SMA even in the context of reduced E-cadherin.

Effects of vasopressin on the isolated perfused human collecting tubule.

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Yanagawa, N; Trizna, W; Bar-Khayim, Y; Fine, L G

1981-05-01

Cortical collecting tubules (CCT) were dissected from the surviving normal tissue of human kidneys removed at operation for either carcinoma or calculus. These CCT's were perfused in vitro shortly after the nephrectomy was performed. Transtubular potential differences in different tubules varied from +3.2 to -2.0 mV and were reduced towards zero by lowering the temperature or by adding ouabain to the bath. In the absence of vasopressin, tubules were essentially impermeable to water with extremely low net water fluxes even in the presence of a transtubular osmotic gradient. Addition of vasopressin to the bath caused the transtubular osmotic water permeability coefficient to increase to values of 125, 175, and 155 X 10(-4) cm/sec in three tubules thus studied. These results demonstrate close similarities between the human CCT and the more extensively studied rabbit CCT.

Effect of dental materials on gluconeogenesis in rat kidney tubules

NARCIS (Netherlands)

Reichl, F.X.; Durner, J.; Mückter, H.; Elsenhans, B.; Forth, W.; Kunzelmann, K.H.; Hickel, R.; Spahl, W.; Hume, W.R.; Moes, G.W.

1999-01-01

The effect of dental composite components triethyleneglycoldimethacrylate (TEGDMA) and hydroxyethylmethacrylate (HEMA) as well as mercuric chloride (HgCl2) and methylmercury chloride (MeHgCl) on gluconeogenesis was investigated in isolated rat kidney tubules. From starved rats kidney tubules were

Natural history of seminiferous tubule degeneration in Klinefelter syndrome

DEFF Research Database (Denmark)

Aksglaede, Lise; Wikström, Anne M; Rajpert-De Meyts, Ewa

2006-01-01

Klinefelter syndrome (47,XXY) is characterized by small, firm testis, gynaecomastia, azoospermia and hypergonadotropic hypogonadism. Degeneration of the seminiferous tubules in 47,XXY males is a well-described phenomenon. It begins in the fetus, progresses through infancy and accelerates dramatic......Klinefelter syndrome (47,XXY) is characterized by small, firm testis, gynaecomastia, azoospermia and hypergonadotropic hypogonadism. Degeneration of the seminiferous tubules in 47,XXY males is a well-described phenomenon. It begins in the fetus, progresses through infancy and accelerates...... summarize current knowledge on the development of the classical endocrinological and histological features of 47,XXY males from fetus to adulthood and review the literature concerning the degeneration of the seminiferous tubules in this syndrome....

In vivo model for microbial invasion of tooth root dentinal tubules

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Jane L. BRITTAN

2016-04-01

Full Text Available ABSTRACT Objective Bacterial penetration of dentinal tubules via exposed dentine can lead to root caries and promote infections of the pulp and root canal system. The aim of this work was to develop a new experimental model for studying bacterial invasion of dentinal tubules within the human oral cavity. Material and Methods Sections of human root dentine were mounted into lower oral appliances that were worn by four human subjects for 15 d. Roots were then fixed, sectioned, stained and examined microscopically for evidence of bacterial invasion. Levels of invasion were expressed as Tubule Invasion Factor (TIF. DNA was extracted from root samples, subjected to polymerase chain reaction amplification of 16S rRNA genes, and invading bacteria were identified by comparison of sequences with GenBank database. Results All root dentine samples with patent tubules showed evidence of bacterial cell invasion (TIF value range from 5.7 to 9.0 to depths of 200 mm or more. A spectrum of Gram-positive and Gram-negative cell morphotypes were visualized, and molecular typing identified species of Granulicatella, Streptococcus, Klebsiella, Enterobacter, Acinetobacter, and Pseudomonas as dentinal tubule residents. Conclusion A novel in vivo model is described, which provides for human root dentine to be efficiently infected by oral microorganisms. A range of bacteria were able to initially invade dentinal tubules within exposed dentine. The model will be useful for testing the effectiveness of antiseptics, irrigants, and potential tubule occluding agents in preventing bacterial invasion of dentine.

Puerarin Facilitates T-Tubule Development of Murine Embryonic Stem Cell-Derived Cardiomyocytes

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Lu Wang

2014-07-01

Full Text Available Aims: The embryonic stem cell-derived cardiomyocytes (ES-CM is one of the promising cell sources for repopulation of damaged myocardium. However, ES-CMs present immature structure, which impairs their integration with host tissue and functional regeneration. This study used murine ES-CMs as an in vitro model of cardiomyogenesis to elucidate the effect of puerarin, the main compound found in the traditional Chinese medicine the herb Radix puerariae, on t-tubule development of murine ES-CMs. Methods: Electron microscope was employed to examine the ultrastructure. The investigation of transverse-tubules (t-tubules was performed by Di-8-ANEPPS staining. Quantitative real-time PCR was utilized to study the transcript level of genes related to t-tubule development. Results: We found that long-term application of puerarin throughout cardiac differentiation improved myofibril array and sarcomeres formation, and significantly facilitated t-tubules development of ES-CMs. The transcript levels of caveolin-3, amphiphysin-2 and junctophinlin-2, which are crucial for the formation and development of t-tubules, were significantly upregulated by puerarin treatment. Furthermore, puerarin repressed the expression of miR-22, which targets to caveolin-3. Conclusion: Our data showed that puerarin facilitates t-tubule development of murine ES-CMs. This might be related to the repression of miR-22 by puerarin and upregulation of Cav3, Bin1 and JP2 transcripts.

Self-(Un)rolling Biopolymer Microstructures: Rings, Tubules, and Helical Tubules from the Same Material.

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Ye, Chunhong; Nikolov, Svetoslav V; Calabrese, Rossella; Dindar, Amir; Alexeev, Alexander; Kippelen, Bernard; Kaplan, David L; Tsukruk, Vladimir V

2015-07-13

We have demonstrated the facile formation of reversible and fast self-rolling biopolymer microstructures from sandwiched active-passive, silk-on-silk materials. Both experimental and modeling results confirmed that the shape of individual sheets effectively controls biaxial stresses within these sheets, which can self-roll into distinct 3D structures including microscopic rings, tubules, and helical tubules. This is a unique example of tailoring self-rolled 3D geometries through shape design without changing the inner morphology of active bimorph biomaterials. In contrast to traditional organic-soluble synthetic materials, we utilized a biocompatible and biodegradable biopolymer that underwent a facile aqueous layer-by-layer (LbL) assembly process for the fabrication of 2D films. The resulting films can undergo reversible pH-triggered rolling/unrolling, with a variety of 3D structures forming from biopolymer structures that have identical morphology and composition. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Effects of intravenous bumetanide administration on renal haemodynamics and proximal and distal tubular sodium reabsorption in conscious rats

Energy Technology Data Exchange (ETDEWEB)

Shalmi, M.; Petersen, J.S.; Christensen, S. (Department of pharmacology, University of Copenhagen (Denmark))

1989-01-01

The renal effects of 0.02-62.5 mg/kg bumetanide given as intravenous bolus injections were studied in water diuretic conscious rats. Clearances of {sup 14}C-tetraethylammonium, {sup 3}H-inulin and lithium were used as markers for renal plasma flow (RPF), glomerular filtion rate (GFR) and proximal tubular output, respectively. Bumetanide caused biphasic, transient and dose-independent changes in the renal haemodynamics without significant alterations of the filtration fraction. At dose-levels above 0.02 mg/kg bumetanide increased urine flow, absolute and fractional Na excretion as well as the indices for fractional output of Na from the proximal tubules (C{sub Li}/C{sub I}n) and the distal nephron segments (C{sub Na}/C{sub Li}). The changes in C{sub Li}/C{sub In} became maximal at doses above 0.5 mg/kg, whereas C{sub Na}/C{sub Li} was increased with the dose up to 12.5 mg/kg. Paradoxically, doses above 12.5 mg/kg were less natriuretic due to a decrease of C{sub Na}/C{sub Li}. It is concluded that in rats bumetanide is an effective although short-acting diuretic when administered intravenously. When comparing peak responses bumetanide is equipotent to furosemide but has a lower maximal efficacy. Judged from the changes in fractional lithium excretion, the natriuretic effect of bumetanide is effected by inhibition of Na reabsorption in the proximal tubule in addition to the well-known effect on the distal nephron segment. (author).

Effect of theobromine-containing toothpaste on dentin tubule occlusion in situ.

Science.gov (United States)

Amaechi, Bennett T; Mathews, Sapna M; Mensinkai, Poornima K

2015-01-01

Dentin hypersensitivity (DH) is treated by either occlusion of dentin tubules or nerve desensitization. This in situ study compared dentin tubules occlusion by theobromine-containing dentifrices with (Theodent-classic-F®, TCF) and without (Theodent-classic®, TC) fluoride with 1,500 ppm fluoride toothpaste, Colgate®-Regular (Fluoride) and Novamin®-containing toothpaste, Sensodyne®-5000-Nupro (Novamin®). Each subject wore four intraoral appliances bearing dentin blocks while using one of four test dentifrices (n = 20/dentifrice) twice daily for 7 days. The four appliances were removed successively after 1, 2, 3, and 7 days. Treated blocks and their control (untreated) blocks were examined with scanning electron microscopy (SEM). Effects were compared statistically (ANOVA/Tukey's) based on percentage of surface area covered by deposited precipitate layer (%DPL) and percentage of fully open (%FOT), partially occluded (%POT), and completely occluded (%COT) tubules in each block calculated relative to the number of tubules in their control blocks. SEM observation indicated an increased %COT and %DPL over time. After 1 and 2 days, %COT was comparable with TC and TCF, and significantly (p Theobromine-containing toothpastes with and without fluoride have equal potential in occluding dentin tubules within a shorter time period than Novamin®-containing toothpaste; however, the three demonstrated equal potential after 1 week, but not the fluoride toothpaste. Theobromine-containing toothpaste promoted dentin tubule occlusion thus shows potential to relief DH.

Clinical Importance of Morphological Appearance of Seminiferous Tubules During MicroTESE in NOA Cases

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A. H. Haliloglu

2005-12-01

Full Text Available Design: Clinical study. Setting: Research Center on Infertility, Ankara University; and Urology Department. Patients: 65 men with nonobstructive azoospermia (NOA.\tInterventions: Microscopical appearance of seminiferous tubules was recorded during TESE surgery. Differing from others, the largest opaque-white in color tubules were cut and removed. When all the tubules have no discriminating appearance, randomized biopsies were obtained. Removed tissue pieces were subjected to mechanical mincing under the stereomicroscope and then enzymatic digestion processes. Using inversion microscope (x32 magnification spermatozoa were searched. Main Outcome Measures: Morphological appearance of seminiferous tubules under optical magnification, spermatozoa recovery rates and histopathological findings were compared.\tRESULTS: In cases of Sertoli cell-only syndrome (SCOS, maturation arrest, hypospermatogenesis and focal spermatogenesis TESE yielded at least one spermatozoon in 37%, 52%, 100% and 63% of the cases, respectively. When all the seminiferous tubules were homogenously swollen, histopathological diagnosis was hypospermatogenesis in 100% of the cases. Homogenously thin and transparent tubules corresponded to SCOS or maturation arrest in 90% and 10% of the cases, respectively. Mature spermatozoa recovery rates were 100% and zero in homogenously-swollen observed and homogenously-thin observed tubules, respectively. CONCLUSIONS: Present data indicate that in cases of all tubules are homogenous in appearance and none of them can be discriminated from others, using microscope has no advantage in selection of the tubuli to be removed, but randomizely selection would also be sufficient. MicroTESE significantly increases the success in NOA cases with seminiferous tubules dispersed heterogeneously.

RNA sequencing of kidney distal tubule cells reveals multiple mediators of chronic aldosterone action

DEFF Research Database (Denmark)

Poulsen, Søren Brandt; Limbutara, Kavee; Fenton, Robert Andrew

2018-01-01

The renal aldosterone-sensitive distal tubule (ASDT) is crucial for sodium reabsorption and blood pressure regulation. The ASDT consists of the late distal convoluted tubule (DCT2), connecting tubule (CNT) and collecting duct. Due to difficulties in isolating epithelial cells from the ASDT in lar...

Histological and three dimensional organizations of lymphoid tubules in normal lymphoid organ of Penaeus monodon.

Science.gov (United States)

Duangsuwan, Pornsawan; Phoungpetchara, Ittipon; Tinikul, Yotsawan; Poljaroen, Jaruwan; Wanichanon, Chaitip; Sobhon, Prasert

2008-04-01

The normal lymphoid organ of Penaeus monodon (which tested negative for WSSV and YHV) was composed of two parts: lymphoid tubules and interstitial spaces, which were permeated with haemal sinuses filled with large numbers of haemocytes. There were three permanent types of cells present in the wall of lymphoid tubules: endothelial, stromal and capsular cells. Haemocytes penetrated the endothelium of the lymphoid tubule's wall to reside among the fixed cells. The outermost layer of the lymphoid tubule was covered by a network of fibers embedded in a PAS-positive extracellular matrix, which corresponded to a basket-like network that covered all the lymphoid tubules as visualized by a scanning electron microscope (SEM). Argyrophilic reticular fibers surrounded haemal sinuses and lymphoid tubules. Together they formed the scaffold that supported the lymphoid tubule. Using vascular cast and SEM, the three dimensional structure of the subgastric artery that supplies each lobe of the lymphoid organ was reconstructed. This artery branched into highly convoluted and blind-ending terminal capillaries, each forming the lumen of a lymphoid tubule around which haemocytes and other cells aggregated to form a cuff-like wall. Stromal cells which form part of the tubular scaffold were immunostained for vimentin. Examination of the whole-mounted lymphoid organ, immunostained for vimentin, by confocal microscopy exhibited the highly branching and convoluted lymphoid tubules matching the pattern of the vascular cast observed in SEM.

Proteomic changes in response to crystal formation in Drosophila Malpighian tubules.

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Chung, Vera Y; Konietzny, Rebecca; Charles, Philip; Kessler, Benedikt; Fischer, Roman; Turney, Benjamin W

2016-04-02

Kidney stone disease is a major health burden with a complex and poorly understood pathophysiology. Drosophila Malpighian tubules have been shown to resemble human renal tubules in their physiological function. Herein, we have used Drosophila as a model to study the proteomic response to crystal formation induced by dietary manipulation in Malpighian tubules. Wild-type male flies were reared in parallel groups on standard medium supplemented with lithogenic agents: control, Sodium Oxalate (NaOx) and Ethylene Glycol (EG). Malpighian tubules were dissected after 2 weeks to visualize crystals with polarized light microscopy. The parallel group was dissected for protein extraction. A new method of Gel Assisted Sample Preparation (GASP) was used for protein extraction. Differentially abundant proteins (p<0.05) were identified by label-free quantitative proteomic analysis in flies fed with NaOx and EG diet compared with control. Their molecular functions were further screened for transmembrane ion transporter, calcium or zinc ion binder. Among these, 11 candidate proteins were shortlisted in NaOx diet and 16 proteins in EG diet. We concluded that GASP is a proteomic sample preparation method that can be applied to individual Drosophila Malpighian tubules. Our results may further increase the understanding of the pathophysiology of human kidney stone disease.

3D variations in human crown dentin tubule orientation: a phase-contrast microtomography study.

Science.gov (United States)

Zaslansky, Paul; Zabler, Simon; Fratzl, Peter

2010-01-01

Tubules dominate the microstructure of dentin, and in crowns of human teeth they are surrounded by thick mineralized peritubular cuffs of high stiffness. Here we examine the three-dimensional (3D) arrangement of tubules in relation to enamel on the buccal and lingual aspects of intact premolars and molars. Specifically we investigate the angular orientation of tubules relative to the plane of the junction of dentin with enamel (DEJ) by means of wet, non-destructive and high-resolution phase-contrast (coherent) tomography. Enamel capped dentin samples (n=16), cut from the buccal and lingual surfaces of upper and lower premolar and molar teeth, were imaged in water by high-resolution synchrotron-based phase-contrast X-ray radiography. Reconstructed 3D virtual images were co-aligned with respect to the DEJ plane. The average tubule orientation was determined at increasing distances from the DEJ, based on integrated projections onto orthogonal virtual planes. The angle and curl of the tubules were determined every 100 microm to a depth of 1.4mm beneath the DEJ. Most tubules do not extend at right angles from the DEJ. Even when they do, tubules always change their orientations substantially within the first half-millimeter zone beneath the DEJ, both on the buccal and lingual aspects of premolar and molar teeth. Tubules also tend to curl and twist within this zone. Student t-tests indicate that lower teeth seem to have greater tilts in the tubule orientations relative to the DEJ normal with an average angle of 42 degrees (+/-2.0 degrees), whereas upper teeth exhibit a smaller change of orientation, with an average of 32 degrees (+/-2.1 degrees). Tubules are a central characteristic of dentin, with important implications on how it is arranged and what the properties are. Knowing about the path that tubules follow is important for various reasons, ranging form improving control over restorative procedures to understanding or simulating the mechanical properties of teeth

Role of ARF6 in internalization of metal-binding proteins, metallothionein and transferrin, and cadmium-metallothionein toxicity in kidney proximal tubule cells

International Nuclear Information System (INIS)

Wolff, Natascha A.; Lee, Wing-Kee; Abouhamed, Marouan; Thevenod, Frank

2008-01-01

Filtered metal-protein complexes, such as cadmium-metallothionein-1 (CdMT-1) or transferrin (Tf) are apically endocytosed partly via megalin/cubilin by kidney proximal tubule (PT) cells where CdMT-1 internalization causes apoptosis. Small GTPase ARF (ADP-ribosylation factor) proteins regulate endocytosis and vesicular trafficking. We investigated roles of ARF6, which has been shown to be involved in internalization of ligands and endocytic trafficking in PT cells, following MT-1/CdMT-1 and Tf uptake by PT cells. WKPT-0293 Cl.2 cells derived from rat PT S1 segment were transfected with hemagglutinin-tagged wild-type (ARF6-WT) or dominant negative (ARF6-T27N) forms of ARF6. Using immunofluorescence, endogenous ARF6 was associated with the plasma membrane (PM) as well as juxtanuclear and co-localized with Rab5a and Rab11 involved in early and recycling endosomal trafficking. Immunofluorescence staining of megalin showed reduced surface labelling in ARF6 dominant negative (ARF6-DN) cells. Intracellular Alexa Fluor 546-conjugated MT-1 uptake was reduced in ARF6-DN cells and CdMT-1 (14.8 μM for 24 h) toxicity was significantly attenuated from 27.3 ± 3.9% in ARF6-WT to 11.1 ± 4.0% in ARF6-DN cells (n = 6, P < 0.02). Moreover, reduced Alexa Fluor 546-conjugated Tf uptake was observed in ARF-DN cells (75.0 ± 4.6% versus 3.9 ± 3.9% of ARF6-WT cells, n = 3, P < 0.01) and/or remained near the PM (89.3 ± 5. 6% versus 45.2 ± 14.3% of ARF6-WT cells, n = 3, P < 0.05). In conclusion, the data support roles for ARF6 in receptor-mediated endocytosis and trafficking of MT-1/Tf to endosomes/lysosomes and CdMT-1 toxicity of PT cells

Human Papillomavirus 16 Infection Induces VAP-Dependent Endosomal Tubulation.

Science.gov (United States)

Siddiqa, Abida; Massimi, Paola; Pim, David; Broniarczyk, Justyna; Banks, Lawrence

2018-03-15

Human papillomavirus (HPV) infection involves complex interactions with the endocytic transport machinery, which ultimately facilitates the entry of the incoming viral genomes into the trans -Golgi network (TGN) and their subsequent nuclear entry during mitosis. The endosomal pathway is a highly dynamic intracellular transport system, which consists of vesicular compartments and tubular extensions, although it is currently unclear whether incoming viruses specifically alter the endocytic machinery. In this study, using MICAL-L1 as a marker for tubulating endosomes, we show that incoming HPV-16 virions induce a profound alteration in global levels of endocytic tubulation. In addition, we also show a critical requirement for the endoplasmic reticulum (ER)-anchored protein VAP in this process. VAP plays an essential role in actin nucleation and endosome-to-Golgi transport. Indeed, the loss of VAP results in a dramatic decrease in the level of endosomal tubulation induced by incoming HPV-16 virions. This is also accompanied by a marked reduction in virus infectivity. In VAP knockdown cells, we see that the defect in virus trafficking occurs after capsid disassembly but prior to localization at the trans -Golgi network, with the incoming virion-transduced DNA accumulating in Vps29/TGN46-positive hybrid vesicles. Taken together, these studies demonstrate that infection with HPV-16 virions induces marked alterations of endocytic transport pathways, some of which are VAP dependent and required for the endosome-to-Golgi transport of the incoming viral L2/DNA complex. IMPORTANCE Human papillomavirus infectious entry involves multiple interactions with the endocytic transport machinery. In this study, we show that incoming HPV-16 virions induce a dramatic increase in endocytic tubulation. This tubulation requires ER-associated VAP, which plays a critical role in ensuring the delivery of cargoes from the endocytic compartments to the trans -Golgi network. Indeed, the loss of

Natural history of seminiferous tubule degeneration in Klinefelter syndrome

DEFF Research Database (Denmark)

Aksglaede, Lise; Wikström, Anne M; Rajpert-De Meyts, Ewa

2006-01-01

Klinefelter syndrome (47,XXY) is characterized by small, firm testis, gynaecomastia, azoospermia and hypergonadotropic hypogonadism. Degeneration of the seminiferous tubules in 47,XXY males is a well-described phenomenon. It begins in the fetus, progresses through infancy and accelerates dramatic......Klinefelter syndrome (47,XXY) is characterized by small, firm testis, gynaecomastia, azoospermia and hypergonadotropic hypogonadism. Degeneration of the seminiferous tubules in 47,XXY males is a well-described phenomenon. It begins in the fetus, progresses through infancy and accelerates...

The sodium-bicarbonate cotransporter NBCe2 (slc4a5) expressed in human renal proximal tubules shows increased apical expression under high-salt conditions.

Science.gov (United States)

Gildea, John J; Xu, Peng; Carlson, Julia M; Gaglione, Robert T; Bigler Wang, Dora; Kemp, Brandon A; Reyes, Camellia M; McGrath, Helen E; Carey, Robert M; Jose, Pedro A; Felder, Robin A

2015-12-01

The electrogenic sodium bicarbonate cotransporter (NBCe2) is encoded by SLC4A5, variants of which have been associated with salt sensitivity of blood pressure, which affects 25% of the adult population. NBCe2 is thought to mediate sodium bicarbonate cotransport primarily in the renal collecting duct, but NBCe2 mRNA is also found in the rodent renal proximal tubule (RPT). The protein expression or function of NBCe2 has not been demonstrated in the human RPT. We validated an NBCe2 antibody by shRNA and Western blot analysis, as well as overexpression of an epitope-tagged NBCe2 construct in both RPT cells (RPTCs) and human embryonic kidney 293 (HEK293) cells. Using this validated NBCe2 antibody, we found NBCe2 protein expression in the RPT of fresh and frozen human kidney slices, RPTCs isolated from human urine, and isolated RPTC apical membrane. Under basal conditions, NBCe2 was primarily found in the Golgi, while NBCe1 was primarily found at the basolateral membrane. Following an acute short-term increase in intracellular sodium, NBCe2 expression was increased at the apical membrane in cultured slices of human kidney and polarized, immortalized RPTCs. Sodium bicarbonate transport was increased by monensin and overexpression of NBCe2, decreased by NBCe2 shRNA, but not by NBCe1 shRNA, and blocked by 2,2'-(1,2-ethenediyl)bis[5-isothiocyanato-benzenesulfonic acid]. NBCe2 could be important in apical sodium and bicarbonate cotransport under high-salt conditions; the implication of the ex vivo studies to the in vivo situation when salt intake is increased remains unclear. Therefore, future studies will examine the role of NBCe2 in mediating increased renal sodium transport in humans whose blood pressures are elevated by an increase in sodium intake. Copyright © 2015 the American Physiological Society.

Palladium nanotubes formed by lipid tubule templating and their application in ethanol electrocatalysis.

Science.gov (United States)

Wang, Yinan; Ma, Shenghua; Su, Yingchun; Han, Xiaojun

2015-04-13

Palladium nanotubes were fabricated by using lipid tubules as templates for the first time in a controlled manner. The positively charged lipid 1,2-dioleoyl-3-trimethylammoniumpropane (DOTAP) was doped into lipid tubules to adsorb PdCl4 (2-) on the tubule surfaces for further reduction. The lipid tubule formation was optimized by studying the growing dynamics and ethanol/water ratio. The DOTAP-doped tubules showed pH stability from 0 to 14, which makes them ideal templates for metal plating. The Pd nanotubes are open-ended with a tunable wall thickness. They exhibited good electrocatalytic performance in ethanol. Their electrochemically active surface areas were 6.5, 10.6, and 83.2 m(2)  g(-1) for Pd nanotubes with 77, 101, and 150 nm wall thickness, respectively. These Pd nanotubes have great potential in fuel cells. The method demonstrated also opens up a way to synthesize hollow metal nanotubes. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Jellyfish stinging is driven by the moving front of the nematocyst's tubule

Science.gov (United States)

Shavit, Uri; Park, Sinwook; Piriatinskiy, Gadi; Yossifon, Gilad; Lotan, Tamar

2017-11-01

Nematocysts are ultra-fast stinging organelles that are utilized by the Cnidaria phylum for prey capture, defense and locomotion. They consist of a capsule and a tubule and exert high pressure and acceleration to penetrate the target organism. Previous studies report that the ejection and elongation of the tubule are driven by a buildup of osmotic potential in the capsule. We question this explanation using a microfluidic system that controls the osmotic potential by directing the tubule through oil, where no osmotic potential can develop, while keeping the capsule in water. It was found that the time needed for elongation through oil is orders of magnitude larger than through water. Our mathematical model shows that the p γGlu concentration in the tubule is higher than in the capsule and the internal pressure that develops there serves as the elongation driving force. These findings imply that modifications of the environment along the tubule route have the potential to slow down the process and reduce its impact. This may shed light on prey defense strategies, human protection against jellyfish stinging, the use of nematocysts for drug delivery and exploration of osmotic based methods for nanotubes production and elongation.

Role of CAP350 in centriolar tubule stability and centriole assembly.

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Mikael Le Clech

Full Text Available BACKGROUND: Centrioles are microtubule-based cylindrical structures composed of nine triplet tubules and are required for the formation of the centrosome, flagella and cilia. Despite theirs importance, centriole biogenesis is poorly understood. Centrosome duplication is initiated at the G1/S transition by the sequential recruitment of a set of conserved proteins under the control of the kinase Plk4. Subsequently, the procentriole is assembled by the polymerization of centriolar tubules via an unknown mechanism involving several tubulin paralogs. METHODOLOGY/PRINCIPAL FINDINGS: Here, we developed a cellular assay to study centrosome duplication and procentriole stability based on its sensitivity to the microtubule-depolymerizing drug nocodazole. By using RNA interference experiments, we show that the stability of growing procentrioles is regulated by the microtubule-stabilizing protein CAP350, independently of hSAS-6 and CPAP which initiate procentriole growth. Furthermore, our analysis reveals the critical role of centriolar tubule stability for an efficient procentriole growth. CONCLUSIONS/SIGNIFICANCE: CAP350 belongs to a new class of proteins which associate and stabilize centriolar tubules to control centriole duplication.

Hierarchically assembled DNA origami tubules with reconfigurable chirality

International Nuclear Information System (INIS)

Chen, Haorong; Cha, Tae-Gon; Pan, Jing; Choi, Jong Hyun

2013-01-01

The dynamic reconfiguration of a hierarchically assembled tubular structure is demonstrated using the DNA origami technique. Short cylindrical DNA origami monomers are synthesized and linked into elongated tubules, which can then be disassembled via toehold-mediated strand displacement. The disassembled subunits are subsequently linked into tubules of a different chirality. The reconfiguration is performed with the subunits carrying dumbbell hairpin DNA oligonucleotides or gold nanoparticles (AuNPs). The reconfiguration of higher order origami structures presented here is useful for constructing dynamic nanostructures that exceed the size limit of single DNA origami and may facilitate the study of molecular or particle interactions by tuning their relative distance and organization. (paper)

Annexin IV (Xanx-4) has a functional role in the formation of pronephric tubules.

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Seville, Rachel A; Nijjar, Sarbjit; Barnett, Mark W; Massé, Karine; Jones, Elizabeth A

2002-04-01

Vertebrate kidney organogenesis is characterised by the successive formation of the pronephros, the mesonephros and the metanephros. The pronephros is the first to form and is the functional embryonic kidney of lower vertebrates; although it is vestigial in higher vertebrates, it is a necessary precursor for the other kidney types. The Xenopus pronephros is a simple paired organ; each nephron consists of a single large glomus, one set of tubules and a single duct. The simple organisation of the pronephros and the amenability of Xenopus laevis embryos to manipulation make the Xenopus pronephros an attractive system in which to study organogenesis. It has been shown that pronephric tubules can be induced to form in presumptive ectodermal tissue by treatment with RA and activin. We have used this system in a subtractive hybridisation screen that resulted in the cloning of Xenopus laevis annexin IV (Xanx-4). Xanx-4 transcripts are specifically located to the developing pronephric tubules, and the protein to the luminal surface of these tubules. Temporal expression shows zygotic transcription is upregulated at the time of pronephric tubule specification and persists throughout pronephric development. The temporal and spatial expression pattern of Xanx-4 suggests it may have a role in pronephric tubule development. Overexpression of Xanx-4 yields no apparent phenotype, but Xanx-4 depletion, using morpholinos, produces a shortened, enlarged tubule phenotype. The phenotype observed can be rescued by co-injection of Xanx-4 mRNA. Although the function of annexins is not yet clear, studies have suggested a role for annexins in a number of cellular processes. Annexin IV has been shown to have an inhibitory role in the regulation of epithelial calcium-activated chloride ion conductance. The enlarged pronephric tubule phenotype observed may be attributed to incorrect modulation of exocytosis, membrane plasticity or ion channels and/or water homeostasis. In this study, we

Sodium bicarbonate cotransporter NBCe2 gene variants increase sodium and bicarbonate transport in human renal proximal tubule cells.

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Gildea, John J; Xu, Peng; Kemp, Brandon A; Carlson, Julia M; Tran, Hanh T; Bigler Wang, Dora; Langouët-Astrié, Christophe J; McGrath, Helen E; Carey, Robert M; Jose, Pedro A; Felder, Robin A

2018-01-01

Salt sensitivity of blood pressure affects >30% of the hypertensive and >15% of the normotensive population. Variants of the electrogenic sodium bicarbonate cotransporter NBCe2 gene, SLC4A5, are associated with increased blood pressure in several ethnic groups. SLC4A5 variants are also highly associated with salt sensitivity, independent of hypertension. However, little is known about how NBCe2 contributes to salt sensitivity, although NBCe2 regulates renal tubular sodium bicarbonate transport. We hypothesized that SLC4A5 rs10177833 and rs7571842 increase NBCe2 expression and human renal proximal tubule cell (hRPTC) sodium transport and may be a cause of salt sensitivity of blood pressure. To characterize the hRPTC ion transport of wild-type (WT) and homozygous variants (HV) of SLC4A5. The expressions of NBCe2 mRNA and protein were not different between hRPTCs carrying WT or HV SLC4A5 before or after dopaminergic or angiotensin (II and III) stimulation. However, luminal to basolateral sodium transport, NHE3 protein, and Cl-/HCO3- exchanger activity in hRPTCs were higher in HV than WT SLC4A5. Increasing intracellular sodium enhanced the apical location of NBCe2 in HV hRPTCs (4.24±0.35% to 11.06±1.72% (P<0.05, N = 3, 2-way ANOVA, Holm-Sidak test)) as determined by Total Internal Reflection Fluorescence Microscopy (TIRFM). In hRPTCs isolated from kidney tissue, increasing intracellular sodium enhanced bicarbonate-dependent pH recovery rate and increased NBCe2 mRNA and protein expressions to a greater extent in HV than WT SLC4A5 (+38.00±6.23% vs HV normal salt (P<0.01, N = 4, 2-way ANOVA, Holm-Sidak test)). In hRPTCs isolated from freshly voided urine, bicarbonate-dependent pH recovery was also faster in those from salt-sensitive and carriers of HV SLC4A5 than from salt-resistant and carriers of WT SLC4A5. The faster NBCe2-specific bicarbonate-dependent pH recovery rate in HV SCL4A5 was normalized by SLC4A5- but not SLC4A4-shRNA. The binding of purified hepatocyte

Changes in gene expression in human renal proximal tubule cells exposed to low concentrations of S-(1,2-dichlorovinyl)-L-cysteine, a metabolite of trichloroethylene

International Nuclear Information System (INIS)

Lock, Edward A.; Barth, Jeremy L.; Argraves, Scott W.; Schnellmann, Rick G.

2006-01-01

Epidemiology studies suggest that there may be a weak association between high level exposure to trichloroethylene (TCE) and renal tubule cell carcinoma. Laboratory animal studies have shown an increased incidence of renal tubule carcinoma in male rats but not mice. TCE can undergo metabolism via glutathione (GSH) conjugation to form metabolites that are known to be nephrotoxic. The GSH conjugate, S-(1,2-dichlorovinyl)glutathione (DCVG), is processed further to the cysteine conjugate, S-(1,2-dichlorovinyl)-L-cysteine (DCVC), which is the penultimate nephrotoxic species. We have cultured human renal tubule cells (HRPTC) in serum-free medium under a variety of different culture conditions and observed growth, respiratory control and glucose transport over a 20 day period in medium containing low glucose. Cell death was time- and concentration-dependent, with the EC 5 for DCVG being about 3 μM and for DCVC about 7.5 μM over 10 days. Exposure of HRPTC to sub-cytotoxic doses of DCVC (0.1 μM and 1 μM for 10 days) led to a small number of changes in gene expression, as determined by transcript profiling with Affymetrix human genome chips. Using the criterion of a mean 2-fold change over control for the four samples examined, 3 genes at 0.1 μM DCVC increased, namely, adenosine kinase, zinc finger protein X-linked and an enzyme with lyase activity. At 1 μM DCVC, two genes showed a >2-fold decrease, N-acetyltransferase 8 and complement factor H. At a lower stringency (1.5-fold change), a total of 63 probe sets were altered at 0.1 μM DCVC and 45 at 1 μM DCVC. Genes associated with stress, apoptosis, cell proliferation and repair and DCVC metabolism were altered, as were a small number of genes that did not appear to be associated with the known mode of action of DCVC. Some of these genes may serve as molecular markers of TCE exposure and effects in the human kidney

Dentine tubule infection and endodontic therapy implications.

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Oguntebi, B R

1994-07-01

A critical review of the literature suggests that the microenvironment of dentinal tubules appears to favour the selection of relatively few bacterial types irrespective of the aetiology of the infection process; coronal dental caries or pulpar necrosis. These bacteria may constitute an important reservoir from which root canal infection and reinfection may occur following pulp necrosis or during and after endodontic treatment. Previous studies of this microflora have utilized microbiological culture techniques which need to be supplemented by those that allow in situ demonstration as well as identification of the bacteria. Newer treatment strategies that are designed to eliminate this microflora must include agents that can penetrate the dentinal tubules and destroy these microorganisms, since they are located in an area beyond the host defence mechanisms where they cannot be reached by systemically administered antimicrobial agents.

Model-assisted measurements of suspension-feeding flow velocities.

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Du Clos, Kevin T; Jones, Ian T; Carrier, Tyler J; Brady, Damian C; Jumars, Peter A

2017-06-01

Benthic marine suspension feeders provide an important link between benthic and pelagic ecosystems. The strength of this link is determined by suspension-feeding rates. Many studies have measured suspension-feeding rates using indirect clearance-rate methods, which are based on the depletion of suspended particles. Direct methods that measure the flow of water itself are less common, but they can be more broadly applied because, unlike indirect methods, direct methods are not affected by properties of the cleared particles. We present pumping rates for three species of suspension feeders, the clams Mya arenaria and Mercenaria mercenaria and the tunicate Ciona intestinalis , measured using a direct method based on particle image velocimetry (PIV). Past uses of PIV in suspension-feeding studies have been limited by strong laser reflections that interfere with velocity measurements proximate to the siphon. We used a new approach based on fitting PIV-based velocity profile measurements to theoretical profiles from computational fluid dynamic (CFD) models, which allowed us to calculate inhalant siphon Reynolds numbers ( Re ). We used these inhalant Re and measurements of siphon diameters to calculate exhalant Re , pumping rates, and mean inlet and outlet velocities. For the three species studied, inhalant Re ranged from 8 to 520, and exhalant Re ranged from 15 to 1073. Volumetric pumping rates ranged from 1.7 to 7.4 l h -1 for M . arenaria , 0.3 to 3.6 l h -1 for M . m ercenaria and 0.07 to 0.97 l h -1 for C . intestinalis We also used CFD models based on measured pumping rates to calculate capture regions, which reveal the spatial extent of pumped water. Combining PIV data with CFD models may be a valuable approach for future suspension-feeding studies. © 2017. Published by The Company of Biologists Ltd.

Isolation and characterization of a primary proximal tubular epithelial cell model from human kidney by CD10/CD13 double labeling.

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Cynthia Van der Hauwaert

Full Text Available Renal proximal tubular epithelial cells play a central role in renal physiology and are among the cell types most sensitive to ischemia and xenobiotic nephrotoxicity. In order to investigate the molecular and cellular mechanisms underlying the pathophysiology of kidney injuries, a stable and well-characterized primary culture model of proximal tubular cells is required. An existing model of proximal tubular cells is hampered by the cellular heterogeneity of kidney; a method based on cell sorting for specific markers must therefore be developed. In this study, we present a primary culture model based on the mechanical and enzymatic dissociation of healthy tissue obtained from nephrectomy specimens. Renal epithelial cells were sorted using co-labeling for CD10 and CD13, two renal proximal tubular epithelial markers, by flow cytometry. Their purity, phenotypic stability and functional properties were evaluated over several passages. Our results demonstrate that CD10/CD13 double-positive cells constitute a pure, functional and stable proximal tubular epithelial cell population that displays proximal tubule markers and epithelial characteristics over the long term, whereas cells positive for either CD10 or CD13 alone appear to be heterogeneous. In conclusion, this study describes a method for establishing a robust renal proximal tubular epithelial cell model suitable for further experimentation.

Deep-apical tubules: dynamic lipid-raft microdomains in the brush-border region of enterocytes

DEFF Research Database (Denmark)

Hansen, Gert H; Pedersen, Jens; Niels-Christiansen, Lise-Lotte

2003-01-01

microdomains. Deep-apical tubules were positioned close to the actin rootlets of adjacent microvilli in the terminal web region, which had a diameter of 50-100 nm, and penetrated up to 1 microm into the cytoplasm. Markers for transcytosis, IgA and the polymeric immunoglobulin receptor, as well as the resident...... lipid raft-containing compartments, but little is otherwise known about these raft microdomains. We therefore studied in closer detail apical lipid-raft compartments in enterocytes by immunogold electron microscopy and biochemical analyses. Novel membrane structures, deep-apical tubules, were visualized...... brush-border enzyme aminopeptidase N, were present in these deep-apical tubules. We propose that deep-apical tubules are a specialized lipid-raft microdomain in the brush-border region functioning as a hub in membrane trafficking at the brush border. In addition, the sensitivity to cholesterol depletion...

Developmentally regulated GTP-binding protein 2 is required for stabilization of Rac1-positive membrane tubules.

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Mani, Muralidharan; Lee, Unn Hwa; Yoon, Nal Ae; Yoon, Eun Hye; Lee, Byung Ju; Cho, Wha Ja; Park, Jeong Woo

2017-11-04

Previously we have reported that developmentally regulated GTP-binding protein 2 (DRG2) localizes on Rab5 endosomes and plays an important role in transferrin (Tfn) recycling. We here identified DRG2 as a key regulator of membrane tubule stability. At 30 min after Tfn treatment, DRG2 localized to membrane tubules which were enriched with phosphatidylinositol 4-monophosphate [PI(4)P] and did not contain Rab5. DRG2 interacted with Rac1 more strongly with GTP-bound Rac1 and tubular localization of DRG2 depended on Rac1 activity. DRG2 depletion led to destabilization of membrane tubules, while ectopic expression of DRG2 rescued the stability of the membrane tubules in DRG2-depleted cells. Our results reveal a novel mechanism for regulation of membrane tubule stability mediated by DRG2. Copyright © 2017 Elsevier Inc. All rights reserved.

Strontium effects on root dentin tubule occlusion and nanomechanical properties.

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Saeki, Kuniko; Marshall, Grayson W; Gansky, Stuart A; Parkinson, Charles R; Marshall, Sally J

2016-02-01

Dentin hypersensitivity often is treated by promotion of dentin tubule occlusion. In this in vitro study we evaluated nanomechanical properties and degree of tubule occlusion conferred to sound and demineralized human root dentin following treatment with a 10% (w/w) strontium acetate solution and its relation to the treatment duration and delivery method. 24 human cervical root dentin disks (8 groups of 3) were polished through 0.25 μm. 12 disks were subjected to an acid challenge (1% citric acid, pH 3.8) for 2 min. The specimens were incubated in artificial saliva, treated by soaking or brushing with deionized (DI) water or a solution of 10% strontium acetate for 2 min twice a day for 28 days. The occlusion percent and nanomechanical properties were determined at the baseline, 5, 14 and 28 days. Cross-sectioned specimens were prepared to evaluate the depth affected by strontium acetate / dentin interaction by SEM. Statistical analysis was performed using linear mixed effects models. A 10% strontium acetate treatment over 5-28 days significantly increased tubule occlusion for normal root dentin and to a lesser extent for demineralized dentin and increased the AFM based nanomechanical properties of demineralized dentin. Brushing was more effective than soaking in recovery of properties of demineralized dentin when treated with strontium. No difference in tubuleocclusion was found between the two delivery methods. Strontium acetate itself proved to have the ability to occlude dentin tubules and result in small changes in the mechanical properties of dentin. Copyright © 2015 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

Detection of avian influenza antigens in proximity fiber, droplet, and optical waveguide microfluidics

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Yoon, Jeong-Yeol; Heinze, Brian C.; Gamboa, Jessica; You, David J.

2009-05-01

Virus antigens of avian influenza subtype H3N2 were detected on two different microfluidic platforms: microchannel and droplet. Latex immunoagglutination assays were performed using 920-nm highly carboxylated polystyrene beads that are conjugated with antibody to avian influenza virus. The bead suspension was merged with the solutions of avian influenza virus antigens in a Y-junction of a microchannel made by polydimethylsiloxane soft lithography. The resulting latex immunoagglutinations were measured with two optical fibers in proximity setup to detect 45° forward light scattering. Alternatively, 10 μL droplets of a bead suspension and an antigen solution were merged on a superhydrophobic surface (water contact angle = 155°), whose movement was guided by a metal wire, and 180° back light scattering is measured with a backscattering optical probe. Detection limits were 0.1 pg mL-1 for both microchannel with proximity fibers and droplet microfluidics, thanks to the use of micro-positioning stages to help generate reproducible optical signals. Additionally, optical waveguide was tested by constructing optical waveguide channels (filled with mineral oil) within a microfluidic device to detect the same light scattering. Detection limit was 0.1 ng mL-1 for an optical waveguide device, with a strong potential of improvement in the near future. The use of optical waveguide enabled smaller device setup, easier operation, smaller standard deviations and broader linear range of assay than proximity fiber microchannel and droplet microfluidics. Total assay time was less than 10 min.

Numerical Analysis of the Effect of T-tubule Location on Calcium Transient in Ventricular Myocytes

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George, Uduak Z.; Wang, Jun; Yu, Zeyun

2013-01-01

Intracellular calcium (Ca2+) signaling in cardiac myocytes is vital for proper functioning of the heart. Understanding the intracellular Ca2+ dynamics would give an insight into the functions of normal and diseased hearts. In the current study, spatiotemporal Ca2+ dynamics is investigated in ventricular myocytes by considering Ca2+ release and re-uptake via sarcolemma and transverse tubules (T-tubules), Ca2+ diffusion and buffering in the cytosol, and the blockade of Ca2+ activities associated with the sarcoplasmic reticulum. This study is carried out using a three dimensional (3D) geometric model of a branch of T-tubule extracted from the electron microscopy (EM) images of a partial ventricular myocyte. Mathematical modeling is done by using a system of partial differential equations involving Ca2+ , buffers, and membrane channels. Numerical simulation results suggest that a lack of T-tubule structure at the vicinity of the cell surface could increase the peak time of Ca2+ concentration in myocytes. The results also show that T-tubules and mobile buffers play an important role in the regulation of Ca2+ transient in ventricular myocytes. PMID:24212025

Tubulation of class II MHC compartments is microtubule dependent and involves multiple endolysosomal membrane proteins in primary dendritic cells.

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Vyas, Jatin M; Kim, You-Me; Artavanis-Tsakonas, Katerina; Love, J Christopher; Van der Veen, Annemarthe G; Ploegh, Hidde L

2007-06-01

Immature dendritic cells (DCs) capture exogenous Ags in the periphery for eventual processing in endolysosomes. Upon maturation by TLR agonists, DCs deliver peptide-loaded class II MHC molecules from these compartments to the cell surface via long tubular structures (endolysosomal tubules). The nature and rules that govern the movement of these DC compartments are unknown. In this study, we demonstrate that the tubules contain multiple proteins including the class II MHC molecules and LAMP1, a lysosomal resident protein, as well as CD63 and CD82, members of the tetraspanin family. Endolysosomal tubules can be stained with acidotropic dyes, indicating that they are extensions of lysosomes. However, the proper trafficking of class II MHC molecules themselves is not necessary for endolysosomal tubule formation. DCs lacking MyD88 can also form endolysosomal tubules, demonstrating that MyD88-dependent TLR activation is not necessary for the formation of this compartment. Endolysosomal tubules in DCs exhibit dynamic and saltatory movement, including bidirectional travel. Measured velocities are consistent with motor-based movement along microtubules. Indeed, nocodazole causes the collapse of endolysosomal tubules. In addition to its association with microtubules, endolysosomal tubules follow the plus ends of microtubules as visualized in primary DCs expressing end binding protein 1 (EB1)-enhanced GFP.

Piecewise-Constant-Model-Based Interior Tomography Applied to Dentin Tubules

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Peng He

2013-01-01

Full Text Available Dentin is a hierarchically structured biomineralized composite material, and dentin’s tubules are difficult to study in situ. Nano-CT provides the requisite resolution, but the field of view typically contains only a few tubules. Using a plate-like specimen allows reconstruction of a volume containing specific tubules from a number of truncated projections typically collected over an angular range of about 140°, which is practically accessible. Classical computed tomography (CT theory cannot exactly reconstruct an object only from truncated projections, needless to say a limited angular range. Recently, interior tomography was developed to reconstruct a region-of-interest (ROI from truncated data in a theoretically exact fashion via the total variation (TV minimization under the condition that the ROI is piecewise constant. In this paper, we employ a TV minimization interior tomography algorithm to reconstruct interior microstructures in dentin from truncated projections over a limited angular range. Compared to the filtered backprojection (FBP reconstruction, our reconstruction method reduces noise and suppresses artifacts. Volume rendering confirms the merits of our method in terms of preserving the interior microstructure of the dentin specimen.

Masonry structures built with fictile tubules: Experimental and numerical analyses

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Tiberti, Simone; Scuro, Carmelo; Codispoti, Rosamaria; Olivito, Renato S.; Milani, Gabriele

2017-11-01

Masonry structures with fictile tubules were a distinctive building technique of the Mediterranean area. This technique dates back to Roman and early Christian times, used to build vaulted constructions and domes with various geometrical forms by virtue of their modular structure. In the present work, experimental tests were carried out to identify the mechanical properties of hollow clay fictile tubules and a possible reinforcing technique for existing buildings employing such elements. The experimental results were then validated by devising and analyzing numerical models with the FE software Abaqus, also aimed at investigating the structural behavior of an arch via linear and nonlinear static analyses.

Chemically triggered ejection of membrane tubules controlled by intermonolayer friction.

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Fournier, J-B; Khalifat, N; Puff, N; Angelova, M I

2009-01-09

We report a chemically driven membrane shape instability that triggers the ejection of a tubule growing exponentially toward a chemical source. The instability is initiated by a dilation of the exposed monolayer, which is coupled to the membrane spontaneous curvature and slowed down by intermonolayer friction. Our experiments are performed by local delivery of a basic pH solution to a giant vesicle. Quantitative fits of the data give an intermonolayer friction coefficient b approximately 2x10;{9} J s/m;{4}. The exponential growth of the tubule may be explained by a Marangoni stress yielding a pulling force proportional to its length.

Revealing t-tubules in striated muscle with new optical super-resolution microscopy techniques

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Isuru D. Jayasinghe

2014-12-01

Full Text Available The t-tubular system plays a central role in the synchronisation of calcium signalling and excitation-contraction coupling in most striated muscle cells. Light microscopy has been used for imaging t-tubules for well over 100 years and together with electron microscopy (EM, has revealed the three-dimensional complexities of the t-system topology within cardiomyocytes and skeletal muscle fibres from a range of species. The emerging super-resolution single molecule localisation microscopy (SMLM techniques are offering a near 10-fold improvement over the resolution of conventional fluorescence light microscopy methods, with the ability to spectrally resolve nanometre scale distributions of multiple molecular targets. In conjunction with the next generation of electron microscopy, SMLM has allowed the visualisation and quantification of intricate t-tubule morphologies within large areas of muscle cells at an unprecedented level of detail. In this paper, we review recent advancements in the t-tubule structural biology with the utility of various microscopy techniques. We outline the technical considerations in adapting SMLM to study t-tubules and its potential to further our understanding of the molecular processes that underlie the sub-micron scale structural alterations observed in a range of muscle pathologies.

Tubulation of Class II MHC Compartments Is Microtubule Dependent and Involves Multiple Endolysosomal Membrane Proteins in Primary Dendritic Cells1

Science.gov (United States)

Vyas, Jatin M.; Kim, You-Me; Artavanis-Tsakonas, Katerina; Love, J. Christopher; Van der Veen, Annemarthe G.; Ploegh, Hidde L.

2009-01-01

Immature dendritic cells (DCs) capture exogenous Ags in the periphery for eventual processing in endolysosomes. Upon maturation by TLR agonists, DCs deliver peptide-loaded class II MHC molecules from these compartments to the cell surface via long tubular structures (endolysosomal tubules). The nature and rules that govern the movement of these DC compartments are unknown. In this study, we demonstrate that the tubules contain multiple proteins including the class II MHC molecules and LAMP1, a lysosomal resident protein, as well as CD63 and CD82, members of the tetraspanin family. Endolysosomal tubules can be stained with acidotropic dyes, indicating that they are extensions of lysosomes. However, the proper trafficking of class II MHC molecules themselves is not necessary for endolysosomal tubule formation. DCs lacking MyD88 can also form endolysosomal tubules, demonstrating that MyD88-dependent TLR activation is not necessary for the formation of this compartment. Endolysosomal tubules in DCs exhibit dynamic and saltatory movement, including bidirectional travel. Measured velocities are consistent with motor-based movement along microtubules. Indeed, nocodazole causes the collapse of endolysosomal tubules. In addition to its association with microtubules, endolysosomal tubules follow the plus ends of microtubules as visualized in primary DCs expressing end binding protein 1 (EB1)-enhanced GFP. PMID:17513769

Administrative license suspension: Does length of suspension matter?

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Fell, James C; Scherer, Michael

2017-08-18

Administrative license revocation (ALR) laws, which provide that the license of a driver with a blood alcohol concentration at or over the illegal limit is subject to an immediate suspension by the state department of motor vehicles, are an example of a traffic law in which the sanction rapidly follows the offense. The power of ALR laws has been attributed to how swiftly the sanction is applied, but does the length of suspension matter? Our objectives were to (a) determine the relationship of the ALR suspension length to the prevalence of drinking drivers relative to sober drivers in fatal crashes and (b) estimate the extent to which the relationship is associated to the general deterrent effect compared to the specific deterrent effect of the law. Data comparing the impact of ALR law implementation and ALR law suspension periods were analyzed using structural equation modeling techniques on the ratio of drinking drivers to nondrinking drivers in fatal crashes from the Fatality Analysis Reporting System (FARS). States with an ALR law with a short suspension period (1-30 days) had a significantly lower drinking driver ratio than states with no ALR law. States with a suspension period of 91-180 days had significantly lower ratios than states with shorter suspension periods, while the three states with suspension lengths of 181 days or longer had significantly lower ratios than states with shorter suspension periods. The implementation of any ALR law was associated with a 13.1% decrease in the drinking/nondrinking driver fatal crash ratio but only a 1.8% decrease in the intoxicated/nonintoxicated fatal crash ratio. The ALR laws and suspension lengths had a significant general deterrent effect, but no specific deterrent effect. States might want to keep (or adopt) ALR laws for their general deterrent effects and pursue alternatives for specific deterrent effects. States with short ALR suspension periods should consider lengthening them to 91 days or longer.

THE NEPHROTOXICITY RISK IN RATS SUBJECTED TO HEAVY MUSCLE ACTIVITY

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Gülsen Öner

2009-09-01

Full Text Available When the body is exposed to insults, the kidneys exhibit adaptive changes termed renal cytoresistance, characterized by cholesterol accumulation in the membranes of the tubule cells. However, heavy muscle activity has not yet been accepted as one of the stressors that could lead to cytoresistance. In order to study the renal functional characteristics of animals exposed to heavy muscle activity, rats were subjected to exhaustive treadmill exercise for 5 days and their data was compared to those of sedentary controls. It was found that in exercised rats, blood lactate, muscle citrate synthase and proximal tubule peroxynitrite levels were all elevated, suggesting the presence of oxidative stress in the proximal tubule segments. However, mean arterial pressure, renal blood flow, glomerular filtration rate, fractional excretion of sodium and potassium, and organic anion excretion remained normal. Despite unchanged blood cholesterol levels, cholesterol loading in the proximal tubule segments, especially the free form, and decreased lactate dehydrogenase release from cytoresistant proximal tubule segments indicated the development of renal cytoresistance. However, this resistance did not seem to have protected the kidneys as expected because organic anion accumulation associated with glycosuria and proteinuria, in addition to the elevated urinary cholesterol levels, all imply the presence of an impaired glomerular permeability and reabsorption in the proximal tubule cells. Therefore, we suggest that in response to heavy muscle activity the tubular secretion may remain intact, although cytoresistance in the proximal tubule cells may affect the tubular reabsorptive functions and basolateral uptake of substances. Thus, this differential sensitivity in the cytoresistance should be taken into account during functional evaluation of the kidneys

Antioxidant Effects of Selenium on Seminiferous Tubules of Immature Mice Testis

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Davoud Kushki

2015-12-01

Full Text Available Background: The freezing of immature testis tissue and then the transplant of it can be considered as a major step in fertility preservation for young boys with cancer, the survival of animal generation exposed to extinction and cloning animalistic desirable species. One of the most prevalent of damages in during the freezing-thawing process is oxidative stress. Objectives: The objective of this study was to investigate the antioxidant effects of selenium compound (Na2SeO3 on rate of seminiferous tubules injury in during of cryopreservation. Materials and Methods: In this experimental study, 8 BALB/c immature male mice (6 - 8 days old were randomly selected, and the testes removed surgically (n = 16. The testes divided into 2 groups: experimental group, control group (opposite testes. For each of the two experimental and control groups, two types of soluble (freezing solution and thawing solution were prepared. These solutions, which contain 2 mg/mL solution of Na2SeO3 and control solution, were prepared in the DMEM (Dulbecco’s modified eagle medium base medium. Of each group were 4 testes into fast freezing-thawing procedure and 4 testes were into slow freezing-thawing procedure. Then this testis for analyzing injury, after preparatory process, was stained with hematoxylin-eosin. Results: At the slow freezing-thawing procedure, seminiferous tubules injury significantly reduced in experimental group compared to control group. At the fast freezing-thawing procedure, seminiferous tubules injury significantly reduced in experimental group compared with of control group. Conclusions: It seems that Se due to its antioxidant properties, the harmful effects of freezing-thawing process reduces and protects seminiferous tubules from oxidative injury.

In Vitro Evaluation of Dentin Tubule Occlusion for Novel Calcium Lactate Phosphate (CLP Paste

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Jen-Chang Yang

2017-02-01

Full Text Available Introduction: The objective of this in vitro study is to evaluate the effective and long-term occlusion of dentinal tubules using a novel calcium lactate phosphate (CLP based desensitizing agent. Methods: Dentin disks (n = 9 were pre-etched using 1 M lactic acid for 30 s and individually treated with Colgate® Pro-Relief™ paste, CLP paste, and double distilled water (ddH2O by a rubber-cupped handpiece. Dentin disks were analyzed under optical micrographs for pre-treatment, directly after treatment, and 14 days post-treatment. One-way ANOVA and post-hoc Tukey’s test were used to determine whether there were any statistically significant differences in dentinal tubule diameter. Results: A significant decrease occurred in the mean tubule diameter for dentin disks treated with CLP paste. A decrease was observed from 3.52 ± 0.83 µm to 2.62 ± 0.42 µm right after treatment, further decreasing to 1.71 ± 0.45 µm after immersion in artificial saliva for 14 days (p < 0.05. Conclusions: The results suggest that the CLP based desensitizing paste has remineralization properties and provides instant and lasting effectiveness in dentinal tubule occlusion.

Tumor-promoting phorbol esters effect alkalinization of canine renal proximal tubular cells

International Nuclear Information System (INIS)

Mellas, J.; Hammerman, M.R.

1986-01-01

We have demonstrated the presence of specific receptors for tumor-promoting phorbol esters in the plasma membrane of the canine renal proximal tubular cell. These compounds affect proximal tubular metabolism in vitro. For example, we have shown that they inhibit gluconeogenesis in canine renal proximal tubular segments. Tumor-promoting phorbol esters have been shown to effect alkalinization of non-renal cells, by enhancing Na + -H + exchange across the plasma membrane. To determine whether the actions of tumor-promoting phorbol esters in proximal tubular segments might be mediated by a similar process, we incubated suspensions of segments from dog kidney with these compounds and measured changes in intracellular pH using [ 14 C]-5,5-dimethoxazoladine-2-4-dione (DMO) and flow dialysis. Incubation of segments with phorbol 12,13 dibutyrate, but not inactive phorbol ester, 4 γ phorbol, effected alkalinization of cells within the segments in a concentration-dependent manner. Alkalinization was dependent upon the presence of extracellular [Na + ] > intracellular [Na + ], was prevented by amiloride and was demonstrable in the presence of SITS. Our findings suggest that tumor-promoting esters stimulate the Na + -H + exchanger known to be present in the brush border membrane of the renal proximal tubular cell. It is possible that the stimulation reflects a mechanism by which phorbol esters affect metabolic processes in these cells

Cadmium transport by the gut and Malpighian tubules of Chironomus riparius

International Nuclear Information System (INIS)

Leonard, Erin M.; Pierce, Laura M.; Gillis, Patricia L.; Wood, Chris M.; O'Donnell, Michael J.

2009-01-01

Many aquatic insects are very insensitive to cadmium in short-term laboratory studies. LC50 values for larvae of the midge Chironomus riparius are over 25,000 times the Criterion Maximum Concentration in the United States Environmental Protection Agency (U.S. EPA (2000)) species sensitivity distribution (SSD). Excretion or sequestration of cadmium may contribute to insensitivity and we have therefore examined cadmium transport by isolated guts and renal tissues of C. riparius larvae. Regional differences of Cd transport along the gut were identified using a Cd 2+ -selective microelectrode in conjunction with the Scanning Ion-Selective Electrode Technique (SIET). Cd is transported into the anterior midgut (AMG) cells from the lumen and out of the cells into the hemolymph. The transport of Cd from the gut lumen to the hemolymph exposes other tissues such as the nervous system and muscles to Cd. The gut segments which remove Cd from the hemolymph at the highest rate are the posterior midgut (PMG) and the ileum. In addition, assays using an isolated Malpighian (renal) tubule preparation have shown that the Malpighian tubules (MT) both sequester and secrete Cd. For larvae bathed in 10 μmol l -1 Cd, the tubules can secrete the entire hemolymph burden of Cd in ∼15 h.

Tubule-Derived Wnts Are Required for Fibroblast Activation and Kidney Fibrosis.

Science.gov (United States)

Zhou, Dong; Fu, Haiyan; Zhang, Lu; Zhang, Ke; Min, Yali; Xiao, Liangxiang; Lin, Lin; Bastacky, Sheldon I; Liu, Youhua

2017-08-01

Cell-cell communication via Wnt ligands is necessary in regulating embryonic development and has been implicated in CKD. Because Wnt ligands are ubiquitously expressed, the exact cellular source of the Wnts involved in CKD remains undefined. To address this issue, we generated two conditional knockout mouse lines in which Wntless (Wls), a dedicated cargo receptor that is obligatory for Wnt secretion, was selectively ablated in tubular epithelial cells or interstitial fibroblasts. Blockade of Wnt secretion by genetic deletion of Wls in renal tubules markedly inhibited myofibroblast activation and reduced renal fibrosis after unilateral ureteral obstruction. This effect associated with decreased activation of β -catenin and downstream gene expression and preserved tubular epithelial integrity. In contrast, fibroblast-specific deletion of Wls exhibited little effect on the severity of renal fibrosis after obstructive or ischemia-reperfusion injury. In vitro , incubation of normal rat kidney fibroblasts with tubule-derived Wnts promoted fibroblast proliferation and activation. Furthermore, compared with kidney specimens from patients without CKD, biopsy specimens from patients with CKD also displayed increased expression of multiple Wnt proteins, predominantly in renal tubular epithelium. These results illustrate that tubule-derived Wnts have an essential role in promoting fibroblast activation and kidney fibrosis via epithelial-mesenchymal communication. Copyright © 2017 by the American Society of Nephrology.

EOS suspension test for the assessment of spinal flexibility in adolescent idiopathic scoliosis.

Science.gov (United States)

Hirsch, Caroline; Ilharreborde, Brice; Mazda, Keyvan

2015-07-01

The assessment of spinal flexibility is essential for the planning of adolescent idiopathic scoliosis (AIS) surgery. Various radiographic methods have been used but none of them has shown any superiority. The new low-dose stereography system EOS (EOS imaging, Paris, France) captures whole body images in a single scan without vertical distortion. EOS is now used in routine clinical use for AIS follow-up. The aim of this study was to prospectively evaluate the feasibility and the reproducibility of a new suspension test during the EOS imaging for the assessment of spinal flexibility in AIS. Fifty AIS patients scheduled for surgery were prospectively included. For each patient, a standard EOS radiograph was obtained, then a suspension test in the EOS and a classic traction test on the cotrel frame were performed. The examinations were compared in terms of radiation exposure, tolerance, mean traction force, and Cobb angle reduction for each curve. Axial and sagittal reductions during suspension were analyzed on three-dimensional EOS reconstructions. The tolerance of the suspension test was lower than the traction test but it was less operator dependent. Radiation exposure was 7 times lower during the suspension test. Cobb angle reductions achieved in the proximal and main curves by the two tests were similar. The traction test achieved greater reduction of the distal curve. Flexibility in the axial plane and in the sagittal plane was analyzed with the suspension test. The reduction in apical rotation was not correlated with the reduction in Cobb angle. The EOS suspension test can be used for the assessment of spinal flexibility in AIS. It gives a global vision of the deformity with new flexibility indices in the axial and sagittal planes.

Morphometry of testis and seminiferous tubules of the adult crab-eating fox (Cerdocyon thous, Linnaeus, 1766

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Bianca Cabral Caldeira

2010-10-01

Full Text Available Body and testicular biometric parameters are very important for establishing reproductive patterns and, consequently, the development of protocols for assisted reproduction in different species. A direct correlation between the testis weight and the sperm population was observed in other studied species, because the testis size primarily reflects the total volume of the seminiferous tubule, its main component. The objective of this study was to determine the testicular volume parameters and correlate data from morphometry of testis and seminiferous tubules with body mass in six adult crab-eating foxes. The mean body weight of the crab-eating foxes in this study was 6.53 kg, with approximately 0.068% allocated to the testicular mass and 0.042% specifically to seminiferous tubules, which represented 87.5% of the testicular parenchyma. The albuginea comprised 12.5% of the testicular mass. The mean diameter of seminiferous tubules was 236 µm, and the mean thickness of the seminiferous epithelium was 62.9 µm. Values of tubular parameters indicate a sperm productivity close to those observed in previously studied carnivores.

Studies on the origin and structure of tubules made by the movement protein of Cowpea mosaic virus

NARCIS (Netherlands)

Pouwels, J.; Velden, van der T.; Willemse, J.; Borst, J.W.; Lent, van J.W.M.; Bisseling, T.; Wellink, J.E.

2004-01-01

Cowpea mosaic virus (CPMV) moves from cell to cell by transporting virus particles via tubules formed through plasmodesmata by the movement protein (MP). On the surface of protoplasts, a fusion between the MP and the green fluorescent protein forms similar tubules and peripheral punctate spots. Here

Isolation and Characterization of Adhesive Secretion from Cuvierian Tubules of Sea Cucumber Holothuria forskåli (Echinodermata: Holothuroidea

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Malgorzata Baranowska

2011-01-01

Full Text Available The sea cucumber Holothuria forskåli possesses a specialized system called Cuvierian tubules. During mechanical stimulation white filaments (tubules are expelled and become sticky upon contact with any object. We isolated a protein with adhesive properties from protein extracts of Cuvierian tubules from H. forskåli. This protein was identified by antibodies against recombinant precollagen D which is located in the byssal threads of the mussel Mytilus galloprovincialis. To find out the optimal procedure for extraction and purification, the identified protein was isolated by several methods, including electroelution, binding to glass beads, immunoprecipitation, and gel filtration. Antibodies raised against the isolated protein were used for localization of the adhesive protein in Cuvierian tubules. Immunostaining and immunogold electron microscopical studies revealed the strongest immunoreactivity in the mesothelium; this tissue layer is involved in adhesion. Adhesion of Cuvierian tubule extracts was measured on the surface of various materials. The extracted protein showed the strongest adhesion to Teflon surface. Increased adhesion was observed in the presence of potassium and EDTA, while cadmium caused a decrease in adhesion. Addition of antibodies and trypsin abolished the adhesive properties of the extract.

The development of enamel tubules during the formation of enamel in the marsupial Monodelphis domestica.

OpenAIRE

Sasagawa, I; Ferguson, M W

1991-01-01

In Monodelphis domestica, although both processes from odontoblasts and projections from ameloblasts were found in developing enamel, the majority of the contents of enamel tubules were probably processes that originated from odontoblasts. Processes from odontoblasts penetrating into enamel touched part of the ameloblasts in the stage of enamel formation. No specialised cell junctions were seen at the adherence between the two. There were no enamel tubules in the aprismatic and pseudoprismati...

Wild boars (Sus scrofa scrofa seminiferous tubules morphometry

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Deiler Sampaio Costa

2006-09-01

Full Text Available The aim of this data was to analyze morphology and function of the seminiferous tubule in adult wild boars. Testes removed by unilateral castration of five animals were used. The testicular parenchyma was composed by 82.1±2.2% of seminiferous tubule and 17.9±2.2% of intertubular tissue. The tubular diameter was 249.2±33.0 µm and the seminiferous tubule lenght per gram of testis was 19.3±4.9m. The spermatogonial mitoses efficiency coefficient, meiotic index and spermatogenesis efficiency were 10.34, 2.71 and 30.5 respectively. Each Sertoli cell supported about 13 germinatives cells. The hystometric parameters studied were very similar to those related for domestic boars, however, the wild boars intrinsic efficiency of spermatogenesis and Sertoli cells indexes were smaller than in domestic boars.Objetivou-se com esta pesquisa estudar as características morfométricas e funcionais dos túbulos seminíferos de javalis adultos. Utilizaram-se testículos de cinco animais submetidos a orquiectomia unilateral. O parênquima testicular foi composto por 82,1 ± 2,2% de túbulos seminíferos e 17,9 ± 2,2% de tecido intertubular. O diâmetro tubular foi de 249,2 ± 33,0µm e o comprimento dos túbulos seminíferos por grama de testículo foi de 19,3 ± 4,9m. O coeficiente de eficiência das mitoses espermatogônias, o rendimento meiótico e o rendimento geral da espermatogênese foram, respectivamente, 10,34, 2,71 e 30,50. Cada célula de Sértoli suportou cerca de 13 células germinativas. Conclui-se que os parâmetros histométricos estudados nesta pesquisa foram muito semelhantes aos valores relatados para suínos domésticos, entretanto, o rendimento intrínseco da espermatogênese e os índices de células de Sértoli de javalis foram relativamente baixos quando comparados com aqueles animais.

Metabolism of cysteine and cysteinesulfinate in rat kidney tubules

International Nuclear Information System (INIS)

De La Rosa, J.; Stipanuk, M.H.

1986-01-01

In studies with rat hepatocytes, hypotaurine plus taurine production accounted for less than 5% of the total amount of cysteine (CYS) catabolized, whereas more than 90% of the metabolized cysteinesulfinate (CSA) was converted to taurine plus hypotaurine. Similar studies have been carried out with kidney tubules isolated from fed rats and incubated with 2 mM [1- 14 C]CYS or 25 mM [1- 14 C]CSA at 37 0 C for up to 40 min. The production of 14 CO 2 from CSA (3.1 +/- 1.3 nmol/sup ./ min -1 /sup ./ mg dry wt -1 ) was equivalent to the accumulation of N in NH 4 + plus glutamate. Substantial oxidation of CYS was observed (16 +/- 11 nmol CO 2 x min -1 x mg dry wt -1 ), but only 12% of the expected amount of N was recovered as NH 4 + plus glutamate. Accumulation of hypotaurine plus taurine was equivalent to 20% of the observed rate of 14 CO 2 production from CSA but accounted for only 2% of the observed rate of 14 CO 2 production from CYS. Addition of unlabeled CSA to incubations with varying levels of CYS had no effect on production of 14 CO 2 . Addition of 2 mM α-ketoglutarate to the incubation mixtures resulted in an increased in 14 CO 2 production from CSA to 290% of the control level but had no effect on CYS oxidation. In agreement with the authors findings for rat hepatocytes, these data suggest that most metabolism of CYS by the rat kidney tubule occurs by a CSA-independent pathway. However, in contrast to the metabolism of CSA almost entirely to taurine in the hepatocyte, kidney tubules appeared to metabolize CSA primarily by the transamination pathway

Reactive Oxygen Species Modulation of Na/K-ATPase Regulates Fibrosis and Renal Proximal Tubular Sodium Handling

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Jiang Liu

2012-01-01

Full Text Available The Na/K-ATPase is the primary force regulating renal sodium handling and plays a key role in both ion homeostasis and blood pressure regulation. Recently, cardiotonic steroids (CTS-mediated Na/K-ATPase signaling has been shown to regulate fibrosis, renal proximal tubule (RPT sodium reabsorption, and experimental Dahl salt-sensitive hypertension in response to a high-salt diet. Reactive oxygen species (ROS are an important modulator of nephron ion transport. As there is limited knowledge regarding the role of ROS-mediated fibrosis and RPT sodium reabsorption through the Na/K-ATPase, the focus of this review is to examine the possible role of ROS in the regulation of Na/K-ATPase activity, its signaling, fibrosis, and RPT sodium reabsorption.

Automated tubule nuclei quantification and correlation with oncotype DX risk categories in ER+ breast cancer whole slide images

Science.gov (United States)

Romo-Bucheli, David; Janowczyk, Andrew; Romero, Eduardo; Gilmore, Hannah; Madabhushi, Anant

2016-03-01

Early stage estrogen receptor positive (ER+) breast cancer (BCa) treatment is based on the presumed aggressiveness and likelihood of cancer recurrence. The primary conundrum in treatment and management of early stage ER+ BCa is identifying which of these cancers are candidates for adjuvant chemotherapy and which patients will respond to hormonal therapy alone. This decision could spare some patients the inherent toxicity associated with adjuvant chemotherapy. Oncotype DX (ODX) and other gene expression tests have allowed for distinguishing the more aggressive ER+ BCa requiring adjuvant chemotherapy from the less aggressive cancers benefiting from hormonal therapy alone. However these gene expression tests tend to be expensive, tissue destructive and require physical shipping of tissue blocks for the test to be done. Interestingly breast cancer grade in these tumors has been shown to be highly correlated with the ODX risk score. Unfortunately studies have shown that Bloom-Richardson (BR) grade determined by pathologists can be highly variable. One of the constituent categories in BR grading is the quantification of tubules. The goal of this study was to develop a deep learning neural network classifier to automatically identify tubule nuclei from whole slide images (WSI) of ER+ BCa, the hypothesis being that the ratio of tubule nuclei to overall number of nuclei would correlate with the corresponding ODX risk categories. The performance of the tubule nuclei deep learning strategy was evaluated with a set of 61 high power fields. Under a 5-fold cross-validation, the average precision and recall measures were 0:72 and 0:56 respectively. In addition, the correlation with the ODX risk score was assessed in a set of 7513 high power fields extracted from 174 WSI, each from a different patient (At most 50 high power fields per patient study were used). The ratio between the number of tubule and non-tubule nuclei was computed for each WSI. The results suggests that for BCa

Structural and functional alterations in Malpighian tubules as biomarkers of environmental pollution: synopsis and prospective.

Science.gov (United States)

Giglio, Anita; Brandmayr, Pietro

2017-08-01

Although a number of biomarkers of pollutant exposure have been identified in invertebrate species, little is known about the effect on Malpighian tubules playing an essential role in excretion and osmoregulation. Analyses of structural and functional alterations on this organ can be useful to predict the effects at the organism and population level in monitoring studies of environmental pollution. The aim of the present review is to provide a synthesis of existing knowledge on cellular damages induced by xenobiotics in Malpighian tubules both under laboratory and field conditions. We compared studies of exposure to pesticides and heavy metals as mainly environmental contaminants from anthropogenic activities. This report provided evidence that the exposure to xenobiotics has an effect on this organ and reinforces the need for further research integrating molecular biomarkers with analysis on Malpighian tubules. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Effects of bioactive glass with and without mesoporous structures on desensitization in dentinal tubule occlusion

Energy Technology Data Exchange (ETDEWEB)

Chen, Wen-Cheng [Advanced Medical Devices and Composites Laboratory, Department of Fiber and Composite Materials, College of Engineering, Feng Chia University, Taichung 40724, Taiwan (China); Kung, Jung-Chang [Department of Family Dentistry, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China); Chen, Cheng-Hwei [School of Dentistry, College of Dental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan (China); Hsiao, Yu-Cheng [Department of Fragrance and Cosmetic Science, Kaohsiung Medical University, Kaohsiung 807, Taiwan (China); Shih, Chi-Jen, E-mail: cjshih@kmu.edu.tw [Department of Fragrance and Cosmetic Science, Kaohsiung Medical University, Kaohsiung 807, Taiwan (China); Chien, Chi-Sheng, E-mail: jannie.gissing@msa.hinet.net [Department of Biomedical Engineering, National Cheng Kung University, Tainan, Taiwan (China); Department of Orthopaedics, Chi Mei Foundation Hospital, Tainan, Taiwan (China); Department of Electrical Engineering, Southern Taiwan University of Science and Technology, Tainan, Taiwan (China)

2013-10-15

Bioactive glass (BG) is a potential material for treating dentin hypersensitivity due to its high ability of dissolution. In this study, conventional BG and BG with well-ordered mesopore structures (MBG) were applied for dentinal tubule occlusion. We used X-ray diffractometer (XRD), scanning electronic microscope (SEM), and Fourier transform infrared (FTIR) to investigate the physiochemical properties and the dentinal tubule occlusion ability of BG and MBG groups. The results showed that the major crystallite phase of MBG and BG agents was monocalcium phosphate monohydrate. MBG pastes, mixed with 30 and 40 wt% phosphoric acid hardening solutions, had the ability to create a penetration depth greater than 50 μm. These results showed that BG with mesoporous structures turned the pastes mixed with suitable phosphoric acid solution into a material with great ability for occluding dentinal tubules; it has a short reaction time and good operability, and these agents have better potential for the treatment of dentin hypersensitivity than BG without mesoporous structures.

Effects of bioactive glass with and without mesoporous structures on desensitization in dentinal tubule occlusion

International Nuclear Information System (INIS)

Chen, Wen-Cheng; Kung, Jung-Chang; Chen, Cheng-Hwei; Hsiao, Yu-Cheng; Shih, Chi-Jen; Chien, Chi-Sheng

2013-01-01

Bioactive glass (BG) is a potential material for treating dentin hypersensitivity due to its high ability of dissolution. In this study, conventional BG and BG with well-ordered mesopore structures (MBG) were applied for dentinal tubule occlusion. We used X-ray diffractometer (XRD), scanning electronic microscope (SEM), and Fourier transform infrared (FTIR) to investigate the physiochemical properties and the dentinal tubule occlusion ability of BG and MBG groups. The results showed that the major crystallite phase of MBG and BG agents was monocalcium phosphate monohydrate. MBG pastes, mixed with 30 and 40 wt% phosphoric acid hardening solutions, had the ability to create a penetration depth greater than 50 μm. These results showed that BG with mesoporous structures turned the pastes mixed with suitable phosphoric acid solution into a material with great ability for occluding dentinal tubules; it has a short reaction time and good operability, and these agents have better potential for the treatment of dentin hypersensitivity than BG without mesoporous structures.

Role of delta-tubulin and the C-tubule in assembly of Paramecium basal bodies

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Beisson Janine

2001-03-01

Full Text Available Abstract Background A breakthrough in the understanding of centriole assembly was provided by the characterization of the UNI3 gene in Chlamydomonas. Deletion of this gene, found to encode a novel member of the tubulin superfamily, delta-tubulin, results in the loss of the C-tubule, in the nine microtubule triplets which are the hallmark of centrioles and basal bodies. Delta-tubulin homologs have been identified in the genomes of mammals and protozoa, but their phylogenetic relationships are unclear and their function is not yet known. Results Using the method of gene-specific silencing, we have inactivated the Paramecium delta-tubulin gene, which was recently identified. This inactivation leads to loss of the C-tubule in all basal bodies, without any effect on ciliogenesis. This deficiency does not directly affect basal body duplication, but perturbs the cortical cytoskeleton, progressively leading to mislocalization and loss of basal bodies and to altered cell size and shape. Furthermore, additional loss of B- and even A-tubules at one or more triplet sites are observed: around these incomplete cylinders, the remaining doublets are nevertheless positioned according to the native ninefold symmetry. Conclusions The fact that in two distinct phyla, delta-tubulin plays a similar role provides a new basis for interpreting phylogenetic relationships among delta-tubulins. The role of delta-tubulin in C-tubule assembly reveals that tubulins contribute subtle specificities at microtubule nucleation sites. Our observations also demonstrate the existence of a prepattern for the ninefold symmetry of the organelle which is maintained even if less than 9 triplets develop.

Destruction and regeneration of seminiferous tubules after local x-irradiation of testes of the adult rats

International Nuclear Information System (INIS)

Kurnosova, T.R.; Rajtsina, S.S.

1987-01-01

It was established that the local X-irradiation (1000 R) of testes of the adult rats results in a total destruction of seminiferous tubules. The restitution of the organ structure proceeds via formation of new seminiferous tubules in which spermatogenic epithelium later develops. Rete testis and germ cells preserved in its epithelium from embryogenesis are a source of regeneration material. The results obtained favour the suggestion about the dynamic structure of mammalian testis

Effects of two desensitizing dentifrices on dentinal tubule occlusion with citric acid challenge: Confocal laser scanning microscopy study

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Sneha Anil Rajguru

2017-01-01

Full Text Available Background: Dentin hypersensitivity results when patent tubules are exposed to pain-inducing external stimuli. Aim: This study aims to compare the effects of two desensitizing dentifrices containing NovaMin and arginine on dentinal tubule occlusion with and without citric acid challenge in vitro using confocal laser scanning microscopy (CLSM. Materials and Methods: Forty dentin discs were randomly divided into Groups I and II containing twenty specimens each, treated with NovaMin and arginine-containing dentifrices, respectively. Groups I and II were divided into subgroups A and B where IA and IIA underwent CLSM analysis to determine the percentage of tubule occlusion while IB and IIB underwent 0.3% citric acid challenge and CLSM analysis. A novel grading system was devised to categorize tubule occlusion. Results: In Group II, the percentage of occluded tubules was highest for IIA (72.25% ± 10.57% and least for IIB (42.55% ± 8.65% having statistical significance (P < 0.0005. In Group I, the difference between IA (49.9% ± 12.96% and IB (43.15% ± 12.43% was statistically insignificant (P = 0.249. On the comparison between IB and IIB statistically indifferent result was obtained (P = 0.901, whereas the difference between IA and IIA was statistically significant (P < 0.001. The results of grading system were for IA 50% of samples belonged to Grade 2, for IIA 60% - Grade 3, and for IB 70% and for IIB 90% - Grade 2. Conclusion: Dentinal tubule occlusion with arginine-containing dentifrice was significantly higher than NovaMin. However, it could not resist citric acid challenge as effectively as NovaMin. The effects of NovaMin were more sustainable as compared to arginine-containing dentifrice, thus proving to be a better desensitizing agent.

Disruption of Core Planar Cell Polarity Signaling Regulates Renal Tubule Morphogenesis but Is Not Cystogenic.

Science.gov (United States)

Kunimoto, Koshi; Bayly, Roy D; Vladar, Eszter K; Vonderfecht, Tyson; Gallagher, Anna-Rachel; Axelrod, Jeffrey D

2017-10-23

Oriented cell division (OCD) and convergent extension (CE) shape developing renal tubules, and their disruption has been associated with polycystic kidney disease (PKD) genes, the majority of which encode proteins that localize to primary cilia. Core planar cell polarity (PCP) signaling controls OCD and CE in other contexts, leading to the hypothesis that disruption of PCP signaling interferes with CE and/or OCD to produce PKD. Nonetheless, the contribution of PCP to tubulogenesis and cystogenesis is uncertain, and two major questions remain unanswered. Specifically, the inference that mutation of PKD genes interferes with PCP signaling is untested, and the importance of PCP signaling for cystogenic PKD phenotypes has not been examined. We show that, during proliferative stages, PCP signaling polarizes renal tubules to control OCD. However, we find that, contrary to the prevailing model, PKD mutations do not disrupt PCP signaling but instead act independently and in parallel with PCP signaling to affect OCD. Indeed, PCP signaling that is normally downregulated once development is completed is retained in cystic adult kidneys. Disrupting PCP signaling results in inaccurate control of tubule diameter, a tightly regulated parameter with important physiological ramifications. However, we show that disruption of PCP signaling is not cystogenic. Our results suggest that regulating tubule diameter is a key function of PCP signaling but that loss of this control does not induce cysts. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Single Kinin Receptor Signals to Separate and Independent Physiological Pathways in Malpighian Tubules of the Yellow Fever Mosquito

Science.gov (United States)

2010-06-10

mortar and pestle . On the day of the experiment a female mosquito, 4-7 days post-eclosion, was cold anesthetized and decapitated. Malpighian tubules...tubules was analyzed with the electron probe as described previously (7, 62), except that we used the JEOL JXA 8900 EPMA Microprobe (Tokyo, Japan

Minicollagen-15, a novel minicollagen isolated from Hydra, forms tubule structures in nematocysts.

Science.gov (United States)

Adamczyk, Patrizia; Meier, Sebastian; Gross, Thomas; Hobmayer, Bert; Grzesiek, Stephan; Bächinger, Hans Peter; Holstein, Thomas W; Ozbek, Suat

2008-02-29

Minicollagens constitute a family of unusually short collagen molecules isolated from cnidarians. They are restricted to the nematocyst, a cylindrical explosive organelle serving in defense and capture of prey. The nematocyst capsule contains a long tubule inside of its matrix, which is expelled and everted during an ultrafast discharge process. Here, we report the cloning and characterization of a novel minicollagen in Hydra, designated minicollagen-15 (NCol-15). NCol-15, like NCol-3 and NCol-4, shows deviations from the canonical cysteine pattern in its terminal cysteine-rich domains (CRDs). Minicollagens share common domain architectures with a central collagen sequence flanked by polyproline stretches and short N- and C-terminal CRDs. The CRDs are involved in the formation of a highly resistant cysteine network, which constitutes the basic structure of the nematocyst capsule. Unlike NCol-1, which is part of the capsule wall, NCol-15 is localized to tubules, arguing for a functional differentiation of minicollagens within the nematocyst architecture. NMR analysis of the altered C-terminal CRD of NCol-15 showed a novel disulfide-linked structure within the cysteine-containing region exhibiting similar folding kinetics and stability as the canonical CRDs. Our data provide evidence for evolutionary diversification among minicollagens, which probably facilitated alterations in the morphology of the nematocyst wall and tubule.

Scattering of neutrons by catalase: a study of molecules, subunits, and tubules

International Nuclear Information System (INIS)

Randall, J.; Starling, D.; Baldwin, J.P.; Ibel, K.

1976-01-01

The paper deals with small-angle scattering of neutrons by catalase tetramers, dimers, and monomers and with neutron diffraction by helical assemblies of tetramers in the form of tubules. A preliminary study of catalase is described

Hydropneumatic suspension systems

Energy Technology Data Exchange (ETDEWEB)

Bauer, Wolfgang

2011-07-01

Hydropneumatic suspensions systems combine the excellent properties of gas springs with the favourable damping properties of hydraulic fluids. The advantages of these systems are particularly appropriate for automotive applications, such as passenger cars, trucks and agricultural equipment. In this book, Dr. Bauer provides an extensive overview of hydropneumatic suspension systems. Starting with a comparison of different types of suspension systems, the author subsequently describes the theoretical background associated with spring and damping characteristics of hydropneumatic systems and furthermore explains the design of the most important system components. Additionally he gives an overview of level control systems and various special functions. Finally the technology is illustrated by design examples and the outlook for future hydropneumatic suspensions is discussed. (orig.)

Visualizing the origins of selfish de novo mutations in individual seminiferous tubules of human testes.

Science.gov (United States)

Maher, Geoffrey J; McGowan, Simon J; Giannoulatou, Eleni; Verrill, Clare; Goriely, Anne; Wilkie, Andrew O M

2016-03-01

De novo point mutations arise predominantly in the male germline and increase in frequency with age, but it has not previously been possible to locate specific, identifiable mutations directly within the seminiferous tubules of human testes. Using microdissection of tubules exhibiting altered expression of the spermatogonial markers MAGEA4, FGFR3, and phospho-AKT, whole genome amplification, and DNA sequencing, we establish an in situ strategy for discovery and analysis of pathogenic de novo mutations. In 14 testes from men aged 39-90 y, we identified 11 distinct gain-of-function mutations in five genes (fibroblast growth factor receptors FGFR2 and FGFR3, tyrosine phosphatase PTPN11, and RAS oncogene homologs HRAS and KRAS) from 16 of 22 tubules analyzed; all mutations have known associations with severe diseases, ranging from congenital or perinatal lethal disorders to somatically acquired cancers. These results support proposed selfish selection of spermatogonial mutations affecting growth factor receptor-RAS signaling, highlight its prevalence in older men, and enable direct visualization of the microscopic anatomy of elongated mutant clones.

Particle interactions in concentrated suspensions

International Nuclear Information System (INIS)

Mondy, L.A.; Graham, A.L.; Abbott, J.R.; Brenner, H.

1993-01-01

An overview is presented of research that focuses on slow flows of suspensions in which colloidal and inertial effects are negligibly small. The authors describe nuclear magnetic resonance imaging experiments to quantitatively measure particle migration occurring in concentrated suspensions undergoing a flow with a nonuniform shear rate. These experiments address the issue of how the flow field affects the microstructure of suspensions. In order to understand the local viscosity in a suspension with such a flow-induced, spatially varying concentration, one must know how the viscosity of a homogeneous suspension depends on such variables as solids concentration and particle orientation. The authors suggest the technique of falling ball viscometry, using small balls, as a method to determine the effective viscosity of a suspension without affecting the original microstructure significantly. They also describe data from experiments in which the detailed fluctuations of a falling ball's velocity indicate the noncontinuum nature of the suspension and may lead to more insights into the effects of suspension microstructure on macroscopic properties. Finally, they briefly describe other experiments that can be performed in quiescent suspensions (in contrast to the use of conventional shear rotational viscometers) in order to learn more about boundary effects in concentrated suspensions

Could grape seed extract modulate nephritic damage induced by ...

African Journals Online (AJOL)

RBCs). Preadministration of GSO to Metho-induced rats revealed apparent normal renal parenchyma. The proximal convoluted tubules and collecting tubules appeared near to normal with their narrow lumen. Preadministration with GSO ...

Self-powered suspension criterion and energy regeneration implementation scheme of motor-driven active suspension

Science.gov (United States)

Yan, Shuai; Sun, Weichao

2017-09-01

Active suspension systems have advantages on mitigating the effects of vehicle vibration caused by road roughness, which are one of the most important component parts in influencing the performances of vehicles. However, high amount of energy consumption restricts the application of active suspension systems. From the point of energy saving, this paper presents a self-powered criterion of the active suspension system to judge whether a motor-driven suspension can be self-powered or not, and then a motor parameter condition is developed as a reference to design a self-powered suspension. An energy regeneration implementation scheme is subsequently proposed to make the active suspension which has the potential to be self-powered achieve energy-saving target in the real application. In this implementation scheme, operating electric circuits are designed based on different working status of the actuator and power source and it is realizable to accumulate energy from road vibration and supply energy to the actuator by switching corresponding electric circuits. To apply the self-powered suspension criterion and energy regeneration implementation scheme, an active suspension system is designed with a constrained H∞ controller and calculation results indicate that it has the capability to be self-powered. Simulation results show that the performances of the self-powered active suspension are nearly the same as those of the active suspension with an external energy source and can achieve energy regeneration at the same time.

Biomechanical Comparison of 3 Inferiorly Directed Versus 3 Superiorly Directed Locking Screws on Stability in a 3-Part Proximal Humerus Fracture Model.

Science.gov (United States)

Donohue, David M; Santoni, Brandon G; Stoops, T Kyle; Tanner, Gregory; Diaz, Miguel A; Mighell, Mark

2018-06-01

To quantify the stability of 3 points of inferiorly directed versus 3 points of superiorly directed locking screw fixation compared with the full contingent of 6 points of locked screw fixation in the treatment of a 3-part proximal humerus fracture. A standardized 3-part fracture was created in 10 matched pairs (experimental groups) and 10 nonmatched humeri (control group). Osteosynthesis was performed using 3 locking screws in the superior hemisphere of the humeral head (suspension), 3 locking screws in the inferior hemisphere (buttress), or the full complement of 6 locking screws (control). Specimens were tested in varus cantilever bending (7.5 Nm) to 10,000 cycles or failure. Construct survival (%) and the cycles to failure were compared. Seven of 10 controls survived the 10,000-cycle runout (70%: 8193 average cycles to failure). No experimental constructs survived the 10,000-cycle runout. Suspension and buttress screw groups failed an average of 331 and 516 cycles, respectively (P = 1.00). The average number of cycles to failure and the number of humeri surviving the 10,000-cycle runout were greater in the control group than in the experimental groups (P ≤ 0.006). Data support the use of a full contingent of 6 points of locking screw fixation over 3 superior or 3 inferior points of fixation in the treatment of a 3-part proximal humerus fracture with a locking construct. No biomechanical advantage to the 3 buttress or 3 suspension screws used in isolation was observed.

Vitality of Enterococcus faecalis inside dentinal tubules after five root canal disinfection methods.

Science.gov (United States)

Vatkar, Niranjan Ashok; Hegde, Vivek; Sathe, Sucheta

2016-01-01

To compare the vitality of Enterococcus faecalis within dentinal tubules after subjected to five root canal disinfection methods. Dentin blocks (n = 60) were colonized with E. faecalis. After 4 weeks of incubation, the dentin blocks were divided into one control and five test groups (n = 10 each). The root canals of test groups were subjected to one of the disinfection methods, namely, normal saline (NS), sodium hypochlorite (NaOCl), chlorhexidine digluconate (CHX), neodymium-doped yttrium aluminum garnet (Nd: YAG) laser, and diode laser. The effect of disinfection methods was assessed by LIVE/DEAD BacLight stain under the confocal laser scanning microscopy to determine the "zone of dead bacteria" (ZDB). Mean values were calculated for ZDB and the difference between groups was established. Penetration of E. faecalis was seen to a depth of >1000 μm. Viable bacteria were detected with NS irrigation. NaOCl and CHX showed partial ZDB. When the root canals were disinfected with Nd: YAG and diode lasers, no viable bacteria were found. E. faecalis has the ability to colonize inside dentinal tubules to a depth of >1000 μm. In contrast to conventional irrigants, both Nd: YAG and diode lasers were effective in eliminating the vitality of E. faecalis. NS, NaOCl, and CHX showed viable bacteria remaining in dentinal tubules.

Ribavirin exposure induces histopathological changes in the seminiferous tubules of testes in albino rats

International Nuclear Information System (INIS)

Batool, A.

2013-01-01

Study objectives: The objectives of the study are to describe and compare histopathological changes in the seminiferous tubules of testes of rat, with different doses of Ribavirin at different time intervals. Introduction: The chemical disturbances may affect a vast number of potential sites in male reproductive system as well as its complex hormonal regulation. Testicular toxicity may reduce the fertility of the male. The current study was conducted to evaluate the effects of Ribavirin on the histological structure of seminiferous tubules in the testes of albino rats. Materials and Methods: Seventy two sexually mature adult male albino rats weighing 180-200gms were divided into four groups: A, B, C and D; each group having 18 rats. Ribavirin was administered intraperitoneally in different doses to these groups that were 20mg, 100mg and 200mg/kg body weight, while group A was control. Each group was further divided into three subgroups according to three time points which were selected for sacrifice that were 20th, 40th and 60th day from the last exposure to drug. Six randomly selected rats from each group were sacrificed on every sacrifice time. Results and Conclusion: The seminiferous tubules with degenerative changes like appearance of vacuole and necrotic material were observed in comparison to control groups, on 20th day of sacrifice in all groups. In rats sacrificed on day 40th and 60th, the sign of recovery in the form of regeneration of seminiferous epithelium was observed that was more marked in low dose groups than high dose groups which showed late recovery. We conclude that ribavirin being used as antiviral drug induces reversible degenerative changes in the seminiferous tubules of testes of albino rats. (author)

Methomyl is a water-soluble crystalline solid that gives off a ...

African Journals Online (AJOL)

NBU

RBCs). Pre- administration of GSO to Metho-induced rats revealed apparent normal renal parenchyma. The proximal convoluted tubules and collecting tubules appeared near to normal with their narrow lumen. Pre- administration with GSO ...

Regulation of MRP2-mediated transport in shark rectal salt gland tubules.

NARCIS (Netherlands)

Miller, D.S.; Masereeuw, R.; Karnaky Jr, K.J.

2002-01-01

We examined endothelin-1 (ET-1) regulation of the xenobiotic efflux pump, multidrug resistance-associated protein isoform 2 (MRP2), in intact dogfish shark rectal salt gland tubules using a fluorescent substrate sulforhodamine 101 and confocal microscopy. Subnanomolar to nanomolar concentrations of

Performance Testing of Suspension Plasma Sprayed Thermal Barrier Coatings Produced with Varied Suspension Parameters

Directory of Open Access Journals (Sweden)

Nicholas Curry

2015-07-01

Full Text Available Suspension plasma spraying has become an emerging technology for the production of thermal barrier coatings for the gas turbine industry. Presently, though commercial systems for coating production are available, coatings remain in the development stage. Suitable suspension parameters for coating production remain an outstanding question and the influence of suspension properties on the final coatings is not well known. For this study, a number of suspensions were produced with varied solid loadings, powder size distributions and solvents. Suspensions were sprayed onto superalloy substrates coated with high velocity air fuel (HVAF -sprayed bond coats. Plasma spray parameters were selected to generate columnar structures based on previous experiments and were maintained at constant to discover the influence of the suspension behavior on coating microstructures. Testing of the produced thermal barrier coating (TBC systems has included thermal cyclic fatigue testing and thermal conductivity analysis. Pore size distribution has been characterized by mercury infiltration porosimetry. Results show a strong influence of suspension viscosity and surface tension on the microstructure of the produced coatings.

Investigating high-concentration monoclonal antibody powder suspension in nonaqueous suspension vehicles for subcutaneous injection.

Science.gov (United States)

Bowen, Mayumi; Armstrong, Nick; Maa, Yuh-Fun

2012-12-01

Developing high-concentration monoclonal antibody (mAb) liquid formulations for subcutaneous (s.c.) administration is challenging because increased viscosity makes injection difficult. To overcome this obstacle, we investigated a nonaqueous powder suspension approach. Three IgG1 mAbs were spray dried and suspended at different concentrations in Miglyol® 840, benzyl benzoate, or ethyl lactate. Suspensions were characterized for viscosity, particle size, and syringeability; physical stability was visually inspected. Suspensions generally outperformed liquid solutions for injectability despite higher viscosity at the same mAb concentrations. Powder formulations and properties had little effect on viscosity or injectability. Ethyl lactate suspensions had lowest viscosity (Miglyol® 840 improved overall performance in high mAb concentration suspensions. This study demonstrated the viability of high mAb concentration (>300 mg/mL) in suspension formulations for s.c. administration. Copyright © 2012 Wiley Periodicals, Inc.

Four-Wheel Vehicle Suspension System

Science.gov (United States)

Bickler, Donald B.

1990-01-01

Four-wheel suspension system uses simple system of levers with no compliant components to provide three-point suspension of chassis of vehicle while maintaining four-point contact with uneven terrain. Provides stability against tipping of four-point rectangular base, without rocking contact to which rigid four-wheel frame susceptible. Similar to six-wheel suspension system described in "Articulated Suspension Without Springs" (NPO-17354).

Suspension trauma; Le traumatisme de suspension

Energy Technology Data Exchange (ETDEWEB)

Trudel, S. [Le Centre de sante et de services sociaux du rocher Perce, Chandler, PQ (Canada)

2010-07-01

This presentation discussed the precautions that should be taken to avoid falls from wind turbines or transmission towers. Suspension trauma was explained by a medical doctor in terms of physiology and the body's normal circulation and the elements that disturb normal physiology when in suspension. The trauma occurs following a fall, which carries the risk of 1or more disorders, such as massive hemorrhage, high cardiac pulse, and constriction of blood vessels. Nausea, vertigo, cardiac arrhythmia and sweating occur 15 to 20 minutes following the fall. The presentation emphasized the importance of having qualified personnel at the site and wearing proper harnesses and equipment that supports the neck. figs.

Selective Insulin Resistance in the Kidney

Science.gov (United States)

Horita, Shoko; Nakamura, Motonobu; Suzuki, Masashi; Satoh, Nobuhiko; Suzuki, Atsushi; Seki, George

2016-01-01

Insulin resistance has been characterized as attenuation of insulin sensitivity at target organs and tissues, such as muscle and fat tissues and the liver. The insulin signaling cascade is divided into major pathways such as the PI3K/Akt pathway and the MAPK/MEK pathway. In insulin resistance, however, these pathways are not equally impaired. For example, in the liver, inhibition of gluconeogenesis by the insulin receptor substrate (IRS) 2 pathway is impaired, while lipogenesis by the IRS1 pathway is preserved, thus causing hyperglycemia and hyperlipidemia. It has been recently suggested that selective impairment of insulin signaling cascades in insulin resistance also occurs in the kidney. In the renal proximal tubule, insulin signaling via IRS1 is inhibited, while insulin signaling via IRS2 is preserved. Insulin signaling via IRS2 continues to stimulate sodium reabsorption in the proximal tubule and causes sodium retention, edema, and hypertension. IRS1 signaling deficiency in the proximal tubule may impair IRS1-mediated inhibition of gluconeogenesis, which could induce hyperglycemia by preserving glucose production. In the glomerulus, the impairment of IRS1 signaling deteriorates the structure and function of podocyte and endothelial cells, possibly causing diabetic nephropathy. This paper mainly describes selective insulin resistance in the kidney, focusing on the proximal tubule. PMID:27247938

The role of the kidney in lipid metabolism

DEFF Research Database (Denmark)

Moestrup, Søren K; Nielsen, Lars Bo

2005-01-01

PURPOSE OF REVIEW: Cellular uptake of plasma lipids is to a large extent mediated by specific membrane-associated proteins that recognize lipid-protein complexes. In the kidney, the apical surface of proximal tubules has a high capacity for receptor-mediated uptake of filtered lipid-binding plasma...... proteins. We describe the renal receptor system and its role in lipid metabolism in health and disease, and discuss the general effect of the diseased kidney on lipid metabolism. RECENT FINDINGS: Megalin and cubilin are receptors in the proximal tubules. An accumulating number of lipid......-binding and regulating proteins (e.g. albumin, apolipoprotein A-I and leptin) have been identified as ligands, suggesting that their receptors may directly take up lipids in the proximal tubules and indirectly affect plasma and tissue lipid metabolism. Recently, the amnionless protein was shown to be essential...

Immortalization of canine adipose-derived mesenchymal stem cells and their seminiferous tubule transplantation.

Science.gov (United States)

Fang, Jia; Wei, Yudong; Teng, Xin; Zhao, Shanting; Hua, Jinlian

2018-04-01

Adipose-derived mesenchymal stem cells (ADSCs) are proven to provide good effects in numerous tissue engineering application and other cell-based therapies. However, the difficulty in the proliferation of ADSCs, known as the "Hayflick limit" in vitro, limits their clinical application. Here, we immortalized canine ADSCs (cADSCs) with SV40 gene and transplanted them into busulfan-induced seminiferous tubules of infertile mice. The proliferation of these immortalized cells was improved significantly. Then, cellular differentiation assays showed that the immortalized cADSCs could differentiate into three-germ-layer cells, osteogenesis, chondrogenesis, adipogenesis phenotypes, and primordial germ cell-like cells (PGCLCs). In addition, the immortalized cADSCs can proliferate in the busulfan-induced seminiferous tubules of infertile mice. These findings confirmed that the immortalized cADSCs maintain the criteria of cADSCs. © 2017 Wiley Periodicals, Inc.

Structural analysis of compression helical spring used in suspension system

Science.gov (United States)

Jain, Akshat; Misra, Sheelam; Jindal, Arun; Lakhian, Prateek

2017-07-01

The main aim of this work has to develop a helical spring for shock absorber used in suspension system which is designed to reduce shock impulse and liberate kinetic energy. In a vehicle, it increases comfort by decreasing amplitude of disturbances and it improves ride quality by absorbing and dissipating energy. When a vehicle is in motion on a road and strikes a bump, spring comes into action quickly. After compression, spring will attempt to come to its equilibrium state which is on level road. Helical springs can be made lighter with more strength by reducing number of coils and increasing the area. In this research work, a helical spring is modeled and analyzed to substitute the existing steel spring which is used in suspension. By using different materials, stress and deflection of helical spring can be varied. Comparability between existing spring and newly replaced spring is used to verify the results. For finding detailed stress distribution, finite element analysis is used to find stresses and deflection in both the helical springs. Finite element analysis is a method which is used to find proximate solutions of a physical problem defined in a finite domain. In this research work, modeling of spring is accomplished using Solid Works and analysis on Ansys.

Suspension, a Wake-Up Call: Rural Educators' Attitudes toward Suspension.

Science.gov (United States)

Henderson, Joan; Friedland, Billie

Data from the West Virginia Department of Education reveals that from September 1991 to January 1992, school districts reported 18,915 out-of-school suspensions involving 12,997 students. In 1995, the West Virginia State Legislature enacted the Safe Schools Act, which specifically mandates suspension for no less than 12 consecutive months for…

Shape transitions in anisotropic multicomponent lipid tubules

Directory of Open Access Journals (Sweden)

Tim eAtherton

2016-05-01

Full Text Available Abstract Ternary mixtures of saturated and unsaturated lipids together with cholesterol can be induced to phase separate by photo-peroxidation into lipid-ordered Lo and lipid-disordered Ld domains. Because these have different mechanical properties, the phase separation is accompanied by dramatic changes in morphology. This work considers a tubule composed of Ld phase with Lo phase inclusions that possess greater rigidity; this system has been shown experimentally by Yuan and coworkers to spontaneously adopt either banded or disc configurations following phase separation. The static behaviour of inter-domain interactions is analyzed in each of these geometries by solving the linearized shape equations. These calculations suggest a possible mechanism by which the two structures form.

Design of a suspension system and determining suspension parameters of a medium downforce small Formula type car

Directory of Open Access Journals (Sweden)

Biswal Sadjyot

2017-01-01

Full Text Available The focus of the paper is on designing a suspension system for a medium downforce small Formula type race car. The paper not only focusses on step by step design for a double wishbone type suspension but will also show the use and role of kinematics software in determining the optimized suspension of the car. The paper will also focus on the use of tire data in determining suspension parameters and the design of the double wishbone suspension. Various parameters, their design importance and the process to optimize them according to suspension design goals will be covered. The easiest and best ways to change the suspension parameters to get the best results will also be covered.

Microinjection studies of phosphate permeability in rats during mild saline diuresis: influence of acute thyroparathyroidectomy and parathormone administration

International Nuclear Information System (INIS)

Poujeol, P.; Rouffignac, C. de.

1975-01-01

The tubular permeability to phosphate of the different segments of the rat nephron and the influence of parathyroid hormone on such a permeability were investigated. Tracer microinjections of 32 P and 3 H inulin were performed in control, acutely thyroparathyroidectomized (TPTX) and TPTX + PTH animals undergoing saline diuresis. In order to estimate the 32 P reabsorption capacity of the proximal convoluted tubule (PCT), the loop of Henle and the terminal part of the nephron, microinjections were performed in early proximal, late proximal and early distal tubules respectively. The results reported confirm that the renal phosphate reabsorption is under PTH control [fr

Fabrication and characterization of dendrimer-functionalized nano-hydroxyapatite and its application in dentin tubule occlusion.

Science.gov (United States)

Lin, Xuandong; Xie, Fangfang; Ma, Xueling; Hao, Yuhong; Qin, Hejia; Long, Jindong

2017-06-01

The occlusion of dentinal tubules is an effective method to alleviate the symptoms of dentin hypersensitivity. In this paper, we successfully modified nano-hydroxyapatite (n-HAP) with carboxyl-terminated polyamidoamine dendrimers by an aqueous-based chemical method and verified by fourier transform infrared spectroscopy (FTIR) and transmission electron microscope (TEM). Then the demineralization dentin discs were randomly divided into 4 groups, corresponding to subsequent brushing experiments: deionized water and kept in artificial saliva (AS), dendrimer-functionalized n-HAP and stored in AS, n-HAP and saved in AS, dendrimer-functionalized n-HAP and stored in deionized water. After 7 days of simulated brushing, dentin discs followed the in vitro characterization using scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy and microhardness test. These data suggested that dendrimer-functionalized n-HAP could crosslink with collagen fibers and resulted in effective dentinal tubule occlusion. Moreover, the new material can induce the HAP formation with the help of superficial carboxyl and fill the spaces in dentinal tubules furtherly. The microhardness of dendrimer-functionalized n-HAP-treated specimens was significantly higher than others. In summary, dendrimer-functionalized n-HAP can be a new therapeutic material for the treatment of dentin hypersensitivity.

Transport of Streptococcus pneumoniae capsular polysaccharide in MHC Class II tubules.

Directory of Open Access Journals (Sweden)

Tom Li Stephen

2007-03-01

Full Text Available Bacterial capsular polysaccharides are virulence factors and are considered T cell-independent antigens. However, the capsular polysaccharide Sp1 from Streptococcus pneumoniae serotype 1 has been shown to activate CD4(+ T cells in a major histocompatibility complex (MHC class II-dependent manner. The mechanism of carbohydrate presentation to CD4(+ T cells is unknown. We show in live murine dendritic cells (DCs that Sp1 translocates from lysosomal compartments to the plasma membrane in MHCII-positive tubules. Sp1 cell surface presentation results in reduction of self-peptide presentation without alteration of the MHCII self peptide repertoire. In DM-deficient mice, retrograde transport of Sp1/MHCII complexes resulting in T cell-dependent immune responses to the polysaccharide in vitro and in vivo is significantly reduced. The results demonstrate the capacity of a bacterial capsular polysaccharide antigen to use DC tubules as a vehicle for its transport as an MHCII/saccharide complex to the cell surface for the induction of T cell activation. Furthermore, retrograde transport requires the functional role of DM in self peptide-carbohydrate exchange. These observations open new opportunities for the design of vaccines against microbial encapsulated pathogens.

[Anatomy, physiology and clinical relevance of the connecting tubule].

Science.gov (United States)

Miranda, N; Simeoni, M A; Ciriana, E; Panico, C; Cappello, E; Capasso, G B

2009-01-01

The cortical distal nephron is the site of fine regulation of salt and water excretion by peptide and mineralocorticoid hormones and the site for specific actions of diuretics. Some data suggest that sodium reabsorption and potassium secretion in the distal convoluted tubule and the connecting tubule (CNT) are sufficient to maintain the sodium and potassium balance, with little or no contribution of the collecting duct. The homeostatic role of the sodium and potassium transport systems in the collecting duct can be questioned, especially in conditions where dietary sodium intake is high and potassium intake is low compared with the physiological needs of the organism. The functional expression of epithelial sodium channels (ENaC) in the CNT is sufficient for furosemide-stimulated urinary acidification and identifies the CNT as a major segment in electrogenic urinary acidification. In the outer renal cortex, the CNT returns to the glomerular hilus and contacts the renal afferent arterioles (Af-Art). This morphology is compatible with a cross-talk between the CNT and Af-Art. This novel regulatory mechanism of the renal microcirculation may participate in the vasodilatation observed during high salt intake, perhaps by antagonizing tubuloglomerular feedback. In conclusion, the cortical distal nephron appears to be a complex site for several physiological mechanisms; it is mainly involved in salt and fluid homeostasis and in acid-base balance maintenance. Furthermore, the CNT segment appears to promote a CNT-Af-Art feedback loop.

Angled telescopic surgery, an approach for laryngeal diagnosis and surgery without suspension

Directory of Open Access Journals (Sweden)

Plínio Ferreira Morgado

1999-09-01

Full Text Available CONTEXT: Many methods have been used successfully for the diagnosis and treatment of laryngeal diseases. Microscopic and, recently, telescopic surgery represent the state of the art in endoscopic laryngeal surgery but drawbacks are possible during their application. To keep the suspension apparatus adequately positioned, excessive force is sometimes placed on the upper teeth and tongue with the laryngoscope tube causing damage. Complications in relation to the pharynx, larynx and cardiovascular system have also been reported. OBJECTIVE: In order to reduce complications resulting from the manipulation or stimulation of the upper aerodigestive tract and from torque forces on the upper teeth. We present a method of larynx surgery in which laryngeal suspension is not required. DESIGN: Technical report. TECHNIQUES: We have devised a fiber-optic telescope with its 40mm distal portion deviated 60 degrees from the direction of the proximal portion. This angle was taken by measuring patients immediately before standard microlaryngeal surgery was performed. The surgical instruments have the same angle as the telescope, in order to work on the larynx. This technique provides an image that is not limited by the distal aperture of the laryngoscope and has an advantage in that magnification and illumination may be provided by changing the distance of the lesion from the tip of the instrument. we have operated on four patients with laryngeal diseases and have had no complications as a result of this approach. We feel that this technique gives us the freedom to view the lesions better and helps to minimize the drawbacks caused by laryngeal suspension.

In vivo clonal analysis reveals lineage-restricted progenitor characteristics in mammalian kidney development, maintenance, and regeneration

NARCIS (Netherlands)

Rinkevich, Y.; Montoro, D.T.; Contreras-Trujillo, H.; Harari-Steinberg, O.; Newman, A.M.; Tsai, J.M.; Lim, X.; van Amerongen, R.; Bowman, A.; Januszyk, M.; Pleniceanu, O.; Nusse, R.; Longaker, M.T.; Weissman, I.L.; Dekel, B.

2014-01-01

The mechanism and magnitude by which the mammalian kidney generates and maintains its proximal tubules, distal tubules, and collecting ducts remain controversial. Here, we use long-term in vivo genetic lineage tracing and clonal analysis of individual cells from kidneys undergoing development,

Comparative proteomic analysis of kidney distal convoluted tubule and cortical collecting duct cells following long-term hormonal stimulation

DEFF Research Database (Denmark)

Wu, Qi; Moller, Hanne; Rosenbaek, Lena Lindtoft

2017-01-01

The distal convoluted tubule (DCT) and the cortical collecting ducts (CCD) are portions of renal tubule that are partly responsible for maintaining the systemic concentrations of potassium, sodium, calcium and magnesium. Despite being structurally similar, DCT and CCD cells have different transpo...... FDR threshold in one cell type plus the unique proteins in this cell type. These 1025 mpkDCT specific proteins and 1211 mpkCCD specific proteins under the three conditions were subjected to further bioinformatics analyses including Panther and DAVID gene ontology analyses, E3 ligase...

Comparative Evaluation of Efficacy of Iontophoresis with 0.33% Sodium Fluoride Gel and Diode Laser Alone on Occlusion of Dentinal Tubules.

Science.gov (United States)

Patil, Anup Raghunath; Varma, Siddhartha; Suragimath, Girish; Abbayya, Keshava; Zope, Sameer Anil; Kale, Vishwajeet

2017-08-01

Dentinal Hypersensitivity (DH) is one of the most commonly encountered clinical problems. Literature reveals no specific therapy to satisfactorily eliminate dentinal hypersensitivity. The aim of this study was to assess and compare the efficacy of iontophoresis with 0.33% Sodium Fluoride (NaF) gel and diode laser alone in dentinal tubule occlusion. This in vitro study included 20 teeth with intact root surfaces unaltered by extraction procedure for specimen preparation. Each tooth was cleaned, air dried and cut into three sections. Total 60 sections were prepared (30 longitudinal and 30 transverse sections), which were acid etched. In control group, no treatment was carried. In iontophoresis treatment group, samples were inserted into a foam tray containing 0.33 % NaF Gel and subjected to 1.5 mA output current for three minutes. In laser treatment group, specimens were lased with 980 nm diode laser at 0.5 W/PW (62.2J /cm 2 ) in a noncontact mode for 30 seconds. Specimens were evaluated under Scanning Electron Microscope (SEM) at 10KV to 20KV under x 2000, x5000 magnification for surface characteristics and patency of dentinal tubules. Total number of tubules visible, open, completely and partially occluded were recorded in each microphotograph and compared. On comparison, laser group showed the least number of open tubules i.e., 130 (31.1%) followed by iontophoresis group, 155 (51.32%) and control group 417 (100%). Diode laser application provided better results as compared to iontophoresis on occlusion of dentinal tubules. Hence, it can be used to treat the patients with DH.

influence of crude extract of root of telfairia occidentalis (fluted ...

African Journals Online (AJOL)

DJFLEX

Histologically, the architecture of the kidneys in the experimental animals treated with pumpkin root extract orally and intraperitoneally showed enlarged tubules, distorted glomeruli and Bowman's capsule, shrinking of proximal and distal convoluted tubules compared with the control. These results suggest that the root of ...

Controlling active cabin suspensions in commercial vehicles

NARCIS (Netherlands)

Evers, W.J.E.; Besselink, I.J.M.; Teerhuis, A.P.; Knaap, van der A.C.M.; Nijmeijer, H.

2009-01-01

The field of automotive suspensions is changing. Semi-active and active suspensions are starting to become viable options for vehicle designers. Suspension design for commercial vehicles is especially interesting given its potential. An active cabin suspension for a heavy-duty truck is considered,

Methods to Evaluate the Effect of Ethanol on the Folate Analogue: Fluorescein Methotrexate Uptake in Human Proximal Tubular Cells

Directory of Open Access Journals (Sweden)

Sivakumar JT Gowder

2009-01-01

Full Text Available Ethanol-induced folate deficiency is due to effects of ethanol on folate metabolism and absorption. We have already shown by using different methods that ethanol interferes with reabsorption of folate from the proximal tubule. In this study, we have used the folate analogue, the fluorescein methotrexate (FL-MTX, in order to evaluate effects of ethanol on FL-MTX uptake by the human proximal tubular (HPT cells by using a confocal microscope and fluoroskan microplate reader. Since endothelins (ETs play a major role in a number of diseases and also in the damage induced by a variety of chemicals, we have used endothelin-B (ET-B and protein kinase-C (PKC inhibitors to evaluate the role of endothelin in ethanol-mediated FL-MTX uptake by using fluoroskan microplate reader. Confocal microscope and fluoroskan studies reveal that cellular absorption of FL-MTX is concentration-dependent. Moreover, ethanol concentration has an impact on FL-MTX uptake. Fluoroskan studies reveal that the ethanol-induced decrease in FL-MTX uptake is reversed by adding the ET-B receptor antagonist (RES-701-1 or PKC-selective inhibitor (BIM. Thus, we can conclude that ethanol may act via ET and ET in turn may act via ET-B receptor and the PKC signaling pathway to impair FL-MTX transport.

Suspensions with reduced violin string modes

International Nuclear Information System (INIS)

Lee, B H; Ju, L; Blair, D G

2006-01-01

We discuss the possibility of significantly reducing the number and Q-factor of violin string modes in the mirror suspension. Simulations of a bar-flexure suspension and an orthogonal ribbon have shown a reduction in the number of violin string modes when compared to a normal ribbon suspension. By calculating the expected suspension thermal noise, we find that the orthogonal ribbon provides a promising suspension alternative. A lower number of violin modes oscillating in the direction of the laser and a reduction in violin mode peak values of at least 23dB can be achieved with a slight increase in thermal noise above 40Hz

Suspensions with reduced violin string modes

Energy Technology Data Exchange (ETDEWEB)

Lee, B H; Ju, L; Blair, D G [School of Physics, University of Western Australia, Crawley 6009, WA (Australia)

2006-03-02

We discuss the possibility of significantly reducing the number and Q-factor of violin string modes in the mirror suspension. Simulations of a bar-flexure suspension and an orthogonal ribbon have shown a reduction in the number of violin string modes when compared to a normal ribbon suspension. By calculating the expected suspension thermal noise, we find that the orthogonal ribbon provides a promising suspension alternative. A lower number of violin modes oscillating in the direction of the laser and a reduction in violin mode peak values of at least 23dB can be achieved with a slight increase in thermal noise above 40Hz.

Permeation of macromolecules into the renal glomerular basement membrane and capture by the tubules

Science.gov (United States)

Lawrence, Marlon G.; Altenburg, Michael K.; Sanford, Ryan; Willett, Julian D.; Bleasdale, Benjamin; Ballou, Byron; Wilder, Jennifer; Li, Feng; Miner, Jeffrey H.; Berg, Ulla B.; Smithies, Oliver

2017-01-01

How the kidney prevents urinary excretion of plasma proteins continues to be debated. Here, using unfixed whole-mount mouse kidneys, we show that fluorescent-tagged proteins and neutral dextrans permeate into the glomerular basement membrane (GBM), in general agreement with Ogston's 1958 equation describing how permeation into gels is related to molecular size. Electron-microscopic analyses of kidneys fixed seconds to hours after injecting gold-tagged albumin, negatively charged gold nanoparticles, and stable oligoclusters of gold nanoparticles show that permeation into the lamina densa of the GBM is size-sensitive. Nanoparticles comparable in size with IgG dimers do not permeate into it. IgG monomer-sized particles permeate to some extent. Albumin-sized particles permeate extensively into the lamina densa. Particles traversing the lamina densa tend to accumulate upstream of the podocyte glycocalyx that spans the slit, but none are observed upstream of the slit diaphragm. At low concentrations, ovalbumin-sized nanoparticles reach the primary filtrate, are captured by proximal tubule cells, and are endocytosed. At higher concentrations, tubular capture is saturated, and they reach the urine. In mouse models of Pierson’s or Alport’s proteinuric syndromes resulting from defects in GBM structural proteins (laminin β2 or collagen α3 IV), the GBM is irregularly swollen, the lamina densa is absent, and permeation is increased. Our observations indicate that size-dependent permeation into the lamina densa of the GBM and the podocyte glycocalyx, together with saturable tubular capture, determines which macromolecules reach the urine without the need to invoke direct size selection by the slit diaphragm. PMID:28246329

Proximal Humerus

NARCIS (Netherlands)

Diercks, Ron L.; Bain, Gregory; Itoi, Eiji; Di Giacomo, Giovanni; Sugaya, Hiroyuki

2015-01-01

This chapter describes the bony structures of the proximal humerus. The proximal humerus is often regarded as consisting of four parts, which assists in understanding function and, more specially, describes the essential parts in reconstruction after fracture or in joint replacement. These are the

Effect of suspension characteristics on in-flight particle properties and coating microstructures achieved by suspension plasma spray

Science.gov (United States)

Aubignat, E.; Planche, M. P.; Allimant, A.; Billières, D.; Girardot, L.; Bailly, Y.; Montavon, G.

2014-11-01

This paper focuses on the influence of suspension properties on the manufacturing of coatings by suspension plasma spraying (SPS). For this purpose, alumina suspensions were formulated with two different liquid phases: water and ethanol. Suspensions were atomized with a twin-fluid nozzle and injected in an atmospheric plasma jet. Suspension injection was optimized thanks to shadowgraphy observations and drop size distribution measurements performed by laser diffraction. In-flight particle velocities were evaluated by particle image velocimetry. In addition, splats were collected on glass substrates, with the same conditions as the ones used during the spray process. Scanning electron microscopy (SEM) and profilometry analyses were then performed to observe the splat morphology and thus to get information on plasma / suspension interactions, such as particle agglomeration. Finally, coatings were manufactured, characterized by SEM and compared to each other.

A Molecular Mechanism to Regulate Lysosome Motility for Lysosome Positioning and Tubulation

Science.gov (United States)

Li, Xinran; Rydzewski, Nicholas; Hider, Ahmad; Zhang, Xiaoli; Yang, Junsheng; Wang, Wuyang; Gao, Qiong; Cheng, Xiping; Xu, Haoxing

2016-01-01

To mediate the degradation of bio-macromolecules, lysosomes must traffic towards cargo-carrying vesicles for subsequent membrane fusion or fission. Mutations of the lysosomal Ca2+ channel TRPML1 cause lysosome storage disease (LSD) characterized by disordered lysosomal membrane trafficking in cells. Here we show that TRPML1 activity is required to promote Ca2+-dependent centripetal movement of lysosomes towards the perinuclear region, where autophagosomes accumulate, upon autophagy induction. ALG-2, an EF-hand-containing protein, serves as a lysosomal Ca2+ sensor that associates physically with the minus-end directed dynactin-dynein motor, while PI(3,5)P2, a lysosome-localized phosphoinositide, acts upstream of TRPML1. Furthermore, the PI(3,5)P2-TRPML1-ALG-2-dynein signaling is necessary for lysosome tubulation and reformation. In contrast, the TRPML1 pathway is not required for the perinuclear accumulation of lysosomes observed in many LSDs, which is instead likely caused by secondary cholesterol accumulation that constitutively activates Rab7-RILP-dependent retrograde transport. Collectively, Ca2+ release from lysosomes provides an on-demand mechanism regulating lysosome motility, positioning, and tubulation. PMID:26950892

49 CFR 570.8 - Suspension systems.

Science.gov (United States)

2010-10-01

... 49 Transportation 6 2010-10-01 2010-10-01 false Suspension systems. 570.8 Section 570.8 Transportation Other Regulations Relating to Transportation (Continued) NATIONAL HIGHWAY TRAFFIC SAFETY... Pounds or Less § 570.8 Suspension systems. (a) Suspension condition. Ball joint seals shall not be cut or...

50 Years of renal physiology from one man and the perfused tubule: Maurice B. Burg.

Science.gov (United States)

Hamilton, Kirk L; Moore, Antoni B

2016-08-01

Technical advancements in research techniques in science are made in slow increments. Even so, large advances from insight and hard work of an individual with a single technique can have astonishing ramifications. Here, we examine the impact of Dr. Maurice B. Burg and the isolated perfused renal tubule technique and celebrate the 50th anniversary of the publication by Dr. Burg and his colleagues of their landmark paper in the American Journal of Physiology in 1966. In this study, we have taken a scientific visualization approach to study the scientific contributions of Dr. Burg and the isolated perfused tubule preparation as determining research impact by the number of research students, postdoctoral fellows, visiting scientists, and national and international collaborators. Additionally, we have examined the research collaborations (first and second generation scientists), established the migrational visualization of the first generation scientists who worked directly with Dr. Burg, quantified the metrics indices, identified and quantified the network of coauthorship of the first generation scientists with their second generation links, and determined the citations analyses of outputs of Dr. Burg and/or his first generation collaborators as coauthors. We also review the major advances in kidney physiology that have been made with the isolated perfused tubule technique. Finally, we are all waiting for the discoveries that the isolated perfused preparation technique will bring during the next 50 years. Copyright © 2016 the American Physiological Society.

The Lowe syndrome protein OCRL1 is required for endocytosis in the zebrafish pronephric tubule.

Directory of Open Access Journals (Sweden)

Francesca Oltrabella

2015-04-01

Full Text Available Lowe syndrome and Dent-2 disease are caused by mutation of the inositol 5-phosphatase OCRL1. Despite our increased understanding of the cellular functions of OCRL1, the underlying basis for the renal tubulopathy seen in both human disorders, of which a hallmark is low molecular weight proteinuria, is currently unknown. Here, we show that deficiency in OCRL1 causes a defect in endocytosis in the zebrafish pronephric tubule, a model for the mammalian renal tubule. This coincides with a reduction in levels of the scavenger receptor megalin and its accumulation in endocytic compartments, consistent with reduced recycling within the endocytic pathway. We also observe reduced numbers of early endocytic compartments and enlarged vacuolar endosomes in the sub-apical region of pronephric cells. Cell polarity within the pronephric tubule is unaffected in mutant embryos. The OCRL1-deficient embryos exhibit a mild ciliogenesis defect, but this cannot account for the observed impairment of endocytosis. Catalytic activity of OCRL1 is required for renal tubular endocytosis and the endocytic defect can be rescued by suppression of PIP5K. These results indicate for the first time that OCRL1 is required for endocytic trafficking in vivo, and strongly support the hypothesis that endocytic defects are responsible for the renal tubulopathy in Lowe syndrome and Dent-2 disease. Moreover, our results reveal PIP5K as a potential therapeutic target for Lowe syndrome and Dent-2 disease.

Osmotic consolidation of suspensions and gels

International Nuclear Information System (INIS)

Miller, K.T.; Zukoski, C.F.

1994-01-01

An osmotic method for the consolidation of suspensions of ceramic particles is demonstrated. Concentrated solutions of poly(ethylene oxide) are separated from a suspension of ceramic particles by a semipermeable membrane, creating a gradient in solvent chemical potential. Solvent passes from the suspension into the polymer solution, lowering its free energy and consolidating the suspension. Dispersions of stable 8-nm hydrous zirconia particles were consolidated to over 47% by volume. Suspensions of α-alumina in three states of aggregation (dispersed, weakly flocculated, and strongly flocculated) were consolidated to densities greater than or equal to those produced in conventional pressure filtration. Moreover, the as-consolidated alumina bodies were partially drained of fluid during the osmotic consolidation process, producing cohesive partially dried bodies with improved handling characteristics

Decoupling Suspension Controller Based on Magnetic Flux Feedback

Directory of Open Access Journals (Sweden)

Wenqing Zhang

2013-01-01

Full Text Available The suspension module control system model has been established based on MIMO (multiple input and multiple output state feedback linearization. We have completed decoupling between double suspension points, and the new decoupling method has been applied to CMS04 magnetic suspension vehicle in national mid-low-speed maglev experiment field of Tangshan city in China. Double suspension system model is very accurate for investigating stability property of maglev control system. When magnetic flux signal is taken back to the suspension control system, the suspension module’s antijamming capacity for resisting suspension load variety has been proved. Also, the external force interference has been enhanced. As a result, the robustness and stability properties of double-electromagnet suspension control system have been enhanced.

Decoupling suspension controller based on magnetic flux feedback.

Science.gov (United States)

Zhang, Wenqing; Li, Jie; Zhang, Kun; Cui, Peng

2013-01-01

The suspension module control system model has been established based on MIMO (multiple input and multiple output) state feedback linearization. We have completed decoupling between double suspension points, and the new decoupling method has been applied to CMS04 magnetic suspension vehicle in national mid-low-speed maglev experiment field of Tangshan city in China. Double suspension system model is very accurate for investigating stability property of maglev control system. When magnetic flux signal is taken back to the suspension control system, the suspension module's antijamming capacity for resisting suspension load variety has been proved. Also, the external force interference has been enhanced. As a result, the robustness and stability properties of double-electromagnet suspension control system have been enhanced.

Design analysis of formula student race car suspension system

Science.gov (United States)

Wirawan, Julian Wisnu; Ubaidillah, Aditra, Rama; Alnursyah, Rafli; Rahman, Rizki Abdul; Cahyono, Sukmaji Indro

2018-02-01

Design analysis of suspension especially for racecar suspension is very crucial to achieve maximum performance and handling. Suspension design may vary depending on the road terrain and the vehicle purpose itself, such as high speed or off-road vehicle. This paper focused on the suspension which used for racecar vehicle. The suspension type used was unequal double wishbone. This model is used because of its stability for high-speed usage compared to another kind of suspension. The suspension parameter was calculated to achieve desired performance. The result is the motion ratio of the designed suspension geometry. The obtained value of motion ratio was 1:2 for front suspension and 1:1 for the rear suspension. These calculation result the front suspension is still too soft, which the optimal motion ratio should be kept around 1:1 for better handling. This problem caused by the lack of space for suspension linkage.

The testicular sperm ducts and genital kidney of male Ambystoma maculatum (Amphibia, Urodela, Ambystomatidae).

Science.gov (United States)

Siegel, Dustin S; Aldridge, Robert D; Rheubert, Justin L; Gribbins, Kevin M; Sever, David M; Trauth, Stanley E

2013-03-01

The ducts associated with sperm transport from the testicular lobules to the Wolffian ducts in Ambystoma maculatum were examined with transmission electron microscopy. Based on the ultrastructure and historical precedence, new terminology for this network of ducts is proposed that better represents primary hypotheses of homology. Furthermore, the terminology proposed better characterizes the distinct regions of the sperm transport ducts in salamanders based on anatomy and should, therefore, lead to more accurate comparisons in the future. While developing the above ontology, we also tested the hypothesis that nephrons from the genital kidney are modified from those of the pelvic kidney due to the fact that the former nephrons function in sperm transport. Our ultrastructural analysis of the genital kidney supports this hypothesis, as the basal plasma membrane of distinct functional regions of the nephron (proximal convoluted tubule, distal convoluted tubule, and collecting tubule) appear less folded (indicating decreased surface area and reduced reabsorption efficiency) and the proximal convoluted tubule possesses ciliated epithelial cells along its entire length. Furthermore, visible luminal filtrate is absent from the nephrons of the genital kidney throughout their entire length. Thus, it appears that the nephrons of the genital kidney have reduced reabsorptive capacity and ciliated cells of the proximal convoluted tubule may increase the movement of immature sperm through the sperm transport ducts or aid in the mixing of seminal fluids within the ducts. Copyright © 2012 Wiley Periodicals, Inc.

49 CFR 570.61 - Suspension system.

Science.gov (United States)

2010-10-01

... 49 Transportation 6 2010-10-01 2010-10-01 false Suspension system. 570.61 Section 570.61... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION VEHICLE IN USE INSPECTION STANDARDS Vehicles With GVWR of More Than 10,000 Pounds § 570.61 Suspension system. (a) Suspension condition. Ball joint seals shall not be cut...

Reconstruction of mouse testicular cellular microenvironments in long-term seminiferous tubule culture.

Directory of Open Access Journals (Sweden)

Juho-Antti Mäkelä

Full Text Available Research on spermatogonia is hampered by complex architecture of the seminiferous tubule, poor viability of testicular tissue ex vivo and lack of physiologically relevant long-term culture systems. Therefore there is a need for an in vitro model that would enable long term survival and propagation of spermatogonia. We aimed at the most simplified approach to enable all different cell types within the seminiferous tubules to contribute to the creation of a niche for spermatogonia. In the present study we describe the establishment of a co-culture of mouse testicular cells that is based on proliferative and migratory activity of seminiferous tubule cells and does not involve separation, purification or differential plating of individual cell populations. The co-culture is composed of the constituents of testicular stem cell niche: Sertoli cells [identified by expression of Wilm's tumour antigen 1 (WT1 and secretion of glial cell line-derived neurotrophic factor, GDNF], peritubular myoid cells (expressing alpha smooth muscle actin, αSMA and spermatogonia [expressing MAGE-B4, PLZF (promyelocytic leukaemia zinc finger, LIN28, Gpr125 (G protein-coupled receptor 125, CD9, c-Kit and Nanog], and can be maintained for at least five weeks. GDNF was found in the medium at a sufficient concentration to support proliferating spermatogonial stem cells (SSCs that were able to start spermatogenic differentiation after transplantation to an experimentally sterile recipient testis. Gdnf mRNA levels were elevated by follicle-stimulating hormone (FSH which shows that the Sertoli cells in the co-culture respond to physiological stimuli. After approximately 2-4 weeks of culture a spontaneous formation of cord-like structures was monitored. These structures can be more than 10 mm in length and branch. They are formed by peritubular myoid cells, Sertoli cells, fibroblasts and spermatogonia as assessed by gene expression profiling. In conclusion, we have managed to

Finite Element Modelling of a Field-Sensed Magnetic Suspended System for Accurate Proximity Measurement Based on a Sensor Fusion Algorithm with Unscented Kalman Filter.

Science.gov (United States)

Chowdhury, Amor; Sarjaš, Andrej

2016-09-15

The presented paper describes accurate distance measurement for a field-sensed magnetic suspension system. The proximity measurement is based on a Hall effect sensor. The proximity sensor is installed directly on the lower surface of the electro-magnet, which means that it is very sensitive to external magnetic influences and disturbances. External disturbances interfere with the information signal and reduce the usability and reliability of the proximity measurements and, consequently, the whole application operation. A sensor fusion algorithm is deployed for the aforementioned reasons. The sensor fusion algorithm is based on the Unscented Kalman Filter, where a nonlinear dynamic model was derived with the Finite Element Modelling approach. The advantage of such modelling is a more accurate dynamic model parameter estimation, especially in the case when the real structure, materials and dimensions of the real-time application are known. The novelty of the paper is the design of a compact electro-magnetic actuator with a built-in low cost proximity sensor for accurate proximity measurement of the magnetic object. The paper successively presents a modelling procedure with the finite element method, design and parameter settings of a sensor fusion algorithm with Unscented Kalman Filter and, finally, the implementation procedure and results of real-time operation.

Compressible Fluid Suspension Performance Testing

National Research Council Canada - National Science Library

Hoogterp, Francis

2003-01-01

... compressible fluid suspension system that was designed and installed on the vehicle by DTI. The purpose of the tests was to evaluate the possible performance benefits of the compressible fluid suspension system...

In vitro remineralization of enamel subsurface lesions and assessment of dentine tubule occlusion from NaF dentifrices with and without calcium

Directory of Open Access Journals (Sweden)

A R Prabhakar

2013-01-01

Full Text Available Currently, fluoride is the most effective preventive treatment for remineralization of incipient carious lesions and dentinal hypersensitivity due to wasting disorders. The products containing fluoride, calcium and phosphate are also claim to remineralize early, non-cavitated enamel demineralization. The aim of this study was to investigate and compare the efficacy of two such products, Tooth Mousse and Clinpro tooth crème on remineralization and tubule occluding ability with 5000ppm fluoride-containing toothpaste. Materials and Methods :Thirty third molar teeth were placed in demineralizing solution for 5 days such that only a window of 1mm x 5mm was exposed to the environment to produce artificial caries-like lesions and randomly assigned to three groups: Group I, 5000ppm sodium fluoride; Group II, GC MI paste plus and Group III, Clinpro tooth crème. Axial longitudinal sections of 140-160 μm of each tooth which included the artificial carious lesion taken and were photographed under polarized light microscope. The demineralized areas were then quantified with a computerized imaging system. The experimental materials were applied onto the tooth sections as a topical coating and subjected to pH-cycling for 28 days. To evaluate tubule occlusion ability, thirty dentin specimens of 2mm thickness were obtained from cervical third of sound third molars. Specimens were ultrasonicated and etched with 6% citric acid for 2 minutes to simulate the hypersensitive dentin. Specimens were randomly divided into above mentioned three groups (n=10. The test agents were brushed over the specimens with an electric toothbrush, prepared and observed under Scanning Electron Microscope for calculation of the percentage of occluded tubules. Results: Group I showed a significantly greater percentage of remineralization than Group III and Group II. Comparison of the remineralization potential between group II and group III were not significant.In case of dentine

Distribution of anticancer antibiotic daunomycin in the rat heart and kidney revealed by immunocytochemistry using monoclonal antibodies

DEFF Research Database (Denmark)

Fujiwara, Kunio; Shin, Masashi; Hougaard, David M.

2007-01-01

.v. or i.p. administration of the drug. In the heart, accumulation of DM occurred in nuclei and in the cytoplasm. In the kidney, DM immunoreactivity accumulated in all segments of the nephron except for the proximal tubules. Since the proximal tubules are known to be where a variety of transport systems...... possibilities for understanding toxic side effects of this drug on the heart and kidney. Moreover, the immunocytochemical methodology developed may prove useful for the localization of other low molecular weight drugs that can be fixed in situ by glutaraldehyde....

A universal suspension test rig for electrohydraulic active and passive automotive suspension system

Directory of Open Access Journals (Sweden)

Mahmoud Omar

2017-12-01

Full Text Available A fully active electro-hydraulic and passive automotive quarter car suspensions with their experimental test-rigs are designed and implemented. Investigation of the active performance compared against the passive is performed experimentally and numerically utilizing SIMULINK's Simscape library. Both systems are modeled as single-degree-of-freedom in order to simplify the validation process. Economic considerations were considered during the rig's implementation. The rig consists of two identical platforms fixed side by side allowing testing two independent suspensions simultaneously. Position sensors for sprung and unsprung masses on both platforms are installed. The road input is introduced by a cam and a roller follower mechanism driven by 1.12 kW single phase induction motor with speed reduction assembly. The active hydraulic cylinder was the most viable choice due to its high power-to-weight ratio. The active control is of the proportional-integral-differential (PID type. Though this technique is quite simple and not new, yet the emphasis of this paper is the engineering, design and implementation of the experimental setup and controller. A successful validation process is performed. Ride comfort significantly improved with active suspension, as shown by the results; 24.8% sprung mass vibration attenuation is achieved. The details of the developed system with the analytical and experimental results are presented. Keywords: Active suspension, Passive suspension, Servo, Hydraulic, Control, PID

Photoelectrochemical reactivity of polyoxophosphotungstates embedded in titania tubules

International Nuclear Information System (INIS)

Xie Yibing

2006-01-01

A highly ordered and crystallized titania (TiO 2 ) nanotube array is fabricated by a low-voltage anodization plus a post-embedding calcination process. Polyoxophosphotungstate-titania (POPTA-TiO 2 ) composite catalyst is synthesized by embedding POPTA in TiO 2 tubule channels to improve the photoelectrochemical properties. The morphological characteristics and crystal behaviour of POPTA-TiO 2 are examined by field-emission scanning electron microscopy and x-ray diffraction. The stability of the chemical structure has been analysed by Fourier transformed infrared spectroscopy measurements. The photoelectrochemical properties are investigated by means of the polarization current response. Photocatalytic and photoelectrocatalytic reactivities for the degradation of an endocrine disrupting chemical have also been investigated to examine the photoelectrochemical reaction efficiency of POPTA-TiO 2 composite catalyst

Elucidation of density profile of self-assembled sitosterol + oryzanol tubules with small-angle neutron scattering

NARCIS (Netherlands)

Bot, A.; Gilbert, E.P.; Bouwman, W.G.; Sawalha, H.I.M.; Adel, den R.; Garamus, V.M.; Venema, P.; Linden, van der E.; Flöter, E.

2012-01-01

Small-angle neutron scattering (SANS) experiments have been performed on self-assembled tubules of sitosterol and oryzanol in triglyceride oils to investigate details of their structure. Alternative organic phases (deuterated and non-deuterated decane, limonene, castor oil and eugenol) were used to

The Mystical Suspension

Directory of Open Access Journals (Sweden)

Héctor Santiesteban Oliva

2016-11-01

Full Text Available Mistical suspension, silence, time, absolute, ontology, ineffability, aletheiaIn the mystical ecstasy there is a sensorial and intellectual suspension when contemplating the absolute, the ontological Being. Silence is not only significant: it is revealing. The greatest expression of experience inner silence . The word is insufficient when the ontological reality is revealed. Revelation or truth , the Greek concept of aletheia, takes on greater significance in that transcendental experience. It is also suspended phenomenological time and remains eternity open.

Equivalent complex conductivities representing the effects of T-tubules and folded surface membranes on the electrical admittance and impedance of skeletal muscles measured by external-electrode method

Science.gov (United States)

Sekine, Katsuhisa

2017-12-01

In order to represent the effects of T-tubules and folded surface membranes on the electrical admittance and impedance of skeletal muscles measured by the external-electrode method, analytical relations for the equivalent complex conductivities of hypothetical smooth surface membranes were derived. In the relations, the effects of each tubule were represented by the admittance of a straight cable. The effects of the folding of a surface membrane were represented by the increased area of surface membranes. The equivalent complex conductivities were represented as summation of these effects, and the effects of the T-tubules were different between the transversal and longitudinal directions. The validity of the equivalent complex conductivities was supported by the results of finite-difference method (FDM) calculations made using three-dimensional models in which T-tubules and folded surface membranes were represented explicitly. FDM calculations using the equivalent complex conductivities suggested that the electrically inhomogeneous structure due to the existence of muscle cells with T-tubules was sufficient for explaining the experimental results previously obtained using the external-electrode method. Results of FDM calculations in which the structural changes caused by muscle contractions were taken into account were consistent with the reported experimental results.

Efficacy of 4 Irrigation Protocols in Killing Bacteria Colonized in Dentinal Tubules Examined by a Novel Confocal Laser Scanning Microscope Analysis.

Science.gov (United States)

Azim, Adham A; Aksel, Hacer; Zhuang, Tingting; Mashtare, Terry; Babu, Jegdish P; Huang, George T-J

2016-06-01

The aim of this study was to determine the efficiency of 4 irrigation systems in eliminating bacteria in root canals, particularly in dentinal tubules. Roots of human teeth were prepared to 25/04, autoclaved, and inoculated with Enterococcus faecalis for 3 weeks. Canals were then disinfected by (1) standard needle irrigation, (2) sonically agitating with EndoActivator, (3) XP Endo finisher, or (4) erbium:yttrium aluminum garnet laser (PIPS) (15 roots/group). The bacterial reduction in the canal was determined by MTT assays. For measuring live versus dead bacteria in the dentinal tubules (4 teeth/group), teeth were split open and stained with LIVE/DEAD BackLight. Coronal, middle, and apical thirds of the canal dentin were scanned by using a confocal laser scanning microscope (CLSM) to determine the ratio of dead/total bacteria in the dentinal tubules at various depths. All 4 irrigation protocols significantly eliminated bacteria in the canal, ranging from 89.6% to 98.2% reduction (P bacteria in the coronal, middle, and apical segments at 50-μm depth. On the other hand, PIPS had the greatest bacterial killing efficiency at the 150-μm depth in all 3 root segments. XP Endo appears to be more efficient than other 3 techniques in disinfecting the main canal space and up to 50 μm deep into the dentinal tubules. PIPS appears to be most effective in killing the bacteria deep in the dentinal tubules. Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Assessment of drug salt release from solutions, suspensions and in situ suspensions using a rotating dialysis cell

DEFF Research Database (Denmark)

Parshad, Henrik; Frydenvang, Karla; Liljefors, Tommy

2003-01-01

buffer is used as release media. Generally, the initial release of the drug salt from in situ suspensions occurred faster as compared to conventional suspensions, probably due to incomplete precipitation of the drug salt, and hence formation of supersaturated solutions where the rate of release......A rotating dialysis cell consisting of a small (10 ml) and a large compartment (1000 ml) was used to study the release of drug salt (bupivacaine 9-anthracene carboxylate) from (i). solutions, (ii). suspensions and (iii). in situ formed suspensions. Initial release experiments from suspensions...... indicated that the release of drug salt in deionized water was predominantly limited by the diffusion across the membrane whereas it is essentially dissolution rate controlled in 0.05 M phosphate buffer (pH 7.40). Thus, the in vitro model appears to have a potential in formulation screening when phosphate...

Effects of receptor-mediated endocytosis and tubular protein composition on volume retention in experimental glomerulonephritis

DEFF Research Database (Denmark)

Kastner, Christian; Pohl, Marcus; Sendeski, Mauricio

2009-01-01

Human glomerulonephritis (GN) is characterized by sustained proteinuria, sodium retention, hypertension, and edema formation. Increasing quantities of filtered protein enter the renal tubule, where they may alter epithelial transport functions. Exaggerated endocytosis and consequent protein...... overload may affect proximal tubules, but intrinsic malfunction of distal epithelia has also been reported. A straightforward assignment to a particular tubule segment causing salt retention in GN is still controversial. We hypothesized that 1) trafficking and surface expression of major transporters...

Auto-regeneration of mice testicle seminiferous tubules due to malnutrition based on stem cells mobilization using honey

Directory of Open Access Journals (Sweden)

Erma Safitri

2016-03-01

Conclusions: Results of this study revealed a significantly different of C34 and CD45 expressions between groups, also an increase SSCs expression and testicle seminiferous tubules cells regeneration as well.

Flow-induced structure in colloidal suspensions

Energy Technology Data Exchange (ETDEWEB)

Vermant, J [Department of Chemical Engineering, K U Leuven, W de Croylaan 46, B-3001 Leuven (Belgium); Solomon, M J [Department of Chemical Engineering, University of Michigan, Ann Arbor, MI 48109-2136 (United States)

2005-02-02

We review the sequences of structural states that can be induced in colloidal suspensions by the application of flow. Structure formation during flow is strongly affected by the delicate balance among interparticle forces, Brownian motion and hydrodynamic interactions. The resulting non-equilibrium microstructure is in turn a principal determinant of the suspension rheology. Colloidal suspensions with near hard-sphere interactions develop an anisotropic, amorphous structure at low dimensionless shear rates. At high rates, clustering due to strong hydrodynamic forces leads to shear thickening rheology. Application of steady-shear flow to suspensions with repulsive interactions induces a rich sequence of transitions to one-, two-and three-dimensional order. Oscillatory-shear flow generates metastable ordering in suspensions with equilibrium liquid structure. On the other hand, short-range attractive interactions can lead to a fluid-to-gel transition under quiescent suspensions. Application of flow leads to orientation, breakup, densification and spatial reorganization of aggregates. Using a non-Newtonian suspending medium leads to additional possibilities for organization. We examine the extent to which theory and simulation have yielded mechanistic understanding of the microstructural transitions that have been observed. (topical review)

Fabrication of Collagen Gel Hollow Fibers by Covalent Cross-Linking for Construction of Bioengineering Renal Tubules.

Science.gov (United States)

Shen, Chong; Zhang, Guoliang; Wang, Qichen; Meng, Qin

2015-09-09

Collagen, the most used natural biomacromolecule, has been extensively utilized to make scaffolds for cell cultures in tissue engineering, but has never been fabricated into the configuration of a hollow fiber (HF) for cell culture due to its poor mechanical properties. In this study, renal tubular cell-laden collagen hollow fiber (Col HF) was fabricated by dissolving sacrificial Ca-alginate cores from collagen shells strengthened by carbodiimide cross-linking. The inner/outer diameters of the Col HF were precisely controlled by the flow rates of core alginate/shell collagen solution in the microfluidic device. As found, the renal tubular cells self-assembled into renal tubules with diameters of 50-200 μm post to the culture in Col HF for 10 days. According to the 3D reconstructed confocal images or HE staining, the renal cells appeared as a tight tubular monolayer on the Col HF inner surface, sustaining more 3D cell morphology than the cell layer on the 2D flat collagen gel surface. Moreover, compared with the cultures in either a Transwell or polymer HF membrane, the renal tubules in Col HF exhibited at least 1-fold higher activity on brush border enzymes of alkaline phosphatase and γ-glutamyltransferase, consistent with their gene expressions. The enhancement occurred similarly on multidrug resistance protein 2 and glucose uptake. Such bioengineered renal tubules in Col HF will present great potential as alternatives to synthetic HF in both clinical use and pharmaceutical investigation.

A Role for Tubular Necroptosis in Cisplatin-Induced AKI

Science.gov (United States)

Xu, Yanfang; Ma, Huabin; Shao, Jing; Wu, Jianfeng; Zhou, Linying; Zhang, Zhirong; Wang, Yuze; Huang, Zhe; Ren, Junming; Liu, Suhuan; Chen, Xiangmei

2015-01-01

Cell death and inflammation in the proximal tubules are the hallmarks of cisplatin-induced AKI, but the mechanisms underlying these effects have not been fully elucidated. Here, we investigated whether necroptosis, a type of programmed necrosis, has a role in cisplatin-induced AKI. We found that inhibition of any of the core components of the necroptotic pathway—receptor-interacting protein 1 (RIP1), RIP3, or mixed lineage kinase domain-like protein (MLKL)—by gene knockout or a chemical inhibitor diminished cisplatin-induced proximal tubule damage in mice. Similar results were obtained in cultured proximal tubular cells. Furthermore, necroptosis of cultured cells could be induced by cisplatin or by a combination of cytokines (TNF-α, TNF-related weak inducer of apoptosis, and IFN-γ) that were upregulated in proximal tubules of cisplatin-treated mice. However, cisplatin induced an increase in RIP1 and RIP3 expression in cultured tubular cells in the absence of cytokine release. Correspondingly, overexpression of RIP1 or RIP3 enhanced cisplatin-induced necroptosis in vitro. Notably, inflammatory cytokine upregulation in cisplatin-treated mice was partially diminished in RIP3- or MLKL-deficient mice, suggesting a positive feedback loop involving these genes and inflammatory cytokines that promotes necroptosis progression. Thus, our data demonstrate that necroptosis is a major mechanism of proximal tubular cell death in cisplatin-induced nephrotoxic AKI. PMID:25788533

Fluoride-associated ultrastructural changes and apoptosis in human renal tubule: a pilot study.

Science.gov (United States)

Quadri, J A; Sarwar, S; Sinha, A; Kalaivani, M; Dinda, A K; Bagga, A; Roy, T S; Das, T K; Shariff, A

2018-01-01

The susceptibility of the kidneys to fluoride toxicity can largely be attributed to its anatomy and function. As the filtrate moves along the complex tubular structure of each nephron, it is concentrated in the proximal and distal tubules and collecting duct. It has been frequently observed that the children suffering from renal impairments also have some symptoms of dental and skeletal fluorosis. The findings suggest that fluoride somehow interferes with renal anatomy and physiology, which may lead to renal pathogenesis. The aim of this study was to evaluate the fluoride-associated nephrotoxicity. A total of 156 patients with childhood nephrotic syndrome were screened and it was observed that 32 of them had significantly high levels ( p ≤ 0.05) of fluoride in urine (4.01 ± 1.83 ppm) and serum (0.1 ± 0.013 ppm). On the basis of urinary fluoride concentration, patients were divided into two groups, namely group 1 (G-1) ( n = 32) containing normal urine fluoride (0.61 ± 0.17 ppm) and group 2 (G-2) ( n = 32) having high urine fluoride concentration (4.01 ± 1.83 ppm). Age-matched healthy subjects ( n = 33) having normal levels of urinary fluoride (0.56 ± 0.15 ppm) were included in the study as control (group 0 (G-0)). Kidney biopsies were taken from G-1 and G-2 only, who were subjected to ultrastructural (transmission electron microscopy) and apoptotic (terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling) analysis. Various subcellular ultrastructural changes including nuclear disintegration, chromosome condensation, cytoplasmic ground substance lysis, and endoplasmic reticulum blebbing were observed. Increased levels of apoptosis were observed in high fluoride group (G-2) compared to normal fluoride group (G-1). Various degrees of fluoride-associated damages to the architecture of tubular epithelia, such as cell swelling and lysis, cytoplasmic vacuolation, nuclear condensation, apoptosis, and necrosis, were observed.

Naratriptan hydrochloride in extemporaneosly compounded oral suspensions.

Science.gov (United States)

Zhang, Y P; Trissel, L A; Fox, J L

2000-01-01

The purpose of this study was to determine the pharmaceutical acceptability and chemical stability of naratriptan hydrochloride in three extemporaneously compounded suspension formulations. The naratriptan-hydrochloride oral suspensions were prepared from 2.5-mg commercial tablets yielding a nominal naratriptan concentration of 0.5 mg/mL. The suspension vehicles selected for testing were Syrpalta, an equal-parts mixture of Ora-Plus and Ora-Sweet, and an equal-parts mixture of Ora-Plus and Ora-Sweet SF. The tablets were crushed and thoroughly triturated to a fine powder using a porcelain mortar and pestle. The powder was incorporated into a portion of the Syrpalta or Ora-Plus suspension vehicle and mixed until homogeneous. The mixtures were then brought to volume with Syrpalta, Ora-Sweet or Ora-Sweet SF, as appropriate. The suspensions were packaged in amber, plastic, screw-cap prescription bottles and stored at 23 deg C for seven days and 4 deg C for 90 days. An adequate suspension was never achieved in Syrpalta. The crushed-tablet powder did not produce a uniformly dispersed mixture and exhibited clumping and a high rate of sedimentation. A distinct layer of the solid tablet material settled immediately after shaking. Over the next four hours, a densely packed, yellow, caked layer formed at the bottom of the containers, making resuspension difficult. During storage, the caking became worse. Chemical analysis was not performed. The Ora-Plus and Ora-Sweet or Ora-Sweet SF suspensions had a slight greenish cast and were resuspended without difficulty by shaking for approximately ten seconds, yielding easily poured and homogeneous mixtures throughout the study. Visible settling and layering did not begin for four hours with the Ora-Sweet suspension and 24 hours for the Ora-Sweet SF suspension. High pressure liquid chromatographic analysis found that the naratriptan concentration in both suspension-vehicle combinations exhibited little or no loss for seven days at 23

Heavy vehicle pitch dynamics and suspension tuning

OpenAIRE

Cao, Dongpu; Rakheja, Subhash; Su, Chun-Yi

2008-01-01

The influence of suspension tuning of passenger cars on bounce and pitch ride performance has been explored in a number of studies, while only minimal efforts have been made for establishing similar rules for heavy vehicles. This study aims to explore pitch dynamics and suspension tunings of a two-axle heavy vehicle with unconnected suspension, which could also provide valuable information for heavy vehicles with coupled suspensions. Based on a generalised pitch-plane model of a two-axle heav...

The Influence of Concentration and Temperature on the Formation of γ-Oryzanol + β-Sitosterol Tubules in Edible Oil Organogels.

Science.gov (United States)

Sawalha, Hassan; Venema, Paul; Bot, Arjen; Flöter, Eckhard; van der Linden, Erik

2011-03-01

The gelation process of mixtures of γ-oryzanol and sitosterol structurants in sunflower oil was studied using light scattering, rheology, and micro-scanning calorimetry (Micro-DSC). The relation between temperature and the critical aggregation concentration (CAC) of tubule formation of γ-oryzanol and sitosterol was determined using these techniques. The temperature dependence of the CAC was used to estimate the binding energy and enthalpic and entropic contribution to the tubular formation process. The binding energy calculated at the corresponding temperatures and CACs were relatively low, in order of 2 RT (4.5 kJ mol(-1)), which is in accord with the reversibility of the tubular formation process. The formation of the tubules was associated with negative (exothermic) enthalpy change (ΔH(0)) compared with positive entropy term (-T ΔS(0) >0), indicating that the aggregation into tubules is an enthalpy-driven process. The oryzanol-sitosterol ratio affected the aggregation process; solutions with ratio of (60 oryzanol-40 sitosterol) started aggregation at higher temperature compared with other ratios.

Regulation of proximal tubular cell differentiation and proliferation in primary culture by matrix stiffness and ECM components.

Science.gov (United States)

Chen, Wan-Chun; Lin, Hsi-Hui; Tang, Ming-Jer

2014-09-15

To explore whether matrix stiffness affects cell differentiation, proliferation, and transforming growth factor (TGF)-β1-induced epithelial-mesenchymal transition (EMT) in primary cultures of mouse proximal tubular epithelial cells (mPTECs), we used a soft matrix made from monomeric collagen type I-coated polyacrylamide gel or matrigel (MG). Both kinds of soft matrix benefited primary mPTECs to retain tubular-like morphology with differentiation and growth arrest and to evade TGF-β1-induced EMT. However, the potent effect of MG on mPTEC differentiation was suppressed by glutaraldehyde-induced cross-linking and subsequently stiffening MG or by an increasing ratio of collagen in the soft mixed gel. Culture media supplemented with MG also helped mPTECs to retain tubular-like morphology and a differentiated phenotype on stiff culture dishes as soft MG did. We further found that the protein level and activity of ERK were scaled with the matrix stiffness. U-0126, a MEK inhibitor, abolished the stiff matrix-induced dedifferentiation and proliferation. These data suggest that the ERK signaling pathway plays a vital role in matrix stiffness-regulated cell growth and differentiation. Taken together, both compliant property and specific MG signals from the matrix are required for the regulation of epithelial differentiation and proliferation. This study provides a basic understanding of how physical and chemical cues derived from the extracellular matrix regulate the physiological function of proximal tubules and the pathological development of renal fibrosis. Copyright © 2014 the American Physiological Society.

Exposure of cultured human proximal tubular cells to cadmium, mercury, zinc and bismuth: toxicity and metallothionein induction.

Science.gov (United States)

Rodilla, V; Miles, A T; Jenner, W; Hawksworth, G M

1998-08-14

The kidney, in particular the proximal convoluted tubule, is a major target site for the toxic effects of various metals. However, little is known about the early effects of these metals after acute exposure in man. In the present study we have evaluated the toxicity of several inorganic metal compounds (CdCl2, HgCl2, ZnCl2, and Bi(NO3)3) and the induction of metallothionein by these compounds in cultured human proximal tubular (HPT) cells for up to 4 days. The results showed that bismuth was not toxic even at the highest dose (100 microM) used, while zinc, cadmium and mercury exhibited varying degrees of toxicity, zinc being the least toxic and mercury the most potent. A significant degree of interindividual variation between the different isolates used in these experiments was also observed. All metals used in the present study induced MT, as revealed by immunocytochemistry. All metals showed maximal induction between 1 and 3 days after treatment. Although a certain amount of constitutive MT was present in the cultures, the intensity of the staining varied with time in culture and between the different isolates studied. No correlation could be made between the intensity of the staining in control cultures (indicating total amount of constitutive MT) and the susceptibility of a given isolate to metal toxicity. Furthermore, no correlation could be made between metal-induced MT and the susceptibility of a given isolate to that particular metal.

A de novo transcriptome of the Malpighian tubules in non-blood-fed and blood-fed Asian tiger mosquitoes Aedes albopictus: insights into diuresis, detoxification, and blood meal processing

Directory of Open Access Journals (Sweden)

Carlos J. Esquivel

2016-03-01

Full Text Available Background. In adult female mosquitoes, the renal (Malpighian tubules play an important role in the post-prandial diuresis, which removes excess ions and water from the hemolymph of mosquitoes following a blood meal. After the post-prandial diuresis, the roles that Malpighian tubules play in the processing of blood meals are not well described. Methods. We used a combination of next-generation sequencing (paired-end RNA sequencing and physiological/biochemical assays in adult female Asian tiger mosquitoes (Aedes albopictus to generate molecular and functional insights into the Malpighian tubules and how they may contribute to blood meal processing (3–24 h after blood ingestion. Results/Discussion. Using RNA sequencing, we sequenced and assembled the first de novo transcriptome of Malpighian tubules from non-blood-fed (NBF and blood-fed (BF mosquitoes. We identified a total of 8,232 non-redundant transcripts. The Malpighian tubules of NBF mosquitoes were characterized by the expression of transcripts associated with active transepithelial fluid secretion/diuresis (e.g., ion transporters, water channels, V-type H+-ATPase subunits, xenobiotic detoxification (e.g., cytochrome P450 monoxygenases, glutathione S-transferases, ATP-binding cassette transporters, and purine metabolism (e.g., xanthine dehydrogenase. We also detected the expression of transcripts encoding sodium calcium exchangers, G protein coupled-receptors, and septate junctional proteins not previously described in mosquito Malpighian tubules. Within 24 h after a blood meal, transcripts associated with active transepithelial fluid secretion/diuresis exhibited a general downregulation, whereas those associated with xenobiotic detoxification and purine catabolism exhibited a general upregulation, suggesting a reinvestment of the Malpighian tubules’ molecular resources from diuresis to detoxification. Physiological and biochemical assays were conducted in mosquitoes and isolated

Synthesis and secretion of proteins by perifused caput epididymal tubules, and association of secreted proteins with spermatozoa

International Nuclear Information System (INIS)

Klinefelter, G.R.; Hamilton, D.W.

1985-01-01

We have used perifusion organ culture of proximal and distal caput epididymal tubules of the rat to study the secretion of proteins by epididymal epithelium and uptake of the luminal radioactive proteins by sperm. The amount of incorporation of L-[35S]methionine into luminal fluid proteins was time dependent and completely inhibited by cycloheximide. The association of labeled proteins with cultured sperm was also dependent on time and continuous, with sperm still acquiring labeled luminal proteins after protein synthesis was arrested. A Mr = 46,000 molecule was found to be heavily labeled in luminal fluid and sperm extracts. Fluorograms of all L-[35S]methionine extracts immunoprecipitated using an antiepididymal alpha-lactalbumin antibody (Klinefelter and Hamilton, 1984) showed labeling of an Mr = 18,000 molecule and, in addition, the Mr = 46,000 molecule, but immunostaining was specific only for the Mr = 18,000 molecule and the heavy chain of the immunoglobulin. We suggest that the Mr = 46,000 molecule may be galactosyltransferase. Galactose oxidase-NaB[3H]4 labeling of the cultured caput sperm cell surface revealed a Mr = 23,000 molecule that was able to be immunoprecipitated with antiepididymal alpha-lactalbumin antibody. Our data suggest that this cell surface molecule is similar to one component of the fluid epididymal alpha-lactalbumin-like complex and, in addition, show that glycosylation of the sperm surface can occur in the caput epididymidis

Characterization of cell suspensions from solid tumors

International Nuclear Information System (INIS)

Pallavicini, M.

1985-01-01

The desirable features of cells in suspension will necessarily be dependent upon the use for which the cells were prepared. Adequate cell yield or recovery is defined by the measurement to be performed. Retention of cellular morphology is important for microscopic identification of cell types in a heterogenous cell suspension, and may be used to determine whether the cells in suspension are representative of those in the tumor in situ. Different dispersal protocols may yield cells with different degrees of clonogenicity, as well as altered biochemical features, such as loss of cellular proteins, surface antigens, nucleotide pools, etc. The quality of the cell suspension can be judged by the degree of cell clumping and level of cellular debris, both of which impact on flow cytometric measurements and studies in which the number of cells be known accurately. Finally, if the data measured on the cells in suspension are to be extrapolated to phenomena occurring in the tumor in situ, it is desirable that the cells in suspension are representative of those in the solid tumor in vivo. This report compares characteristics of tumor cell suspensions obtained by different types of selected disaggregation methods. 33 refs., 2 figs., 4 tabs

13 CFR 120.660 - Suspension or revocation.

Science.gov (United States)

2010-01-01

... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Suspension or revocation. 120.660 Section 120.660 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Secondary Market Suspension Or Revocation of Participant in Secondary Market § 120.660 Suspension or revocation. (a...

Clay-cement suspensions - rheological and functional properties

Science.gov (United States)

Wojcik, L.; Izak, P.; Mastalska-Poplawska, J.; Gajek, M.

2017-01-01

The piping erosion in soil is highly unexpected in civil engineering. Elimination of such damages is difficult, expensive and time-consuming. One of the possibility is the grouting method. This method is still developed into direction of process automation as well as other useful properties of suspensions. Main way of modernization of the grouting method is connected it with rheology of injection and eventuality of fitting them to specific problems conditions. Very popular and useful became binders based on modified clays (clay-cement suspensions). Important principle of efficiency of the grouting method is using of time-dependent pseudothixotropic properties of the clay-cement suspensions. The pseudo-rheounstability aspect of the suspensions properties should be dedicated and fitted to dynamic changes of soil conditions destructions. Whole process of the modification of the suspension rheology is stimulated by the specific agents. This article contains a description of practical aspects of the rheological parameters managing of the clay-cement suspensions, dedicated to the building damages, hydrotechnic constructions etc.

Collective cell migration drives morphogenesis of the kidney nephron.

Directory of Open Access Journals (Sweden)

Aleksandr Vasilyev

2009-01-01

Full Text Available Tissue organization in epithelial organs is achieved during development by the combined processes of cell differentiation and morphogenetic cell movements. In the kidney, the nephron is the functional organ unit. Each nephron is an epithelial tubule that is subdivided into discrete segments with specific transport functions. Little is known about how nephron segments are defined or how segments acquire their distinctive morphology and cell shape. Using live, in vivo cell imaging of the forming zebrafish pronephric nephron, we found that the migration of fully differentiated epithelial cells accounts for both the final position of nephron segment boundaries and the characteristic convolution of the proximal tubule. Pronephric cells maintain adherens junctions and polarized apical brush border membranes while they migrate collectively. Individual tubule cells exhibit basal membrane protrusions in the direction of movement and appear to establish transient, phosphorylated Focal Adhesion Kinase-positive adhesions to the basement membrane. Cell migration continued in the presence of camptothecin, indicating that cell division does not drive migration. Lengthening of the nephron was, however, accompanied by an increase in tubule cell number, specifically in the most distal, ret1-positive nephron segment. The initiation of cell migration coincided with the onset of fluid flow in the pronephros. Complete blockade of pronephric fluid flow prevented cell migration and proximal nephron convolution. Selective blockade of proximal, filtration-driven fluid flow shifted the position of tubule convolution distally and revealed a role for cilia-driven fluid flow in persistent migration of distal nephron cells. We conclude that nephron morphogenesis is driven by fluid flow-dependent, collective epithelial cell migration within the confines of the tubule basement membrane. Our results establish intimate links between nephron function, fluid flow, and morphogenesis.

Effect of Hypodynamy on Structure and Alkaline Phosphatase Activity of Kidney in Japanese Quails

Directory of Open Access Journals (Sweden)

V. Almášiová

2008-01-01

Full Text Available The objective of the study was to observe the effect of experimental hypodynamy simulating weightlessness in space on the structure, ultrastructure and alkaline phosphatase activity of kidney in Japanese quail (Coturnix coturnix japonica. Two days after hatching, the quails were suspended in special shirts below the cage ceiling so their feet did not touch the floor. They could consume food and water ad libitum. Experimental animals were sacrificed after 14, 21, 28, 35, 42, 49 and 56 days of hypodynamy. Birds of the same age, hatched at the same time, and fed the same diet were used as a control. Samples of kidney were processed for light (LM and transmission electron microscopy (TEM, and alkaline phosphatase (AP analysis. Short-term (14–28 days hypodynamy caused no marked damage to the structure and ultrastructure of kidneys. However, after long-term (35–59 days hypodynamy, morphological changes were observed in some cells of the proximal and distal tubules. The dying cells in proximal tubules, observed in semi-thin sections by LM, were dark and contained a nucleus of irregular shape. Observation by TEM showed that their nucleus was dark and shrivelled and the electron-dense cytoplasm contained long, dense, rod-shaped mitochondria with thin mitochondrial cristae. Microvilli were present on the apical surface of cells and formed a brush border. Sporadic dying cells were also observed in distal tubules. Large, light vacuoles were found in the cytoplasm of cells of collecting tubules, however, the structure of renal corpuscles and medullary loops remained undisturbed. Microscopical analysis by means of a direct TUNEL reaction on days 35 to 59 of hypodynamy showed a moderate occurrence of cellular apoptosis in the proximal and distal tubules of experimental Japanese quail. The activity of AP in the brush border of the proximal tubules on days 14–29 of hypodynamy was normal in experimental animals and showed no significant differences in

Time Varying Behavior of the Loudspeaker Suspension

DEFF Research Database (Denmark)

Pedersen, Bo Rohde; Agerkvist, Finn T.

2007-01-01

The suspension part of the electrodynamic loudspeaker is often modelled as a simple linear spring with viscous damping, however the dynamic behaviour of the suspension is much more complicated than predicted by such a simple model. At higher levels the compliance becomes non-linear and often chan...... changes during excitation at high levels. This paper investigates how the compliance of the suspension depends on the excitation, i.e. level and frequency content. The measurements are compared with other known measurement methods of the suspension....

Study on kinematic and compliance test of suspension

Science.gov (United States)

Jing, Lixin; Wu, Liguang; Li, Xuepeng; Zhang, Yu

2017-09-01

Chassis performance development is a major difficulty in vehicle research and development, which is the main factor restricting the independent development of vehicles in China. These years, through a large number of studies, chassis engineers have found that the suspension K&C characteristics as a quasi-static characteristic of the suspension provides a technical route for the suspension performance R&D, and the suspension K&C test has become an important means of vehicle benchmarking, optimization and verification. However, the research on suspension K&C test is less in china, and the test conditions and setting requirements vary greatly from OEM to OEM. In this paper, the influence of different settings on the characteristics of the suspension is obtained through experiments, and the causes of the differences are analyzed; in order to fully reflect the suspension characteristics, the author recommends the appropriate test case and settings.

Pair-correlations in swimmer suspensions

Science.gov (United States)

Nambiar, Sankalp; Subramanian, Ganesh

2017-11-01

Suspensions of rear-actuated swimming microorganisms, such as E.coli, exhibit several interesting phenomena including spontaneous pattern formation above a critical concentration, novel rheological properties, shear-induced concentration banding etc. Explanations based on mean-field theory are only qualitative, since interactions between swimmers are important for typical experimental concentrations. We analytically characterize the hydrodynamic pair-interactions in a quiescent suspension of slender straight swimmers. The pair-correlation, calculated at leading order by integrating the swimmer velocity disturbances along straight trajectories, decays as 1/r2 for r >> L (L being the swimmer size). This allows us to characterize both polar and nematic correlations in an interacting swimmer suspension. In the absence of correlations, the velocity covariance asymptotes from a constant for r > L, the latter being characteristic of a suspension of non-interacting point force-dipoles. On including correlations, the slow decay of the pair-orientation correlation leads to an additional contribution to the velocity covariance that diverges logarithmically with system size.

21 CFR 1301.36 - Suspension or revocation of registration; suspension of registration pending final order...

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Suspension or revocation of registration; suspension of registration pending final order; extension of registration pending final order. 1301.36... registration pending final order; extension of registration pending final order. (a) For any registration...

39 CFR 3001.114 - Suspension pending review.

Science.gov (United States)

2010-07-01

... 39 Postal Service 1 2010-07-01 2010-07-01 false Suspension pending review. 3001.114 Section 3001... Suspension pending review. (a) Application. Application for suspension of a determination of the Postal Service to close or consolidate any post office pending the outcome of an appeal to the Postal Regulatory...

21 CFR 520.905a - Fenbendazole suspension.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Fenbendazole suspension. 520.905a Section 520.905a... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.905a Fenbendazole suspension. (a) Specifications. Each milliliter of suspension contains 100 milligrams (mg) fenbendazole. (b...

Proximal Alternating Direction Method with Relaxed Proximal Parameters for the Least Squares Covariance Adjustment Problem

Directory of Open Access Journals (Sweden)

Minghua Xu

2014-01-01

Full Text Available We consider the problem of seeking a symmetric positive semidefinite matrix in a closed convex set to approximate a given matrix. This problem may arise in several areas of numerical linear algebra or come from finance industry or statistics and thus has many applications. For solving this class of matrix optimization problems, many methods have been proposed in the literature. The proximal alternating direction method is one of those methods which can be easily applied to solve these matrix optimization problems. Generally, the proximal parameters of the proximal alternating direction method are greater than zero. In this paper, we conclude that the restriction on the proximal parameters can be relaxed for solving this kind of matrix optimization problems. Numerical experiments also show that the proximal alternating direction method with the relaxed proximal parameters is convergent and generally has a better performance than the classical proximal alternating direction method.

Non-homogeneous flow profiles in sheared bacterial suspensions

Science.gov (United States)

Samanta, Devranjan; Cheng, Xiang

Bacterial suspensions under shear exhibit interesting rheological behaviors including the remarkable ``superfluidic'' state with vanishing viscosity at low shear rates. Theoretical studies have shown that such ``superfluidic'' state is linked with non-homogeneous shear flows, which are induced by coupling between nematic order of active fluids and hydrodynamics of shear flows. However, although bulk rheology of bacterial suspensions has been experimentally studied, shear profiles within bacterial suspensions have not been explored so far. Here, we experimentally investigate the flow behaviors of E. coli suspensions under planar oscillatory shear. Using confocal microscopy and PIV, we measure velocity profiles across gap between two shear plates. We find that with increasing shear rates, high-concentration bacterial suspensions exhibit an array of non-homogeneous flow behaviors like yield-stress flows and shear banding. We show that these non-homogeneous flows are due to collective motion of bacterial suspensions. The phase diagram of sheared bacterial suspensions is systematically mapped as functions of shear rates an bacterial concentrations. Our experiments provide new insights into rheology of bacterial suspensions and shed light on shear induced dynamics of active fluids. Chemical Engineering and Material Science department.

On the Benefits of Semi-Active Suspensions with Inerters

Directory of Open Access Journals (Sweden)

Xin-Jie Zhang

2012-01-01

Full Text Available Inerters have become a hot topic in recent years especially in vehicle, train, building suspension systems, etc. Eight different layouts of suspensions were analyzed with a quarter-car model in this paper. Dimensionless root mean square (RMS responses of the sprung mass vertical acceleration, the suspension travel, and the tire deflection are derived which were used to evaluate the performance of the quarter-car model. The behaviour of semi-active suspensions with inerters using Groundhook, Skyhook, and Hybrid control has been evaluated and compared to the performance of passive suspensions with inerters. Sensitivity analysis was applied to the development of a high performance semi-active suspension with an inerter. Numerical simulations indicate that a semi-active suspension with an inerter has much better performance than the passive suspension with an inerter, especially with the Hybrid control method, which has the best compromise between comfort and road holding quality.

Boundary Effects and Shear Thickening of Colloidal Suspensions: A study based on measurement of Suspension Microstructure

Science.gov (United States)

Perera, M. Tharanga D.

Microstructure is key to understanding rheological behaviors of flowing particulate suspensions. During the past decade, Stokesian Dynamics simulations have been the dominant method of determining suspension microstructure. Structure results obtained numerically reveal that an anisotropic structure is formed under high Peclet (Pe) number conditions. Researchers have used various experimental techniques such as small angle neutron scattering (SANS) and light scattering methods to validate microstructure. This work outlines an experimental technique based on confocal microscopy to study microstructure of a colloidal suspension in an index-matched fluid flowing in a microchannel. High resolution scans determining individual particle locations in suspensions 30-50 vol % yield quantitative results of the local microstructure in the form of the pair distribution function, g(r). From these experimentally determined g(r), the effect of shear rate, quantified by the Peclet number as a ratio of shear and Brownian stress, on the suspension viscosity and normal stress follow that seen in macroscopic rheological measurements and simulations. It is generally believed that shear thickening behavior of colloidal suspensions is driven by the formation of hydroclusters. From measurements of particle locations, hydroclusters are identified. The number of hydroclusters grows exponentially with increasing Pe, and the onset of shear thickening is driven by the increase in formation of clusters having 5-8 particles. At higher Pe, we notice the emergence of 12 or more particle clusters. The internal structure of these hydroclusters has been investigated, and there is some evidence that particles internal to hydroclusters preferentially align along the 45° and 135° axis. Beyond observations of bulk suspension behavior, the influence of boundaries on suspension microstructure is also investigated. Experiments were performed for suspensions flowing over smooth walls, made of glass

Introducing Dual Suspension System in Road Vehicles

Directory of Open Access Journals (Sweden)

Imtiaz Hussain

2013-04-01

Full Text Available The main objective of suspension system is to reduce the motions of the vehicle body with respect to road disturbances. The conventional suspension systems in road vehicles use passive elements such as springs and dampers to suppress the vibrations induced by the irregularities in the road. But these conventional suspension systems can suppress vibrations to a certain limit. This paper presents a novel idea to improve the ride quality of roads vehicles without compromising vehicle?s stability. The paper proposes the use of primary and secondary suspension to suppress the vibrations more effectively.

Direct physical contact between intercalated cells in the distal convoluted tubule and the afferent arteriole in mouse kidneys.

Directory of Open Access Journals (Sweden)

Hao Ren

Full Text Available Recent physiological studies in the kidney proposed the existence of a secondary feedback mechanism termed 'crosstalk' localized after the macula densa. This newly discovered crosstalk contact between the nephron tubule and its own afferent arteriole may potentially revolutionize our understanding of renal vascular resistance and electrolyte regulation. However, the nature of such a crosstalk mechanism is still debated due to a lack of direct and comprehensive morphological evidence. Its exact location along the nephron, its prevalence among the different types of nephrons, and the type of cells involved are yet unknown. To address these issues, computer assisted 3-dimensional nephron tracing was applied in combination with direct immunohistochemistry on plastic sections and electron microscopy. 'Random' contacts in the cortex were identified by the tracing and excluded. We investigated a total of 168 nephrons from all cortical regions. The results demonstrated that the crosstalk contact existed, and that it was only present in certain nephrons (90% of the short-looped and 75% of the long-looped nephrons. The crosstalk contacts always occurred at a specific position--the last 10% of the distal convoluted tubule. Importantly, we demonstrated, for the first time, that the cells found in the tubule wall at the contact site were always type nonA-nonB intercalated cells. In conclusion, the present work confirmed the existence of a post macula densa physical crosstalk contact.

Direct physical contact between intercalated cells in the distal convoluted tubule and the afferent arteriole in mouse kidneys.

Science.gov (United States)

Ren, Hao; Liu, Ning-Yu; Andreasen, Arne; Thomsen, Jesper S; Cao, Liu; Christensen, Erik I; Zhai, Xiao-Yue

2013-01-01

Recent physiological studies in the kidney proposed the existence of a secondary feedback mechanism termed 'crosstalk' localized after the macula densa. This newly discovered crosstalk contact between the nephron tubule and its own afferent arteriole may potentially revolutionize our understanding of renal vascular resistance and electrolyte regulation. However, the nature of such a crosstalk mechanism is still debated due to a lack of direct and comprehensive morphological evidence. Its exact location along the nephron, its prevalence among the different types of nephrons, and the type of cells involved are yet unknown. To address these issues, computer assisted 3-dimensional nephron tracing was applied in combination with direct immunohistochemistry on plastic sections and electron microscopy. 'Random' contacts in the cortex were identified by the tracing and excluded. We investigated a total of 168 nephrons from all cortical regions. The results demonstrated that the crosstalk contact existed, and that it was only present in certain nephrons (90% of the short-looped and 75% of the long-looped nephrons). The crosstalk contacts always occurred at a specific position--the last 10% of the distal convoluted tubule. Importantly, we demonstrated, for the first time, that the cells found in the tubule wall at the contact site were always type nonA-nonB intercalated cells. In conclusion, the present work confirmed the existence of a post macula densa physical crosstalk contact.

The pelvic kidney of male Ambystoma maculatum (Amphibia, urodela, ambystomatidae) with special reference to the sexual collecting ducts.

Science.gov (United States)

Siegel, Dustin S; Sever, David M; Aldridge, Robert D

2010-12-01

This study details the gross and microscopic anatomy of the pelvic kidney in male Ambystoma maculatum. The nephron of male Ambystoma maculatum is divided into six distinct regions leading sequentially away from a renal corpuscle: (1) neck segment, which communicates with the coelomic cavity via a ventrally positioned pleuroperitoneal funnel, (2) proximal tubule, (3) intermediate segment, (4) distal tubule, (5) collecting tubule, and (6) collecting duct. The proximal tubule is divided into a vacuolated proximal region and a distal lysosomic region. The basal plasma membrane is modified into intertwining microvillus lamellae. The epithelium of the distal tubule varies little along its length and is demarcated by columns of mitochondria with their long axes oriented perpendicular to the basal lamina. The distal tubule possesses highly interdigitating microvillus lamellae from the lateral membranes and pronounced foot processes of the basal membrane that are not intertwined, but perpendicular to the basal lamina. The collecting tubule is lined by an epithelium with dark and light cells. Light cells are similar to those observed in the distal tuble except with less mitochondria and microvillus lamellae of the lateral and basal plasma membrane. Dark cells possess dark euchromatic nuclei and are filled with numerous small mitochondria. The epithelium of the neck segment, pleuroperitoneal funnel, and intermediate segment is composed entirely of ciliated cells with cilia protruding from only the central portion of the apical plasma membrane. The collecting duct is lined by a highly secretory epithelium that produces numerous membrane bound granules that stain positively for neutral carbohydrates and proteins. Apically positioned ciliated cells are intercalated between secretory cells. The collecting ducts anastomose caudally and unite with the Wolffian duct via a common collecting duct. The Wolffian duct is secretory, but not to the extent of the collecting duct

Proximity credentials: A survey

International Nuclear Information System (INIS)

Wright, L.J.

1987-04-01

Credentials as a means of identifying individuals have traditionally been a photo badge and more recently, the coded credential. Another type of badge, the proximity credential, is making inroads in the personnel identification field. This badge can be read from a distance instead of being veiewed by a guard or inserted into a reading device. This report reviews proximity credentials, identifies the companies marketing or developing proximity credentials, and describes their respective credentials. 3 tabs

Electrostratic stabilization of suspensions in non-aqueous media

NARCIS (Netherlands)

Hoeven, van der P.C.

1991-01-01

Concentrated suspensions of detergent powder solids in a liquid nonionic surfactant are considered for practical application as liquid detergent products. If no precautions are taken, upon storage the viscosity of such suspensions increases and the pourability drops because the suspensions are

Adaptive suspension strategy for a double wishbone suspension through camber and toe optimization

Directory of Open Access Journals (Sweden)

C. Kavitha

2018-02-01

Full Text Available A suspension system is responsible for the safety of vehicle during its manoeuvre. It serves the dual purpose of providing stability to the vehicle while providing a comfortable ride quality to the occupants. Recent trends in suspension system have focused on improving comfort and handling of vehicles while keeping the cost, space and feasibility of manufacturing in the constraint. This paper proposes a method for improving handling characteristics of a vehicle by controlling camber and toe angle using variable length arms in an adaptive manner. In order to study the effect of dynamic characteristics of the suspension system, a simulation study has been done in this work. A quarter car physical model with double wishbone suspension geometry is modelled in SolidWorks. It is then imported and simulated using SimMechanics platform in MATLAB. The output characteristics of the passive system (without variable length arms were validated on MSC ADAMS software. The adaptive system intends to improve vehicle handling characteristics by controlling the camber and toe angles. This is accomplished by two telescopic arms with an actuator which changes the camber and toe angle of the wheel dynamically to deliver best possible traction and manoeuvrability. Two PID controllers are employed to trigger the actuators based on the camber and toe angle from the sensors for reducing the error existing between the actual and desired value. The arms are driven by actuators in a closed loop feedback manner with help of a separate control system. Comparison between active and passive systems is carried out by analysing graphs of various parameters obtained from MATLAB simulation. From the results, it is observed that there is a reduction of 58% in the camber and 96% in toe gain. Hence, the system provides the scope of considerable adaptive strategy in controlling dynamic characteristics of the suspension system.

System and technique for ultrasonic characterization of settling suspensions

Energy Technology Data Exchange (ETDEWEB)

Greenwood, Margaret S [Richland, WA; Panetta, Paul D [Richland, WA; Bamberger, Judith A [Richland, WA; Pappas, Richard A [Richland, WA

2006-11-28

A system for determining properties of settling suspensions includes a settling container, a mixer, and devices for ultrasonic interrogation transverse to the settling direction. A computer system controls operation of the mixer and the interrogation devices and records the response to the interrogating as a function of settling time, which is then used to determine suspension properties. Attenuation versus settling time for dilute suspensions, such as dilute wood pulp suspension, exhibits a peak at different settling times for suspensions having different properties, and the location of this peak is used as one mechanism for characterizing suspensions. Alternatively or in addition, a plurality of ultrasound receivers are arranged at different angles to a common transmitter to receive scattering responses at a variety of angles during particle settling. Angular differences in scattering as a function of settling time are also used to characterize the suspension.

Megalin is a receptor for apolipoprotein M, and kidney-specific megalin-deficiency confers urinary excretion of apolipoprotein M

DEFF Research Database (Denmark)

Faber, Kirsten; Hvidberg, Vibeke; Moestrup, Søren K

2006-01-01

. In addition, apoM is expressed at high levels in the kidney tubule cells. In this study, we show that the multiligand receptor megalin, which is expressed in kidney proximal tubule cells, is a receptor for apoM and mediates its uptake in the kidney. To examine apoM binding to megalin, a recombinant apo....... To examine the importance of apoM binding by megalin in vivo, we analyzed mice with a tissue-specific deficiency of megalin in the kidney. Megalin deficiency was associated with pronounced urinary excretion of apoM, whereas apoM was not detected in normal mouse, human, or rat urine. Gel filtration analysis...... showed that the urinary apoM-containing particles were small and devoid of apoA-I. The results suggest that apoM binds to megalin and that megalin-mediated endocytosis in kidney proximal tubules prevents apoM excretion in the urine....

Pathophysiological aspect of metabolic acid-base disorders

Directory of Open Access Journals (Sweden)

Nešović-Ostojić Jelena

2016-01-01

Full Text Available Maintaing the arterial pH values (in normal range of 7,35-7,45 is one of the main principles of homeostasis. Regulatory responses, including chemical buffering (extracellular, intracellular, sceletal, the regulation of pCO2 by the respiratory system, and the regulation of [HCO3-] by the kidneys, act in concert to maintain normal arterial pH value. The main extracellular chemical buffer is bicarbonate-carbonic acid buffer system. The kidneys contribute to the regulation of hydrogen (and bicarbonate in body fluids in two ways. Proximal tubules are important in bicarbonate reabsorption and distal tubules excrete hydrogen ion (as ammonium ion or titratable acid. There are four simple acid-base disorders: metabolic acidosis and metabolic alkalosis; respiratory acidosis and respiratory alkalosis. Metabolic acidosis can occur because of an increase in endogenous acid production (such as lactate and ketoacids, loss of bicarbonate (as in diarrhea, or accumulation of endogenous acids (as in renal failure. Metabolic acidosis can also be with high and normal (hyperchloremic metabolic acidosis anion gap. Renal tubular acidosis (RTA is a form of hyperchloremic metabolic acidosis which occurs when the renal damage primarily affects tubular function. The main problem in distal RTA is reduced H+ excretion in distal tubule. Type 2 RTA is also called proximal RTA because the main problem is greatly impaired reabsorption of bicarbonate in proximal tubule. Impaired cation exchange in distal tubule is the main problem in RTA type 4. Metabolic alkalosis occurs as a result of net gain of [HCO3-] or loss of nonvolatile acid from extracellular fluids. Metabolic alkalosis can be associated with reduced or increased extracellular volume.

Hybrid superconducting magnetic suspensions

International Nuclear Information System (INIS)

Tixador, P.; Hiebel, P.; Brunet, Y.; Chaud, X.; Gautier-Picard, P.

1996-01-01

Superconductors, especially high T c ones, are the most attractive materials to design stable and fully passive magnetic suspensions which have to control five degrees of freedom. The hybrid superconducting magnetic suspensions present high performances and a simple cooling mode. They consist of a permanent magnet bearing, stabilized by a suitable magnet-superconductor structure. Several designs are given and compared in terms of forces and stiffnesses. The design of the magnet bearing plays an important part. The superconducting magnetic bearing participates less in levitation but must provide a high stabilizing stiffness. This is achieved by the magnet configuration, a good material in term of critical current density and field cooling. A hybrid superconducting suspension for a flywheel is presented. This system consists of a magnet thrust bearing stabilized by superconductors interacting with an alternating polarity magnet structure. First tests and results are reported. Superconducting materials are magnetically melt-textured YBaCuO

The adult Drosophila malphigian tubules are maintained by multipotent stem cells | Center for Cancer Research

Science.gov (United States)

All animals must excrete the waste products of metabolism. Excretion is performed by the kidney in vertebrates and by the Malpighian tubules in Drosophila. The mammalian kidney has an inherent ability for recovery and regeneration after ischemic injury. Stem cells and progenitor cells have been proposed to be responsible for repair and regeneration of injured renal tissue.

Study on Dynamic Behaviour of Wishbone Suspension System

International Nuclear Information System (INIS)

Kamal, M; Rahman, M M

2012-01-01

This paper presents the characteristic model of the wishbone suspension system using the quarter car model approach. Suspension system in an automobile provides vehicle control and passenger comfort by providing isolation from road disturbances. This makes it essential that the detailed behavior of suspension should be known to optimize the performance. A kinetic study is performed using multi body system (MBS) analysis. The dirt road profile is considered as an applied loading. The spring constant, damping coefficient and sprung mass are studied on the performance of the suspension system. It can be observed that the spring constant is inversely related with time required to return to initial position and the amount of deformations. The damping ratio affects the suppression of spring oscillations, beyond a certain limit damping ration has the negligible effect. Sprung mass effected the equilibrium position of the suspension system with a small effect on its oscillation behavior. It is shown that the spring constant, damping ratio and sprung mass are significant parameters to design the suspension system. This study is essential for complete understanding of working of the suspension system and a future study with real geometries.

Protein kinase C-mediated ATP stimulation of Na(+)-ATPase activity in LLC-PK1 cells involves a P2Y2 and/or P2Y4 receptor.

Science.gov (United States)

Wengert, M; Ribeiro, M C; Abreu, T P; Coutinho-Silva, R; Leão-Ferreira, L R; Pinheiro, A A S; Caruso-Neves, C

2013-07-15

ATP-activated P2Y receptors play an important role in renal sodium excretion. The aim of this study was to evaluate the modulation of ATPase-driven sodium reabsorption in the proximal tubule by ATP or adenosine (Ado). LLC-PK1 cells, a model of porcine proximal tubule cells, were used. ATP (10(-6)M) or Ado (10(-6)M) specifically stimulated Na(+)-ATPase activity without any changes in (Na(+)+K(+))-ATPase activity. Our results show that the Ado effect is mediated by its conversion to ATP. Furthermore, it was observed that the effect of ATP was mimicked by UTP, ATPγS and 2-thio-UTP, an agonist of P2Y2 and P2Y4 receptors. In addition, ATP-stimulated Na(+)-ATPase activity involves protein kinase C (PKC). Our results indicate that ATP-induced stimulation of proximal tubule Na(+)-ATPase activity is mediated by a PKC-dependent P2Y2 and/or P2Y4 pathway. These findings provide new perspectives on the role of the effect of P2Y-mediated extracellular ATP on renal sodium handling. Copyright © 2013 Elsevier Inc. All rights reserved.

Protective Effect of Urtica dioica L. (Urticaceae) on Morphometric and Morphologic Alterations of Seminiferous Tubules in STZ Diabetic Rats.

Science.gov (United States)

Golalipour, Mohammad Jafar; Kabiri Balajadeh, Babak; Ghafari, Soraya; Azarhosh, Ramin; Khori, Vahid

2011-09-01

Urtica dioica L. has been known as a medicinal plant in the world. This study was conducted to determine the effects of the hydroalcoholic extract of Urtica dioica leaves on seminiferous tubules of diabetic rats. Animals were allocated to control, diabetic and protective groups. Treated animals received extract of U. dioica (100 mg/ kg/ day) IP for the first 5 days and STZ injection on the 6th day. After 5 weeks, testes removed and stained with H&E technique. Tubular cell disintegration, sertoli and spermatogonia cell vacuolization, and decrease in sperm concentration observed in diabetic in comparison with control and protective groups. External seminiferous tubular diameter and seminiferous epithelial height significantly reduced (Pdioica, before induction of diabetes; has protective role on seminiferous tubules alterations.

The myopathy-causing mutation DNM2-S619L leads to defective tubulation in vitro and in developing zebrafish

Directory of Open Access Journals (Sweden)

Elizabeth M. Gibbs

2014-01-01

Full Text Available DNM2 is a ubiquitously expressed GTPase that regulates multiple subcellular processes. Mutations in DNM2 are a common cause of centronuclear myopathy, a severe disorder characterized by altered skeletal muscle structure and function. The precise mechanisms underlying disease-associated DNM2 mutations are unresolved. We examined the common DNM2-S619L mutation using both in vitro and in vivo approaches. Expression of DNM2-S619L in zebrafish led to the accumulation of aberrant vesicular structures and to defective excitation-contraction coupling. Expression of DNM2-S619L in COS7 cells resulted in defective BIN1-dependent tubule formation. These data suggest that DNM2-S619L causes disease, in part, by interfering with membrane tubulation.

Attractive and repulsive magnetic suspension systems overview

Science.gov (United States)

Cope, David B.; Fontana, Richard R.

1992-01-01

Magnetic suspension systems can be used in a wide variety of applications. The decision of whether to use an attractive or repulsive suspension system for a particular application is a fundamental one which must be made during the design process. As an aid to the designer, we compare and contrast attractive and repulsive magnetic suspension systems and indicate whether and under what conditions one or the other system is preferred.

Ensemble-average versus suspension-scale Cauchy continuum-mechanical definitions of stress in polarized suspensions: Global homogenization of a dilute suspension of dipolar spherical particles

International Nuclear Information System (INIS)

Almog, Y.; Brenner, H.

1999-01-01

The macroscale rheological properties of a dilute suspension exposed to a uniform external field and composed of identical, rigid, inhomogeneous, dipolar, spherical particles dispersed in an incompressible Newtonian fluid and possessing the same mean density as the latter fluid are derived from knowledge of its microscale properties by applying a global ensemble-averaging technique. Each dipole, which is permanently embedded in the particle, is assumed to be generated by the presence of an inhomogeneous external body-force field in the particle interior resulting from the action of the uniform external field on an inhomogeneous distribution of interior matter. It is shown that although the ensemble-average stress tensor is symmetric, the suspension nevertheless behaves macroscopically as if it possessed an asymmetric stress tensor. This seeming contradiction can be traced to the fact that the average body force acting on the contents of any arbitrarily drawn volume lying in the interior of the suspension does not vanish despite the fact that each particle is 'neutrally buoyant'. That this force is not zero stems from the fact that some particles necessarily straddle the closed surface bounding that volume, and that the distribution of external body forces over the interiors of these particles is nonuniform. As such, that portion of the spherical particle lying outside of the surface enclosing the domain exerts a force on the remaining portion of the sphere lying within that domain. We then demonstrate that the natural macroscopic model, which is derived by equating the divergence of the suspension-scale stress appearing in that model to the ensemble-average external body-force field, and which predicts a symmetric stress tensor, is macroscopically deficient with respect to the more intuitive asymmetric stress model usually proposed by continuum mechanicians for such a suspension. It is shown that the latter, continuum-mechanical model recovers all the physically

Autoradiographic localization of Na+-K+-ATPase with 3H-ouabain

International Nuclear Information System (INIS)

Dormans, J.A.M.A.

1976-01-01

Using 3 H-ouabain as an inhibitor, the site of the Na + -K + -ATPase system in cells was determined autoradiographically. Experiments were performed woth guinea pig's kidney tissue. The application of light microscopical autoradiography to freeze-dried tissue showed that especially the distal tubule, and to a smaller extent the proximal tubule and the collecting tubule have Na + -K + -ATPase. Electron microscopical autoradiography showed that this activity is restricted to the baso-lateral plasmamembranes. The quantity of specific bound ouabain turns out to be correlated to the quantity of baso-lateral plasmamembrane's surface

Na⁺ Recirculation and Isosmotic Transport

DEFF Research Database (Denmark)

Larsen, Erik Hviid; Møbjerg, N

2006-01-01

of the absorbate. Mathematical modeling reproducing bioelectric and hydrosmotic properties of small intestine and proximal tubule, respectively, predicts a significant range of observations such as isosmotic transport, hyposmotic transport, solvent drag, anomalous solvent drag, the residual hydraulic permeability...... in proximal tubule of AQP1 (-/-) mice, and the inverse relationship between hydraulic permeability and the concentration difference needed to reverse transepithelial water flow. The model reproduces the volume responses of cells and lateral intercellular space (lis) following replacement of luminal Na...... external baths. Hyperosmolarity of lis is governed by the hydraulic permeability of the apical plasma membrane and tight junction with 6-7 mOsm in small intestine and

Fracture in Kaolinite clay suspensions

Science.gov (United States)

Kosgodagan Acharige, Sebastien; Jerolmack, Douglas J.; Arratia, Paulo E.

2017-11-01

Clay minerals are involved in many natural (landslides, river channels) and industrial processes (ceramics, cosmetics, oil recovery). They are plate shaped charged colloids and exhibit different flow properties than simpler colloids when suspended in a liquid such as thixotropy and shear-banding. kaolinite platelets are non-swelling, meaning that the stacks formed by the platelets do not have water layers, and thus the suspension does not have a sol-gel transition. However, it has been shown that kaolinite suspensions possesses a non-zero yield stress even at low concentrations, indicating that the particles arrange themselves in a structure through attractive interactions. Here, we experimentally investigate the sedimentation of kaolinite suspensions in a Hele-Shaw cell. The sedimentation of these dilute suspensions can display solid behavior like fracture, revealed in cross-polarized light, which is linked to the failure of the weakly-bonded structure (typical yield stress 10-2 Pa). By changing the interaction potential of the particles (by sonication or introducing salts), we show through these sedimentation experiments, how the fracture pattern can be avoided. Research was sponsored by the Army Research Laboratory and was accomplished under Grant Number 569074.

Effect of Tamoxifen on Seminiferous Tubules Structure during Pregnancy in Adult Mice

Directory of Open Access Journals (Sweden)

J Soleimani Rad

2016-03-01

Full Text Available Introduction: Tamoxifen is a nonsteroidal drug which mainly treats breast cancer. It is also applied for stimulation of ovulation and remedy of infertility. Regarding the tamoxifen binding to estrogen receptors and the possible role of estrogens in spermatogenesis, the present study aimed to histologically evaluate spermatogenesis in the seminiferous ducts of mice, whose mothers had received tamoxifen during pregnancy. Methods: In the present study, 30 female and 15 male mice of NMRI race were selected for mating. Since 13th day of pregnancy, the experimental group received tamoxifen with the dosage of 5 mg/kg intra-peritoneally for 7 days, wherease the control group received normal saline. After childbirth of the mated mice, male infants were selected and monitored in the standard laboratory conditions. After reaching the age of puberty (6-8Weeks, adult mice were sacrificed by the cervical dislocation, and the testes were removed for histological evaluation of spermatogenesis. After routine histological processing, the samples were studied by the light microscope. Results: Histological studies showed that spermatogenic and Sertoli cells in the seminiferous tubules in control and experimental groups were significantly different, though no difference was observed in the number of Leydig cells in the both groups. Conclusion: The findings of the present study showed that tamoxifen exposure during development can cause histological changes in the seminiferous tubules, which can lead to infertility in the male rat.

A proximal point algorithm with generalized proximal distances to BEPs

OpenAIRE

Bento, G. C.; Neto, J. X. Cruz; Lopes, J. O.; Soares Jr, P. A.; Soubeyran, A.

2014-01-01

We consider a bilevel problem involving two monotone equilibrium bifunctions and we show that this problem can be solved by a proximal point method with generalized proximal distances. We propose a framework for the convergence analysis of the sequences generated by the algorithm. This class of problems is very interesting because it covers mathematical programs and optimization problems under equilibrium constraints. As an application, we consider the problem of the stability and change dyna...

36 CFR 296.10 - Suspension and revocation of permits.

Science.gov (United States)

2010-07-01

... AGRICULTURE PROTECTION OF ARCHAEOLOGICAL RESOURCES: UNIFORM REGULATIONS § 296.10 Suspension and revocation of... correct the situation which led to suspension of the permit. (b) Suspension or revocation for management...

Linear viscoelastic properties of aging suspensions

NARCIS (Netherlands)

Purnomo, E.H.; Purnomo, E.H; van den Ende, Henricus T.M.; Mellema, J.; Mugele, Friedrich Gunther

2006-01-01

We have examined the linear viscoelastic behavior of poly-N-isopropylacrylamide (PNIPAM) microgel suspensions in order to obtain insight in the aging processes in these densely packed suspensions at various temperatures below the volume transition temperature. The system is found to display a strong

Vitality of Enterococcus faecalis inside dentinal tubules after five root canal disinfection methods

OpenAIRE

Vatkar, Niranjan Ashok; Hegde, Vivek; Sathe, Sucheta

2016-01-01

Aim: To compare the vitality of Enterococcus faecalis within dentinal tubules after subjected to five root canal disinfection methods. Materials and Methods: Dentin blocks (n = 60) were colonized with E. faecalis. After 4 weeks of incubation, the dentin blocks were divided into one control and five test groups (n = 10 each). The root canals of test groups were subjected to one of the disinfection methods, namely, normal saline (NS), sodium hypochlorite (NaOCl), chlorhexidine digluconate (C...

Pengaruh Pemberian Valsartan Dan Kurkumin Terhadap Pembentukan Fibrosis Di Tubulus Proksimal Ginjal Akibat Obstruksi Ureter Unilateral pada Tikus Wistar.

Directory of Open Access Journals (Sweden)

Lubis M

2013-01-01

. Perbedaan bermakna terbentuKata kunci: Obstruksi ureter, Valsartan, Kurkumin, Fibrosis, Degenerasi hidrofilik, AtrofiAbstractIntroduction: ureter obstruction is a condition where is an obstacle for urine flow from renal to blast (vesica urinaria. The obstruction in ureter will decrease glomerulus filtration flow and it destroys renal parenchym. Fibroses in obstructed renal present through two mediators, there are necrotizing tumor factors-α (TNF-α and angiotension-II. Obstruction of this two mediators will decrease fibroses grading in proximal tubules of renal caused by obtruction. One of TNF-α inhibitors is curcumene and angiotension-II will be obstructed by valsartan. Methods: this experiment is kind of experimental type using animal experiment (Wistar Mice. Wistar Mice are divided into two groups, each group consist of 15 mice, so the total are 30 mice. This animals tighted with at proximal ureter The first group is control one, given valsartan. The second group is given valsartan and curcumene. Oral route and dilution before given. Medicine is given use 1 cc spuit. Giving action in 14 days. The fifteenth day, we take renal of Wistar and do histology examination. Significant difference between fibroses forming in proximal tubulus analyzed by Chi Square Statistic Test with correction of Yates and T-Test, beside that, hydofic degeneration and atrophy in proximal tubulus analyzed by T-Test Statistic Test. Result: there is significant difference in forming of fibroses in proximal tubules of renal between action group and controlled group (Chi Square with p ≤ 0.0001 and T-Test with p ≤ 0.000. In hydrophilic degeneration forming in proximal tubules gotten significant difference between two groups ( T-Test with p ≤ 0.000. In atrophy forming in proximal tubules, there is important difference between two groups (T-Test with p ≤ 0.000.Concultion. There is an effect in giving valsartan and curcumene to fibroses forming in proximal tubules of renal. There is significant

39 CFR 320.9 - Revocation or amendment of suspensions.

Science.gov (United States)

2010-07-01

... SUSPENSION OF THE PRIVATE EXPRESS STATUTES § 320.9 Revocation or amendment of suspensions. These suspensions... of operations (in dollar or volume terms, whichever is larger) lower than that antedating the...

Nonlinear Predictive Sliding Mode Control for Active Suspension System

Directory of Open Access Journals (Sweden)

Dazhuang Wang

2018-01-01

Full Text Available An active suspension system is important in meeting the requirements of the ride comfort and handling stability for vehicles. In this work, a nonlinear model of active suspension system and a corresponding nonlinear robust predictive sliding mode control are established for the control problem of active suspension. Firstly, a seven-degree-of-freedom active suspension model is established considering the nonlinear effects of springs and dampers; and secondly, the dynamic model is expanded in the time domain, and the corresponding predictive sliding mode control is established. The uncertainties in the controller are approximated by the fuzzy logic system, and the adaptive controller reduces the approximation error to increase the robustness of the control system. Finally, the simulation results show that the ride comfort and handling stability performance of the active suspension system is better than that of the passive suspension system and the Skyhook active suspension. Thus, the system can obviously improve the shock absorption performance of vehicles.

High-resolution imaging of selenium in kidneys: a localized selenium pool associated with glutathione peroxidase 3

Energy Technology Data Exchange (ETDEWEB)

Malinouski, M.; Kehr, S.; Finney, L.; Vogt, S.; Carlson, B.A.; Seravalli, J.; Jin, R.; Handy, D.E.; Park, T.J.; Loscalzo, J.; Hatfield, D.L.; Gladyshev, V.N. (Harvard-Med)

2012-04-17

Recent advances in quantitative methods and sensitive imaging techniques of trace elements provide opportunities to uncover and explain their biological roles. In particular, the distribution of selenium in tissues and cells under both physiological and pathological conditions remains unknown. In this work, we applied high-resolution synchrotron X-ray fluorescence microscopy (XFM) to map selenium distribution in mouse liver and kidney. Liver showed a uniform selenium distribution that was dependent on selenocysteine tRNA{sup [Ser]Sec} and dietary selenium. In contrast, kidney selenium had both uniformly distributed and highly localized components, the latter visualized as thin circular structures surrounding proximal tubules. Other parts of the kidney, such as glomeruli and distal tubules, only manifested the uniformly distributed selenium pattern that co-localized with sulfur. We found that proximal tubule selenium localized to the basement membrane. It was preserved in Selenoprotein P knockout mice, but was completely eliminated in glutathione peroxidase 3 (GPx3) knockout mice, indicating that this selenium represented GPx3. We further imaged kidneys of another model organism, the naked mole rat, which showed a diminished uniformly distributed selenium pool, but preserved the circular proximal tubule signal. We applied XFM to image selenium in mammalian tissues and identified a highly localized pool of this trace element at the basement membrane of kidneys that was associated with GPx3. XFM allowed us to define and explain the tissue topography of selenium in mammalian kidneys at submicron resolution.

Aging Selectively Modulates Vitamin C Transporter Expression Patterns in the Kidney.

Science.gov (United States)

Forman, Katherine; Martínez, Fernando; Cifuentes, Manuel; Bertinat, Romina; Salazar, Katterine; Nualart, Francisco

2017-09-01

In the kidney, vitamin C is reabsorbed from the glomerular ultrafiltrate by sodium-vitamin C cotransporter isoform 1 (SVCT1) located in the brush border membrane of the proximal tubules. Although we know that vitamin C levels decrease with age, the adaptive physiological mechanisms used by the kidney for vitamin C reabsorption during aging remain unknown. In this study, we used an animal model of accelerated senescence (SAMP8 mice) to define the morphological alterations and aging-induced changes in the expression of vitamin C transporters in renal tissue. Aging induced significant morphological changes, such as periglomerular lymphocytic infiltrate and glomerular congestion, in the kidneys of SAMP8 mice, although no increase in collagen deposits was observed using 2-photon microscopy analysis and second harmonic generation. The most characteristic histological alteration was the dilation of intracellular spaces in the basolateral region of proximal tubule epithelial cells. Furthermore, a combination of laser microdissection, qRT-PCR, and immunohistochemical analyses allowed us to determine that SVCT1 expression specifically increased in the proximal tubules from the outer strip of the outer medulla (segment S3) and cortex (segment S2) during aging and that these tubules also express GLUT1. We conclude that aging modulates vitamin C transporter expression and that renal over-expression of SVCT1 enhances vitamin C reabsorption in aged animals that may synthesize less vitamin C. J. Cell. Physiol. 232: 2418-2426, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

41 CFR 105-74.670 - Suspension.

Science.gov (United States)

2010-07-01

... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false Suspension. 105-74.670 Section 105-74.670 Public Contracts and Property Management Federal Property Management Regulations System...-GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 105-74.670 Suspension...

Behaviour of humic-bentonite aggregates in diluted suspensions ...

African Journals Online (AJOL)

Formation and disaggregation of micron-size aggregates in a diluted suspension made up of HSs and bentonite (B) were studied by tracing distribution of aggregate sizes and their counts in freshly prepared and aged suspensions, and at high (10 000) and low (1.0) [HS]/[B] ratios. Diluted HSB suspensions are unstable ...

Yield stress of alumina-zirconia suspensions

International Nuclear Information System (INIS)

Ramakrishnan, V.; Pradip; Malghan, S.G.

1996-01-01

The yield stress of concentrated suspensions of alumina, zirconia, and mixed alumina-zirconia powders was measured by the vane technique as a function of solids loading, relative amounts of alumina and zirconia, and pH. At the isoelectric point (IEP), the yield stress varied as the fourth power of the solids loading. The relative ratio of alumina and zirconia particles was important in determining the yield stress of the suspension at the IEP. The yield stress of single and mixed suspensions showed a marked variation with pH. The maximum value occurred at or near the IEP of the suspension. The effect of electrical double-layer forces on the yield stress can be described on the basis of the Derjaguin-Landau-Verwey-Overbeek (DLVO) theory. A normalized yield stress--that is, the ratio of the yield stress at a given pH to the yield stress at the IEP predicted by this model--showed good correlation with experimental data

Vaginal vault suspension during hysterectomy for benign indications

DEFF Research Database (Denmark)

Bonde, Lisbeth; Noer, Mette Calundann; Møller, Lars Alling

2017-01-01

Introduction and hypothesis: Several suspension methods are used to try to prevent pelvic organ prolapse (POP) after hysterectomy. We aimed to evaluate agreement on terminology and surgical procedure of these methods. Methods: We randomly chose 532 medical records of women with a history......: Regarding medical records, agreement on terminology was good among patients undergoing pooled suspension in cases of hysterectomy via the abdominal and vaginal route (agreement 78.7, 92.3%). Regarding videos, agreement on surgical procedure was good among pooled suspension patients in cases of hysterectomy...... via the abdominal, laparoscopic, and vaginal routes (agreement 88.9, 97.8, 100%). Agreement on individual suspension methods differed regarding both medical records (agreement 0–90.1%) and videos (agreement 0–100%). Conclusions: Agreement on terminology and surgical procedure regarding suspension...

Microstructural Dynamics and Rheology of Suspensions of Rigid Fibers

Science.gov (United States)

Butler, Jason E.; Snook, Braden

2018-01-01

The dynamics and rheology of suspensions of rigid, non-Brownian fibers in Newtonian fluids are reviewed. Experiments, theories, and computer simulations are considered, with an emphasis on suspensions at semidilute and concentrated conditions. In these suspensions, interactions between the particles strongly influence the microstructure and rheological properties of the suspension. The interactions can arise from hydrodynamic disturbances, giving multibody interactions at long ranges and pairwise lubrication forces over short distances. For concentrated suspensions, additional interactions due to excluded volume (contacts) and adhesive forces are addressed. The relative importance of the various interactions as a function of fiber concentration is assessed.

Introducing Dual Suspension System in Road Vehicles

OpenAIRE

Imtiaz Hussain; Jawaid Daudpoto; Ali Asghar Memon

2013-01-01

The main objective of suspension system is to reduce the motions of the vehicle body with respect to road disturbances. The conventional suspension systems in road vehicles use passive elements such as springs and dampers to suppress the vibrations induced by the irregularities in the road. But these conventional suspension systems can suppress vibrations to a certain limit. This paper presents a novel idea to improve the ride quality of roads vehicles without compromising vehicle?s stability...

Rheology of dense suspensions of non colloidal particles

Science.gov (United States)

Guazzelli, Élisabeth

2017-06-01

Dense suspensions are materials with broad applications both in industrial processes (e.g. waste disposal, concrete, drilling muds, metalworking chip transport, and food processing) and in natural phenomena (e.g. flows of slurries, debris, and lava). Despite its long research history and its practical relevance, the mechanics of dense suspensions remain poorly understood. The major difficulty is that the grains interact both by hydrodynamic interactions through the liquid and by mechanical contact. These systems thus belong to an intermediate regime between pure suspensions and granular flows. We show that we can unify suspension and granular rheology under a common framework by transferring the frictional approach of dry granular media to wet suspensions of spherical particles. We also discuss non-Newtonian behavior such as normal-stress differences and shear-induced migration. Beyond the classical problem of dense suspension of hard spheres which is far from being completely resolved, there are also entirely novel avenues of study concerning more complex mixtures of particles and fluids such as those involving other types of particles (e.g. fibers) or non-Newtonian fluids that we will also address.

Development of A New Automotive Active Suspension System

Science.gov (United States)

Yousef Abdulhammed, Eng.; Eng. Hisham Elsherif, Dr, Prof.

2017-12-01

The main objective was to develop a smart new vehicle suspension system that minimizes the road irregularities impact on the driver, also to increase performance and stability of the vehicle at high speeds. The central idea is based on modifying the normal passive suspension system into a computer controller hydraulic actuated active suspension system simply by adding a new component such as a hydraulic cylinder on a normal passive system. The new suspension system is economical to be wildly used in consumer’s cars with low prices. The new added components was analytically tested and modeled according to different parameters. A new test rig was implemented to simulate a real quarter suspension system. The new suspension model was controlled by feedback controller according to the road conditions; the controller output controls the cylinder actuator to compensate the road oscillations and increases the vehicle stability for the passenger. Finally, to maximize the aerodynamics coefficients of the vehicle during high speeds by controlling the vehicle clearance level from the ground to achieve full stability, steering and fuel economy.

Analysis of Train Suspension System Using MR dampers

Science.gov (United States)

RamaSastry, DVA; Ramana, K. V.; Mohan Rao, N.; Siva Kumar, SVR; Priyanka, T. G. L.

2016-09-01

This paper deals with introducing MR dampers to the Train Suspension System for improving the ride comfort of the passengers. This type of suspension system comes under Semi-active suspension system which utilizes the properties of MR fluid to damp the vibrations. In case of high speed trains, the coach body is subjected to vibrations due to vertical displacement, yaw and pitch movements. When the body receives these disturbances from the ground,the transmission of vibrations to the passenger increases which affect the ride comfort. In this work, the equations of motion of suspension system are developed for both conventional passive system and semi-active system and are modelled in Matlab/Simulink and analysis has been carried out. The passive suspension system analysis shows that it is taking more time to damp the vibrations and at the same time the transmissibility of vibrations is more.Introducing MR dampers,vertical and angular displacements of the body are computed and compared. The results show that the introduction of MR dampers into the train suspension system improves ride comfort.

Denervation and high-fat diet reduce insulin signaling in T-tubules in skeletal muscle of living mice

DEFF Research Database (Denmark)

Lauritzen, Hans P M; Ploug, Thorkil; Ai, Hua

2008-01-01

OBJECTIVE: Insulin stimulates muscle glucose transport by translocation of GLUT4 to sarcolemma and T-tubules. Despite muscle glucose uptake playing a major role in insulin resistance and type 2 diabetes, the temporal and spatial changes in insulin signaling and GLUT4 translocation during these co...

Reducing αENaC expression in kidney connecting tubule induces pseudohypoaldosteronism type 1 symptoms during K+ loading

DEFF Research Database (Denmark)

Poulsen, Søren Brandt; Praetorius, Jeppe; Damkier, Helle H

2015-01-01

Genetic inactivation of the epithelial Na(+) channel α-subunit (αENaC) in the renal collecting duct (CD) does not interfere with Na(+) and K(+) homeostasis in mice. However, inactivation in the CD and a part of the connecting tubule (CNT) induces autosomal recessive pseudohypoaldosteronism type 1...

Pitched Blade Turbine Efficiency at Particle Suspension

Directory of Open Access Journals (Sweden)

D. Ceres

2010-01-01

Full Text Available Mixing suspensions is a very important hydraulic operation. The pitched six-blade turbine is a widely-used axial-flow impeller. This paper deals with effect relative impeller size and particle content on theefficiency of a pitched six-blade turbine at particle suspension. Two pitched six-blade turbines were used in model measurements of just suspension impeller speed. The ratios of the vessel to agitator diameter D/d were 3 and 4.5. The measurements were carried out in a dish-bottomed vessel 300 mm in diameter. The just suspension impeller speeds were measured using an electrochemical method, and were checked visually. A 2.5 % NaCl water solution was used as the liquid phase, and glass particles with four equivalent diameters between 0.18 and 0.89 mmand volumetric concentration from 2.5 % to 40% were usedasthesolid phase. The criterion values πs=Po√Fr'3(d/D7 were calculated from the particle suspension and power consumption measurements. The dependencies of πs on particle content cv show that larger agitators are more efficient for higher particle content.

Dentinal tubule occluding capability of nano-hydroxyapatite; The in-vitro evaluation.

Science.gov (United States)

Baglar, Serdar; Erdem, Umit; Dogan, Mustafa; Turkoz, Mustafa

2018-04-29

In this in-vitro study, the effectiveness of experimental pure nano-hydroxyapatite (nHAP) and 1%, 2%, and 3% F¯ doped nano-HAp on dentine tubule occlusion was investigated. And also, the cytotoxicity of materials used in the experiment was evaluated. Nano-HAp types were synthesized by the precipitation method. Forty dentin specimens were randomly divided into five groups of; 1-no treatment (control), 2-specimens treated with 10% pure nano-HAp and 3, 4, 5 specimens treated with 1%, 2%, and 3% F - doped 10% nano-HAp, respectively. To evaluate the effectiveness of the materials used; pH, FTIR, and scanning electron microscopy evaluations were performed before and after degredation in simulated body fluid. To determine cytotoxicity of the materials, MTT assay was performed. Statistical evaluations were performed with F and t tests. All of the nano-HAp materials used in this study built up an effective covering layer on the dentin surfaces even with plugs in tubules. It was found that this layer had also a resistance to degradation. None of the evaluated nano-HAp types were have toxicity. Fluoride doping showed a positive effect on physical and chemical stability until a critical value of 1% F - . The all evaluated nano-HAp types may be effectively used in dentin hypersensitivity treatment. The formed nano-HAp layers were seem to resistant to hydrolic deletion. The pure and 1% F - doped nano-HAp showed the highest biocompatibility thus it was assessed that pure and 1% F - doped materials may be used as an active ingredient in dentin hypersensitivity agents. © 2018 Wiley Periodicals, Inc.

Suspension for the low frequency facility

CERN Document Server

Cella, G; Di Virgilio, A; Gaddi, A; Viceré, A

2000-01-01

We introduce the working principles of the VIRGO Low Frequency Facility (LFF), whose main aim is the measurement of the thermal noise in the VIRGO suspension system. We evaluate the displacement thermal noise of a mirror, which is an intermediate element of a double pendulum suspension system. This double pendulum will be suspended to the last stage of a VIRGO Super-Attenuator (SA), the prototype VIRGO suspension system being tested at the Pisa section of INFN. In the proposed configuration, we evaluate the spectrum of the thermal noise for different choices of the parameters: based on this study, we comment on the future directions to be undertaken in the LFF experiment.

Network synthesis and parameter optimization for vehicle suspension with inerter

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Long Chen

2016-12-01

Full Text Available In order to design a comfortable-oriented vehicle suspension structure, the network synthesis method was utilized to transfer the problem into solving a timing robust control problem and determine the structure of “inerter–spring–damper” suspension. Bilinear Matrix Inequality was utilized to obtain the timing transfer function. Then, the transfer function of suspension system can be physically implemented by passive elements such as spring, damper, and inerter. By analyzing the sensitivity and quantum genetic algorithm, the optimized parameters of inerter–spring–damper suspension were determined. A quarter-car model was established. The performance of the inerter–spring–damper suspension was verified under random input. The simulation results manifested that the dynamic performance of the proposed suspension was enhanced in contrast with traditional suspension. The root mean square of vehicle body acceleration decreases by 18.9%. The inerter–spring–damper suspension can inhibit the vertical vibration within the frequency of 1–3 Hz effectively and enhance the performance of ride comfort significantly.

49 CFR 393.207 - Suspension systems.

Science.gov (United States)

2010-10-01

... braking system. The vehicle shall be level (not tilting to the left or right). Air leakage shall not be... 49 Transportation 5 2010-10-01 2010-10-01 false Suspension systems. 393.207 Section 393.207... NECESSARY FOR SAFE OPERATION Frames, Cab and Body Components, Wheels, Steering, and Suspension Systems § 393...

Magnetic Suspension Technology Workshop

International Nuclear Information System (INIS)

Keckler, C.R.; Groom, N.J.; Britcher, C.P.

1993-01-01

In order to identify the state of magnetic suspension technology in such areas as rotating systems, pointing of experiments or subsystems, payload isolation, and superconducting materials, a workshop on Magnetic Suspension Technology was held at the Langley Research Center in Hampton, Virginia, on 2-4 Feb. 1988. The workshop included five technical sessions in which a total of 24 papers were presented. The technical sessions covered the areas of pointing, isolation, and measurement, rotating systems, modeling and control, and superconductors. A list of attendees is provided. Separate abstracts have been prepared for articles from this report

Na(+)-D-glucose cotransporter in the kidney of Squalus acanthias: molecular identification and intrarenal distribution.

Science.gov (United States)

Althoff, Thorsten; Hentschel, Hartmut; Luig, Jutta; Schütz, Hendrike; Kasch, Myriam; Kinne, Rolf K-H

2006-04-01

Using primers against conserved regions of mammalian Na(+)-d-glucose cotransporters (SGLT), a cDNA was cloned from the kidney of spiny dogfish shark (Squalus acanthias). On the basis of comparison of amino acid sequence, membrane topology, and putative glycosylation and phosphorylation sites, the cDNA could be shown to belong to the family of sglt genes. Indeed, Na(+)-dependent d-glucose uptake could be demonstrated after expression of the gene in Xenopus laevis oocytes. In a dendrogram, the SGLT from shark kidney has a high homology to the mammalian SGLT2. Computer analysis revealed that the elasmobranch protein is most similar to the mammalian proteins in the transmembrane regions and contains already all the amino acids identified to be functionally important, suggesting early conservation during evolution. Extramembraneous loops show larger variations. This holds especially for loop 13, which has been implied as a phlorizin-binding domain. Antibodies were generated and the intrarenal distribution of the SGLT was studied in cryosections. In parallel, the nephron segments were identified by lectins. Positive immunoreactions were found in the proximal tubule in the early parts PIa and PIb and the late segment PIIb. The large PIIa segment of the proximal tubule showed no reaction. In contrast to the mammalian kidney also the late distal tubule, the collecting tubule, and the collecting duct showed immunoreactivity. The molecular information confirms previous vesicle studies in which a low affinity SGLT with a low stoichiometry has been observed and supports the notion of a similarity of the shark kidney SGLT to the mammalian SGLT2. Despite its presence in the late parts of the nephron, the absence of SGLT in the major part of the proximal tubule, the relatively low affinity, and in particular the low stoichiometry might explain the lack of a T(m) for d-glucose in the shark kidney.

36 CFR 25.3 - Supervision; suspensions.

Science.gov (United States)

2010-07-01

... 36 Parks, Forests, and Public Property 1 2010-07-01 2010-07-01 false Supervision; suspensions. 25.3 Section 25.3 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR NATIONAL MILITARY PARKS; LICENSED GUIDE SERVICE REGULATIONS § 25.3 Supervision; suspensions. (a) The guide service will operate under the direction...

Rheology of dense suspensions of non colloidal particles

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Guazzelli Élisabeth

2017-01-01

Full Text Available Dense suspensions are materials with broad applications both in industrial processes (e.g. waste disposal, concrete, drilling muds, metalworking chip transport, and food processing and in natural phenomena (e.g. flows of slurries, debris, and lava. Despite its long research history and its practical relevance, the mechanics of dense suspensions remain poorly understood. The major difficulty is that the grains interact both by hydrodynamic interactions through the liquid and by mechanical contact. These systems thus belong to an intermediate regime between pure suspensions and granular flows. We show that we can unify suspension and granular rheology under a common framework by transferring the frictional approach of dry granular media to wet suspensions of spherical particles. We also discuss non-Newtonian behavior such as normal-stress differences and shear-induced migration. Beyond the classical problem of dense suspension of hard spheres which is far from being completely resolved, there are also entirely novel avenues of study concerning more complex mixtures of particles and fluids such as those involving other types of particles (e.g. fibers or non-Newtonian fluids that we will also address.

Rheological Properties of Aqueous Nanometric Alumina Suspensions

Energy Technology Data Exchange (ETDEWEB)

Li, Chuanping [Iowa State Univ., Ames, IA (United States)

2004-01-01

Colloidal processing is an effective and reliable approach in the fabrication of the advanced ceramic products. Successful colloidal processing of fine ceramic powders requires accurate control of the rheological properties. The accurate control relies on the understanding the influences of various colloidal parameters on the rheological properties. Almost all research done on the rheology paid less attention to the interactions of particle and solvent. However, the interactions of the particles are usually built up through the media in which the particles are suspended. Therefore, interactions of the particle with the media, the adsorbed layers on the particle surface, and chemical and physical properties of media themselves must influence the rheology of the suspension, especially for the dense suspensions containing nanosized particles. Relatively little research work has been reported in this area. This thesis addresses the rheological properties of nanometric alumina aqueous suspensions, and paying more attention to the interactions between particle and solvent, which in turn influence the particle-particle interactions. Dense nanometric alumina aqueous suspensions with low viscosity were achieved by environmentally-benign fructose additives. The rheology of nanometric alumina aqueous suspensions and its variation with the particle volume fraction and concentration of fructose were explored by rheometry. The adsorptions of solute (fructose) and solvent (water) on the nanometric alumina particle surfaces were measured and analyzed by TG/DSC, TOC, and NMR techniques. The mobility of water molecules in the suspensions and its variation with particle volume fractions and fructose additive were determined by the ¹⁷O NMR relaxation method. The interactions between the nanometric alumina particles in water and fructose solutions were investigated by AFM. The results indicated that a large number of water layers were physically bound on the particles

Well-dispersed gold nanowire suspension for assembly application

International Nuclear Information System (INIS)

Xu Cailing; Zhang Li; Zhang Haoli; Li Hulin

2005-01-01

A method for fabricating well-dispersed nanowire suspension has been demonstrated in the paper. Thin gold nanowires were prepared by template synthesis, and then functionalized with sulphonate group-terminated thiols before suspended in different solvents. The degree of aggregation of the obtained suspension was evaluated with transmission electron microscopy (TEM) and UV-vis spectroscopy. It was found that the degree of aggregation was predominated by the solvents, and the best degree of dispersion was obtained when isopropyl alcohol (IPA) was used as the solvent. The gold nanowires from the suspension can be selectively assembled onto chemically patterned substrates. This well-dispersed nanowire suspension is potentially useful for fabricating novel nanodevices

Rheological properties of purified illite clays in glycerol/water suspensions

Science.gov (United States)

Dusenkova, I.; Malers, J.; Berzina-Cimdina, L.

2015-04-01

There are many studies about rheological properties of clay-water suspensions, but no published investigations about clay-glycerol suspensions. In this work apparent viscosity of previously purified illite containing clay fraction clay minerals were almost totally removed by centrifugation. All obtained suspensions behaved as shear-thinning fluids with multiple times higher viscosity than pure glycerol/water solutions. Reduction of clay fraction concentration by 5% decreased the apparent viscosity of 50% glycerol/water suspensions approximately 5 times. There was basically no difference in apparent viscosity between all four 50% glycerol/water suspensions, but in 90% glycerol/water suspensions samples from Iecava deposit showed slightly higher apparent viscosity, which could be affected by the particle size distribution.

Preview based control of suspension systems for commercial vehicles

NARCIS (Netherlands)

Muijderman, J.H.E.A.; Kok, J.J.; Huisman, R.G.M.; Veldpaus, F.E.; van Heck, J.G.A.M.

1999-01-01

An active suspension with preview is developed for the rear axle of a commercial vehicle. The obtained improvements are promising and justify further investigation of the more feasible semi-active suspensions with preview. The inherent non-linearity of semi-active suspensions with switching shock

Research on Dynamic Optimization for Road-friendly Vehicle Suspension

Directory of Open Access Journals (Sweden)

Lu Yongjie

2014-10-01

Full Text Available The heavy vehicle brings large dynamic loads to the road surface, which would reduce vehicle ride comfort and shorten road service life. The structure characteristic of heavy vehicle suspension has a significant impact on vehicle performance. Based on the D'Alembert principle, the dynamics models of independent and integral balanced suspension are proposed considering mass and inertia of balancing rod. The sprung mass acceleration and the tire dynamic force for two kinds of balanced suspension and the traditional quarter vehicle model are compared in frequency-domain and time-domain respectively. It is concluded that a quarter vehicle model simplified for balanced suspension could be used to evaluate the ride comfort of vehicle well, but it has some limitations in assessing the vehicle road-friendliness. Then, the sprung mass acceleration and the road damage coefficients are also analyzed under different vehicle design and running parameters at detail. Some conclusions are obtained: low suspension stiffness, high suspension damping and low tire stiffness are all favorable to improve vehicle performance; there is a saturation range of suspension damping enhancing vehicle performance; improving the road surface roughness and avoiding the no-load running are two effective methods to accomplish the better ride comfort and road-friendliness. The suspension stiffness and damping parameters are chosen for optimal parameters matching of road friendliness based on the approximation optimization method.

Genetic ablation of AQP2 in the mouse connecting tubules results in a mild urinary concentrating defect

DEFF Research Database (Denmark)

Kortenoeven, Marleen; Pedersen, Nis Borbye; Miller, Lance

Body water balance is regulated in the kidney via the vasopressin (AVP) regulated water channel aquaporin-2 (AQP2) expressed in the connecting tubule (CNT) and the collecting duct (CD). Although crucial for the urinary concentrating mechanism, the relative role of AQP2 in the CNT and CD are not f...

Numerical study of suspensions of deformable particles.

Science.gov (United States)

Brandt, Luca; Rosti, Marco Edoardo

2017-11-01

We consider a model non-Newtonian fluid consisting of a suspension of deformable particles in a Newtonian solvent. Einstein showed in his pioneering work that the relative increase in effective viscosity is a linear function of the particle volume fraction for dilute suspensions of rigid particles. Inertia has been shown to introduce deviations from the behaviour predicted by the different empirical fits, an effect that can be related to an increase of the effective volume fraction. We here focus on the effect of elasticity, i.e. visco-elastic deformable particles. To tackle the problem at hand, we perform three-dimensional Direct Numerical Simulation of a plane Couette flow with a suspension of neutrally buoyant deformable viscous hyper-elastic particles. We show that elasticity produces a shear-thinning effect in elastic suspensions (in comparison to rigid ones) and that it can be understood in terms of a reduction of the effective volume fraction of the suspension. The deformation modifies the particle motion reducing the level of mutual interaction. Normal stress differences will also be considered. European Research Council, Grant No. ERC-2013-CoG- 616186, TRITOS; SNIC (the Swedish National Infrastructure for Computing).

Minimally invasive brow suspension for facial paralysis.

Science.gov (United States)

Costantino, Peter D; Hiltzik, David H; Moche, Jason; Preminger, Aviva

2003-01-01

To report a new technique for unilateral brow suspension for facial paralysis that is minimally invasive, limits supraciliary scar formation, does not require specialized endoscopic equipment or expertise, and has proved to be equal to direct brow suspension in durability and symmetry. Retrospective survey of a case series of 23 patients between January 1997 and December 2000. Metropolitan tertiary care center. Patients with head and neck tumors and brow ptosis caused by facial nerve paralysis. The results of the procedure were determined using the following 3-tier rating system: outstanding (excellent elevation and symmetry); acceptable (good elevation and fair symmetry); and unacceptable (loss of elevation). The results were considered outstanding in 12 patients, acceptable in 9 patients, and unacceptable in only 1 patient. One patient developed a hematoma, and 1 patient required a secondary adjustment. The technique has proved to be superior to standard brow suspension procedures with regard to scar formation and equal with respect to facial symmetry and suspension. These results have caused us to abandon direct brow suspension and to use this minimally invasive method in all cases of brow ptosis due to facial paralysis.

Antioxidative effects of fermented sesame sauce against hydrogen peroxide-induced oxidative damage in LLC-PK1 porcine renal tubule cells

Science.gov (United States)

Song, Jia-Le; Choi, Jung-Ho; Seo, Jae-Hoon; Kil, Jeung-Ha

2014-01-01

BACKGROUND/OBJECTIVES This study was performed to investigate the in vitro antioxidant and cytoprotective effects of fermented sesame sauce (FSeS) against hydrogen peroxide (H2O2)-induced oxidative damage in renal proximal tubule LLC-PK1 cells. MATERIALS/METHODS 1,1-diphenyl-2-picrylhydrazyl (DPPH), hydroxyl radical (•OH), and H2O2 scavenging assay was used to evaluate the in vitro antioxidant activity of FSeS. To investigate the cytoprotective effect of FSeS against H2O2-induced oxidative damage in LLC-PK1 cells, the cellular levels of reactive oxygen species (ROS), lipid peroxidation, and endogenous antioxidant enzymes including catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-px) were measured. RESULTS The ability of FSeS to scavenge DPPH, •OH and H2O2 was greater than that of FSS and AHSS. FSeS also significantly inhibited H2O2-induced (500 µM) oxidative damage in the LLC-PK1 cells compared to FSS and AHSS (P sauces, FSeS also significantly increased cellular CAT, SOD, and GSH-px activities and mRNA expression (P < 0.05). CONCULUSIONS These results from the present study suggest that FSeS is an effective radical scavenger and protects against H2O2-induced oxidative damage in LLC-PK1 cells by reducing ROS levels, inhibiting lipid peroxidation, and stimulating antioxidant enzyme activity. PMID:24741396

Toward a general psychological model of tension and suspense.

Science.gov (United States)

Lehne, Moritz; Koelsch, Stefan

2015-01-01

Tension and suspense are powerful emotional experiences that occur in a wide variety of contexts (e.g., in music, film, literature, and everyday life). The omnipresence of tension and suspense suggests that they build on very basic cognitive and affective mechanisms. However, the psychological underpinnings of tension experiences remain largely unexplained, and tension and suspense are rarely discussed from a general, domain-independent perspective. In this paper, we argue that tension experiences in different contexts (e.g., musical tension or suspense in a movie) build on the same underlying psychological processes. We discuss key components of tension experiences and propose a domain-independent model of tension and suspense. According to this model, tension experiences originate from states of conflict, instability, dissonance, or uncertainty that trigger predictive processes directed at future events of emotional significance. We also discuss possible neural mechanisms underlying tension and suspense. The model provides a theoretical framework that can inform future empirical research on tension phenomena.

Shear-induced changes of electrical conductivity in suspensions

Energy Technology Data Exchange (ETDEWEB)

Crawshaw, John; Meeten, Gerald [Schlumberger Cambridge Research, Cambridge (United Kingdom)

2006-12-15

The effect of shear on electrical conductivity (rheo-conduction) is studied to give information about particle behaviour in suspensions. Past work is reviewed, and expressions are derived for the rheo-conduction of a suspension of nonconducting spheroids in a conducting matrix for current flow, parallel and normal to the suspension flow direction. A simple apparatus to study rheo-conduction in pipe flow is described, and measurements of steady and time-dependent effects are reported for various suspensions of colloidal particles. Suspensions of anisometric rod- and platelike particles at low concentrations showed rheo-conductive changes of sign, magnitude and relaxation that were consistent with the particle shape, concentration and interactions. The rheo-conductive response decreased with increasing volume fraction for platelike kaolinite particles, attributed to orientational jamming. Spherical latex particles gave unexpected rheo-conductive changes consistent with shear disruption of a conductive network of particles. It is concluded that rheo-conduction measurements are a useful adjunct to conventional rheometry. (orig.)

15 CFR 2011.207 - Suspension of the certificate system.

Science.gov (United States)

2010-01-01

..., SYRUPS AND MOLASSES Specialty Sugar § 2011.207 Suspension of the certificate system. (a) Suspension. The.... Notice of such suspension and the effective date thereof shall be published in the Federal Register. (b... such reinstatement and the effective date thereof shall be published in the Federal Register. (c...

Early effects of aldosterone on Na-K pump in rat cortical collecting tubules

International Nuclear Information System (INIS)

Fujii, Y.; Takemoto, F.; Katz, A.I.

1990-01-01

Sustained exposure to aldosterone (Aldo) increases the abundance and activity of the Na-K pump in cortical collecting tubules (CCT). However, the onset and mechanism of the early interaction of Aldo with the CCT pump, especially in adrenal-intact animals, are unclear. We evaluated the short-term effects of the hormone on Na-K-adenosinetriphosphatase (ATPase) activity and on ouabain-sensitive 86Rb uptake, a measure of the transporting rate of the pump, in microdissected CCT from adrenal-intact rats. Incubation with Aldo (10(-8) M, 2 h) had no effect on Na-K-ATPase activity (Vmax), whereas it produced at least a twofold increase in 86Rb uptake. This effect was generated by physiological concentrations of the hormone (threshold 10(-10) M; apparent K1/2 approximately 10(-9) M), after a short lag of less than or equal to 30 min. Incubation with Aldo in the presence of amiloride or nystatin or in a Na-free medium (choline chloride) did not prevent the enhanced 86Rb uptake seen after Aldo alone; possible interpretations of these observations are discussed. We conclude that Aldo produces a rapid stimulation of pump function in CCT that precedes its induction of new pump synthesis; the physiological significance of this effect is suggested by its occurrence in tubules from adrenal-intact animals within the time frame and concentration range of the hormone's effects on electrolyte transport

Optimal Vibration Control for Tracked Vehicle Suspension Systems

Directory of Open Access Journals (Sweden)

Yan-Jun Liang

2013-01-01

Full Text Available Technique of optimal vibration control with exponential decay rate and simulation for vehicle active suspension systems is developed. Mechanical model and dynamic system for a class of tracked vehicle suspension vibration control is established and the corresponding system of state space form is described. In order to prolong the working life of suspension system and improve ride comfort, based on the active suspension vibration control devices and using optimal control approach, an optimal vibration controller with exponential decay rate is designed. Numerical simulations are carried out, and the control effects of the ordinary optimal controller and the proposed controller are compared. Numerical simulation results illustrate the effectiveness of the proposed technique.

Heat and mass transfer in particulate suspensions

CERN Document Server

Michaelides, Efstathios E (Stathis)

2013-01-01

Heat and Mass Transfer in Particulate Suspensions is a critical review of the subject of heat and mass transfer related to particulate Suspensions, which include both fluid-particles and fluid-droplet Suspensions. Fundamentals, recent advances and industrial applications are examined. The subject of particulate heat and mass transfer is currently driven by two significant applications: energy transformations –primarily combustion – and heat transfer equipment. The first includes particle and droplet combustion processes in engineering Suspensions as diverse as the Fluidized Bed Reactors (FBR’s) and Internal Combustion Engines (ICE’s). On the heat transfer side, cooling with nanofluids, which include nanoparticles, has attracted a great deal of attention in the last decade both from the fundamental and the applied side and has produced several scientific publications. A monograph that combines the fundamentals of heat transfer with particulates as well as the modern applications of the subject would be...

Utility of Iron Staining in Identifying the Cause of Renal Allograft Dysfunction in Patients with Sickle Cell Disease

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Yingchun Wang

2015-01-01

Full Text Available Sickle cell nephropathy (SCN is associated with iron/heme deposition in proximal renal tubules and related acute tubular injury (ATI. Here we report the utility of iron staining in differentiating causes of renal allograft dysfunction in patients with a history of sickle cell disease. Case 1: the patient developed acute allograft dysfunction two years after renal transplant. Her renal biopsy showed ATI, supported by patchy loss of brush border and positive staining of kidney injury molecule-1 in proximal tubular epithelial cells, where diffuse increase in iron staining (2+ was present. This indicated that ATI likely resulted from iron/heme toxicity to proximal tubules. Electron microscope confirmed aggregated sickle RBCs in glomeruli, indicating a recurrent SCN. Case 2: four years after renal transplant, the patient developed acute allograft dysfunction and became positive for serum donor-specific antibody. His renal biopsy revealed thrombotic microangiopathy (TMA and diffuse positive C4d stain in peritubular capillaries. Iron staining was negative in the renal tubules, implying that TMA was likely associated with acute antibody-mediated rejection (AAMR, type 2 rather than recurrent SCN. These case reports imply that iron staining is an inexpensive but effective method in distinguishing SCN-associated renal injury in allograft kidney from other etiologies.

Library of monoclonal antibodies against brush border membrane epithelial antigens

International Nuclear Information System (INIS)

Behar, M.; Katz, A.; Silverman, M.

1986-01-01

A purified fraction of proximal tubule brush border membranes (BBM) was prepared from dog kidney and used to immunize mice. The standard technique of hybridoma production was followed as described by Kohler and Milstein. Production of antibodies was detected by indirect immunofluorescence on dog kidney slices and by immunodot against the purified fraction on nitrocellulose. Five hybrids exhibited anti BBM activity. These were cloned twice and yielded stable cell lines producing IgG type monoclonal antibodies against BBM. They were designated A 1 , C 7 , D 3 , D 7 and H 4 . As a family these five monoclonals have broad tissue specificity, i.e. positive staining of the surface mucosa of intestinal kidney proximal tubules. D 3 exhibits even broader specificity for epithelium reacting with bile canaliculi and choroid plexus. The authors have verified that at least 4/5 antibodies are directed against BBM protein as revealed by immunoprecipitation of solubilized BBM and detected by Coomassie blue staining or autoradiography of lactoperoxidase labelled BBM. Most interestingly all antibodies bind to the surface of LL CPK 1 cells, a continuous pig kidney cell line of undefined origin but exhibiting many characteristics of proximal tubule cells. The library of monoclonal antibodies obtained provide important probes with which to study membrane biogenesis and polarization in epithelial cells

Impaired Urine Dilution Capability in HIV Stable Patients

Directory of Open Access Journals (Sweden)

Waldo H. Belloso

2014-01-01

Full Text Available Renal disease is a well-recognized complication among patients with HIV infection. Viral infection itself and the use of some antiretroviral drugs contribute to this condition. The thick ascending limb of Henle’s loop (TALH is the tubule segment where free water clearance is generated, determining along with glomerular filtration rate the kidney’s ability to dilute urine. Objective. We analyzed the function of the proximal tubule and TALH in patients with HIV infection receiving or not tenofovir-containing antiretroviral treatment in comparison with healthy seronegative controls, by applying a tubular physiological test, hyposaline infusion test (Chaimowitz’ test. Material & Methods. Chaimowitz’ test was performed on 20 HIV positive volunteers who had normal renal functional parameters. The control group included 10 healthy volunteers. Results. After the test, both HIV groups had a significant reduction of serum sodium and osmolarity compared with the control group. Free water clearance was lower and urine osmolarity was higher in both HIV+ groups. Proximal tubular function was normal in both studied groups. Conclusion. The present study documented that proximal tubule sodium reabsorption was preserved while free water clearance and maximal urine dilution capability were reduced in stable HIV patients treated or not with tenofovir.

Mechanism of phosphaturia elicited by administration of phosphonoformate in vivo

International Nuclear Information System (INIS)

VanScoy, M.; Loghman-Adham, M.; Onsgard, M.; Szczepanska-Konkel, M.; Homma, Sumiko; Knox, F.G.; Dousa, T.P.

1988-01-01

The authors examined whether phosphonoformate (PFA) can cause phosphaturia through its direct action on brush-border membrane (BBM) in vivo. Infusion of PFA or of parathyroid hormone (PTH) to thyroparathyroidectomized rats caused a marked increase in fractional excretion of phosphate without changes in excretion of Na + or of GFR. The PFA-induced phosphaturia was not accompanied by an increase in urinary adenosine-3',5'-cyclic monophosphate (cAMP); moreover, PFA added in vitro did not influence the PTH-sensitive adenylate cyclase and cAMP-phosphodiesterase in proximal convoluted tubules. In BBM vesicles (BBMV) from rats with PFA-elicited phosphaturia, neither the rate of Na + -P i symport nor Na + -dependent binding of [ 14 C]PFA on BBMV was changed, whereas in BBMV from PTH-infused rats the V max of Na + -P i symport decreased. PFA is almost completely ultrafiltrable; no metabolic transformation of PFA was detected after [ 14 C]PFA exposure to rat renal cortical slices, homogenate, or to blood. They conclude that PFA causes phosphaturia by direct inhibition of Na + -P i symport across BBM in proximal tubules, acting from the luminal side. Thus PFA (foscarnet) has a unique direct mechanism of phosphaturic effect, via its action on P i reabsorption in proximal tubules in vivo

Caulimoviridae Tubule-Guided Transport Is Dictated by Movement Protein Properties ▿

Science.gov (United States)

Sánchez-Navarro, Jesús; Fajardo, Thor; Zicca, Stefania; Pallás, Vicente; Stavolone, Livia

2010-01-01

Plant viruses move through plasmodesmata (PD) either as nucleoprotein complexes (NPCs) or as tubule-guided encapsidated particles with the help of movement proteins (MPs). To explore how and why MPs specialize in one mechanism or the other, we tested the exchangeability of MPs encoded by DNA and RNA virus genomes by means of an engineered alfalfa mosaic virus (AMV) system. We show that Caulimoviridae (DNA genome virus) MPs are competent for RNA virus particle transport but are unable to mediate NPC movement, and we discuss this restriction in terms of the evolution of DNA virus MPs as a means of mediating DNA viral genome entry into the RNA-trafficking PD pathway. PMID:20130061

High-Resolution Imaging of Selenium in Kidneys: A Localized Selenium Pool Associated with Glutathione Peroxidase 3

Science.gov (United States)

Malinouski, Mikalai; Kehr, Sebastian; Finney, Lydia; Vogt, Stefan; Carlson, Bradley A.; Seravalli, Javier; Jin, Richard; Handy, Diane E.; Park, Thomas J.; Loscalzo, Joseph; Hatfield, Dolph L.

2012-01-01

Abstract Aim: Recent advances in quantitative methods and sensitive imaging techniques of trace elements provide opportunities to uncover and explain their biological roles. In particular, the distribution of selenium in tissues and cells under both physiological and pathological conditions remains unknown. In this work, we applied high-resolution synchrotron X-ray fluorescence microscopy (XFM) to map selenium distribution in mouse liver and kidney. Results: Liver showed a uniform selenium distribution that was dependent on selenocysteine tRNA[Ser]Sec and dietary selenium. In contrast, kidney selenium had both uniformly distributed and highly localized components, the latter visualized as thin circular structures surrounding proximal tubules. Other parts of the kidney, such as glomeruli and distal tubules, only manifested the uniformly distributed selenium pattern that co-localized with sulfur. We found that proximal tubule selenium localized to the basement membrane. It was preserved in Selenoprotein P knockout mice, but was completely eliminated in glutathione peroxidase 3 (GPx3) knockout mice, indicating that this selenium represented GPx3. We further imaged kidneys of another model organism, the naked mole rat, which showed a diminished uniformly distributed selenium pool, but preserved the circular proximal tubule signal. Innovation: We applied XFM to image selenium in mammalian tissues and identified a highly localized pool of this trace element at the basement membrane of kidneys that was associated with GPx3. Conclusion: XFM allowed us to define and explain the tissue topography of selenium in mammalian kidneys at submicron resolution. Antioxid. Redox Signal. 16, 185–192. PMID:21854231

Structural and ultrastructural study of the rabbit kidney exposed to carbamate insecticide

Directory of Open Access Journals (Sweden)

Viera Almášiová

2014-01-01

Full Text Available The aim of the present study was to determine the influence of orally administered insecticide bendiocarb on the structure and ultrastructure of the kidney parenchyma in rabbits. Bendiocarb in the form of capsules (96% Bendiocarb, Bayer, at a dose of 5 mg/kg of body weight was fed daily for 3 days. After sampling, kidney sections of experimental and control animals were evaluated. Under a light and electron microscope the diffuse degenerative changes in kidney cortex and medulla were noted. Light microscopy revealed that the renal corpuscles had normal structure, but other nephron components and the collecting ducts were invariably changed. The epithelial cells inside the proximal and distal tubules and collecting ducts possessed increased quantity of cytoplasmic vacuoles and some tubular sections showed cellular sloughing and necrotization. The cells within the thin limbs of the Henley’s loops had normal histological structure except for sporadic necrotizing cells within some segments. The ultrastructural evaluation showed extensive cytoplasmic vacuolisation and degenerative changes, such as mitochondrial swelling and shortening of basal infoldings within proximal and distal tubules, and microvilli reduction within proximal tubules. Cells of the collecting tubules exhibited a higher number of vacuoles and some cells had apparently reduced organelles. The cells of the thin limbs of the Henle’s loop showed more vacuolised cytoplasm, some tubular sections revealed cellular detachment between the adjacent epithelial cells and rare necrotising epithelial cells were observed. The described findings addressed in the present study indicate an adverse effect of bendiocarb on the kidney parenchyma in rabbits.

Localization of Secondary Metabolites in Marine Invertebrates: Contribution of MALDI MSI for the Study of Saponins in Cuvierian Tubules of H. forskali

Science.gov (United States)

Meriaux, Céline; Bonnel, David; Salzet, Michel; Fournier, Isabelle; Wisztorski, Maxence

2010-01-01

Background Several species of sea cucumbers of the family Holothuriidae possess a particular mechanical defense system called the Cuvierian tubules (Ct). It is also a chemical defense system as triterpene glycosides (saponins) appear to be particularly concentrated in Ct. In the present study, the precise localization of saponins in the Ct of Holothuria forskali is investigated. Classical histochemical labeling using lectin was firstly performed but did not generate any conclusive results. Thus, MALDI mass spectrometry Imaging (MALDI-MSI) was directly applied and completed by statistical multivariate tests. A comparison between the tubules of relaxed and stressed animals was realized. Results These analyses allowed the detection of three groups of ions, corresponding to the isomeric saponins of the tubules. Saponins detected at m/z 1287 and 1303 were the most abundant and were apparently localized in the connective tissue of the tubules of both relaxed and stressed individuals. Saponins at m/z 1125 and 1141 were detected in lower amount and were present in tissues of relaxed animals. Finally, saponin ions at 1433, 1449, 1463 and 1479 were observed in some Ct of stressed holothuroids in the outer part of the connective tissue. The saponin group m/z 14xx seems therefore to be stress-specific and could originate from modifications of the saponins with m/z of 11xx. Conclusions All the results taken together indicate a complex chemical defense mechanism with, for a single organ, different sets of saponins originating from different cell populations and presenting different responses to stress. The present study also reflects that MALDI-MSI is a valuable tool for chemical ecology studies in which specific chemical signalling molecules like allelochemicals or pheromones have to be tracked. This report represents one of the very first studies using these tools to provide a functional and ecological understanding of the role of natural products from marine invertebrates

Proteomic-based insight into Malpighian tubules of silkworm Bombyx mori.

Directory of Open Access Journals (Sweden)

Xiao-wu Zhong

Full Text Available Malpighian tubules (MTs are highly specific organs of arthropods (Insecta, Myriapoda and Arachnida for excretion and osmoregulation. In order to highlight the important genes and pathways involved in multi-functions of MTs, we performed a systematic proteomic analysis of silkworm MTs in the present work. Totally, 1,367 proteins were identified by one-dimensional gel electrophoresis coupled with liquid chromatography-tandem mass spectrometry, and as well as by Trans Proteomic Pipeline (TPP and Absolute protein expression (APEX analyses. Forty-one proteins were further identified by two-dimensional gel electrophoresis. Some proteins were revealed to be significantly associated with various metabolic processes, organic solute transport, detoxification and innate immunity. Our results might lay a good foundation for future functional studies of MTs in silkworm and other lepidoptera.

A novel member of the trehalose transporter family functions as an H+-dependent trehalose transporter in the reabsorption of trehalose in Malpighian tubules.

Directory of Open Access Journals (Sweden)

Shingo eKikuta

2012-07-01

Full Text Available In insects, Malpighian tubules are functionally analogous to mammalian kidneys in that they not only are essential to excrete waste molecules into the lumen but also are responsible for the reabsorption of indispensable molecules, such as sugars, from the lumen to the principal cells. Among sugars, the disaccharide trehalose is highly important to insects because it is the main hemolymph sugar to serve as a source of energy and carbon. The trehalose transporter TRET1 participates in the transfer of newly synthesized trehalose from the fat body across the cellular membrane into the hemolymph. Although transport proteins must play a pivotal role in the reabsorption of trehalose in Malpighian tubules, the molecular context underlying this process remains obscure. Previously, we identified a Tret1 homolog (Nlst8 that is expressed principally in the Malpighian tubules of the brown planthopper (BPH. Here, we used the Xenopus oocyte expression system to show that NlST8 exerts trehalose transport activity that is elevated under low pH conditions. These functional assays indicate that Nlst8 encodes a proton-dependent trehalose transporter (H-TRET1. To examine the involvement of Nlst8 in trehalose reabsorption, we analyzed the sugar composition of honeydew by using BPH with RNAi gene silencing. Trehalose was detected in the honeydew as waste excreted from Nlst8-dsRNA-injected BPH under hyperglycemic conditions. However, trehalose was not expelled from GFP-dsRNA-injected BPH even under hyperglycemic conditions. We conclude that NlST8 could participate in trehalose reabsorption driven by a H+ gradient from the lumen to the principal cells of the Malpighian tubules.

Feulgen-DNA response and chromatin condensation in Malpighian tubules of Melipona rufiventris and Melipona quadrifasciata (Hymenoptera, Apoidea).

Science.gov (United States)

Mampumbu, André Roberto; Mello, Maria Luiza S

2008-08-01

Melipona quadrifasciata and Melipona rufiventris are stingless bee species which present low and high heterochromatin content, respectively, on their mitotic chromosomes as assessed visually after a C-banding assay. However, these species do not show differences in the C-banding responses of their Malpighian tubule interphase nuclei. In the present study, the Feulgen-DNA response, which could inform on differences in DNA depurination due to differences in chromatin condensation, was compared in the cell nuclei of the Malpighian tubules of these species. It was hypothesized that differences in acid hydrolysis kinetics patterns, as assessed by Feulgen reaction and studied microspectrophotometrically, could discriminate M. quadrifasciata and M. rufiventris interphase nuclei not distinguishable with the C-banding method. Feulgen-DNA values corresponding to more than one ploidy class were found in both species; these values at the hydrolysis time corresponding to the maximal DNA depurination for each ploidy degree were higher in M. quadrifasciata, reflecting a higher DNA content in the Malpighian tubule cell nuclei of this species compared to those of M. rufiventris at the same larval instar. The maximal Feulgen-DNA values of M. quadrifasciata after short (50 min) and long (90 min) hydrolysis times were found to be closer to each other, while those of M. rufiventris occurred sharply at the long hydrolysis time, indicating that DNA depurination in M. quadrifasciata occurred faster. This result is probably related to the involvement of differences in chromatin condensation; it agrees with the idea that M. rufiventris contains more heterochromatin than M. quadrifasciata, which is supported by the analysis of results obtained with the image analysis parameter average absorption ratio. The depurination kinetics studied here with the Feulgen reaction were revealed to be more pertinent than the C-banding technique in establishing differences in levels of chromatin condensation

PROXIMITY MANAGEMENT IN CRISIS CONDITIONS

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Ion Dorin BUMBENECI

2010-01-01

Full Text Available The purpose of this study is to evaluate the level of assimilation for the terms "Proximity Management" and "Proximity Manager", both in the specialized literature and in practice. The study has two parts: the theoretical research of the two terms, and an evaluation of the use of Proximity management in 32 companies in Gorj, Romania. The object of the evaluation resides in 27 companies with less than 50 employees and 5 companies with more than 50 employees.

Bidisperse and polydisperse suspension rheology at large solid fraction

Energy Technology Data Exchange (ETDEWEB)

Pednekar, Sidhant [Benjamin Levich Institute and Department of Chemical Engineering, The City College of New York, New York, New York 10031; Chun, Jaehun [Pacific Northwest National Laboratory, Richland, Washington 99352; Morris, Jeffrey F. [Benjamin Levich Institute and Department of Chemical Engineering, The City College of New York, New York, New York 10031

2018-03-01

At the same solid volume fraction, bidisperse and polydisperse suspensions display lower viscosities, and weaker normal stress response, compared to monodisperse suspensions. The reduction of viscosity associated with size distribution can be explained by an increase of the maximum flowable, or jamming, solid fraction. In this work, concentrated or "dense" suspensions are simulated under strong shearing, where thermal motion and repulsive forces are negligible, but we allow for particle contact with a mild frictional interaction with interparticle friction coefficient of 0.2. Aspects of bidisperse suspension rheology are first revisited to establish that the approach reproduces established trends; the study of bidisperse suspensions at size ratios of large to small particle radii (2 to 4) shows that a minimum in the viscosity occurs for zeta slightly above 0.5, where zeta=phi_{large}/phi is the fraction of the total solid volume occupied by the large particles. The simple shear flows of polydisperse suspensions with truncated normal and log normal size distributions, and bidisperse suspensions which are statistically equivalent with these polydisperse cases up to third moment of the size distribution, are simulated and the rheologies are extracted. Prior work shows that such distributions with equivalent low-order moments have similar phi_{m}, and the rheological behaviors of normal, log normal and bidisperse cases are shown to be in close agreement for a wide range of standard deviation in particle size, with standard correlations which are functionally dependent on phi/phi_{m} providing excellent agreement with the rheology found in simulation. The close agreement of both viscosity and normal stress response between bi- and polydisperse suspensions demonstrates the controlling in influence of the maximum packing fraction in noncolloidal suspensions. Microstructural investigations and the stress distribution according to particle size are also presented.

The Influence of Concentration and Temperature on the Formation of ¿-Oryzanol + ß-Sitosterol Tubules in Edible Oil Organogels

NARCIS (Netherlands)

Sawalha, H.I.M.; Venema, P.; Bot, A.; Flöter, E.; Linden, van der E.

2011-01-01

The gelation process of mixtures of ¿-oryzanol and sitosterol structurants in sunflower oil was studied using light scattering, rheology, and micro-scanning calorimetry (Micro-DSC). The relation between temperature and the critical aggregation concentration (CAC) of tubule formation of ¿-oryzanol

Experimental Evaluation of Mountain Bike Suspension Systems

Directory of Open Access Journals (Sweden)

J. Titlestad

2003-01-01

Full Text Available A significant distinction between competitive mountain bikes is whether they have a suspension system. Research studies indicate that a suspension system gives advantages, but it is difficult to quantify the benefits because they depend on so many variables, including the physiology and psychology of the cyclist, the roughness of the track and the design of the suspension system. A laboratory based test rig has been built that allows the number of variables in the system to be reduced and test conditions to be controlled. The test rig simulates regular impacts of the rear wheel with bumps in a rolling road. The physiological variables of oxygen consumption and heart rate were measured, together with speeds and forces at various points in the system. Physiological and mechanical test results both confirm a significant benefit in using a suspension system on the simulated rough track, with oxygen consumption reduced by around 30 % and power transmitted through the pedals reduced by 30 % to 60 %.

Stability of allopurinol and of five antineoplastics in suspension.

Science.gov (United States)

Dressman, J B; Poust, R I

1983-04-01

The stability of allopurinol, azathioprine, chlorambucil, melphalan, mercaptopurine, and thioguanine each in an extemporaneously prepared suspension was studied. Tablets of each drug were crushed, mixed with a suspending agent, and brought to a final volume of 10, 15, or 20 ml with a 2:1 mixture of simple syrup and wild cherry syrup. Suspensions were prepared in the following concentrations: allopurinol (20 mg/ml), azathioprine (50 mg/ml), chlorambucil (2 mg/ml), melphalan (2 mg/ml), mercaptopurine (50 mg/ml), and thioguanine (40 mg/ml). Using high-performance liquid chromatography or ultraviolet scans, duplicate assays were performed on each suspension periodically during storage for up to 84 days at ambient room temperature or 5 degrees C. The time required for the suspensions to drop below 90% of labeled strength was used as an indicator of drug stability. Allopurinol and azathioprine were stable for at least 56 days at room temperature and at 5 degrees C. Chlorambucil decomposed rapidly at room temperature but was stable for seven days when stored at 5 degrees C. Melphalan suspensions did not meet the stated criteria for stability even at the time of initial assay. Mercaptopurine and thioguanine were stable for 14 and 84 days, respectively, at room temperature; at 5 degrees C, assay values dropped below those obtained at room temperature. In the suspension formulation tested, allopurinol, azathioprine, mercaptopurine, and thioguanine are stable for at least 14 days at room temperature; chlorambucil suspensions should be refrigerated and discarded after seven days. Melphalan decomposes too rapidly to make this suspension formulation feasible for extemporaneous compounding.

Correlation between structure and rheological properties of suspension of nanosized powders

Energy Technology Data Exchange (ETDEWEB)

Tabellion, J.; Clasen, R. [Saarland Univ., Saarbruecken (Germany). Dept. of Powder Technology; Reinshagen, J.; Oberacker, R.; Hoffmann, M.J. [Karlsruhe Univ. (Germany). Inst. for Ceramics in Mechanical Engineering

2002-07-01

Since the properties of a ceramic green body and compact produced thereof are strongly influenced by the properties of the suspension used, controlling structure and properties of a suspension is a very important issue in ceramic manufacturing. Macroscopically, the rheological properties of a suspension are the key parameters that influence the behaviour during the shaping process. The rheological behaviour of aqueous suspensions of nanosized fumed silica (DEGUSSA, Aerosil OX50) with different amounts of OX50 (10 to 50 wt.%) was measured over a pH-range from 1 to 13 by means of rotational viscosimetry. A distinct maximum of the viscosity was observed for a pH of about 7 to 8, independent of the solid content of the suspensions. Since the rheological behaviour of the suspensions could not be explained by the {zeta}-Potential measured for OX50, the suspensions were investigated by means of so-called cryo-SEM characterization. A droplet of the suspension is quench-frozen in subcooled nitrogen (-210 C), prepared and the water is sublimed at -90 C. Thus it was possible to visualize the agglomerate structure of the primary OX50-particles within the suspensions. (orig.)

3D modeling design and engineering analysis of automotive suspension beam

Directory of Open Access Journals (Sweden)

Ju Zhi Lan

2016-01-01

Full Text Available Automotive suspension is an important device for transmission and torque. The main parameters and dimensions of 40 tons of heavy duty truck spring suspension system are designed in the paper. According to the data, the 3D modeling and virtual assembly of the leaf spring suspension are carried out by using parametric design. Structural stress of spring suspension is analyzed which can provide a guide and basis for the design of the leaf spring suspension.

Pathology and proposed pathophysiology of diclofenac poisoning in free-living and experimentally exposed oriental white-backed vultures (Gyps bengalensis)

Science.gov (United States)

Meteyer, C.U.; Rideout, B.A.; Gilbert, M.; Shivaprasad, H.L.; Oaks, J.L.

2005-01-01

Oriental white-backed vultures (Gyps bengalensis; OWBVs) died of renal failure when they ingested diclofenac, a nonsteroidal anti-inflammatory drug (NSAID), in tissues of domestic livestock. Acute necrosis of proximal convoluted tubules in these vultures was severe. Glomeruli, distal convoluted tubules, and collecting tubules were relatively spared in the vultures that had early lesions. In most vultures, however, lesions became extensive with large urate aggregates obscuring renal architecture. Inflammation was minimal. Extensive urate precipitation on the surface and within organ parenchyma (visceral gout) was consistently found in vultures with renal failure. Very little is known about the physiologic effect of NSAIDs in birds. Research in mammals has shown that diclofenac inhibits formation of prostaglandins. We propose that the mechanism by which diclofenac induces renal failure in the OWBV is through the inhibition of the modulating effect of prostaglandin on angiotensin II-mediated adrenergic stimulation. Renal portal valves open in response to adrenergic stimulation, redirecting portal blood to the caudal vena cava and bypassing the kidney. If diclofenac removes a modulating effect of prostaglandins on the renal portal valves, indiscriminant activation of these valves would redirect the primary nutrient blood supply away from the renal cortex. Resulting ischemic necrosis of the cortical proximal convoluted tubules would be consistent with our histologic findings in these OWBVs.

Phagocytosis in phosphate chromium (III) suspensions

International Nuclear Information System (INIS)

Cruz-Arencibia, Jorge; Fano Machín, Yoiz; Cruz-Morales, Ahmed; Tamayo Fuente, Radamés; Morín-Zorrilla, José

2015-01-01

Phagocytosis in vivo and in vitro of a suspension of chromic phosphate (III) labeled with 51 Cr and 32 P is studied. The radioactive particles dispersed in a media of 2 % gelatin in acetate buffer pH 4-4.5 have a predominant size of 0.8 μm and 5 μm. According with biodistribution experiments in rats after 30 minutes near the 80 % of radioactivity is registered in the liver, probably associated with phagocytosis of the particles by liver Kupffer cells. Is also showed that the suspension particles are phagocytized in vitro by mouse peritoneal macrophages. This facts indicate that the studied suspension have appropriate characteristics to be used in radiosynoviorthesis according to the principal action mechanism described for this procedure, particles phagocytosis by cells present in the inflamed synovium. (author)

Crust formation in drying colloidal suspensions

KAUST Repository

Style, R. W.

2010-06-30

During the drying of colloidal suspensions, the desiccation process causes the suspension near the air interface to consolidate into a connected porous matrix or crust. Fluid transport in the porous medium is governed by Darcy\\'s law and the equations of poroelasticity, while the equations of colloid physics govern processes in the suspension. We derive new equations describing this process, including unique boundary conditions coupling the two regions, yielding a moving-boundary model of the concentration and stress profiles during drying. A solution is found for the steady-state growth of a nedimensional crust during constant evaporation rate from the surface. The solution is used to demonstrate the importance of the system boundary conditions on stress profiles and diffusivity in a drying crust. © 2011 The Royal Society.

15 CFR 14.13 - Debarment and suspension.

Science.gov (United States)

2010-01-01

... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Debarment and suspension. 14.13 Section 14.13 Commerce and Foreign Trade Office of the Secretary of Commerce UNIFORM ADMINISTRATIVE... shall comply with the nonprocurement debarment and suspension common rule implementing E.O.s 12549 and...

19 CFR 210.23 - Suspension of investigation.

Science.gov (United States)

2010-04-01

... 19 Customs Duties 3 2010-04-01 2010-04-01 false Suspension of investigation. 210.23 Section 210.23 Customs Duties UNITED STATES INTERNATIONAL TRADE COMMISSION INVESTIGATIONS OF UNFAIR PRACTICES IN IMPORT TRADE ADJUDICATION AND ENFORCEMENT Motions § 210.23 Suspension of investigation. Any party may move to...

Suspension tests on a larger scale. Report from the status seminar on magnetic suspension techniques. Testing of the electrodynamic system started

Energy Technology Data Exchange (ETDEWEB)

Rogg, D; Muckli, W

1976-07-01

A world record speed for electromagnetically suspended vehicles as well as successful suspension tests with forced-circulation cooled superconducting magnets were the outstanding success reports at the fifth status seminar 'Magnetic suspension techniques' on 31st March and 1st April in Bad Kissingen. The research work on magnetic suspension techniques in the railborne long-distance travel is supported by the Federal Ministry of Research and Technology (BMFT) within the frameworke of the programme 'Railway engineering - New technologies'.

Active Control of Suspension Bridges

DEFF Research Database (Denmark)

Thoft-Christensen, Palle

In this paper some recent research on active control of very long suspension bridges, is presented. The presentation is based on research work at Aalborg University, Denmark. The active control system is based on movable flaps attached to the bridge girder. Wind load on bridges with or without...... flaps attached to the girder is briefly presented. A simple active control system is discussed. Results from wind tunnel experiments with a bridge section show that flaps can be used effectively to control bridge girder vibrations. Flutter conditions for suspension bridges with and without flaps...

On reactive suspension plasma spraying of calcium titanate

OpenAIRE

Kotlan, J. (Jiří); Pala, Z. (Zdeněk); Mušálek, R. (Radek); Ctibor, P. (Pavel)

2016-01-01

This study shows possibility of preparation of calcium titanate powder and coatings by reactive suspension plasma spraying. Suspension of mixture of calcium carbonate (CaCO3) and titanium dioxide (TiO2) powders in ethanol was fed into hybrid plasma torch with a DC-arc stabilized by a water–argon mixture (WSP-H 500). Various feeding distances and angles were used in order to optimize suspension feeding conditions. In the next step, the coatings were deposited on stainless steel substrates and ...

Vehicle lateral dynamics stabilization using active suspension

Directory of Open Access Journals (Sweden)

Drobný V.

2008-12-01

Full Text Available The paper deals with the investigation of active nonlinear suspension control in order to stabilize the lateral vehicle motion in similar way as systems like ESP do. The lateral stabilization of vehicle based on braking forces can be alternatively provided by the different setting of suspension forces. The basis of this control is the nonlinear property of the tyres. The vehicle has at least four wheels and it gives one or more redundant vertical forces that can be used for the different distribution of vertical suspension forces in such a way that resulting lateral and/or longitudinal forces create the required correction moment for lateral dynamic vehicle stabilization.

Fractures of the proximal humerus

DEFF Research Database (Denmark)

Brorson, Stig

2013-01-01

Fractures of the proximal humerus have been diagnosed and managed since the earliest known surgical texts. For more than four millennia the preferred treatment was forceful traction, closed reduction, and immobilization with linen soaked in combinations of oil, honey, alum, wine, or cerate......, classification of proximal humeral fractures remains a challenge for the conduct, reporting, and interpretation of clinical trials. The evidence for the benefits of surgery in complex fractures of the proximal humerus is weak. In three systematic reviews I studied the outcome after locking plate osteosynthesis...

Gastrointestinal tract wall visualization and distention during abdominal and pelvic multidetector CT with a neutral barium sulphate suspension: comparison with positive barium sulphate suspension and with water.

Science.gov (United States)

Oliva, M R; Erturk, S M; Ichikawa, T; Rocha, T; Ros, P R; Silverman, S G; Mortele, K J

2012-01-01

When examining patients with contrast-enhanced multidetector-row CT, we determined if the stomach and small bowel were visualized and distended better with a neutral barium sulphate suspension than with positive barium sulphate suspension or water. After obtaining approval from our institutional review board, 156 patients (women: 84; mean age: 54 yrs) with no history of gastrointestinal tract disease were randomized prospectively to receive orally either 900 ml of neutral (0.1% w/v) barium sulphate suspension (n = 53), 900 ml of positive (2.1% w/v) barium sulphate suspension (n = 53), or 900 ml of water (n = 50), prior to undergoing contrast-enhanced abdominal and pelvic multidetector-row CT. Two independent radiologists evaluated the stomach, and small bowel, for luminal distension and wall visualization, using a five point scale. Results were compared using Kruskal-Wallis and Mann-Whitney U tests. The walls of the stomach, and small bowel were visualized better in patients who were administered neutral barium sulphate suspension than those who were administered either positive barium sulphate suspension (p barium sulphate suspension, the stomach and small bowel were distended better compared to patients administered water (p barium sulphate suspension (p contrast-enhanced abdominal and pelvic multidetector-row CT, orally administered neutral barium sulphate suspension allows the gastrointestinal tract to be visualized and distended better than either positive barium sulphate suspension, or water.

Chain Dynamics in Magnetorheological Suspensions

Science.gov (United States)

Gast, A. P.; Furst, E. M.

1999-01-01

Magnetorheological (MR) suspensions are composed of colloidal particles which acquire dipole moments when subjected to an external magnetic field. At sufficient field strengths and concentrations, the dipolar particles rapidly aggregate to form long chains. Subsequent lateral cross-linking of the dipolar chains is responsible for a rapid liquid-to-solid-like rheological transition. The unique, magnetically-activated rheological properties of MR suspensions make them ideal for interfacing mechanical systems to electronic controls. Additionally, the ability to experimentally probe colloidal suspensions interacting through tunable anisotropic potentials is of fundamental interest. Our current experimental work has focused on understanding the fluctuations of dipolar chains. It has been proposed by Halsey and Toor (HT) that the strong Landau-Peierls thermal fluctuations of dipolar chains could be responsible for long-range attractions between chains. Such interactions will govern the long-time relaxation of MR suspensions. We have synthesized monodisperse neutrally buoyant MR suspensions by density matching stabilized ferrofluid emulsion droplets with D2O. This allows us to probe the dynamics of the dipolar chains using light scattering without gravitational, interfacial, and polydispersity effects to resolve the short-wavelength dynamics of the dipolar chains. We used diffusing wave spectroscopy to measure these dynamics. The particle displacements at short times that show an independence to the field strength, but at long times exhibit a constrained, sub-diffusive motion that slows as the dipole strength is increased. The experiments are in good qualitative agreement with Brownian dynamics simulations of dipolar chains. Although there have been several important and detailed studies of the structure and interactions in MR suspensions, there has not been conclusive evidence that supports or contradicts the HT model prediction that long-range interactions exist between

A magneto rheological hybrid damper for railway vehicles suspensions

Directory of Open Access Journals (Sweden)

Gheorghe GHITA

2012-09-01

Full Text Available High speed railway vehicles features a specific lateral oscillation resulting from the coupled lateral displacement and yaw of the wheelset which leads to a sinusoid movement of the wheelset along the track, transferred to the entire vehicle. The amplitude of this oscillation is strongly dependant on vehicle’s velocity. Over a certain value, namely the critical speed, the instability phenomenon so-called hunting occurs. To raise the vehicle’s critical speed different designs of the suspension all leading to a much stiffer vehicle can be envisaged. Different simulations prove that a stiffer central suspension will decrease the passenger’s comfort in terms of lateral accelerations of the carboy. The authors propose a semi-active magneto rheological suspension to improve the vehicle’s comfort at high speeds. The suspension has as executive elements hybrid magneto rheological dampers operating under sequential control strategy type balance logic. Using an original mathematical model for the lateral dynamics of the vehicle the responses of the system with passive and semi-active suspensions are simulated. It is shown that the semi-active suspension can improve the vehicle performances.

Preparation of conjugated polymer suspensions by using ultrasonic atomizer

Energy Technology Data Exchange (ETDEWEB)

Tada, Kazuya, E-mail: tada@eng.u-hyogo.ac.jp; Onoda, Mitsuyoshi

2010-11-30

The electrophoretic deposition is a method useful to prepare conjugated polymer films for electronic devices. This method provides high material recovery rate on the substrate from the suspension, in contrast to the conventional spin-coating in which most of the material placed on the substrate is blown away. Although manual reprecipitation technique successfully yields suspensions of various conjugated polymers including polyfluorene derivatives, it is favorable to control the preparation process of suspensions. In this context, this paper reports preliminary results on the preparation of suspension of conjugated polymer by using an ultrasonic atomizer. While the resultant films do not show particular difference due to the preparation methods of the suspension, the electric current profiles during the electrophoretic deposition suggests that the ultrasonic atomization of polymer solution prior to be mixed with poor solvent results in smaller and less uniform colloidal particles than the conventional manual pouring method.

45 CFR 99.4 - Suspension of rules.

Science.gov (United States)

2010-10-01

... 45 Public Welfare 1 2010-10-01 2010-10-01 false Suspension of rules. 99.4 Section 99.4 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION PROCEDURE FOR HEARINGS FOR THE CHILD CARE AND DEVELOPMENT FUND General § 99.4 Suspension of rules. With notice to all parties, the...

Absorption Spectra of Gold Nanoparticle Suspensions

Science.gov (United States)

Anan'eva, M. V.; Nurmukhametov, D. R.; Zverev, A. S.; Nelyubina, N. V.; Zvekov, A. A.; Russakov, D. M.; Kalenskii, A. V.; Eremenko, A. N.

2018-02-01

Three gold nanoparticle suspensions are obtained, and mean radii in distributions - (6.1 ± 0.2), (11.9 ± 0.3), and (17.3 ± 0.7) nm - are determined by the transmission electron microscopy method. The optical absorption spectra of suspensions are obtained and studied. Calculation of spectral dependences of the absorption index of suspensions at values of the gold complex refractive index taken from the literature showed a significant deviation of experimental and calculated data in the region of 450-800 nm. Spectral dependences of the absorption of suspensions are simulated within the framework of the Mie-Drude theory taking into account the interband absorption in the form of an additional term in the imaginary part of the dielectric permittivity of the Gaussian type. It is shown that to quantify the spectral dependences in the region of the plasmon absorption band of nanoparticles, correction of the parameters of the interband absorption is necessary in addition to the increase of the relaxation parameter of the Drude theory. Spectral dependences of the dielectric permittivity of gold in nanodimensional state are refined from the solution of the inverse problem. The results of the present work are important for predicting the special features of operation of photonic devices and optical detonators based on gold nanoparticles.

Self-organization of engineered epithelial tubules by differential cellular motility

Energy Technology Data Exchange (ETDEWEB)

Mori, Hidetoshi; Gjorevski, Nikolce; Inman, Jamie L; Bissell, Mina J; Nelson, Celeste M

2009-02-04

Patterning of developing tissues arises from a number of mechanisms, including cell shape change, cell proliferation, and cell sorting from differential cohesion or tension. Here, we reveal that differences in cell motility can also lead to cell sorting within tissues. Using mosaic engineered mammary epithelial tubules, we found that cells sorted depending on their expression level of the membrane-anchored collagenase matrix metalloproteinase (MMP)-14. These rearrangements were independent of the catalytic activity of MMP14 but absolutely required the hemopexin domain. We describe a signaling cascade downstream of MMP14 through Rho kinase that allows cells to sort within the model tissues. Cell speed and persistence time were enhanced by MMP14 expression, but only the latter motility parameter was required for sorting. These results indicate that differential directional persistence can give rise to patterns within model developing tissues.

Initial outcome and efficacy of S3 proximal humerus locking plate in the treatment of proximal humerus fractures

International Nuclear Information System (INIS)

Zhang Zhiming; Zhu Xuesong; Bao Zhaohua; Yang Huilin

2012-01-01

Objective: to explore the initial outcome and efficacy of S 3 proximal humerus locking plate in the treatment of proximal humerus fractures. Methods: Twenty-two patients with proximal humerus fracture were treated with the S 3 proximal humerus locking plate. Most of the fractures were complex, two-part (n=4), three-part (n=11) and four-part (n=7) fractures according to the Neer classification of the proximal humerus fractures. Results: All patients were followed up for 3∼15 months. There were no complications related to the implant including loosening or breakage of the plate. Good and excellent results were documented in 17 patients fair results in 4 patients according the Neer scores of shoulder. Conclusion: New design concepts of S 3 proximal humerus plate provide the subchondral support and the internal fixation support. With the addition of the proper exercise of the shoulder joint, the outcomes would be satisfied. (authors)

Plasma protein haptoglobin modulates renal iron loading

DEFF Research Database (Denmark)

Fagoonee, Sharmila; Gburek, Jakub; Hirsch, Emilio

2005-01-01

Haptoglobin is the plasma protein with the highest binding affinity for hemoglobin. The strength of hemoglobin binding and the existence of a specific receptor for the haptoglobin-hemoglobin complex in the monocyte/macrophage system clearly suggest that haptoglobin may have a crucial role in heme...... distribution of hemoglobin in haptoglobin-deficient mice resulted in abnormal iron deposits in proximal tubules during aging. Moreover, iron also accumulated in proximal tubules after renal ischemia-reperfusion injury or after an acute plasma heme-protein overload caused by muscle injury, without affecting...... morphological and functional parameters of renal damage. These data demonstrate that haptoglobin crucially prevents glomerular filtration of hemoglobin and, consequently, renal iron loading during aging and following acute plasma heme-protein overload....

Fuzzy logic control of vehicle suspensions with dry friction nonlinearity

Indian Academy of Sciences (India)

We design and investigate the performance of fuzzy logic-controlled (FLC) active suspensions on a nonlinear vehicle model with four degrees of freedom, without causing any degeneration in suspension working limits. Force actuators were mounted parallel to the suspensions. In this new approach, linear combinations of ...

31 CFR 19.605 - How does suspension differ from debarment?

Science.gov (United States)

2010-07-01

... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false How does suspension differ from debarment? 19.605 Section 19.605 Money and Finance: Treasury Office of the Secretary of the Treasury GOVERNMENTWIDE DEBARMENT AND SUSPENSION (NONPROCUREMENT) General Principles Relating to Suspension and Debarment...

12 CFR 513.4 - Suspension and debarment.

Science.gov (United States)

2010-01-01

... 12 Banks and Banking 5 2010-01-01 2010-01-01 false Suspension and debarment. 513.4 Section 513.4 Banks and Banking OFFICE OF THRIFT SUPERVISION, DEPARTMENT OF THE TREASURY PRACTICE BEFORE THE OFFICE § 513.4 Suspension and debarment. (a) The Office may censure any person practicing before it or may deny...

Effective viscosity of 2D suspensions - Confinement effects

Science.gov (United States)

Peyla, Philippe; Priem, Stephane; Vincent, Doyeux; Farutin, Alexander; Ismail, Mourad

2014-11-01

We study the rheology of a sheared 2D suspension of non-Brownian disks in presence of walls. Although, it is of course possible today with modern computers and powerful algorithms to perform direct numerical simulations that fully account for multiparticle 3D interactions, the analysis of the simple case of a 2D suspension, provides valuable insights and helps to understand 3D results. For instance, we examine the role of particle-wall and particle-particle interactions in determining the rheology of confined sheared suspensions. In addition we evaluate the intrinsic viscosity as well as the contribution of hydrodynamic interactions to the dissipation as a function of a wide range of confinements. Thanks to the direct visualisation of the whole 2D Stokes flow, we are able to give a clear interpretation about the rheology of semi-dilute confined suspensions.

Caveolin-3 is associated with the T-tubules of mature skeletal muscle fibers

DEFF Research Database (Denmark)

Ralston, E; Ploug, Thorkil

1999-01-01

Caveolae are abundant in skeletal muscle and their coat contains a specific isoform of caveolin, caveolin-3. It has been suggested that during muscle development, caveolin-3 is associated with the T-tubules, but that in adult muscle it is found on the plasma membrane only. We have studied...... the distribution of caveolin-3 in single skeletal muscle fibers from adult rat soleus by confocal immunofluorescence and by immunogold electron microscopy. We found that caveolin-3 occurs at the highest density on the plasma membrane but is also present in the core of the fibers, at the I-band/A-band interface...

Preliminary study on leadership proximity

Directory of Open Access Journals (Sweden)

Ghinea Valentina Mihaela

2017-07-01

Full Text Available In general, it is agreed that effective leadership requires a certain degree of proximity, either physical or mental, which enables leaders to maintain control over their followers and communicate their vision. Although we agree with the leadership proximity principles which states that leaders are able to efficiently serve only those people with whom they interact frequently, in this article we focus instead on the disadvantages of being too close and the way in which close proximity can actually hurt the effectiveness of leadership. The main effects that we discuss regard the way in which proximity and familiarity allow followers to see the weaknesses and faults of the leader much more easily and thus diminish the leader’s heroic aura, and the emotional bias that results from a leader being too familiar with his followers which will impede the process of rational decision making. As a result, we argue that there exists a functional proximity which allows the leader the necessary space in which to perform effective identity work and to hide the backstage aspects of leadership, while also allowing him an emotional buffer zone which will enable him to maintain the ability to see clearly and make rational decisions.

Heavy metals toxicity after acute exposure of cultured renal cells. Intracellular accumulation and repartition

International Nuclear Information System (INIS)

Khodja, Hicham; Carriere, Marie; Avoscan, Laure; Gouget, Barbara

2005-01-01

Lead (Pb), cadmium (Cd) and uranium (U) present no known biological function but are toxic in various concentration ranges. Pb and Cd lead generally to nephrotoxicity consisting in proximal renal tubular dysfunction and accumulation while U has been reported to induce chemical kidney toxicity, functional and histological damages being as well mainly observed in proximal tubule cells. This work address the question of Cd, Pb, and U cytotoxicity, intracellular accumulation and repartition after acute intoxication of renal proximal tubule epithelial cells. After cells exposure to different concentrations of metals for various times, morphological changes were observed and intracellular concentrations and distributions of toxic metals were specified by PIXE coupled to RBS. Cell viability, measured by biochemical tests, was used as toxicity indicator. A direct correlation between cytotoxicity and intracellular accumulation in renal epithelial cells have been established. Finally, intracellular Pb and U localizations were detected while Cd was found to be uniformly distributed in renal cells. (author)

Determination of Weight Suspension Rigidity in the Transport-Erector Aggregates

Directory of Open Access Journals (Sweden)

V. A. Zverev

2016-01-01

Full Text Available The aim is to determine weight suspension rigidity in aggregates designed to perform technological transport-erector operations at the miscellaneous launch complexes.We consider the weight suspension comprising the following distinctive structural components: the executive weight-lowering mechanism, polyspast mechanism, rope, traverse, and rods. A created structural dynamic model of suspension allowed us to define weight suspension rigidity. Within the framework of design analysis of a dynamic model we determined the rigidity of its structural units, i.e. traverse, rope, and polyspast.Known analytical relationships were used to calculate the rope rigidity. To determine rigidity of polyspast and traverse have been created special models based on the finite element method. For each model deformation in the specific points under the test load have been defined. Data obtained were used to determine trigidity of traverses and polyspast, and also rigidity of suspension in total. The rigidity models of polispast mechanism and traverse have been developed and calculated using the software complex "Zenit-95".As the research results, the paper presents a dynamic model of the weight suspension of the transport-erector aggregate, the finite element models of the polispast mechanism and traverse, an algorithm for determining the weight suspension rigidity and relevant analytical relationships.Independent calculation of weight suspension rigidity enables us to simplify further dynamic calculation of the aggregate-weight system because it allows attaining a simpler model of the aggregate-weight system that uses the weight suspension model as an element of equivalent rigidity. Despite this simplification the model allows us to determine correctly weight movement parameters and overloads in the aggregate-weight system in the process of technical operations.

Viscosity of aqueous and cyanate ester suspensions containing alumina nanoparticles

Energy Technology Data Exchange (ETDEWEB)

Lawler, Katherine [Iowa State Univ., Ames, IA (United States)

2009-01-01

The viscosities of both aqueous and cyanate ester monomer (BECy) based suspensions of alumina nanoparticle were studied. The applications for these suspensions are different: aqueous suspensions of alumina nanoparticles are used in the production of technical ceramics made by slip casting or tape casting, and the BECy based suspensions are being developed for use in an injection-type composite repair resin. In the case of aqueous suspensions, it is advantageous to achieve a high solids content with low viscosity in order to produce a high quality product. The addition of a dispersant is useful so that higher solids content suspensions can be used with lower viscosities. For BECy suspensions, the addition of nanoparticles to the BECy resin is expected to enhance the mechanical properties of the cured composite. The addition of saccharides to aqueous suspensions leads to viscosity reduction. Through DSC measurements it was found that the saccharide molecules formed a solution with water and this resulted in lowering the melting temperature of the free water according to classic freezing point depression. Saccharides also lowered the melting temperature of the bound water, but this followed a different rule. The shear thinning and melting behaviors of the suspensions were used to develop a model based on fractal-type agglomeration. It is believed that the structure of the particle flocs in these suspensions changes with the addition of saccharides which leads to the resultant viscosity decrease. The viscosity of the BECy suspensions increased with solids content, and the viscosity increase was greater than predicted by the classical Einstein equation for dilute suspensions. Instead, the Mooney equation fits the viscosity behavior well from 0-20 vol% solids. The viscosity reduction achieved at high particle loadings by the addition of benzoic acid was also investigated by NMR. It appears that the benzoic acid interacts with the surface of the alumina particle which may

21 CFR 520.1182 - Iron dextran suspension.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Iron dextran suspension. 520.1182 Section 520.1182... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1182 Iron dextran suspension... hydroxide in complex with a low molecular weight dextran. (b) Sponsor. See No. 051311 in § 510.600(c) of...

Non-linear dielectric spectroscopy of microbiological suspensions

Science.gov (United States)

Treo, Ernesto F; Felice, Carmelo J

2009-01-01

Background Non-linear dielectric spectroscopy (NLDS) of microorganism was characterized by the generation of harmonics in the polarization current when a microorganism suspension was exposed to a sinusoidal electric field. The biological nonlinear response initially described was not well verified by other authors and the results were susceptible to ambiguous interpretation. In this paper NLDS was performed to yeast suspension in tripolar and tetrapolar configuration with a recently developed analyzer. Methods Tripolar analysis was carried out by applying sinusoidal voltages up to 1 V at the electrode interface. Tetrapolar analysis was carried on with sinusoidal field strengths from 0.1 V cm-1 to 70 V cm-1. Both analyses were performed within a frequency range from 1 Hz through 100 Hz. The harmonic amplitudes were Fourier-analyzed and expressed in dB. The third harmonic, as reported previously, was investigated. Statistical analysis (ANOVA) was used to test the effect of inhibitor an activator of the plasma membrane enzyme in the measured response. Results No significant non-linearities were observed in tetrapolar analysis, and no observable changes occurred when inhibitor and activator were added to the suspension. Statistical analysis confirmed these results. When a pure sinus voltage was applied to an electrode-yeast suspension interface, variations higher than 25 dB for the 3rd harmonic were observed. Variation higher than 20 dB in the 3rd harmonics has also been found when adding an inhibitor or activator of the membrane-bounded enzymes. These variations did not occur when the suspension was boiled. Discussion The lack of result in tetrapolar cells suggest that there is no, if any, harmonic generation in microbiological bulk suspension. The non-linear response observed was originated in the electrode-electrolyte interface. The frequency and voltage windows observed in previous tetrapolar analysis were repeated in the tripolar measurements, but maximum were not

Non-linear dielectric spectroscopy of microbiological suspensions

Directory of Open Access Journals (Sweden)

Felice Carmelo J

2009-09-01

Full Text Available Abstract Background Non-linear dielectric spectroscopy (NLDS of microorganism was characterized by the generation of harmonics in the polarization current when a microorganism suspension was exposed to a sinusoidal electric field. The biological nonlinear response initially described was not well verified by other authors and the results were susceptible to ambiguous interpretation. In this paper NLDS was performed to yeast suspension in tripolar and tetrapolar configuration with a recently developed analyzer. Methods Tripolar analysis was carried out by applying sinusoidal voltages up to 1 V at the electrode interface. Tetrapolar analysis was carried on with sinusoidal field strengths from 0.1 V cm-1 to 70 V cm-1. Both analyses were performed within a frequency range from 1 Hz through 100 Hz. The harmonic amplitudes were Fourier-analyzed and expressed in dB. The third harmonic, as reported previously, was investigated. Statistical analysis (ANOVA was used to test the effect of inhibitor an activator of the plasma membrane enzyme in the measured response. Results No significant non-linearities were observed in tetrapolar analysis, and no observable changes occurred when inhibitor and activator were added to the suspension. Statistical analysis confirmed these results. When a pure sinus voltage was applied to an electrode-yeast suspension interface, variations higher than 25 dB for the 3rd harmonic were observed. Variation higher than 20 dB in the 3rd harmonics has also been found when adding an inhibitor or activator of the membrane-bounded enzymes. These variations did not occur when the suspension was boiled. Discussion The lack of result in tetrapolar cells suggest that there is no, if any, harmonic generation in microbiological bulk suspension. The non-linear response observed was originated in the electrode-electrolyte interface. The frequency and voltage windows observed in previous tetrapolar analysis were repeated in the tripolar

ProxImaL: efficient image optimization using proximal algorithms

KAUST Repository

Heide, Felix; Diamond, Steven; Nieß ner, Matthias; Ragan-Kelley, Jonathan; Heidrich, Wolfgang; Wetzstein, Gordon

2016-01-01

domain-specific language and compiler for image optimization problems that makes it easy to experiment with different problem formulations and algorithm choices. The language uses proximal operators as the fundamental building blocks of a variety

17 CFR 240.12d2-1 - Suspension of trading.

Science.gov (United States)

2010-04-01

... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Suspension of trading. 240... Securities Exchange Act of 1934 Suspension of Trading, Withdrawal, and Striking from Listing and Registration § 240.12d2-1 Suspension of trading. (a) A national securities exchange may suspend from trading a...

Effects of transients in LIGO suspensions on searches for gravitational waves.

Science.gov (United States)

Walker, M; Abbott, T D; Aston, S M; González, G; Macleod, D M; McIver, J; Abbott, B P; Abbott, R; Adams, C; Adhikari, R X; Anderson, S B; Ananyeva, A; Appert, S; Arai, K; Ballmer, S W; Barker, D; Barr, B; Barsotti, L; Bartlett, J; Bartos, I; Batch, J C; Bell, A S; Betzwieser, J; Billingsley, G; Birch, J; Biscans, S; Biwer, C; Blair, C D; Bork, R; Brooks, A F; Ciani, G; Clara, F; Countryman, S T; Cowart, M J; Coyne, D C; Cumming, A; Cunningham, L; Danzmann, K; Da Silva Costa, C F; Daw, E J; DeBra, D; DeRosa, R T; DeSalvo, R; Dooley, K L; Doravari, S; Driggers, J C; Dwyer, S E; Effler, A; Etzel, T; Evans, M; Evans, T M; Factourovich, M; Fair, H; Fernández Galiana, A; Fisher, R P; Fritschel, P; Frolov, V V; Fulda, P; Fyffe, M; Giaime, J A; Giardina, K D; Goetz, E; Goetz, R; Gras, S; Gray, C; Grote, H; Gushwa, K E; Gustafson, E K; Gustafson, R; Hall, E D; Hammond, G; Hanks, J; Hanson, J; Hardwick, T; Harry, G M; Heintze, M C; Heptonstall, A W; Hough, J; Izumi, K; Jones, R; Kandhasamy, S; Karki, S; Kasprzack, M; Kaufer, S; Kawabe, K; Kijbunchoo, N; King, E J; King, P J; Kissel, J S; Korth, W Z; Kuehn, G; Landry, M; Lantz, B; Lockerbie, N A; Lormand, M; Lundgren, A P; MacInnis, M; Márka, S; Márka, Z; Markosyan, A S; Maros, E; Martin, I W; Martynov, D V; Mason, K; Massinger, T J; Matichard, F; Mavalvala, N; McCarthy, R; McClelland, D E; McCormick, S; McIntyre, G; Mendell, G; Merilh, E L; Meyers, P M; Miller, J; Mittleman, R; Moreno, G; Mueller, G; Mullavey, A; Munch, J; Nuttall, L K; Oberling, J; Oliver, M; Oppermann, P; Oram, Richard J; O'Reilly, B; Ottaway, D J; Overmier, H; Palamos, J R; Paris, H R; Parker, W; Pele, A; Penn, S; Phelps, M; Pierro, V; Pinto, I; Principe, M; Prokhorov, L G; Puncken, O; Quetschke, V; Quintero, E A; Raab, F J; Radkins, H; Raffai, P; Reid, S; Reitze, D H; Robertson, N A; Rollins, J G; Roma, V J; Romie, J H; Rowan, S; Ryan, K; Sadecki, T; Sanchez, E J; Sandberg, V; Savage, R L; Schofield, R M S; Sellers, D; Shaddock, D A; Shaffer, T J; Shapiro, B; Shawhan, P; Shoemaker, D H; Sigg, D; Slagmolen, B J J; Smith, B; Smith, J R; Sorazu, B; Staley, A; Strain, K A; Tanner, D B; Taylor, R; Thomas, M; Thomas, P; Thorne, K A; Thrane, E; Torrie, C I; Traylor, G; Tuyenbayev, D; Vajente, G; Valdes, G; van Veggel, A A; Vecchio, A; Veitch, P J; Venkateswara, K; Vo, T; Vorvick, C; Ward, R L; Warner, J; Weaver, B; Weiss, R; Weßels, P; Willke, B; Wipf, C C; Worden, J; Wu, G; Yamamoto, H; Yancey, C C; Yu, Hang; Yu, Haocun; Zhang, L; Zucker, M E; Zweizig, J

2017-12-01

This paper presents an analysis of the transient behavior of the Advanced LIGO (Laser Interferometer Gravitational-wave Observatory) suspensions used to seismically isolate the optics. We have characterized the transients in the longitudinal motion of the quadruple suspensions during Advanced LIGO's first observing run. Propagation of transients between stages is consistent with modeled transfer functions, such that transient motion originating at the top of the suspension chain is significantly reduced in amplitude at the test mass. We find that there are transients seen by the longitudinal motion monitors of quadruple suspensions, but they are not significantly correlated with transient motion above the noise floor in the gravitational wave strain data, and therefore do not present a dominant source of background noise in the searches for transient gravitational wave signals. Using the suspension transfer functions, we compared the transients in a week of gravitational wave strain data with transients from a quadruple suspension. Of the strain transients between 10 and 60 Hz, 84% are loud enough that they would have appeared above the sensor noise in the top stage quadruple suspension monitors if they had originated at that stage at the same frequencies. We find no significant temporal correlation with the suspension transients in that stage, so we can rule out suspension motion originating at the top stage as the cause of those transients. However, only 3.2% of the gravitational wave strain transients are loud enough that they would have been seen by the second stage suspension sensors, and none of them are above the sensor noise levels of the penultimate stage. Therefore, we cannot eliminate the possibility of transient noise in the detectors originating in the intermediate stages of the suspension below the sensing noise.

The single kinin receptor signals to separate and independent physiological pathways in Malpighian tubules of the yellow fever mosquito

Science.gov (United States)

In the past we have used the leucokinins, the kinins of the cockroach Leucophaea, to evaluate the mechanism of diuretic action of kinin peptides in Malpighian tubules of the yellow fever mosquito Aedes aegypti. Now using aedeskinins, the kinins of Aedes, are available, we find that in isolated Aede...

Impaired Albumin Uptake and Processing Promote Albuminuria in OVE26 Diabetic Mice

Science.gov (United States)

Long, Y. S.; Zheng, S.; Kralik, P. M.; Benz, F. W.

2016-01-01

The importance of proximal tubules dysfunction to diabetic albuminuria is uncertain. OVE26 mice have the most severe albuminuria of all diabetic mouse models but it is not known if impaired tubule uptake and processing are contributing factors. In the current study fluorescent albumin was used to follow the fate of albumin in OVE26 and normal mice. Compared to normal urine, OVE26 urine contained at least 23 times more intact fluorescent albumin but only 3-fold more 70 kD fluorescent dextran. This indicated that a function other than size selective glomerular sieving contributed to OVE26 albuminuria. Imaging of albumin was similar in normal and diabetic tubules for 3 hrs after injection. However 3 days after injection a subset of OVE26 tubules retained strong albumin fluorescence, which was never observed in normal mice. OVE26 tubules with prolonged retention of injected albumin lost the capacity to take up albumin and there was a significant correlation between tubules unable to eliminate fluorescent albumin and total albuminuria. TUNEL staining revealed a 76-fold increase in cell death in OVE26 tubules that retained fluorescent albumin. These results indicate that failure to process and dispose of internalized albumin leads to impaired albumin uptake, increased albuminuria, and tubule cell apoptosis. PMID:27822483

PROXIMAL DISABILITY AND SPINAL DEFORMITY INDEX IN PATIENTS WITH PROXIMAL FEMUR FRACTURES

Directory of Open Access Journals (Sweden)

Sylvio Mistro Neto

2015-12-01

Full Text Available Objective : To evaluate the quality of life related to the spine in patients with proximal femoral fractures. Methods : Study conducted in a tertiary public hospital in patients with proximal femoral fractures caused by low-energy trauma, through the Oswestry Disability Index questionnaire to asses complaints related to the spine at the time of life prior to the femoral fracture. The thoracic and lumbar spine of patients were also evaluated applying the radiographic index described by Gennant (Spinal Deformity Index, which assesses the number and severity of fractures. Results : Seventeen subjects completed the study. All had some degree of vertebral fracture. Patients were classified in the categories of severe and very severe disability in the questionnaire about quality of life. It was found that the higher SDI, the better the quality of life. Conclusion : There is a strong association of disability related to the spine in patients with proximal femoral fracture, and this complaint must be systematically evaluated in patients with appendicular fracture.

Magnetic suspension and guidance of high speed vehicles. Final report

Energy Technology Data Exchange (ETDEWEB)

Alston, I A; Clark, J M; Hayden, J T

1972-12-01

Technical and economical assessments of magnetic suspensions for high speed vehicles and transport systems are reported. In these suspensions the suspending magnet takes the form of a powerful superconducting electromagnet that induces currents while it moves over conducting sheets or loops. A number of vehicle track designs are evaluated for operating cost effectiveness. It is shown that propulsion systems using power collected from the track are more expensive than those using power generated onboard the vehicle, and that the conducting sheet suspension is slightly more expensive than the null flux suspension.

Xenon-Water Interaction in Bacterial Suspensions as Studied by NMR

DEFF Research Database (Denmark)

Rodin, V.; Ponomarev, Alexander; Gerasimov, Maxim

2017-01-01

suspensions of Escherichia coli in the presence of xenon using nuclear magnetic resonance (NMR). The work studied how the spin-lattice relaxation times of water protons in suspension change under xenon conditions. Xenon is able to form clathrate hydrates with water molecules at a temperature above the melting...... point of ice. The work studied NMR relaxation times which reflect the rotation freedom of water molecules in suspension. Lower relaxation times indicate reduced rotational freedom of water. Single exponential behavior of spin-lattice relaxation of protons in the suspensions of microorganisms has been...

Design and analysis of an intelligent controller for active geometry suspension systems

Science.gov (United States)

Goodarzi, Avesta; Oloomi, Ehsan; Esmailzadeh, Ebrahim

2011-02-01

An active geometry suspension (AGS) system is a device to optimise suspension-related factors such as toe angle and roll centre height by controlling vehicle's suspension geometry. The suspension geometry could be changed through control of suspension mounting point's position. In this paper, analysis and control of an AGS system is addressed. First, the effects of suspension geometry change on roll centre height and toe angle are studied. Then, based on an analytical approach, the improvement of the vehicle's stability and handling due to the control of suspension geometry is investigated. In the next section, an eight-degree-of-freedom handling model of a sport utility vehicle equipped with an AGS system is introduced. Finally, a self-tuning proportional-integral controller has been designed, using the fuzzy control theory, to control the actuator that changes the geometry of the suspension system. The simulation results show that an AGS system can improve the handling and stability of the vehicle.

Effect of a novel bioactive glass-ceramic on dentinal tubule occlusion: an in vitro study.

Science.gov (United States)

Zhong, Y; Liu, J; Li, X; Yin, W; He, T; Hu, D; Liao, Y; Yao, X; Wang, Y

2015-03-01

This in vitro study aimed to assess the ability and efficacy of HX-BGC, a novel bioactive glass-ceramic (SiO2-P2 O5-CaO-Na2 O-SrO), to reduce dentine tubule permeability. Dentine discs from human third molars were etched and randomly allocated into five groups: Group 1--distilled water; Group 2--Sensodyne Repair toothpaste (containing NovaMin®); Group 3--HX-BGC toothpaste (containing 7.5% HX-BGC); Group 4--control toothpaste (without HX-BGC); and Group 5--HX-BGC powder. Specimens were treated daily by brushing with an electric toothbrush for 20 seconds. Between daily treatments (7 days total), specimens were immersed in artificial saliva for 24 hours. Dentine permeability was measured at baseline, after the first treatment, after the first 24-hour immersion in artificial saliva and at the end of day 7. Dentine morphology and surface deposits were observed by scanning electron microscopy after one day and 7 days of treatment, respectively. Sensodyne Repair and bioactive glass-ceramic toothpaste significantly and immediately lowered dentine permeability. The HX-BGC powder group showed the highest reduction in dentine permeability after 7 days of treatment. The novel bioactive glass-ceramic material HX-BGC is effective in reducing dentine permeability by occluding open dentine tubules, indicating that HX-BGC may be a potential treatment for dentine hypersensitivity. © 2015 Australian Dental Association.

Weakly sheared active suspensions: hydrodynamics, stability, and rheology.

Science.gov (United States)

Cui, Zhenlu

2011-03-01

We present a kinetic model for flowing active suspensions and analyze the behavior of a suspension subjected to a weak steady shear. Asymptotic solutions are sought in Deborah number expansions. At the leading order, we explore the steady states and perform their stability analysis. We predict the rheology of active systems including an activity thickening or thinning behavior of the apparent viscosity and a negative apparent viscosity depending on the particle type, flow alignment, and the anchoring conditions, which can be tested on bacterial suspensions. We find remarkable dualities that show that flow-aligning rodlike contractile (extensile) particles are dynamically and rheologically equivalent to flow-aligning discoid extensile (contractile) particles for both tangential and homeotropic anchoring conditions. Another key prediction of this work is the role of the concentration of active suspensions in controlling the rheological behavior: the apparent viscosity may decrease with the increase of the concentration.

Stability of an extemporaneously compounded minoxidil oral suspension.

Science.gov (United States)

Song, Yunmei; Chin, Zen Whey; Ellis, David; Lwin, Ei Mon Phyo; Turner, Sean; Williams, Desmond; Garg, Sanjay

2018-03-01

Results of a study to determine the stability of an extemporaneously compounded minoxidil oral suspension under various temperature and stress conditions are reported. Commercially available minoxidil tablets (10 mg) were crushed to a fine powder, and predetermined amounts of 2 suspending vehicles were added to produce a 1-mg/mL suspension, which was stored in glass bottles at room temperature (25 ± 2 °C) or in a refrigerator (4 ± 2 °C). To simulate daily patient use, 5 days weekly 1 bottle of the suspension was removed from refrigerated storage and shaken and 0.5 mL of the contents discarded. At each specified time point, samples were analyzed in duplicate ( n = 6 for each test condition) using a validated high-performance liquid chromatography method. Samples were visually observed and their pH measured at each time point. Microbiological studies were performed on day 0 and at week 24. The mean percentage of initial minoxidil concentration remaining in all refrigerated samples exceeded 90% throughout the 24-week study, with no change in appearance, pH, microbial activity, odor, or redispersibility. During storage at room temperature, the suspension exhibited a color change at week 4, with slight sedimentation after 6 weeks, although minoxidil recovery exceeded 90% for 10 weeks. An extemporaneously compounded minoxidil oral suspension was stable for 24 weeks when stored in a refrigerator. This suspension can be used for up to 3 weeks when stored at room temperature. Copyright © 2018 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

ProxImaL: efficient image optimization using proximal algorithms

KAUST Repository

Heide, Felix

2016-07-11

Computational photography systems are becoming increasingly diverse, while computational resources-for example on mobile platforms-are rapidly increasing. As diverse as these camera systems may be, slightly different variants of the underlying image processing tasks, such as demosaicking, deconvolution, denoising, inpainting, image fusion, and alignment, are shared between all of these systems. Formal optimization methods have recently been demonstrated to achieve state-of-the-art quality for many of these applications. Unfortunately, different combinations of natural image priors and optimization algorithms may be optimal for different problems, and implementing and testing each combination is currently a time-consuming and error-prone process. ProxImaL is a domain-specific language and compiler for image optimization problems that makes it easy to experiment with different problem formulations and algorithm choices. The language uses proximal operators as the fundamental building blocks of a variety of linear and nonlinear image formation models and cost functions, advanced image priors, and noise models. The compiler intelligently chooses the best way to translate a problem formulation and choice of optimization algorithm into an efficient solver implementation. In applications to the image processing pipeline, deconvolution in the presence of Poisson-distributed shot noise, and burst denoising, we show that a few lines of ProxImaL code can generate highly efficient solvers that achieve state-of-the-art results. We also show applications to the nonlinear and nonconvex problem of phase retrieval.

Suspension Trauma / Orthostatic Intolerance

Science.gov (United States)

... Suspension Trauma/Orthostatic Intolerance Safety and Health Information Bulletin SHIB 03-24-2004, updated 2011 This Safety ... the harness, the environmental conditions, and the worker's psychological state all may increase the onset and severity ...

Tuning a Le Mans Car Suspension in ADAMS

CSIR Research Space (South Africa)

Berman, R

2012-09-01

Full Text Available An ADAMS model of South Africa’s first ever Le Mans car was developed and used to tune the suspension parameters. Validation of the model is to be done by comparing simulation results to those obtained in track testing. The suspension parameters...

Elemental imaging of kidneys of adult rats exposed to uranium acetate

Energy Technology Data Exchange (ETDEWEB)

Homma-Takeda, S. [Research Center for Radiation Protection, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan)], E-mail: shino_ht@nirs.go.jp; Terada, Y. [Japan Synchrotron Radiation Research Institute, Mikazuki, Hyogo 679-5198 (Japan); Nakata, A.; Sahoo, S.K.; Yoshida, S. [Research Center for Radiation Protection, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Ueno, S. [School of Veterinary Medicine, Kitasato University, Towada, Aomori 034-8628 (Japan); Inoue, M. [Research Center for Radiation Protection, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Iso, H.; Ishikawa, T.; Konishi, T.; Imaseki, H. [Fundamental Technology Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Shimada, Y. [Research Center for Radiation Protection, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan)

2009-06-15

Concern about the toxicity of depleted uranium for military use has increased recently. Renal toxicity is the hallmark effect of uranium exposure. However, the dynamics and distribution of uranium in the kidney are not well understood. Here, we determined the precise distribution of uranium and essential elements in the rat kidney using microbeam scanning particle-induced X-ray emission (micro-PIXE) and synchrotron radiation X-ray fluorescence (SR-XRF). Uranium accumulation in the rat kidney reached a maximum at 1 day after the subcutaneous (s.c.) administration of 2 mg U/kg of uranium acetate and then gradually decreased. At 3 h after administration, uranium was distributed mainly in the proximal tubules of the inner zone of the cortex and in the outer stripe of the outer medulla, and absorbed by the proximal tubule epithelium. Iron was localized more in the inside of the outer medulla than uranium, while phosphorus, potassium, sulfur and zinc were equally distributed in the cortex and the outer stripe of the outer medulla. At 3 days after administration, the number of apoptotic cells increased and cells were lost from the proximal tubules. Uranium was detectable mainly in the outer stripe of the outer medulla at 15 days, suggesting that the renal distribution of uranium is site-selective and causes site-specific renal lesions.

Sulphonylurea drugs reduce hypoxic damage in the isolated perfused rat kidney.

Science.gov (United States)

Engbersen, R; Moons, M M; Wouterse, A C; Dijkman, H B; Kramers, C; Smits, P; Russel, F G

2000-08-01

Sulphonylurea drugs have been shown to protect against hypoxic damage in isolated proximal tubules of the kidney. In the present study we investigated whether these drugs can protect against hypoxic damage in a whole kidney preparation. Tolbutamide (200 microM) and glibenclamide (10 microM) were applied to the isolated perfused rat kidney prior to changing the gassing from oxygen to nitrogen for 30 min. Hypoxic perfusions resulted in an increased fractional excretion of glucose (FE % glucose 14.3+/-1.5 for hypoxic perfusions vs 4.9+/-1.6 for normoxic perfusions, mean +/- s.e. mean, P<0.05), which could be completely restored by 200 microM tolbutamide (5.7+/-0.4 for tolbutamide vs 14.3+/-1.5 for untreated hypoxic kidneys, P<0.01). Furthermore, tolbutamide reduced the total amount of LDH excreted in the urine (220+/-100 mU for tolbutamide vs. 1220+/-160 mU for untreated hypoxic kidneys, P<0.01). Comparable results were obtained with glibenclamide (10 microM). In agreement with the effect on functional parameters, ultrastructural analysis of proximal tubules showed increased brush border preservation in tolbutamide treated kidneys compared to untreated hypoxic kidneys. We conclude that glibenclamide and tolbutamide are both able to reduce hypoxic damage to proximal tubules in the isolated perfused rat kidney when applied in the appropriate concentrations.

Usefulness of zebrafish larvae to evaluate drug-induced functional and morphological renal tubular alterations.

Science.gov (United States)

Gorgulho, Rita; Jacinto, Raquel; Lopes, Susana S; Pereira, Sofia A; Tranfield, Erin M; Martins, Gabriel G; Gualda, Emilio J; Derks, Rico J E; Correia, Ana C; Steenvoorden, Evelyne; Pintado, Petra; Mayboroda, Oleg A; Monteiro, Emilia C; Morello, Judit

2018-01-01

Prediction and management of drug-induced renal injury (DIRI) rely on the knowledge of the mechanisms of drug insult and on the availability of appropriate animal models to explore it. Zebrafish (Danio rerio) offers unique advantages for assessing DIRI because the larval pronephric kidney has a high homology with its human counterpart and it is fully mature at 3.5 days post-fertilization. Herein, we aimed to evaluate the usefulness of zebrafish larvae as a model of renal tubular toxicity through a comprehensive analysis of the renal alterations induced by the lethal concentrations for 10% of the larvae for gentamicin, paracetamol and tenofovir. We evaluated drug metabolic profile by mass spectrometry, renal function with the inulin clearance assay, the 3D morphology of the proximal convoluted tubule by two-photon microscopy and the ultrastructure of proximal convoluted tubule mitochondria by transmission electron microscopy. Paracetamol was metabolized by conjugation and oxidation with further detoxification with glutathione. Renal clearance was reduced with gentamicin and paracetamol. Proximal tubules were enlarged with paracetamol and tenofovir. All drugs induced mitochondrial alterations including dysmorphic shapes ("donuts", "pancakes" and "rods"), mitochondrial swelling, cristae disruption and/or loss of matrix granules. These results are in agreement with the tubular effects of gentamicin, paracetamol and tenofovir in man and demonstrate that zebrafish larvae might be a good model to assess functional and structural damage associated with DIRI.

Coupling Mechanism and Decoupled Suspension Control Model of a Half Car

Directory of Open Access Journals (Sweden)

Hailong Zhang

2016-01-01

Full Text Available A structure decoupling control strategy of half-car suspension is proposed to fully decouple the system into independent front and rear quarter-car suspensions in this paper. The coupling mechanism of half-car suspension is firstly revealed and formulated with coupled damping force (CDF in a linear function. Moreover, a novel dual dampers-based controllable quarter-car suspension structure is proposed to realize the independent control of pitch and vertical motions of the half car, in which a newly added controllable damper is suggested to be installed between the lower control arm and connection rod in conventional quarter-car suspension structure. The suggested damper constantly regulates the half-car pitch motion posture in a smooth and steady operation condition meantime achieving the expected completely structure decoupled control of the half-car suspension, by compensating the evolved CDF.

Shear-induced particle migration in suspensions of rods

Energy Technology Data Exchange (ETDEWEB)

Mondy, L.A. (Sandia National Laboratories, Albuquerque, New Mexico 87185 (United States)); Brenner, H. (Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139 (United States)); Altobelli, S.A. (The Lovelace Institutes, 2425 Ridgecrest Drive, S. E., Albuquerque, New Mexico 87108 (United States)); Abbott, J.R.; Graham, A.L. (Los Alamos National Laboratory, Los Alamos, New Mexico 87545 (United States))

1994-03-01

Shear-induced migration of particles occurs in suspensions of neutrally buoyant spheres in Newtonian fluids undergoing shear in the annular space between two rotating, coaxial cylinders (a wide-gap Couette), even when the suspension is in creeping flow. Previous studies have shown that the rate of migration of spherical particles from the high-shear-rate region near the inner (rotating) cylinder to the low-shear-rate region near the outer (stationary) cylinder increases rapidly with increasing sphere size. To determine the effect of particle shape, the migration of rods suspended in Newtonian fluids was recently measured. The behavior of several suspensions was studied. Each suspension contained well-characterized, uniform rods with aspect ratios ranging from 2 to 18 at either 0.30 or 0.40 volume fraction. At the same volume fraction of solids, the steady-state, radial concentration profiles for rods were independent of aspect ratio and were indistinguishable from those obtained from suspended spheres. Only minor differences near the walls (attributable to the finite size of the rods relative to the curvature of the walls) appeared to differentiate the profiles. Data taken during the transition from a well-mixed suspension to the final steady state show that the rate of migration increased as the volume of the individual rods increased.

Uniform Suspension of the Clustered Triamcinolone Acetonide Particle

Directory of Open Access Journals (Sweden)

Masahiko Sugimoto

2013-01-01

Full Text Available Purpose. MaQaid (MaQ is a new triamcinolone acetonide commercialised in Japan to visualize the vitreous. Because MaQ is preservative-free, it has a lower risk of ocular toxicities. However, since MaQ is only available as a powder, it needs suspenssion. Suspension does not always result uniformally, which causes poor visibility. This study reports a new MaQ suspension for better visibility. Methods. After medium addition to a MaQ vial, various methods were used. These included the use of (1 vortex mixer, (2 two syringes and a three-way stopcock, and (3 ultrasonic washer. We calculated suspended MaQ concentration (. To evaluate the reproducibility, we estimated the coefficient of variance (CV, . We used this MaQ for pig eyes, and vitreous visualization was simulated. Subsequently, we used this MaQ suspension for humans. Results. MaQ suspensions were sucessfull, and the concentrations of single particles increased significantly (. The CV was 36.1% for the routine method and 9.03% ffor the new method. Administration of a suspended MaQ made it possible to clearly visualize the vitreous in both pig and human eyes. Conclusions. We devised new techniques for uniformal MaQ suspension. These new methods can compensate for the MaQ disadvantages and ensure a safety surgery.

Compressed Air Production Using Vehicle Suspension

OpenAIRE

Ninad Arun Malpure; Sanket Nandlal Bhansali

2015-01-01

Abstract Generally compressed air is produced using different types of air compressors which consumes lot of electric energy and is noisy. In this paper an innovative idea is put forth for production of compressed air using movement of vehicle suspension which normal is wasted. The conversion of the force energy into the compressed air is carried out by the mechanism which consists of the vehicle suspension system hydraulic cylinder Non-return valve air compressor and air receiver. We are co...

Professor Jesse W. Beams and the first practical magnetic suspension

Science.gov (United States)

Allaire, P. E.; Humphris, R. R.; Lewis, D. W.

1992-01-01

Dr. Jesse W. Beams developed the first practical magnetic suspension for high speed rotating devices. The devices included high speed rotating mirrors, ultracentrifuges, and high speed centrifugal field rotors. A brief biography of Dr. Beams is presented, and the following topics are discussed: (1) early axial magnetic suspension for ultracentrifuges; and (2) magnetic suspension for high centrifugal fields.

Vibration control of an energy regenerative seat suspension with variable external resistance

Science.gov (United States)

Ning, Donghong; Sun, Shuaishuai; Du, Haiping; Li, Weihua; Zhang, Nong

2018-06-01

In this paper, an energy regenerative seat suspension with a variable external resistance is proposed and built, and a semi-active controller for its vibration control is also designed and validated. The energy regenerative seat suspension is built with a three-phase generator and a gear reducer, which are installed in the scissors structure centre of the seat suspension, and the vibration energy is directly harvested from the rotary movement of suspension's scissors structure. The electromagnetic torque of the semi-active seat suspension actuator is controlled by an external variable resistor. An integrated model including the seat suspension's kinematics and the generator is built and proven to match the test result very well. A simplified experimental phenomenon model is also built based on the test results for the controller design. A state feedback H∞ controller is proposed for the regenerative seat suspension's semi-active vibration control. The proposed regenerative seat suspension and its controller are validated with both simulations and experiments. A well-tuned passive seat suspension is applied to evaluate the regenerative seat's performance. Based on ISO 2631-1, the frequency-weighted root mean square (FW-RMS) acceleration of the proposed seat suspension has a 22.84% reduction when compared with the passive one, which indicates the improvement of ride comfort. At the same time, the generated RMS power is 1.21 W. The proposed regenerative seat suspension can greatly improve the driver's ride comfort and has the potential to be developed to a self-powered semi-active system.

Assessment of railway wagon suspension characteristics

Science.gov (United States)

Soukup, Josef; Skočilas, Jan; Skočilasová, Blanka

2017-05-01

The article deals with assessment of railway wagon suspension characteristics. The essential characteristics of a suspension are represented by the stiffness constants of the equivalent springs and the eigen frequencies of the oscillating movements in reference to the main central inertia axes of a vehicle. The premise of the experimental determination of these characteristic is the knowledge of the gravity center position and the knowledge of the main central inertia moments of the vehicle frame. The vehicle frame performs the general spatial movement when the vehicle moves. An analysis of the frame movement generally arises from Euler's equations which are commonly used for the description of the spherical movement. This solution is difficult and it can be simplified by applying the specific assumptions. The eigen frequencies solutions and solutions of the suspension stiffness are presented in the article. The solutions are applied on the railway and road vehicles with the simplifying conditions. A new method which assessed the characteristics is described in the article.

15 CFR 2011.110 - Suspension of certificate system.

Science.gov (United States)

2010-01-01

..., SYRUPS AND MOLASSES Certificate of Quota Eligibility § 2011.110 Suspension of certificate system. (a... of such suspension and the effective date thereof shall be published in the Federal Register. (b... such reinstatement and the effective date thereof shall be published in the Federal Register. (c...

Influence of crystal habit on trimethoprim suspension formulation.

Science.gov (United States)

Tiwary, A K; Panpalia, G M

1999-02-01

The role of crystal habit in influencing the physical stability and pharmacokinetics of trimethoprim suspensions was examined. Different habits for trimethoprim (TMP) were obtained by recrystallizing the commercial sample (PD) utilizing solvent-change precipitation method. Four distinct habits (microscopic observation) belonging to the same polymorphic state (DSC studies) were selected for studies. Preformulation and formulation studies were carried out on suspension dosage forms containing these crystals. The freshly prepared suspensions were also evaluated for their pharmacokinetic behaviour on healthy human volunteers using a cross over study. Variation of crystallization conditions produces different habits of TMP. Among the different crystal habits exhibiting same polymorphic state, the most anisometric crystal showed best physical stability in terms of sedimentation volume and redispersibility. However, habit did not significantly affect the extent of TMP excreted in urine. Modification of surface morphology without significantly altering the polymorphic state can be utilized for improving physical stability of TMP suspensions. However, the pharmacokinetic profile remains unaltered.

Study of shear thickening behavior in colloidal suspensions

Directory of Open Access Journals (Sweden)

N Maleki Jirsaraee

2015-01-01

Full Text Available We studied the shear thickening behavior of the nano silica suspension (silica nanoparticles 12 nm in size suspended in ethylene glycol under steady shear. The critical shear rate for transition into shear thickening phase was determined at different concentrations and temperatures. The effect of temperature and concentration was studied on the shear thickening behavior. In silica suspension, it was observed that all the samples had a transition into shear thickening phase and also by increasing the temperature, critical shear rate increased and viscosity decreased. Our observations showed that movement in silica suspension was Brownian and temperature could cause a delay in transition into shear thickening phase. Yet, we observed that increasing the concentration would decrease critical shear rate and increase viscosity. Increasing temperature increased Brownian forces and increasing concentration increased hydrodynamic forces, confirming the contrast between these two forces for transition into shear thickening phase for the suspensions containing nano particles

Efficacy of Modified Bioactive Glass for Dentin Remineralization and Obstruction of Dentinal Tubules

Directory of Open Access Journals (Sweden)

Mahshid Saffarpour

2017-10-01

Full Text Available Objectives: This study assessed the efficacy of modified bioactive glass (MBG for dentin remineralization and obstruction of dentinal tubules.Materials and Methods: Thirty-six dentin discs were made from 20 third molars and were stored in 12% lactic acid solution for two weeks to induce demineralization. The samples were divided into three groups (n=12: 1- BG, 2- BG modified with 5% strontium (Sr and 3- BG modified with 10% Sr. After applying the BG, the samples were stored in artificial saliva for 7, 14 and 21 days. Attenuated Total Reflection-Fourier Transform Infrared Spectroscopy (ATR-FTIR, X-ray Diffraction (XRD analysis, Scanning Electron Microscopy (SEM, and Energy-Dispersive X-ray (EDX analysis were used to assess remineralization. Also, 6 dentin discs were divided into three groups of BG, BG modified with 5% Sr and BG modified with 10% Sr, to examine tubular occlusion. The discs were etched using 0.5M of EDTA for two minutes and were stored in artificial saliva for 7 days. Changes in dentin surface morphology were evaluated under SEM.Results: Group 3 showed high rates of remineralization at days 7 and 14, although the rate decreased at day 21. Group 2 exhibited high rates of remineralization at days 7, 14 and 21. Dentinal tubules were partially occluded by BG and BG modified with 5% Sr, while they were almost completely obstructed after the use of BG modified with 10% Sr.Conclusions: Strontium increases remineralization. Addition of 10% Sr to BG enhances apatite formation; however, the apatite dissolves over time. Addition of 5% Sr to BG stabilizes the apatite lattice and increases the remineralization.

Equivalent Air Spring Suspension Model for Quarter-Passive Model of Passenger Vehicles.

Science.gov (United States)

Abid, Haider J; Chen, Jie; Nassar, Ameen A

2015-01-01

This paper investigates the GENSIS air spring suspension system equivalence to a passive suspension system. The SIMULINK simulation together with the OptiY optimization is used to obtain the air spring suspension model equivalent to passive suspension system, where the car body response difference from both systems with the same road profile inputs is used as the objective function for optimization (OptiY program). The parameters of air spring system such as initial pressure, volume of bag, length of surge pipe, diameter of surge pipe, and volume of reservoir are obtained from optimization. The simulation results show that the air spring suspension equivalent system can produce responses very close to the passive suspension system.

Evaluating Suspension Formulations of Theophylline Cocrystals With Artificial Sweeteners.

Science.gov (United States)

Aitipamula, Srinivasulu; Wong, Annie B H; Kanaujia, Parijat

2018-02-01

Pharmaceutical cocrystals have garnered significant interest as potential solids to address issues associated with formulation development of drug substances. However, studies concerning the understanding of formulation behavior of cocrystals are still at the nascent stage. We present results of our attempts to evaluate suspension formulations of cocrystals of an antiasthmatic drug, theophylline, with 2 artificial sweeteners. Stability, solubility, drug release, and taste of the suspension formulations were evaluated. Suspension that contained cocrystal with acesulfame showed higher drug release rate, while a cocrystal with saccharin showed a significant reduction in drug release rate. The cocrystal with saccharin was found stable in suspension for over 9 weeks at accelerated test condition; in contrast, the cocrystal with acesulfame was found unstable. Taste analysis using an electronic taste-sensing system revealed improved sweetness of the suspension formulations with cocrystals. Theophylline has a narrow therapeutic index with a short half-life which necessitates frequent dosing. This adversely impacts patient compliance and enhances risk of gastrointestinal and cardiovascular adverse effects. The greater thermodynamic stability, sweetness, and sustained drug release of the suspension formulation of theophylline-saccharin could offer an alternative solution to the short half-life of theophylline and make it a promising formulation for treating asthmatic pediatric and geriatric patients. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Particle Image Velocimetry (PIV) Measurements of Suspension-Feeding Velocities

Science.gov (United States)

Du Clos, K.; Jones, I. T.; Carrier, T. J.; Jumars, P. A.

2016-02-01

Active suspension feeders, such as bivalves and tunicates, connect benthic and pelagic ecosystems by packaging suspended matter into larger fecal and pseudofecal particles, greatly enhancing the flux of carbon and nutrients from the water column to the benthos. The volume of water processed by a population of suspension feeders is commonly estimated by scaling up results from experiments that measure the clearance rate (the volume of water cleared of particles per time) of one or a few individual suspension feeders. Clearance rates vary, however, between species, within a species, and over time for a single individual; and the velocity fields produced by suspension feeders are likely to interact in complex ways. We measured the water velocity fields produced by two species of bivalve, Mya arenaria and Mercenaria mercenaria, and the tunicate Ciona intestinalis, using particle image velocimetry (PIV). We used these measurements to calculate flow rates and Reynolds numbers of inhalant and exhalant siphons. We also observed strong entrainment of water by M. arenaria's exhalant siphon jet that may help to explain how the clam avoids depleting the water around it of particles and oxygen as it feeds. We are using these measurements to inform computational fluid mechanics (CFD) models of suspension feeding, allowing us to examine the interactions of flow fields produced by multiple suspension feeders and other effects not quantified by clearance-rate measurements.

Development of the Nissan hydraulic active suspension. Nissan yuatsu active suspension no kaihatsu

Energy Technology Data Exchange (ETDEWEB)

Kawarasaki, y.; Fukunaga, Y.; Hasegawa, S.; Okuyama, Y.; Omura, I.; Takahashi, K.; Abe, S.; Tsuruta, E. (Nissan Motor Co. Ltd., Tokyo (Japan))

1989-12-25

A hydraulic active suspension system, Nissan original product, was developed and mass produced for the first time in the world. The system incorporates a sufficient power source, a high accuracy sensor and a high response device for continuous and intended vehicle control and at the same time delivers high levels of ride comfort and driving performance. The suspension system has four innovative features: skyhook damping, active roll and pitching control, a frequency-dependent damping mechanism, and active steering characteristics control. Under all road and operating conditions, the system actively suppresses vehicle attitude changes and unnecessary movement, and also gently absorbs inputs from the road. This epoch-making system provides a dramatic improvement in vehicle performance, and has been adopted in the Infiniti Q45 luxury sedan. 2 refs., 20 figs., 4 tabs.

14 CFR 1274.927 - Debarment and suspension and Drug-Free Workplace.

Science.gov (United States)

2010-01-01

... Workplace. 1274.927 Section 1274.927 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION... suspension and Drug-Free Workplace. Debarment and Suspension and Drug-Free Workplace April 2007 NASA... Suspension (Nonprocurement) and 14 CFR part 1267, Government-wide requirements for Drug-Free Workplace...

Proximal Probes Facility

Data.gov (United States)

Federal Laboratory Consortium — The Proximal Probes Facility consists of laboratories for microscopy, spectroscopy, and probing of nanostructured materials and their functional properties. At the...

Effect of solvent composition on dispersing ability of reaction sialon suspensions.

Science.gov (United States)

Xu, Xin; Oliveira, Marta; Ferreira, José M F

2003-03-15

This work focuses on the optimization of the rheological behavior of suspensions considering different solvent compositions. The effects of methyl ethyl ketone (MEK)/ethanol (E) solvent mixtures on reaction sialon suspensions were investigated by measuring sedimentation behavior, adsorption of dispersant, and flow behavior. It was shown that both the flow behavior and the sedimentation behavior strongly depended on selection of solvent composition. Using 3 wt% KD1 as dispersant, well-dispersed colloidal suspensions could be obtained in MEK-rich solvents. The suspensions with 60 vol% MEK/40 vol% E as solvent could be fitted to the Bingham model with very low yield stress, while suspensions with pure MEK or ethanol-rich mixtures as solvent showed pseudo plastic behavior with relatively high yield stress values. A model was proposed to explain the different flow behaviors of suspensions considering the different configurations of dispersant at particles' surfaces.

2 CFR 180.740 - Are suspension proceedings formal?

Science.gov (United States)

2010-01-01

... 2 Grants and Agreements 1 2010-01-01 2010-01-01 false Are suspension proceedings formal? 180.740 Section 180.740 Grants and Agreements OFFICE OF MANAGEMENT AND BUDGET GOVERNMENTWIDE GUIDANCE FOR GRANTS... suspension decision. (b) You as a respondent or your representative must submit any documentary evidence you...

12 CFR 19.243 - Removal, suspension, or debarment.

Science.gov (United States)

2010-01-01

... 12 Banks and Banking 1 2010-01-01 2010-01-01 false Removal, suspension, or debarment. 19.243 Section 19.243 Banks and Banking COMPTROLLER OF THE CURRENCY, DEPARTMENT OF THE TREASURY RULES OF PRACTICE AND PROCEDURE Removal, Suspension, and Debarment of Accountants From Performing Audit Services § 19...

Radiation resistivity of frozen insulin solutions and suspensions

Energy Technology Data Exchange (ETDEWEB)

Soboleva, N N; Ivanova, A I; Talrose, V L; Trofimov, V I; Fedotov, V P [AN SSSR, Moscow. Inst. Fizicheskoj Khimii; Research Institute for Biological Testing of Chemicals, Moscow (USSR); Institute of Experimental Endocrinology and Hormon Chemistry, Moscow (USSR))

1981-10-01

The effect of great increase in radiation resistance of insulin solutions and suspensions after irradiation at low temperatures in the frozen state was observed by absorption spectrophotometry, paper chromatography and biological analysis. The data obtained suggest irradiation of frozen insulin solutions and suspensions as a method for its sterilization.

Intelligent systems of the vehicles’ suspension

Science.gov (United States)

Yurlin, D.

2018-02-01

The article is devoted to the current condition of car’s active suspension system. It presents the tendencies in development of the active systems of suspension system, adjustable elements incorporated in them and the companies succeeded in designing such systems. It also mirrors the problem of impact of active systems on car’s safety and their importance for the driver. Advantages and disadvantages of the most common types of active elements are being described, analyzed and compared. The author concludes about the perspectives of these systems’ development.

Rheology of organoclay suspension

CSIR Research Space (South Africa)

Hato, MJ

2011-05-01

Full Text Available The authors have studied the rheological properties of clay suspensions in silicone oil, where clay surfaces were modified with three different types of surfactants. Dynamic oscillation measurements showed a plateau-like behavior for all...

Segmental heterogeneity of enzymatic response during compensatory renal growth

International Nuclear Information System (INIS)

Hoang, T.; Bergeron, M.

1985-01-01

The activities of DNA polymerase α and key enzymes of gluconeogenesis and glycolysis were measured in different segments of the rat nephron at various times (up to 96 hrs) following a unilateral nephrectomy (UNx). Tubule fragments were obtained after collagenase treatment followed by centrifugation on a Percoll gradient. The DNA polymerase α activity in control rats showed moderate and similar values in different segmental extracts as well as in the whole kidney extract (1700-1800 μμmole[ 3 H] dAMP/mg DNA). In Unx rats, activity in proximal tubules (PT) measured at 24, 48, 72 and 96 hrs after nephrectomy represented an increase of 60%, 200%, 420% and 370% respectively over control values. Distal tubule fragments (DT) showed only minor increases. The results demonstrate that the proximal tubule accounts for most of the compensatory renal growth (CRG) in the remaining kidney. The gluconeogenic and glycolytic enzymes were confined to the PT and those of glycolysis to the DT fragments. Following UNx, the specific activities of these enzymes were not modified in the remaining kidney; however, the overall activity of gluconeogenesis was increased as a result of the cell hyperplasia occurring in the PT. The work also illustrates that biochemical studies of CRG on the whole organ may provide misleading information due to the presence of heterogeneous cell populations in the mammalian kidney and to their uneven response in CRG

Origins of microstructural transformations in charged vesicle suspensions: the crowding hypothesis.

Science.gov (United States)

Seth, Mansi; Ramachandran, Arun; Murch, Bruce P; Leal, L Gary

2014-09-02

It is observed that charged unilamellar vesicles in a suspension can spontaneously deflate and subsequently transition to form bilamellar vesicles, even in the absence of externally applied triggers such as salt or temperature gradients. We provide strong evidence that the driving force for this deflation-induced transition is the repulsive electrostatic pressure between charged vesicles in concentrated suspensions, above a critical effective volume fraction. We use volume fraction measurements and cryogenic transmission electron microscopy imaging to quantitatively follow both the macroscopic and microstructural time-evolution of cationic diC18:1 DEEDMAC vesicle suspensions at different surfactant and salt concentrations. A simple model is developed to estimate the extent of deflation of unilamellar vesicles caused by electrostatic interactions with neighboring vesicles. It is determined that when the effective volume fraction of the suspension exceeds a critical value, charged vesicles in a suspension can experience "crowding" due to overlap of their electrical double layers, which can result in deflation and subsequent microstructural transformations to reduce the effective volume fraction of the suspension. Ordinarily in polydisperse colloidal suspensions, particles interacting via a repulsive potential transform into a glassy state above a critical volume fraction. The behavior of charged vesicle suspensions reported in this paper thus represents a new mechanism for the relaxation of repulsive interactions in crowded situations.

Beta-2 Microglobulin Kidney Disease Test

Science.gov (United States)

... Diabetes Diarrhea Disseminated Intravascular Coagulation (DIC) Down Syndrome Ebola Virus Infection Endocrine System and Syndromes Epilepsy Excessive ... is then reabsorbed by the renal proximal tubules , structures that reclaim water, proteins, vitamins, minerals, and other ...

Rheological studies of aqueous stabilised nano-zirconia particle suspensions

Directory of Open Access Journals (Sweden)

Asad Ullah Khan

2012-02-01

Full Text Available In the present investigation aqueous suspensions of nano- and colloidal range particles are stabilised by changing the ambient pH. Rheology is used to establish the stability of the suspensions and it is found that the rheology of the suspensions is strongly dependent on the pH values. The viscosity is highest close to the iso-electric point of the powders. At the iso-electric point the net surface charge on the powder particles is zero and is the cause of the high viscosity. Away from the iso-electric point, the particles are charged, giving rise to a double layer phenomenon and causing the reduction in viscosity. It is also found that increasing the solid contents of the suspensions reduces the pH region of low viscosity.

Neighborhoods and manageable proximity

Directory of Open Access Journals (Sweden)

Stavros Stavrides

2011-08-01

Full Text Available The theatricality of urban encounters is above all a theatricality of distances which allow for the encounter. The absolute “strangeness” of the crowd (Simmel 1997: 74 expressed, in its purest form, in the absolute proximity of a crowded subway train, does not generally allow for any movements of approach, but only for nervous hostile reactions and submissive hypnotic gestures. Neither forced intersections in the course of pedestrians or vehicles, nor the instantaneous crossing of distances by the technology of live broadcasting and remote control give birth to places of encounter. In the forced proximity of the metropolitan crowd which haunted the city of the 19th and 20th century, as well as in the forced proximity of the tele-presence which haunts the dystopic prospect of the future “omnipolis” (Virilio 1997: 74, the necessary distance, which is the stage of an encounter between different instances of otherness, is dissipated.

Digital contrast subtraction radiography for proximal caries diagnosis

International Nuclear Information System (INIS)

Kang, Byung Cheol; Yoon, Suk Ja

2002-01-01

To determine whether subtraction images utilizing contrast media can improve the diagnostic performance of proximal caries diagnosis compared to conventional periapical radiographic images. Thirty-six teeth with 57 proximal surfaces were radiographied using a size no.2 RVG-ui sensor (Trophy Radiology, Marne-la-Vallee, France). The teeth immersed in water-soluble contrast media and subtraction images were taken. Each tooth was then sectioned for histologic examination. The digital radiographic images and subtraction images were examined and interpreted by three dentists for proximal caries. The results of the proximal caries diagnosis were then verified with the results of the histologic examination. The proximal caries sensitivity using digital subtraction radiography was significantly higher than simply examining a single digital radiograph. The sensitivity of the proximal dentinal carious lesion when analyzed with the subtraction radiograph and the radiograph together was higher than with the subtraction radiograph or the radiograph alone. The use of subtraction radiography with contrast media may be useful for detecting proximal dentinal carious lesions.

Nerve Wrapping of the Sciatic Nerve With Acellular Dermal Matrix in Chronic Complete Proximal Hamstring Ruptures and Ischial Apophyseal Avulsion Fractures

Science.gov (United States)

Haus, Brian M.; Arora, Danny; Upton, Joseph; Micheli, Lyle J.

2016-01-01

Background: Patients with chronic injuries of the proximal hamstring can develop significant impairment because of weakness of the hamstring muscles, sciatic nerve compression from scar formation, or myositis ossificans. Purpose: To describe the surgical outcomes of patients with chronic injury of the proximal hamstrings who were treated with hamstring repair and sciatic neurolysis supplemented with nerve wrapping with acellular dermal matrix. Study Design: Retrospective case series; Level of evidence, 4. Methods: Fifteen consecutive patients with a diagnosis of chronic complete proximal hamstring rupture or chronic ischial tuberosity apophyseal avulsion fracture (mean age, 39.67 years; range, 14-69 years) were treated with proximal hamstring repair and sciatic neurolysis supplemented with nerve wrapping with acellular dermal matrix. Nine patients had preoperative sciatica, and 6 did not. Retrospective chart review recorded clinical outcomes measured by the degree of pain relief, the rate of return to activities, and associated postoperative complications. Results: All 15 patients were followed in the postoperative period for an average of 16.6 months. Postoperatively, there were 4 cases of transient sciatic nerve neurapraxia. Four patients (26%) required postoperative betamethasone sodium phosphate (Celestone Soluspan) injectable suspension USP 6 mg/mL. Among the 9 patients with preoperative sciatica, 6 (66%) had a good or excellent outcome and were able to return to their respective activities/sports; 3 (33%) had persistent chronic pain. One of these had persistent sciatic neuropathy that required 2 surgical reexplorations and scar excision after development of recurrent extraneural scar formation. Among the 6 without preoperative sciatica, 100% had a good or excellent outcomes and 83% returned to their respective activities/sports. Better outcomes were observed in younger patients, as the 3 cases of persistent chronic sciatic pain were in patients older than 45

Adaptive tracking control for active suspension systems with non-ideal actuators

Science.gov (United States)

Pan, Huihui; Sun, Weichao; Jing, Xingjian; Gao, Huijun; Yao, Jianyong

2017-07-01

As a critical component of transportation vehicles, active suspension systems are instrumental in the improvement of ride comfort and maneuverability. However, practical active suspensions commonly suffer from parameter uncertainties (e.g., the variations of payload mass and suspension component parameters), external disturbances and especially the unknown non-ideal actuators (i.e., dead-zone and hysteresis nonlinearities), which always significantly deteriorate the control performance in practice. To overcome these issues, this paper synthesizes an adaptive tracking control strategy for vehicle suspension systems to achieve suspension performance improvements. The proposed control algorithm is formulated by developing a unified framework of non-ideal actuators rather than a separate way, which is a simple yet effective approach to remove the unexpected nonlinear effects. From the perspective of practical implementation, the advantages of the presented controller for active suspensions include that the assumptions on the measurable actuator outputs, the prior knowledge of nonlinear actuator parameters and the uncertain parameters within a known compact set are not required. Furthermore, the stability of the closed-loop suspension system is theoretically guaranteed by rigorous mathematical analysis. Finally, the effectiveness of the presented adaptive control scheme is confirmed using comparative numerical simulation validations.

The Evolution of Discipline: Alternative to Suspension Programs.

Science.gov (United States)

Streva, Michael A.

Historically, the chosen method of discipline in United States schools has gone from corporal punishment to an emphasis on suspension. Recently, as principals have become less certain about the extent of their authority to suspend students, many inschool programs have been developed as alternatives to suspension. Among the advantages of such…

21 CFR 1314.155 - Suspension pending final order.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Suspension pending final order. 1314.155 Section 1314.155 Food and Drugs DRUG ENFORCEMENT ADMINISTRATION, DEPARTMENT OF JUSTICE RETAIL SALE OF SCHEDULED LISTED CHEMICAL PRODUCTS Order to Show Cause § 1314.155 Suspension pending final order. (a) The...

38 CFR 21.3043 - Suspension of program; child.

Science.gov (United States)

2010-07-01

... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false Suspension of program; child. 21.3043 Section 21.3043 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS... 38 U.S.C. Chapter 35 Eligibility and Entitlement § 21.3043 Suspension of program; child. For an...

Paricalcitol attenuates lipopolysaccharide-induced inflammation and apoptosis in proximal tubular cells through the prostaglandin E₂ receptor EP4

Directory of Open Access Journals (Sweden)

Yu Ah Hong

2017-06-01

Full Text Available Background: Vitamin D is considered to exert a protective effect on various renal diseases but its underlying molecular mechanism remains poorly understood. This study aimed to determine whether paricalcitol attenuates inflammation and apoptosis during lipopolysaccharide (LPS-induced renal proximal tubular cell injury through the prostaglandin E₂ (PGE₂ receptor EP4. Methods: Human renal tubular epithelial (HK-2 cells were pretreated with paricalcitol (2 ng/mL for 1 hour and exposed to LPS (1 μg/mL. The effects of paricalcitol pretreatment in relation to an EP4 blockade using AH-23848 or EP4 small interfering RNA (siRNA were investigated. Results: The expression of cyclooxygenase-2, PGE₂, and EP4 were significantly increased in LPS-exposed HK-2 cells treated with paricalcitol compared with cells exposed to LPS only. Paricalcitol prevented cell death induced by LPS exposure, and the cotreatment of AH-23848 or EP4 siRNA offset these cell-protective effects. The phosphorylation and nuclear translocation of p65 nuclear factor-kappaB (NF-κB were decreased and the phosphorylation of Akt was increased in LPS-exposed cells with paricalcitol treatment. AH-23848 or EP4 siRNA inhibited the suppressive effects of paricalcitol on p65 NF-κB nuclear translocation and the activation of Akt. The production of proinflammatory cytokines and the number of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive cells were attenuated by paricalcitol in LPS exposed HK-2 cells. The cotreatment with an EP4 antagonist abolished these anti-inflammatory and antiapoptotic effects. Conclusion: EP4 plays a pivotal role in anti-inflammatory and antiapoptotic effects through Akt and NF-κB signaling after paricalcitol pretreatment in LPS-induced renal proximal tubule cell injury.

41 CFR 109-40.103-2 - Disqualification and suspension of carriers.

Science.gov (United States)

2010-07-01

... suspension of carriers. 109-40.103-2 Section 109-40.103-2 Public Contracts and Property Management Federal... AVIATION, TRANSPORTATION, AND MOTOR VEHICLES 40-TRANSPORTATION AND TRAFFIC MANAGEMENT 40.1-General Provision § 109-40.103-2 Disqualification and suspension of carriers. Disqualification and suspension are...

Dysferlin, annexin A1, and mitsugumin 53 are upregulated in muscular dystrophy and localize to longitudinal tubules of the T-system with stretch.

Science.gov (United States)

Waddell, Leigh B; Lemckert, Frances A; Zheng, Xi F; Tran, Jenny; Evesson, Frances J; Hawkes, Joanne M; Lek, Angela; Street, Neil E; Lin, Peihui; Clarke, Nigel F; Landstrom, Andrew P; Ackerman, Michael J; Weisleder, Noah; Ma, Jianjie; North, Kathryn N; Cooper, Sandra T

2011-04-01

Mutations in dysferlin cause an inherited muscular dystrophy because of defective membrane repair. Three interacting partners of dysferlin are also implicated in membrane resealing: caveolin-3 (in limb girdle muscular dystrophy type 1C), annexin A1, and the newly identified protein mitsugumin 53 (MG53). Mitsugumin 53 accumulates at sites of membrane damage, and MG53-knockout mice display a progressive muscular dystrophy. This study explored the expression and localization of MG53 in human skeletal muscle, how membrane repair proteins are modulated in various forms of muscular dystrophy, and whether MG53 is a primary cause of human muscle disease. Mitsugumin 53 showed variable sarcolemmal and/or cytoplasmic immunolabeling in control human muscle and elevated levels in dystrophic patients. No pathogenic MG53 mutations were identified in 50 muscular dystrophy patients, suggesting that MG53 is unlikely to be a common cause of muscular dystrophy in Australia. Western blot analysis confirmed upregulation of MG53, as well as of dysferlin, annexin A1, and caveolin-3 to different degrees, in different muscular dystrophies. Importantly, MG53, annexin A1, and dysferlin localize to the t-tubule network and show enriched labeling at longitudinal tubules of the t-system in overstretch. Our results suggest that longitudinal tubules of the t-system may represent sites of physiological membrane damage targeted by this membrane repair complex.

Calculus Rules for V-Proximal Subdifferentials in Smooth Banach Spaces

Directory of Open Access Journals (Sweden)

Messaoud Bounkhel

2016-01-01

Full Text Available In 2010, Bounkhel et al. introduced new proximal concepts (analytic proximal subdifferential, geometric proximal subdifferential, and proximal normal cone in reflexive smooth Banach spaces. They proved, in p-uniformly convex and q-uniformly smooth Banach spaces, the density theorem for the new concepts of proximal subdifferential and various important properties for both proximal subdifferential concepts and the proximal normal cone concept. In this paper, we establish calculus rules (fuzzy sum rule and chain rule for both proximal subdifferentials and we prove the Bishop-Phelps theorem for the proximal normal cone. The limiting concept for both proximal subdifferentials and for the proximal normal cone is defined and studied. We prove that both limiting constructions coincide with the Mordukhovich constructions under some assumptions on the space. Applications to nonconvex minimisation problems and nonconvex variational inequalities are established.

Bulk and interfacial stresses in suspensions of soft and hard colloids

International Nuclear Information System (INIS)

Truzzolillo, D; Roger, V; Dupas, C; Cipelletti, L; Mora, S

2015-01-01

We explore the influence of particle softness and internal structure on both the bulk and interfacial rheological properties of colloidal suspensions. We probe bulk stresses by conventional rheology, by measuring the flow curves, shear stress versus strain rate, for suspensions of soft, deformable microgel particles and suspensions of near hard-sphere-like silica particles. A similar behaviour is seen for both kinds of particles in suspensions at concentrations up to the random close packing volume fraction, in agreement with recent theoretical predictions for sub-micron colloids. Transient interfacial stresses are measured by analyzing the patterns formed by the interface between the suspensions and their solvent, due to a generalized Saffman–Taylor hydrodynamic instability. At odds with the bulk behaviour, we find that microgels and hard particle suspensions exhibit vastly different interfacial stress properties. We propose that this surprising behaviour results mainly from the difference in particle internal structure (polymeric network for microgels versus compact solid for the silica particles), rather than softness alone. (paper)

Size-selective separation of submicron particles in suspensions with ultrasonic atomization.

Science.gov (United States)

Nii, Susumu; Oka, Naoyoshi

2014-11-01

Aqueous suspensions containing silica or polystyrene latex were ultrasonically atomized for separating particles of a specific size. With the help of a fog involving fine liquid droplets with a narrow size distribution, submicron particles in a limited size-range were successfully separated from suspensions. Performance of the separation was characterized by analyzing the size and the concentration of collected particles with a high resolution method. Irradiation of 2.4MHz ultrasound to sample suspensions allowed the separation of particles of specific size from 90 to 320nm without regarding the type of material. Addition of a small amount of nonionic surfactant, PONPE20 to SiO2 suspensions enhanced the collection of finer particles, and achieved a remarkable increase in the number of collected particles. Degassing of the sample suspension resulted in eliminating the separation performance. Dissolved air in suspensions plays an important role in this separation. Copyright © 2014 Elsevier B.V. All rights reserved.

The role of Omi/HtrA2 protease in neonatal postasphyxial serum-induced apoptosis in human kidney proximal tubule cells

Directory of Open Access Journals (Sweden)

Zhang Yong

2012-01-01

Full Text Available Omi/HtrA2, a proapoptotic mitochondrial serine protease, is involved in both caspase-dependent and caspaseindependent apoptosis. A growing body of evidence indicates that Omi/HtrA2 plays an important role in the pathogenesis of a variety of ischemia-reperfusion (I/R injuries. However, the role of Omi/HtrA2 in renal injuries that occur in neonates with asphyxia remains unknown. The present study was designed to investigate whether Omi/HtrA2 plays an important role in the types of renal injuries that are induced by neonatal postasphyxial serum. Human renal proximal tubular cell line (HK-2 cells were used as targets. A 20% serum taken from neonates one day after asphyxia was applied to target cells as an attacking factor. We initially included control and postasphyxial serum-attacked groups and later included a ucf-101 group in the study. In the postasphyxial serum-treated group, cytosolic Omi/HtrA2 and caspase-3 expression in HK-2 cells was significantly higher than in the control group. Moreover, the concentration of cytosolic caspase-3 was found to be markedly decreased in HK-2 cells in the ucf-101 group. Our results suggest both that postasphyxial serum has a potent apoptosis-inducing effect on HK-2 cells and that this effect can be partially blocked by ucf-101. Taken together, our results demonstrate for the first time that postasphyxial serum from neonates results in Omi/HtrA2 translocation from the mitochondria to the cytosol, where it promotes HK-2 cell apoptosis via a protease activity-dependent, caspase-mediated pathway.

Objectives, Outlines, and Preparation for the Resist Tubule Space Experiment to Understand the Mechanism of Gravity Resistance in Plants

Science.gov (United States)

Hoson, Takayuki; Akamatsu, Haruhiko; Soga, Kouichi; Wakabayashi, Kazuyuki; Hashimoto, Hirofumi; Yamashita, Masamichi; Hasegawa, Katsuya; Yano, Sachiko; Omori, Katsunori; Ishioka, Noriaki; Matsumoto, Shohei; Kasahara, Haruo; Shimazu, Toru; A. Baba, Shoji; Hashimoto, Takashi

Gravity resistance is a principal graviresponse in plants. In resistance to hypergravity, the gravity signal may be perceived by the mechanoreceptors located on the plasma membrane, and then transformed and transduced via the structural continuum or physiological continuity of cortical microtubules-plasma membrane-cell wall, leading to an increase in the cell wall rigidity as the final response. The Resist Tubule experiment, which will be conducted in the Kibo Module on the International Space Station, aims to confirm that this hypothesis is applicable to resistance to 1 G gravity. There are two major objectives in the Resist Tubule experiment. One is to quantify the contributions of cortical microtubules to gravity resistance using Arabidopsis tubulin mutants with different degrees of defects. Another objective is to analyze the modifications to dynamics of cortical microtubules and membrane rafts under microgravity conditions on-site by observing green fluorescent protein (GFP)-expressing Arabidopsis lines with the fluorescence microscope in the Kibo. We have selected suitable mutants, developed necessary hardware, and fixed operation procedure for the experiment.

49 CFR 592.7 - Suspension, revocation, and reinstatement of suspended registrations.

Science.gov (United States)

2010-10-01

... vehicle during the time that its registration has been suspended. (d) Effect of suspension or revocation... date of the suspension or revocation all vehicles that it imported to which it has not affixed a... 49 Transportation 7 2010-10-01 2010-10-01 false Suspension, revocation, and reinstatement of...

29 CFR 98.600 - How do suspension and debarment actions start?

Science.gov (United States)

2010-07-01

... 29 Labor 1 2010-07-01 2010-07-01 true How do suspension and debarment actions start? 98.600 Section 98.600 Labor Office of the Secretary of Labor GOVERNMENTWIDE DEBARMENT AND SUSPENSION... debarment actions start? When we receive information from any source concerning a cause for suspension or...

Super-Relaxed ( -Proximal Point Algorithms, Relaxed ( -Proximal Point Algorithms, Linear Convergence Analysis, and Nonlinear Variational Inclusions

Directory of Open Access Journals (Sweden)

Agarwal RaviP

2009-01-01

Full Text Available We glance at recent advances to the general theory of maximal (set-valued monotone mappings and their role demonstrated to examine the convex programming and closely related field of nonlinear variational inequalities. We focus mostly on applications of the super-relaxed ( -proximal point algorithm to the context of solving a class of nonlinear variational inclusion problems, based on the notion of maximal ( -monotonicity. Investigations highlighted in this communication are greatly influenced by the celebrated work of Rockafellar (1976, while others have played a significant part as well in generalizing the proximal point algorithm considered by Rockafellar (1976 to the case of the relaxed proximal point algorithm by Eckstein and Bertsekas (1992. Even for the linear convergence analysis for the overrelaxed (or super-relaxed ( -proximal point algorithm, the fundamental model for Rockafellar's case does the job. Furthermore, we attempt to explore possibilities of generalizing the Yosida regularization/approximation in light of maximal ( -monotonicity, and then applying to first-order evolution equations/inclusions.

Robustness analysis of bogie suspension components Pareto optimised values

Science.gov (United States)

Mousavi Bideleh, Seyed Milad

2017-08-01

Bogie suspension system of high speed trains can significantly affect vehicle performance. Multiobjective optimisation problems are often formulated and solved to find the Pareto optimised values of the suspension components and improve cost efficiency in railway operations from different perspectives. Uncertainties in the design parameters of suspension system can negatively influence the dynamics behaviour of railway vehicles. In this regard, robustness analysis of a bogie dynamics response with respect to uncertainties in the suspension design parameters is considered. A one-car railway vehicle model with 50 degrees of freedom and wear/comfort Pareto optimised values of bogie suspension components is chosen for the analysis. Longitudinal and lateral primary stiffnesses, longitudinal and vertical secondary stiffnesses, as well as yaw damping are considered as five design parameters. The effects of parameter uncertainties on wear, ride comfort, track shift force, stability, and risk of derailment are studied by varying the design parameters around their respective Pareto optimised values according to a lognormal distribution with different coefficient of variations (COVs). The robustness analysis is carried out based on the maximum entropy concept. The multiplicative dimensional reduction method is utilised to simplify the calculation of fractional moments and improve the computational efficiency. The results showed that the dynamics response of the vehicle with wear/comfort Pareto optimised values of bogie suspension is robust against uncertainties in the design parameters and the probability of failure is small for parameter uncertainties with COV up to 0.1.

Effect of suspension kinematic on 14 DOF vehicle model

Science.gov (United States)

Wongpattananukul, T.; Chantharasenawong, C.

2017-12-01

Computer simulations play a major role in shaping modern science and engineering. They reduce time and resource consumption in new studies and designs. Vehicle simulations have been studied extensively to achieve a vehicle model used in minimum lap time solution. Simulation result accuracy depends on the abilities of these models to represent real phenomenon. Vehicles models with 7 degrees of freedom (DOF), 10 DOF and 14 DOF are normally used in optimal control to solve for minimum lap time. However, suspension kinematics are always neglected on these models. Suspension kinematics are defined as wheel movements with respect to the vehicle body. Tire forces are expressed as a function of wheel slip and wheel position. Therefore, the suspension kinematic relation is appended to the 14 DOF vehicle model to investigate its effects on the accuracy of simulate trajectory. Classical 14 DOF vehicle model is chosen as baseline model. Experiment data is collected from formula student style car test runs as baseline data for simulation and comparison between baseline model and model with suspension kinematic. Results show that in a single long turn there is an accumulated trajectory error in baseline model compared to model with suspension kinematic. While in short alternate turns, the trajectory error is much smaller. These results show that suspension kinematic had an effect on the trajectory simulation of vehicle. Which optimal control that use baseline model will result in inaccuracy control scheme.

Structure and rheology of nanoparticle–polymer suspensions

KAUST Repository

Srivastava, Samanvaya

2012-01-01

Structure and rheology of oligomer-tethered nanoparticles suspended in low molecular weight polymeric host are investigated at various particle sizes and loadings. Strong curvature effects introduced by the small size of the nanoparticle cores are found to be important for understanding both the phase stability and rheology of the materials. Small angle X-ray scattering (SAXS) and transmission electron microscopy measurements indicate that PEG-SiO 2/PEG suspensions are more stable against phase separation and aggregation than expected from theory for interacting brushes. SAXS and rheology measurements also reveal that at high particle loadings, the stabilizing oligomer brush is significantly compressed and produces jamming in the suspensions. The jamming transition is accompanied by what appears to be a unique evolution in the transient suspension rheology, along with large increments in the zero-shear, Newtonian viscosity. The linear and nonlinear flow responses of the jammed suspensions are discussed in the framework of the Soft Glassy Rheology (SGR) model, which is shown to predict many features that are consistent with experimental observations, including a two-step relaxation following flow cessation and a facile method for determining the shear-thinning coefficient from linear viscoelastic measurements. Finally, we show that the small sizes of the particles have a significant effect on inter-particle interactions and rheology, leading to stronger deviations from expectations based on planar brushes and hard-sphere suspension theories. In particular, we find that in the high volume fraction limit, tethered nanoparticles interact in their host polymer through short-range forces, which are more analogous to those between soft particles than between spherical polymer brushes. © 2012 The Royal Society of Chemistry.

Anomalous intrinsic viscosity of octadecylamine-functionalised carbon nanotubes in suspension.

Science.gov (United States)

Donovan, K J; Scott, K

2013-06-28

Single walled carbon nanotubes, SWCNTs, are used as a model cylinder of nanoscopic dimensions for testing rheological theories of how addition of cylindrical particles affects the viscosity of a suspension of such particles. Using the rate of growth of the accompanying induced linear dichroism following application of an applied electric field, the dynamics of carbon nanotube alignment is studied in suspensions of octadecylamine functionalised single walled carbon nanotubes, ODA-SWCNTs, in 1,2 dichloroethane. From such measurements the viscosity of the suspension is measured as the concentration of the suspension is varied. While working within the dilute limit the viscosity is found to increase linearly with concentration and the intrinsic viscosity of the suspension is found to be 8000. This anomalously high intrinsic viscosity is compared with the predictions of various models for a rigid cylinder and found to be incompatible with any of the current models. Some suggestions are made as to the way this ODA-SWCNT result may be eventually accommodated within other models.

Polymorphism in Bacterial Flagella Suspensions

Science.gov (United States)

Schwenger, Walter J.

Bacterial flagella are a type of biological polymer studied for its role in bacterial motility and the polymorphic transitions undertaken to facilitate the run and tumble behavior. The naturally rigid, helical shape of flagella gives rise to novel colloidal dynamics and material properties. This thesis studies methods in which the shape of bacterial flagella can be controlled using in vitro methods and the changes the shape of the flagella have on both single particle dynamics and bulk material properties. We observe individual flagellum in both the dilute and semidilute regimes to observe the effects of solvent condition on the shape of the filament as well as the effect the filament morphology has on reptation through a network of flagella. In addition, we present rheological measurements showing how the shape of filaments effects the bulk material properties of flagellar suspensions. We find that the individual particle dynamics in suspensions of flagella can vary with geometry from needing to reptate linearly via rotation for helical filaments to the prevention of long range diffusion for block copolymer filaments. Similarly, for bulk material properties of flagella suspensions, helical geometries show a dramatic enhancement in elasticity over straight filaments while block copolymers form an elastic gel without the aid of crosslinking agents.

Correlated particle dynamics in concentrated quasi-two-dimensional suspensions

International Nuclear Information System (INIS)

Diamant, H; Cui, B; Lin, B; Rice, S A

2005-01-01

We investigate theoretically and experimentally how the hydrodynamically correlated lateral motion of particles in a suspension confined between two surfaces is affected by the suspension concentration. Despite the long range of the correlations (decaying as 1/r 2 with the inter-particle distance r), the concentration effect is present only at short inter-particle distances for which the static pair correlation is nonuniform. This is in sharp contrast with the effect of hydrodynamic screening in unconfined suspensions, where increasing the concentration changes the prefactor of the large-distance correlation

Biomechanical evaluation of straight antegrade nailing in proximal humeral fractures: the rationale of the "proximal anchoring point".

Science.gov (United States)

Euler, Simon A; Petri, Maximilian; Venderley, Melanie B; Dornan, Grant J; Schmoelz, Werner; Turnbull, Travis Lee; Plecko, Michael; Kralinger, Franz S; Millett, Peter J

2017-09-01

Varus failure is one of the most common failure modes following surgical treatment of proximal humeral fractures. Straight antegrade nails (SAN) theoretically provide increased stability by anchoring to the densest zone of the proximal humerus (subchondral zone) with the end of the nail. The aim of this study was to biomechanically investigate the characteristics of this "proximal anchoring point" (PAP). We hypothesized that the PAP would improve stability compared to the same construct without the PAP. Straight antegrade humeral nailing was performed in 20 matched pairs of human cadaveric humeri for a simulated unstable two-part fracture. Biomechanical testing, with stepwise increasing cyclic axial loading (50-N increments each 100 cycles) at an angle of 20° abduction revealed significantly higher median loads to failure for SAN constructs with the PAP (median, 450 N; range, 200-1.000 N) compared to those without the PAP (median, 325 N; range, 100-500 N; p = 0.009). SAN constructs with press-fit proximal extensions (endcaps) showed similar median loads to failure (median, 400 N; range, 200-650 N), when compared to the undersized, commercially available SAN endcaps (median, 450 N; range, 200-600 N; p = 0.240). The PAP provided significantly increased stability in SAN constructs compared to the same setup without this additional proximal anchoring point. Varus-displacing forces to the humeral head were superiorly reduced in this setting. This study provides biomechanical evidence for the "proximal anchoring point's" rationale. Straight antegrade humeral nailing may be beneficial for patients undergoing surgical treatment for unstable proximal humeral fractures to decrease secondary varus displacement and thus potentially reduce revision rates.

Large Scale Brownian Dynamics of Confined Suspensions of Rigid Particles

Science.gov (United States)

Donev, Aleksandar; Sprinkle, Brennan; Balboa, Florencio; Patankar, Neelesh

2017-11-01

We introduce new numerical methods for simulating the dynamics of passive and active Brownian colloidal suspensions of particles of arbitrary shape sedimented near a bottom wall. The methods also apply for periodic (bulk) suspensions. Our methods scale linearly in the number of particles, and enable previously unprecedented simulations of tens to hundreds of thousands of particles. We demonstrate the accuracy and efficiency of our methods on a suspension of boomerang-shaped colloids. We also model recent experiments on active dynamics of uniform suspensions of spherical microrollers. This work was supported in part by the National Science Foundation under award DMS-1418706, and by the U.S. Department of Energy under award DE-SC0008271.

39 CFR 320.7 - Suspension for advertisements accompanying parcels or periodicals.

Science.gov (United States)

2010-07-01

... 39 Postal Service 1 2010-07-01 2010-07-01 false Suspension for advertisements accompanying parcels or periodicals. 320.7 Section 320.7 Postal Service UNITED STATES POSTAL SERVICE RESTRICTIONS ON PRIVATE CARRIAGE OF LETTERS SUSPENSION OF THE PRIVATE EXPRESS STATUTES § 320.7 Suspension for advertisements accompanying parcels or periodicals. (a) Th...

MEMS mass-spring-damper systems using an out-of-plane suspension scheme

KAUST Repository

Abdel Aziz, Ahmed Kamal Said; Sharaf, Abdel Hameed; Serry, Mohamed Yousef; Sedky, Sherif Salah

2014-01-01

MEMS mass-spring-damper systems (including MEMS gyroscopes and accelerometers) using an out-of-plane (or vertical) suspension scheme, wherein the suspensions are normal to the proof mass, are disclosed. Such out-of-plane suspension scheme helps such MEMS mass-spring-damper systems achieve inertial grade performance. Methods of fabricating out-of-plane suspensions in MEMS mass-spring-damper systems (including MEMS gyroscopes and accelerometers) are also disclosed.

MEMS mass-spring-damper systems using an out-of-plane suspension scheme

KAUST Repository

Abdel Aziz, Ahmed Kamal Said

2014-02-04

MEMS mass-spring-damper systems (including MEMS gyroscopes and accelerometers) using an out-of-plane (or vertical) suspension scheme, wherein the suspensions are normal to the proof mass, are disclosed. Such out-of-plane suspension scheme helps such MEMS mass-spring-damper systems achieve inertial grade performance. Methods of fabricating out-of-plane suspensions in MEMS mass-spring-damper systems (including MEMS gyroscopes and accelerometers) are also disclosed.

Asystole following Reintubation during Suspension Laryngoscopy

Directory of Open Access Journals (Sweden)

Sheryl H. Glassman

2012-01-01

Full Text Available Transient increase in heart rate and mean arterial pressure commonly occur during manipulation of the airway via direct laryngoscopy. This phenomenon is understood to be due to a sympathetic nervous system reflex causing an increase in plasma catecholamines. Rarely, severe bradycardia and possible asystole can occur following laryngoscopy. One previous report described asystole during suspension laryngoscopy after uneventful direct laryngoscopy. Here we report a case of asystole occurring at the time of reinsertion and cuff inflation of an endotracheal tube in a patient who had been hemodynamically stable during initial direct laryngoscopy and the ensuing suspension laryngoscopy. The asystole was immediately recognized and successful cardiopulmonary resuscitation was performed with the patient returning to baseline sinus rhythm. Cardiac arrest following laryngoscopy is rare. This case highlights the importance of continued vigilance even after the initial manipulations of the airway by both direct laryngoscopy and suspension laryngoscopy are to be performed. Identifying patients who may benefit from premedication with a vagolytic drug may prevent adversity. Preoperative heart rate analysis can identify patients with strong vagal tone.

Physical gelation of a microfiber suspension.

Science.gov (United States)

Perazzo, Antonio; Nunes, Janine K.; Guido, Stefano; Stone, Howard A.

2015-11-01

Hydrogels are among the most exploited materials in tissue engineering and there is growing interest in injectable hydrogels, especially as applied to surgical adhesives and bioprinting materials. Here we report a method to produce a hydrogel in a desired location by simply extruding a suspension of high aspect ratio and flexible microfibers from a syringe. The mechanism of gel formation is purely physical and based on irreversible entanglements formed by the microfibers under the action of flow. The single microfibers have been produced and finely tailored by microfluidic methods. Shear rheology has been performed in order to get insights on the entanglements, and results show that the formation of entanglements is related to a shear thickening behavior of the suspension, which in turn depends on shear rate and concentration of fibers. When shearing the suspension, highly non-linear viscoelastic behavior is observed and probed by a highly positive first normal stress difference. We also report the hydrogel swelling behavior and its linear viscoelastic properties as obtained by imposing small oscillatory stress to the material.

Numerical homogenization on approach for stokesian suspensions.

Energy Technology Data Exchange (ETDEWEB)

Haines, B. M.; Berlyand, L. V.; Karpeev, D. A. (Mathematics and Computer Science); (Department of Mathematics, Pennsylvania State Univ.)

2012-01-20

In this technical report we investigate efficient methods for numerical simulation of active suspensions. The prototypical system is a suspension of swimming bacteria in a Newtonian fluid. Rheological and other macroscopic properties of such suspensions can differ dramatically from the same properties of the suspending fluid alone or of suspensions of similar but inactive particles. Elongated bacteria, such as E. coli or B. subtilis, swim along their principal axis, propelling themselves with the help of flagella, attached at the anterior of the organism and pushing it forward in the manner of a propeller. They interact hydrodynamically with the surrounding fluid and, because of their asymmetrical shape, have the propensity to align with the local flow. This, along with the dipolar nature of bacteria (the two forces a bacterium exerts on a fluid - one due to self-propulsion and the other opposing drag - have equal magnitude and point in opposite directions), causes nearby bacteria to tend to align, resulting in a intermittent local ordering on the mesoscopic scale, which is between the microscopic scale of an individual bacterium and the macroscopic scale of the suspension (e.g., its container). The local ordering is sometimes called a collective mode or collective swimming. Thanks to self-propulsion, collective modes inject momentum into the fluid in a coherent way. This enhances the local strain rate without changing the macroscopic stress applied at the boundary of the container. The macroscopic effective viscosity of the suspension is defined roughly as the ratio of the applied stress to the bulk strain rate. If local alignment and therefore local strain-rate enhancement, are significant, the effective viscosity can be appreciably lower than that of the corresponding passive suspension or even of the surrounding fluid alone. Indeed, a sevenfold decrease in the effective viscosity was observed in experiments with B. subtilis. More generally, local collective

On reactive suspension plasma spraying of calcium titanate

Czech Academy of Sciences Publication Activity Database

Kotlan, Jiří; Pala, Zdeněk; Mušálek, Radek; Ctibor, Pavel

2016-01-01

Roč. 42, č. 3 (2016), s. 4607-4615 ISSN 0272-8842 R&D Projects: GA ČR GA15-12145S Institutional support: RVO:61389021 Keywords : Suspensions * X-raymethods * Perovskites * Substrates * Suspension plasma spraying Subject RIV: JH - Ceramics, Fire-Resistant Materials and Glass Impact factor: 2.986, year: 2016 http://www.sciencedirect.com/science/article/pii/S0272884215022646

The molecular aggregation of pyronin Y in natural bentonite clay suspension

International Nuclear Information System (INIS)

Meral, Kadem; Yilmaz, Nuray; Kaya, Mehmet; Tabak, Ahmet; Onganer, Yavuz

2011-01-01

The molecular aggregation and spectroscopic properties of Pyronin Y (PyY) in the suspension containing natural bentonite clay were studied using molecular absorption, steady-state and time-resolved fluorescence spectroscopy techniques. Interaction between the clay particles and the cationic dye compounds in aqueous solution resulted in significant changes in spectral properties of PyY compared to its molecular behavior in deionized water at the same concentration. These changes were due to the formation of dimer and aggregate of PyY in the clay suspension as well as the presence of the dye monomer. The H-type aggregates of PyY in the clay suspension were identified by the observation of a blue-shifted absorption band of the dye compared to that of its monomer. In spite of diluted dye concentrations, the H-aggregate of PyY in the clay suspension was formed. The intensive aggregation in the clay suspension attributed to the localized high dye concentration on the negatively charged clay surfaces. Adsorption sites of PyY on the clay particles were discussed by deconvulated absorption and excitation spectra. Fluorescence spectroscopy studies revealed that the fluorescence intensity of PyY in the clay suspension is decreased by H-aggregates drastically. Moreover, the presence of H-aggregates in the clay suspension resulted in the decrease of fluorescence lifetime and quantum yield of PyY compared to those in deionized water. - Highlights: → Molecular behavior of PyY adsorbed on clay surface was followed spectroscopically. → H-aggregates of PyY in the clay suspension were formed at very low dye concentrations. → The intensive H-aggregate structure drastically reduced the fluorescence intensity of PyY. → The fluorescence lifetime and quantum yield of PyY in the clay suspension was discussed.

Rheological and thermal properties of suspensions of microcapsules containing phase change materials.

Science.gov (United States)

Cao, Vinh Duy; Salas-Bringas, Carlos; Schüller, Reidar Barfod; Szczotok, Anna M; Hiorth, Marianne; Carmona, Manuel; Rodriguez, Juan F; Kjøniksen, Anna-Lena

2018-01-01

The thermal and rheological properties of suspensions of microencapsulated phase change materials (MPCM) in glycerol were investigated. When the microcapsule concentration is raised, the heat storage capacity of the suspensions becomes higher and a slight decline in the thermal conductivity of the suspensions is observed. The temperature-dependent shear-thinning behaviour of the suspensions was found to be strongly affected by non-encapsulated phase change materials (PCM). Accordingly, the rheological properties of the MPCM suspensions could be described by the Cross model below the PCM melting point while a power law model best described the data above the PCM melting point. The MPCM suspensions are interesting for energy storage and heat transfer applications. However, the non-encapsulated PCM contributes to the agglomeration of the microcapsules, which can lead to higher pumping consumption and clogging of piping systems.

Rheological properties of hydrate suspensions in asphaltenic crude oils; Proprietes rheologiques de suspensions d'hydrate dans des bruts asphalteniques

Energy Technology Data Exchange (ETDEWEB)

Marques de Toledo Camargo, R.

2001-03-01

The development of offshore oil exploitation under increasing water depths has forced oil companies to increase their understanding of gas hydrate formation and transportation in multiphase flow lines in which a liquid hydrocarbon phase is present. This work deals with the flow behaviour of hydrate suspensions in which a liquid hydrocarbon is the continuous phase. Three different liquid hydrocarbons are used: an asphaltenic crude oil, a condensate completely free of asphaltenes and a mixture between the asphaltenic oil and heptane. The rheological characterisation of hydrate suspensions is the main tool employed. Two original experimental devices are used: a PVT cell adapted to operate as a Couette type rheometer and a semi-industrial flow loop. Hydrate suspensions using the asphaltenic oil showed shear-thinning behaviour and thixotropy. This behaviour is typically found in flocculated systems, in which the particles attract each other forming flocs of aggregated particles at low shear rates. The suspensions using the condensate showed Newtonian behaviour. Their relative viscosities were high, which suggests that an aggregation process between hydrate particles takes. place during hydrate formation. Finally, hydrate suspensions using the mixture asphaltenic oil-heptane showed shear-thinning behaviour, thixotropy and high relative viscosity. From these results it can be inferred that, after the achievement of the hydrate formation process, the attractive forces between hydrate particles are weak. making unlikely pipeline obstruction by an aggregation process. Nevertheless, during the hydrate formation, these attractive forces can be sufficiently high. It seems that the hydrate surface wettability is an important parameter in this phenomena. (author)

Proximal Tubular Secretion of Creatinine by Organic Cation Transporter OCT2 in Cancer Patients

Science.gov (United States)

Ciarimboli, Giuliano; Lancaster, Cynthia S.; Schlatter, Eberhard; Franke, Ryan M.; Sprowl, Jason A.; Pavenstädt, Hermann; Massmann, Vivian; Guckel, Denise; Mathijssen, Ron H. J.; Yang, Wenjian; Pui, Ching-Hon; Relling, Mary V.; Herrmann, Edwin; Sparreboom, Alex

2012-01-01

Purpose Knowledge of transporters responsible for the renal secretion of creatinine is key to a proper interpretation of serum creatinine and/or creatinine clearance as markers of renal function in cancer patients receiving chemotherapeutic agents. Experimental Design Creatinine transport was studied in transfected HEK293 cells in vitro and in wildtype mice and age-matched organic cation transporter 1 and 2-deficient [Oct1/2(−/−)] mice ex vivo and in vivo. Clinical pharmacogenetic and transport inhibition studies were done in two separate cohorts of cancer patients. Results Compared to wildtype mice, creatinine clearance was significantly impaired in Oct1/2(−/−) mice. Furthermore, creatinine inhibited organic cation transport in freshly-isolated proximal tubules from wild-type mice and humans, but not in those from Oct1/2(−/−) mice. In a genetic-association analysis (n=590), several polymorphisms around the OCT2/SLC22A2 gene locus, including rs2504954 (P=0.000873), were significantly associated with age-adjusted creatinine levels. Furthermore, in cancer patients (n=68), the OCT2 substrate cisplatin caused an acute elevation of serum creatinine (P=0.0083), consistent with inhibition of an elimination pathway. Conclusions Collectively, this study shows that OCT2 plays a decisive role in the renal secretion of creatinine. This process can be inhibited by OCT2 substrates, which impair the usefulness of creatinine as a marker of renal function. PMID:22223530