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

Directory of Open Access Journals (Sweden)

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

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.

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

Directory of Open Access Journals (Sweden)

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.

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

Science.gov (United States)

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.

A microfluidic renal proximal tubule with active reabsorptive function.

Directory of Open Access Journals (Sweden)

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.

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

Directory of Open Access Journals (Sweden)

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.

Update on Mechanisms of Renal Tubule Injury Caused by Advanced Glycation End Products

Directory of Open Access Journals (Sweden)

Hong Sun

2016-01-01

Full Text Available Diabetic nephropathy (DN caused by advanced glycation end products (AGEs may be associated with lipid accumulation in the kidneys. This study was designed to investigate whether Nε-(carboxymethyl lysine (CML, a member of the AGEs family increases lipid accumulation in a human renal tubular epithelial cell line (HK-2 via increasing cholesterol synthesis and uptake and reducing cholesterol efflux through endoplasmic reticulum stress (ERS. Our results showed that CML disrupts cholesterol metabolism in HK-2 cells by activating sterol regulatory element-binding protein 2 (SREBP-2 and liver X receptor (LXR, followed by an increase in 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoAR mediated cholesterol synthesis and low density lipoprotein receptor (LDLr mediated cholesterol uptake and a reduction in ATP-binding cassette transporter A1 (ABCA1 mediated cholesterol efflux, ultimately causing lipid accumulation in HK-2 cells. All of these responses could be suppressed by an ERS inhibitor, which suggests that CML causes lipid accumulation in renal tubule cells through ERS and that the inhibition of ERS is a potential novel approach to treating CML-induced renal tubular foam cell formation.

Malpighian Tubules as Novel Targets for Mosquito Control

Directory of Open Access Journals (Sweden)

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.

Local pH domains regulate NHE3-mediated Na+ reabsorption in the renal proximal tubule

Science.gov (United States)

Burford, James L.; McDonough, Alicia A.; Holstein-Rathlou, Niels-Henrik; Peti-Peterdi, Janos

2014-01-01

The proximal tubule Na+/H+ exchanger 3 (NHE3), located in the apical dense microvilli (brush border), plays a major role in the reabsorption of NaCl and water in the renal proximal tubule. In response to a rise in blood pressure NHE3 redistributes in the plane of the plasma membrane to the base of the brush border, where NHE3 activity is reduced. This NHE3 redistribution is assumed to provoke pressure natriuresis; however, it is unclear how NHE3 redistribution per se reduces NHE3 activity. To investigate if the distribution of NHE3 in the brush border can change the reabsorption rate, we constructed a spatiotemporal mathematical model of NHE3-mediated Na+ reabsorption across a proximal tubule cell and compared the model results with in vivo experiments in rats. The model predicts that when NHE3 is localized exclusively at the base of the brush border, it creates local pH microdomains that reduce NHE3 activity by >30%. We tested the model's prediction experimentally: the rat kidney cortex was loaded with the pH-sensitive fluorescent dye BCECF, and cells of the proximal tubule were imaged in vivo using confocal fluorescence microscopy before and after an increase of blood pressure by ∼50 mmHg. The experimental results supported the model by demonstrating that a rise of blood pressure induces the development of pH microdomains near the bottom of the brush border. These local changes in pH reduce NHE3 activity, which may explain the pressure natriuresis response to NHE3 redistribution. PMID:25298526

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

Energy Technology Data Exchange (ETDEWEB)

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

Influence of extracellular HCO3- and pH on lysine (LYS) and leucine (LEU) uptake and metabolism in swine renal tubules

International Nuclear Information System (INIS)

Patience, J.F.; Esteve-Garcia, E.; Austic, R.E.

1986-01-01

Fragments of renal tubules prepared by collagenase treatment of renal cortex were suspended to Krebs-Henseleit buffers which were modified to contain 10, 25 and 35 mM HCO 3 - at pH 7.4, or 25 mM HCO 3 - at pH 7.1, 7.4 and 7.7. Buffers were oxygenated with O 2 -CO 2 gas mixtures varying in carbon dioxide concentration prior to incubation. Approximately 100 mg tubules were incubated with shaking at 37 0 C for 30 min in serum-stoppered 25 ml Erlenmeyer flasks in 3.0 ml of buffer containing 0.1% dialyzed bovine serum albumin, 5 mM D-glucose and 0.3 mM L-[U- 14 C]-lysine or L-[1- 14 C]-leucine. The incorporation of carbon-14 into CO 2 and into 10% sulfosalicylic acid (SSA)-soluble and SSA-insoluble fractions of the incubation mixture was determined. Low (10mM) bicarbonate reduced the incorporation of lys and leu into protein but did not substantially affect the recovery of 14 CO 2 from either amino acid. High pH (7.7) resulted in reduced incorporation of lys and leu into protein, and decreased the oxidation of lys but not leu. The specific activity of lys (leu was not determined) in the SSA-soluble fraction was unaffected by bicarbonate or pH. The authors conclude that variations in extracellular pH and HCO 3 - (or pCO 2 ) affect the metabolism of amino acids by renal tubules and that low extracellular HCO 3 - (or pCO 2 ) may depress the incorporation of amino acids into protein

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...

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.

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

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.

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

Science.gov (United States)

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

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.

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...

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.

Active ion transport in the renal proximal tubule. II. Ionic dependence of the Na pump

OpenAIRE

1984-01-01

The dependence of Na pump activity on intracellular and extracellular Na+ and K+ was investigated using a suspension of rabbit cortical tubules that contained mostly (86%) proximal tubules. The ouabain- sensitive rate of respiration (QO2) was used to measure the Na pump activity of intact tubules, and the Na,K-ATPase hydrolytic activity was measured using lysed proximal tubule membranes. The dependence (K0.5) of the Na pump on intracellular Na+ was affected by the relative intracellular conce...

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

Science.gov (United States)

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.

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

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

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.

Histochemical Analysis of Renal Dysplasia with Ureteral Atresia

International Nuclear Information System (INIS)

Kawate, Toyoko; Kawamura, Ryuki; Uchida, Takenori; Takahashi, Kyosuke; Hasegawa, Tomohiro; Futamata, Haruo; Katoh, Ryohei; Takeda, Sen

2009-01-01

Unilateral small kidney with ureteral obstruction was discovered in a 74-year-old female cadaver during an anatomical dissection course. In order to elucidate the histogenesis of renal dysplasia, we carried out histochemical and immunohistochemical analyses. On macroscopic view, the kidney was approximately 3 cm in length, 2 cm in width and weighed only 9 g. Although the ureter ran from the renal hilus to the bladder, its width was under 2 mm. The renal parenchyma was extremely thin and there was a large congested vein in the renal sinus. On microscopic examination of the kidney, we observed that numerous developing renal tubules had cytokeratin-positive epithelia, most of which were surrounded by concentric fibrosis. However, we could not detect any structures resembling the collecting duct, renal tubules, renal pelvis, or glomeruli. The concentric mesencymal fibrous tissue surrounding the immature renal tubules contained the smooth muscles that were positive for h-caldesmon. Serial sections of the ureter revealed several small and discontinuous lacunae lined by cuboidal and transitional epithelium, which did not constitute a patent lumen through the bladder. This case is a rare case of renal dysplasia with defect in recanalization of the ureteral bud during the early developmental stage

Polyploidy and Mitotic Cell Death Are Two Distinct HIV-1 Vpr-Driven Outcomes in Renal Tubule Epithelial Cells.

Science.gov (United States)

Payne, Emily H; Ramalingam, Dhivya; Fox, Donald T; Klotman, Mary E

2018-01-15

Prior studies have found that HIV, through the Vpr protein, promotes genome reduplication (polyploidy) in infection-surviving epithelial cells within renal tissue. However, the temporal progression and molecular regulation through which Vpr promotes polyploidy have remained unclear. Here we define a sequential progression to Vpr-mediated polyploidy in human renal tubule epithelial cells (RTECs). We found that as in many cell types, Vpr first initiates G 2 cell cycle arrest in RTECs. We then identified a previously unreported cascade of Vpr-dependent events that lead to renal cell survival and polyploidy. Specifically, we found that a fraction of G 2 -arrested RTECs reenter the cell cycle. Following this cell cycle reentry, two distinct outcomes occur. Cells that enter complete mitosis undergo mitotic cell death due to extra centrosomes and aberrant division. Conversely, cells that abort mitosis undergo endoreplication to become polyploid. We further show that multiple small-molecule inhibitors of the phosphatidylinositol 3-kinase-related kinase (PIKK) family, including those that target ATR, ATM, and mTOR, indirectly prevent Vpr-mediated polyploidy by preventing G 2 arrest. In contrast, an inhibitor that targets DNA-dependent protein kinase (DNA-PK) specifically blocks the Vpr-mediated transition from G 2 arrest to polyploidy. These findings outline a temporal, molecularly regulated path to polyploidy in HIV-positive renal cells. IMPORTANCE Current cure-focused efforts in HIV research aim to elucidate the mechanisms of long-term persistence of HIV in compartments. The kidney is recognized as one such compartment, since viral DNA and mRNA persist in the renal tissues of HIV-positive patients. Further, renal disease is a long-term comorbidity in the setting of HIV. Thus, understanding the regulation and impact of HIV infection on renal cell biology will provide important insights into this unique HIV compartment. Our work identifies mechanisms that distinguish

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.

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 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.

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

Directory of Open Access Journals (Sweden)

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.

Calcineurin inhibitor-induced complement system activation via ERK1/2 signalling is inhibited by SOCS-3 in human renal tubule cells.

Science.gov (United States)

Loeschenberger, Beatrix; Niess, Lea; Würzner, Reinhard; Schwelberger, Hubert; Eder, Iris E; Puhr, Martin; Guenther, Julia; Troppmair, Jakob; Rudnicki, Michael; Neuwirt, Hannes

2018-02-01

One factor that significantly contributes to renal allograft loss is chronic calcineurin inhibitor (CNI) nephrotoxicity (CIN). Among other factors, the complement (C-) system has been proposed to be involved CIN development. Hence, we investigated the impact of CNIs on intracellular signalling and the effects on the C-system in human renal tubule cells. In a qPCR array, CNI treatment upregulated C-factors and downregulated SOCS-3 and the complement inhibitors CD46 and CD55. Additionally, ERK1/-2 was required for these regulations. Following knock-down and overexpression of SOCS-3, we found that SOCS-3 inhibits ERK1/-2 signalling. Finally, we assessed terminal complement complex formation, cell viability and apoptosis. Terminal complement complex formation was induced by CNIs. Cell viability was significantly decreased, whereas apoptosis was increased. Both effects were reversed under complement component-depleted conditions. In vivo, increased ERK1/-2 phosphorylation and SOCS-3 downregulation were observed at the time of transplantation in renal allograft patients who developed a progressive decline of renal function in the follow-up compared to stable patients. The progressive cohort also had lower total C3 levels, suggesting higher complement activity at baseline. In conclusion, our data suggest that SOCS-3 inhibits CNI-induced ERK1/-2 signalling, thereby blunting the negative control of C-system activation. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Physiological Functions and Regulation of the Na+/H+ Exchanger [NHE1] in Renal Tubule Epithelial Cells

Directory of Open Access Journals (Sweden)

Patricia G Vallés

2015-08-01

Full Text Available The sodium-hydrogen exchanger isoform-1 [NHE1] is a ubiquitously expressed plasma membrane protein that plays a central role in intracellular pH and cell volume homeostasis by catalyzing an electroneutral exchange of extracellular sodium and intracellular hydrogen. Outside of this important physiological function, the NHE1 cytosolic tail domain acts as a molecular scaffold regulating cell survival and actin cytoskeleton organization through NHE1-dependent signaling proteins. NHE1 plays main roles in response to physiological stress conditions which in addition to cell shrinkage and acidification, include hypoxia and mechanical stimuli, such as cell stretch. NHE1-mediated modulation of programmed cell death results from the exchanger-mediated changes in pHi, cell volume, and/or [Na+]I; and, it has recently become known that regulation of cellular signaling pathways are involved as well. This review focuses on NHE1 functions and regulations. We describe evidence showing how these structural actions integrate with ion translocation in regulating renal tubule epithelial cell survival.

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

NARCIS (Netherlands)

Schophuizen, C.M.S.; De Napoli, Ilaria; Jansen, J.; Da Silva Teixeira, Sandra; Wilmer, M.; Hoenderop, J.G.; van den Heuvel, L.P.W.; Masereeuw, R.; Stamatialis, Dimitrios

2015-01-01

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

The rebirth of interest in renal tubular function.

Science.gov (United States)

Lowenstein, Jerome; Grantham, Jared J

2016-06-01

The measurement of glomerular filtration rate by the clearance of inulin or creatinine has evolved over the past 50 years into an estimated value based solely on plasma creatinine concentration. We have examined some of the misconceptions and misunderstandings of the classification of renal disease and its course, which have followed this evolution. Furthermore, renal plasma flow and tubular function, which in the past were estimated by the clearance of the exogenous aryl amine, para-aminohippurate, are no longer measured. Over the past decade, studies in experimental animals with reduced nephron mass and in patients with reduced renal function have identified small gut-derived, protein-bound uremic retention solutes ("uremic toxins") that are poorly filtered but are secreted into the lumen by organic anion transporters (OATs) in the proximal renal tubule. These are not effectively removed by conventional hemodialysis or peritoneal dialysis. Residual renal function, urine produced in patients with advanced renal failure or undergoing dialysis treatment, may represent, at least in part, secretion of fluid and uremic toxins, such as indoxyl sulfate, mediated by proximal tubule OATs and might serve as a useful survival function. In light of this new evidence of the physiological role of proximal tubule OATs, we suggest that measurement of renal tubular function and renal plasma flow may be of considerable value in understanding and managing chronic kidney disease. Data obtained in normal subjects indicate that renal plasma flow and renal tubular function might be measured by the clearance of the endogenous aryl amine, hippurate. Copyright © 2016 the American Physiological Society.

[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.

Kidney (Renal Cell) Cancer—Health Professional Version

Science.gov (United States)

Kidney cancer has three main types. Renal cell cancer, or renal cell adenocarcinoma, forms in the tubules of the kidney. Transitional cell carcinoma forms in the renal pelvis and ureter. Wilms tumors are common in children. Find evidence-based information on kidney cancer treatment, research, genetics, and statistics.

[Clinical observation on laparoscopic radiofrequency ablation assisted enucleation for the renal epithelial angimyolipoma].

Science.gov (United States)

Yang, Yang; Yang, Rong; Guo, Hongqian

2014-08-13

To explore the clinicopathological characteristics of epithelial angiomyolipoma (EAML) and examine the clinical efficacy and prognosis of laparoscopic radio frequency ablation assisted enucleation. The clinicopathological data of 7 patients with renal EAML undergoing laparoscopic radio frequency ablation assisted enucleation were reviewed from April 2009 to June 2012. And the clinical efficacy and prognosis of laparoscopic radio frequency ablation assisted enucleation were analyzed. Laparoscopic radio frequency ablation assisted enucleation was successfully performed in all cases without postoperative bleeding, ureteral obstruction, chronic renal insufficiency or urinary leakage. The mean operative duration was 110 min. Renal pedicles were blocked in 4 patients with a mean blockage time of 9 min. The mean intraoperative bleeding was 90 ml. No blood transfusion was required. The absolute bedrest time was 1-3 days and the drainage tube implanted for 3.8 days. Postoperative pathology showed that all cases were EAML. Immunohistochemistry showed HMB-45⁺ and small muscle action⁺ and creatine kinase⁻ in epithelioid cells. During a mean follow-up period of 1.8 years, none of them had local tumor recurrence, chronic renal insufficiency or other complications. Renal EAML is a rare subtype of angiomyolipoma without specific clinical and imaging features. And its definite confirmation depends on pathology. Laparoscopic radio frequency ablation assisted enucleation is both safe and effective in the treatment of renal EAML with pseudocapsule.

Effects of Hyperbaric Oxygen Treatment on Renal System.

Science.gov (United States)

Tezcan, Orhan; Caliskan, Ahmet; Demirtas, Sinan; Yavuz, Celal; Kuyumcu, Mahir; Nergiz, Yusuf; Guzel, Abdulmenap; Karahan, Oguz; Ari, Seyhmus; Soker, Sevda; Yalinkilic, Ibrahim; Turkdogan, Kenan Ahmet

2017-01-01

Hyperbaric oxygen (HBO) treatment is steadily increasing as a therapeutic modality for various types of diseases. Although good clinical outcomes were reported with HBO treatment for various diseases, the multisystemic effects of this modality are still unclear. This study aimed to investigate the renal effects of HBO experimentally. Fourteen New Zealand White rabbits were divided into 2 groups randomly as the control group and the study group. The study group received HBO treatment for 28 days (100% oxygen at 2.5 atmospheres for 90 minutes daily) and the control group was used to obtain normal renal tissue of the animal genus. After the intervention period, venous blood samples were obtained, and renal tissue samples were harvested for comparisons. Normal histological morphology was determined with Masson trichrome staining and periodic acid-Schiff staining in the control group. Atrophic glomerular structures, vacuolated tubule cells, and degeneration were detected in the renal samples of the study group with Masson trichrome staining. Additionally, flattening was observed on the brush borders of the proximal tubules, and tubular dilatation was visualized with periodic acid-Schiff staining. The histopathologic disruption of renal morphology was verified with detection of significantly elevated kidney function laboratory biomarkers in the study group. Our findings suggests that HBO has adverse effects on renal glomerulus and proximal tubules. However, the functional effects of this alteration should be investigated with further studies.

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

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.

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

Directory of Open Access Journals (Sweden)

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.

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

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....

Arginine vasopressin increases cellular free calcium concentration and adenosine 3',5'-monophosphate production in rat renal papillary collecting tubule cells in culture

International Nuclear Information System (INIS)

Ishikawa, S.; Okada, K.; Saito, T.

1988-01-01

The role of calcium (Ca) in the cellular action of arginine vasopressin (AVP) was examined in rat renal papillary collecting tubule cells in culture. AVP increased both the cellular free Ca concentration ([Ca2+]i) using fura-2, and cAMP production in a dose-dependent manner. AVP-induced cellular Ca mobilization was totally blocked by the antagonist to the antidiuretic action of AVP, and somewhat weakened by the antagonist to the vascular action of AVP. 1-Deamino-8-D-AVP (dDAVP). an antidiuretic analog of AVP, also increased [Ca2+] significantly. Cellular Ca mobilization was not obtained with cAMP, forskolin (a diterpene activator of adenylate cyclase), or phorbol-12-myristate-13-acetate. The early phase of [Ca2+]i depended on the intracellular Ca pool, since an AVP-induced rise in [Ca2+]i was obtained in cells pretreated with Ca-free medium containing 1 mM EGTA, verapamil, or cobalt, which blocked cellular Ca uptake. Also, AVP increased 45 Ca2+ influx during the initial 10 min, which initiated the sustained phase of cellular Ca mobilization. However, cellular cAMP production induced by AVP during the 10-min observation period was diminished in the cells pretreated with Ca-free medium, verapamil, or cobalt, but was still significantly higher than the basal level. This was also diminished by a high Ca concentration in medium. These results indicate that 1) AVP concomitantly regulates cellular free Ca as well as its second messenger cAMP production; 2) AVP-induced elevation of cellular free Ca is dependent on both the cellular Ca pool and extracellular Ca; and 3) there is an optimal level of extracellular Ca to modulate the AVP action in renal papillary collecting tubule cells

Regulation of proximal tubule vacuolar H+-ATPase by PKA and AMP-activated protein kinase

Science.gov (United States)

Al-bataineh, Mohammad M.; Gong, Fan; Marciszyn, Allison L.; Myerburg, Michael M.

2014-01-01

The vacuolar H+-ATPase (V-ATPase) mediates ATP-driven H+ transport across membranes. This pump is present at the apical membrane of kidney proximal tubule cells and intercalated cells. Defects in the V-ATPase and in proximal tubule function can cause renal tubular acidosis. We examined the role of protein kinase A (PKA) and AMP-activated protein kinase (AMPK) in the regulation of the V-ATPase in the proximal tubule as these two kinases coregulate the V-ATPase in the collecting duct. As the proximal tubule V-ATPases have different subunit compositions from other nephron segments, we postulated that V-ATPase regulation in the proximal tubule could differ from other kidney tubule segments. Immunofluorescence labeling of rat ex vivo kidney slices revealed that the V-ATPase was present in the proximal tubule both at the apical pole, colocalizing with the brush-border marker wheat germ agglutinin, and in the cytosol when slices were incubated in buffer alone. When slices were incubated with a cAMP analog and a phosphodiesterase inhibitor, the V-ATPase accumulated at the apical pole of S3 segment cells. These PKA activators also increased V-ATPase apical membrane expression as well as the rate of V-ATPase-dependent extracellular acidification in S3 cell monolayers relative to untreated cells. However, the AMPK activator AICAR decreased PKA-induced V-ATPase apical accumulation in proximal tubules of kidney slices and decreased V-ATPase activity in S3 cell monolayers. Our results suggest that in proximal tubule the V-ATPase subcellular localization and activity are acutely coregulated via PKA downstream of hormonal signals and via AMPK downstream of metabolic stress. PMID:24553431

Functional correlates of positional and gender-specific renal asymmetry in Drosophila.

Directory of Open Access Journals (Sweden)

Venkateswara R Chintapalli

Full Text Available In humans and other animals, the internal organs are positioned asymmetrically in the body cavity, and disruption of this body plan can be fatal in humans. The mechanisms by which internal asymmetry are established are presently the subject of intense study; however, the functional significance of internal asymmetry (outside the brain is largely unexplored. Is internal asymmetry functionally significant, or merely an expedient way of packing organs into a cavity?Like humans, Drosophila shows internal asymmetry, with the gut thrown into stereotyped folds. There is also renal asymmetry, with the rightmost pair of renal (Malpighian tubules always ramifying anteriorly, and the leftmost pair always sitting posteriorly in the body cavity. Accordingly, transcriptomes of anterior-directed (right-side and posterior-directed (left-side Malpighian (renal tubules were compared in both adult male and female Drosophila. Although genes encoding the basic functions of the tubules (transport, signalling were uniformly expressed, some functions (like innate immunity showed positional or gender differences in emphasis; others, like calcium handling or the generation of potentially toxic ammonia, were reserved for just the right-side or left-side tubules, respectively. These findings correlated with the distinct locations of each tubule pair within the body cavity. Well known developmental genes (like dorsocross, dachshund and doublesex showed continuing, patterned expression in adult tubules, implying that somatic tissues maintain both left-right and gender identities throughout life. Gender asymmetry was also noted, both in defence and in male-specific expression of receptors for neuropeptide F and sex-peptide: NPF elevated calcium only in male tubules.Accordingly, the physical asymmetry of the tubules in the body cavity is directly adaptive. Now that the detailed machinery underlying internal asymmetry is starting to be delineated, our work invites the

Renal artery aneurysm in hand-assisted laparoscopic donor nephrectomy: case report.

Science.gov (United States)

Maciel, R F; Branco, A J; Branco, A W; Guterres, J C; Silva, A E; Ramos, L B; Rost, C; Vieira, C A; Cicogna, P E S; Daudt, C A; Deboni, L M; Vieira, M A; Luz, H A; Vieira, J A

2003-12-01

We report a living donor who underwent laparoscopic nephrectomy using a hand-assisted device (HALD). At preoperative arteriography the donor showed a renal artery aneurysm. The patient was a 37-year-old female, 166 cm height, white, weighing 87 kg, HLA identical to the recipient. HALD was indicated due to the better visualization of renal pedicle and greater security in an obese patient. Renal artery aneurysm is a rare condition, with many possible complications. The method proved to be adequate and safe for donor nephrectomy, despite a renal artery aneurysm.

Urinary loss of glucose, phosphate, and protein by diffusion into proximal straight tubules injured by D-serine and maleic acid

International Nuclear Information System (INIS)

Carone, F.A.; Nakamura, S.; Goldman, B.

1985-01-01

In several models of acute renal failure leakage of glomerular filtrate out of the tubule is an important pathogenetic mechanism; however, bidirectional diffusion of solute to account for certain pathophysiologic features of acute renal failure has received meager attention. Using micropuncture and clearance methods, the authors assessed sequentially leakage of solutes and inulin across proximal straight tubules (PST) injured by two nephrotoxins. In d-serine-treated rats with extensive necrosis of PST, the basis for glucosuria and tubular leakage of inulin was studied. Glucose absorption by the proximal convoluted tubule and glucose delivery to the PST were normal, but glucose delivery to the distal tubule was increased nearly 8-fold, indicating diffusion of glucose from interstitial to tubular luminal fluid across the necrotic PST. Total kidney inulin clearance was greatly reduced, but single nephron glomerular filtration rate, based on proximal convoluted tubule samples, was normal, indicating tubular loss of inulin. Urinary recovery of [ 14 C]inulin infused into tubular lumina revealed that proximal convoluted tubule and distal tubule were impermeable to inulin and that inulin diffused out of the necrotic PST. The progressive return over 6 days of tubular impermeability for inulin correlated with relining of PST with new cells. In maleic acid-treated rats the site and extent of tubular necrosis and the nature of urinary loss of solutes were studied. Microdissection revealed that maleic acid caused limited necrosis of PST which averaged 7.4% of total proximal tubular length. Increased urinary excretion of protein, phosphate, and glucose and increased tubular permeability to microinfused [ 14 C]inulin occurred with the onset of PST necrosis, and return of these abnormalities to normal correlated with the degree of cellular repair of the PST

Renal rickets-practical approach

Science.gov (United States)

Sahay, Manisha; Sahay, Rakesh

2013-01-01

Rickets/osteomalacia is an important problem in a tropical country. Many cases are due to poor vitamin D intake or calcium deficient diets and can be corrected by administration of calcium and vitamin D. However, some cases are refractory to vitamin D therapy and are related to renal defects. These include rickets of renal tubular acidosis (RTA), hypophosphatemic rickets, and vitamin D dependent rickets (VDDR). The latter is due to impaired action of 1α-hydroxylase in renal tubule. These varieties need proper diagnosis and specific treatment. PMID:24251212

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

Science.gov (United States)

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.

RNA-Seq Comparison of Larval and Adult Malpighian Tubules of the Yellow Fever Mosquito Aedes aegypti Reveals Life Stage-Specific Changes in Renal Function

Directory of Open Access Journals (Sweden)

Yiyi Li

2017-05-01

Full Text Available Introduction: The life history of Aedes aegypti presents diverse challenges to its diuretic system. During the larval and pupal life stages mosquitoes are aquatic. With the emergence of the adult they become terrestrial. This shifts the organism within minutes from an aquatic environment to a terrestrial environment where dehydration has to be avoided. In addition, female mosquitoes take large blood meals, which present an entirely new set of challenges to salt and water homeostasis.Methods: To determine differences in gene expression associated with these different life stages, we performed an RNA-seq analysis of the main diuretic tissue in A. aegypti, the Malpighian tubules. We compared transcript abundance in 4th instar larvae to that of adult females and analyzed the data with a focus on transcripts that encode proteins potentially involved in diuresis, like water and solute channels as well as ion transporters. We compared our results against the model of potassium- and sodium chloride excretion in the Malpighian tubules proposed by Hine et al. (2014, which involves at least eight ion transporters and a proton-pump.Results: We found 3,421 of a total number of 17,478 (19.6% unique transcripts with a P < 0.05 and at least a 2.5 fold change in expression levels between the two groups. We identified two novel transporter genes that are highly expressed in the adult Malpighian tubules, which have not previously been part of the transport model in this species and may play important roles in diuresis. We also identified candidates for hypothesized sodium and chloride channels. Detoxification genes were generally higher expressed in larvae.Significance: This study represents the first comparison of Malpighian tubule transcriptomes between larval and adult A. aegypti mosquitoes, highlighting key differences in their renal systems that arise as they transform from an aquatic filter-feeding larval stage to a terrestrial, blood-feeding adult stage.

Renal handling of drugs in renal failure. I: Differential effects of uranyl nitrate- and glycerol-induced acute renal failure on renal excretion of TEAB and PAH in rats

International Nuclear Information System (INIS)

Lin, J.H.; Lin, T.H.

1988-01-01

Two etiologically different models of experimental acute renal failure were induced in rats by administration of either glycerol or uranyl nitrate. Both compounds caused a substantial decrease in the glomerular filtration rate (GFR) and the net tubular secretion of tetraethylammonium bromide (TEAB) and para-aminohippuric acid (PAH). The degree of renal impairment induced by uranyl nitrate and glycerol appeared to be dose related. Deprivation of drinking water 24 hr before the administration of glycerol potentiated the renal damage. In uranyl nitrate-induced renal failure, the decline of the net tubular secretion for TEAB and PAH was not proportional to the decrease in GFR; the secretion process deteriorated faster than the GFR. For example, when 0.5 mg/kg uranyl nitrate was administered, GFR fell to approximately 65% of normal, whereas the net tubular secretion was decreased to 30% of normal. These results suggest that the tubular transport was preferentially affected by uranyl nitrate. In contrast, in glycerol-induced renal failure, the decline of TEAB secretion fell in a parallel fashion with the GFR, suggesting that the glomeruli and the proximal tubules were equally damaged by glycerol. However, in this latter model, the decline of PAH secretion did not parallel the decrease in GFR, contradicting the proposal that glycerol affects equally the glomeruli and the proximal tubules. This discrepancy may be due to the selective competitive inhibition of PAH secretion by the accumulation of naturally occurring organic acids

The significance of determination of renal tubular markers before and after treatment in the primary nephrotic syndrome

International Nuclear Information System (INIS)

Xie Bing; Jiang Liping

2011-01-01

Objective: To evaluate the damage of renal tubule of patients with primary nephrotic syndrome (PNS) by detecting renal tubule markers and investigate the significance of different therapeutic effects. Methods: Serum levels of interleukin-6(IL-6), ET-1, α 1 -microglobulin(α 1 -m), β 2 -microglobulin(β 2 -m) and plasma level of ET-1 were determined with RIA, fibrinogen degradation product (FDP) with ELISA, automatic biochemistry analysis N-acetyl-β-D-glucosaminidase(NAG), CH 2 O was determined with physico-method respectively. Results: The concentrations of IL-6, ET-1, α 1 -m, β 2 -m, FDP, NAG were significantly decreased in cases of complete remission after therapy (P 2 O excepted (P>0.05), the decrease of IL-6, ET-1, α 1 -m, FDP were no significant in cases of invalid (P>0.05), the concentrations of renal tubule markers in cases of partial remission and invalid were higher than those in cases of complete and significant remission. Conclusion: The determination of several renal tubule markers can be used for diagnose, monitor and judge the therapeutic effects of PNS. (authors)

Two cases of cisplatin-induced permanent renal failure following neoadjuvant chemotherapy for esophageal cancer.

Science.gov (United States)

Sasaki, Tomohiko; Motoyama, Satoru; Komatsuda, Atsushi; Shibata, Hiroyuki; Sato, Yusuke; Yoshino, Kei; Wakita, Akiyuki; Saito, Hajime; Anbai, Akira; Jin, Mario; Minamiya, Yoshihiro

2016-01-01

We experienced two esophageal cancer patients who developed severe acute renal failure after neoadjuvant chemotherapy with cisplatin and 5-fluorourasil. After administration of cisplatin, their serum creatinine increased gradually until they required hemodialysis and their renal failure was permanent. In both cases, renal biopsy examination indicated partial recovery of the proximal tubule, but renal function did not recover. After these events, one patient underwent definitive radiotherapy and the other underwent esophagectomy for their esophageal cancers, while continuing dialysis. Both patients are alive without cancer recurrence. In these two cases of cisplatin-induced renal failure, renal biopsy examination showed only slight disorder of proximal tubules and tendency to recover. Although cisplatin-related nephrotoxicity is a well-recognized complication, there have been few reports of renal failure requiring hemodialysis in cancer patients. In this report, we present their clinical courses and the pathological findings of cisplatin-related renal failure. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

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...

Roles of Akt and SGK1 in the Regulation of Renal Tubular Transport

Directory of Open Access Journals (Sweden)

Nobuhiko Satoh

2015-01-01

Full Text Available A serine/threonine kinase Akt is a key mediator in various signaling pathways including regulation of renal tubular transport. In proximal tubules, Akt mediates insulin signaling via insulin receptor substrate 2 (IRS2 and stimulates sodium-bicarbonate cotransporter (NBCe1, resulting in increased sodium reabsorption. In insulin resistance, the IRS2 in kidney cortex is exceptionally preserved and may mediate the stimulatory effect of insulin on NBCe1 to cause hypertension in diabetes via sodium retention. Likewise, in distal convoluted tubules and cortical collecting ducts, insulin-induced Akt phosphorylation mediates several hormonal signals to enhance sodium-chloride cotransporter (NCC and epithelial sodium channel (ENaC activities, resulting in increased sodium reabsorption. Serum- and glucocorticoid-inducible kinase 1 (SGK1 mediates aldosterone signaling. Insulin can stimulate SGK1 to exert various effects on renal transporters. In renal cortical collecting ducts, SGK1 regulates the expression level of ENaC through inhibition of its degradation. In addition, SGK1 and Akt cooperatively regulate potassium secretion by renal outer medullary potassium channel (ROMK. Moreover, sodium-proton exchanger 3 (NHE3 in proximal tubules is possibly activated by SGK1. This review focuses on recent advances in understanding of the roles of Akt and SGK1 in the regulation of renal tubular transport.

Effect of apricot seeds on renal structure of rabbits

Directory of Open Access Journals (Sweden)

Anna Kolesárová

2017-01-01

Full Text Available Amygdalin is the major cyanogenic glycoside present in apricot seeds and is degraded to cyanide by chewing or grinding. The animal data available did not provide a suitable basis for acute human health hazard. The apricot seeds are potentially useful in human nutrition and for treatment of several diseases especially cancer. The present study demonstrates the potential effect of short-term oral application of apricot seeds on renal structure of rabbit as a biological model. Meat line P91 Californian rabbits from the experimental farm of the Animal Production Research Centre Nitra (Slovak Republic were used in the experiments. The animals were randomly divided into the three groups (C-control, P1, P2 - experimental groups leading to 8 rabbits in each group. The control group received no apricot seeds while the experimental groups P1 and P2 received a daily dose 60 and 300 mg.kg-1 b.w. of crushed apricot seeds mixed with feed during 28 days, respectively. After 28 days all animals were slaughtered and kidney tissue was processed by standard histopathological techniques. Tissue sections were observed under an optical microscope with camera Olympus CX41 (Olympus, Japan at a magnification of 10 x 0.40. The basic morphometric criteria of the preparations were quantified using image program MeasurIT (Olympus, Japan. From each sample (n = 24 three histological sections with five different fields of view in each section were analysed and followed parameters were analysed: diameter of renal corpuscles (RC, diameter of glomeruli (G, diameter of tubules (T and the height of epithelial tubules (E. In our study, we observed a slight increase in the most frequent occurrence parenchyma dystrophy experimental animals. These changes were more pronounced in the experimental group (P2 rabbits received a daily dose of 300 mg.kg-1 of body weight of apricot seeds. Most often, we have found enlarged glomeruli filling the entire space of the capsule, and also glomerular

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...

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

Science.gov (United States)

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.

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

Directory of Open Access Journals (Sweden)

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.

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.

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

Antiangiogenic treatment diminishes renal injury and dysfunction via regulation of local AKT in early experimental diabetes.

Science.gov (United States)

Bai, Xiaoyan; Li, Xiao; Tian, Jianwei; Zhou, Zhanmei

2014-01-01

In view of increased vascular endothelial growth factor-A (VEGF-A) expression and renal dysfunction in early diabetes, we designed a study to test whether VEGF-A inhibition can prevent early renal injury and dysfunction. We investigated the relationship and mechanism between VEGF-A and AKT regulation. In vitro, VEGF-A small interfering RNA (siRNA) and AKT inhibitor MK-2206 were employed to podocytes and NRK-52 cells cultured in high glucose (30 mM). In vivo, the antiangiogenic drug endostatin was administered in 12 week-old streptozotocin-induced male Sprague Dawley rats. The levels of VEGF-A, AKT, phosphorylated Ser⁴⁷³-AKT, phosphorylated Thr³⁰⁸-AKT, nephrin, angiotensin II (Ang II), angiotensin type II receptor 1 (ATR1) were examined using quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR), Western blot analysis and immunohistochemistry. Interactions between phosphorylated Thr³⁰⁸-AKT and either nephrin in podocytes or Ang II in renal tubules were studied, respectively, using confocal immunofluorescence microscopy and immunoprecipitation. Silencing VEGF-A in podocytes upregulated phosphorylated Thr³⁰⁸-AKT and nephrin. Silencing VEGF-A in NRK-52E cells upregulated phosphorylated Thr³⁰⁸-AKT while downregulated Ang II and ATR1. MK-2206 enhanced VEGF-A expression in both podocytes and NRK-52E cells by inhibiting AKT activities. In diabetic rat kidneys, VEGF-A was upregulated and phosphorylated Thr³⁰⁸-AKT colocalized with either nephrin in podocytes or Ang II in renal tubules. With the endostatin treatment, the level of VEGF-A decreased while phosphorylated Thr³⁰⁸-AKT increased in both glomeruli and renal tubules. Treatment with endostatin upregulated nephrin in podocytes while downregulated Ang II and AT1R in renal tubules. Glomerular mesangial expansion was attenuated by the endostatin treatment, however, differences did not reach statistical significance. Endostatin ameliorated the interstitial fibrosis

Antiangiogenic treatment diminishes renal injury and dysfunction via regulation of local AKT in early experimental diabetes.

Directory of Open Access Journals (Sweden)

Xiaoyan Bai

Full Text Available In view of increased vascular endothelial growth factor-A (VEGF-A expression and renal dysfunction in early diabetes, we designed a study to test whether VEGF-A inhibition can prevent early renal injury and dysfunction. We investigated the relationship and mechanism between VEGF-A and AKT regulation. In vitro, VEGF-A small interfering RNA (siRNA and AKT inhibitor MK-2206 were employed to podocytes and NRK-52 cells cultured in high glucose (30 mM. In vivo, the antiangiogenic drug endostatin was administered in 12 week-old streptozotocin-induced male Sprague Dawley rats. The levels of VEGF-A, AKT, phosphorylated Ser⁴⁷³-AKT, phosphorylated Thr³⁰⁸-AKT, nephrin, angiotensin II (Ang II, angiotensin type II receptor 1 (ATR1 were examined using quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR, Western blot analysis and immunohistochemistry. Interactions between phosphorylated Thr³⁰⁸-AKT and either nephrin in podocytes or Ang II in renal tubules were studied, respectively, using confocal immunofluorescence microscopy and immunoprecipitation. Silencing VEGF-A in podocytes upregulated phosphorylated Thr³⁰⁸-AKT and nephrin. Silencing VEGF-A in NRK-52E cells upregulated phosphorylated Thr³⁰⁸-AKT while downregulated Ang II and ATR1. MK-2206 enhanced VEGF-A expression in both podocytes and NRK-52E cells by inhibiting AKT activities. In diabetic rat kidneys, VEGF-A was upregulated and phosphorylated Thr³⁰⁸-AKT colocalized with either nephrin in podocytes or Ang II in renal tubules. With the endostatin treatment, the level of VEGF-A decreased while phosphorylated Thr³⁰⁸-AKT increased in both glomeruli and renal tubules. Treatment with endostatin upregulated nephrin in podocytes while downregulated Ang II and AT1R in renal tubules. Glomerular mesangial expansion was attenuated by the endostatin treatment, however, differences did not reach statistical significance. Endostatin ameliorated the

A local renal renin-angiotensin system activation via renal uptake of prorenin and angiotensinogen in diabetic rats.

Science.gov (United States)

Tojo, Akihiro; Kinugasa, Satoshi; Fujita, Toshiro; Wilcox, Christopher S

2016-01-01

The mechanism of activation of local renal renin-angiotensin system (RAS) has not been clarified in diabetes mellitus (DM). We hypothesized that the local renal RAS will be activated via increased glomerular filtration and tubular uptake of prorenin and angiotensinogen in diabetic kidney with microalbuminuria. Streptozotocin (STZ)-induced DM and control rats were injected with human prorenin and subsequently with human angiotensinogen. Human prorenin uptake was increased in podocytes, proximal tubules, macula densa, and cortical collecting ducts of DM rats where prorenin receptor (PRR) was expressed. Co-immunoprecipitation of kidney homogenates in DM rats revealed binding of human prorenin to the PRR and to megalin. The renal uptake of human angiotensinogen was increased in DM rats at the same nephron sites as prorenin. Angiotensin-converting enzyme was increased in podocytes, but decreased in the proximal tubules in DM rats, which may have contributed to unchanged renal levels of angiotensin despite increased angiotensinogen. The systolic blood pressure increased more after the injection of 20 μg of angiotensinogen in DM rats than in controls, accompanied by an increased uptake of human angiotensinogen in the vascular endothelium. In conclusion, endocytic uptake of prorenin and angiotensinogen in the kidney and vasculature in DM rats was contributed to increased tissue RAS and their pressor response to angiotensinogen.

Distal Renal Tubular Acidosis (dRTA) Among Southeast Asian Ovalocytosis (SAO) Patients in Malaria Endemic Area of Sekotong, Lombok Island

OpenAIRE

Danuyanti, I Gusti Ayu Nyoman; -, Tasmini; Sadewa, Ahmad Hamim

2014-01-01

Introduction: Southeast Asian Ovalocytosis (SAO) is caused by 27 bp deletion of the band 3 protein gene in erythrocyte membrane and characterized by oval erythrocyte. The erythroid band 3 (AE1) gene isexpressed not only in erythrocyte membranes but also in the cell membrane of α-collecting renal tubular functions in the secretion of acid in renal tubules and HCO3 -/Cl- anion exchange. An alteration of the band 3 (AE1) gene functions in cell of α-collecting renal tubules reduces HCO3-/Cl- ion ...

Comparing renal function preservation after laparoscopic radio frequency ablation assisted tumor enucleation and laparoscopic partial nephrectomy for clinical T1a renal tumor: using a 3D parenchyma measurement system.

Science.gov (United States)

Zhu, Liangsong; Wu, Guangyu; Huang, Jiwei; Wang, Jianfeng; Zhang, Ruiyun; Kong, Wen; Xue, Wei; Huang, Yiran; Chen, Yonghui; Zhang, Jin

2017-05-01

To compare the renal function preservation between laparoscopic radio frequency ablation assisted tumor enucleation and laparoscopic partial nephrectomy. Data were analyzed from 246 patients who underwent laparoscopic radio frequency ablation assisted tumor enucleation and laparoscopic partial nephrectomy for solitary cT1a renal cell carcinoma from January 2013 to July 2015. To reduce the intergroup difference, we used a 1:1 propensity matching analysis. The functional renal parenchyma volume preservation were measured preoperative and 12 months after surgery. The total renal function recovery and spilt GFR was compared. Multivariable logistic analysis was used for predictive factors for renal function decline. After 1:1 propensity matching, each group including 100 patients. Patients in the laparoscopic radio frequency ablation assisted tumor enucleation had a smaller decrease in estimate glomerular filtration rate at 1 day (-7.88 vs -20.01%, p renal parenchyma volume preservation (89.19 vs 84.27%, p renal parenchyma volume preservation, warm ischemia time and baseline renal function were the important independent factors in determining long-term functional recovery. The laparoscopic radio frequency ablation assisted tumor enucleation technology has unique advantage and potential in preserving renal parenchyma without ischemia damage compared to conventional laparoscopic partial nephrectomy, and had a better outcome, thus we recommend this technique in selected T1a patients.

Current structure and organization for renal patient assistance in Italy.

Science.gov (United States)

Alloatti, Sandro; Strippoli, Giovanni Fm; Buccianti, Gherardo; Daidone, Giuseppe; Schena, Francesco P

2008-04-01

Given the public health challenge and burden of chronic kidney disease, the Italian Society of Nephrology (SIN) has compiled a national census of Renal Units (RU) existing in the twenty Italian regions related to the year 2004. An on-line questionnaire including 158 items explored structural and human resources, organization aspects, activities and epidemiological data in SIN, 2004. The census identified 363 public RU, 303 satellite Dialysis Centres (DC) and 295 private DC totalling 961 DC [16.4 per million population (pmp)]. The inpatient renal beds were 2742 (47 pmp). Renal and dialysis activity was performed by 3728 physicians (64 pmp), of whom 2964 (80%) were nephrologists. There was no permanent medical assistance in 41% of satellite DC. There were 1802 renal admissions pmp and 99 renal biopsies pmp. The management of acute renal failure (13 456 cases; 230 pmp) represented a relevant proportion of the activities conducted in public RU. In 2004 there were 9858 new cases of end-stage kidney disease requiring renal replacement therapy (RRT) (169 pmp). On 31 December 2004, 60 058 patients were on RRT (1027 pmp), 43 293 of which (740 pmp) were on dialysis and 16 765 (287 pmp) with renal graft. This census of the Italian RU and DC in 2004 provides decision makers and healthcare stakeholders with detailed data for benchmarking and has financial implications for the public health system. Similar analyses may be conducted in other countries permitting standardization of medical and cost-related aspects of renal care.

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.

Leucine-rich repeat kinase 2 (LRRK2-deficient rats exhibit renal tubule injury and perturbations in metabolic and immunological homeostasis.

Directory of Open Access Journals (Sweden)

Daniel Ness

Full Text Available Genetic evidence links mutations in the LRRK2 gene with an increased risk of Parkinson's disease, for which no neuroprotective or neurorestorative therapies currently exist. While the role of LRRK2 in normal cellular function has yet to be fully described, evidence suggests involvement with immune and kidney functions. A comparative study of LRRK2-deficient and wild type rats investigated the influence that this gene has on the phenotype of these rats. Significant weight gain in the LRRK2 null rats was observed and was accompanied by significant increases in insulin and insulin-like growth factors. Additionally, LRRK2-deficient rats displayed kidney morphological and histopathological alterations in the renal tubule epithelial cells of all animals assessed. These perturbations in renal morphology were accompanied by significant decreases of lipocalin-2, in both the urine and plasma of knockout animals. Significant alterations in the cellular composition of the spleen between LRRK2 knockout and wild type animals were identified by immunophenotyping and were associated with subtle differences in response to dual infection with rat-adapted influenza virus (RAIV and Streptococcus pneumoniae. Ontological pathway analysis of LRRK2 across metabolic and kidney processes and pathological categories suggested that the thioredoxin network may play a role in perturbing these organ systems. The phenotype of the LRRK2 null rat is suggestive of a complex biology influencing metabolism, immune function and kidney homeostasis. These data need to be extended to better understand the role of the kinase domain or other biological functions of the gene to better inform the development of pharmacological inhibitors.

Renal content and output of epidermal growth factor in long-term adrenergic agonist-treated rats

DEFF Research Database (Denmark)

Thulesen, J; Nexø, Ebba; Poulsen, Steen Seier

2000-01-01

This study investigates the renal and urinary levels of epidermal growth factor (EGF) in rats under long-term treatment with alpha- or beta-adrenergic agonists. Urine samples were obtained on days 7, 14 and 21, and renal tissue samples on day 21. EGF was quantified by ELISA and tissue sections were...... material in the distal tubules. Concomitantly, reduced levels of EGF and EGF mRNA were observed, and also the urinary levels of EGF were reduced. Together, these observations indicate alpha-adrenergic treatment to affect the distal tubules. Treatment with the beta-adrenergic agonist did not change...... fractional kidney weight, but initially the urinary excretion of EGF was reduced. The data add further evidence to the suggestion that activity of the sympathetic nervous system influences renal homeostasis of EGF, either directly or indirectly through renal histopathological changes....

Histopathological retrospective study of canine renal disease in Korea, 2003~2008

Science.gov (United States)

Yhee, Ji-Young; Yu, Chi-Ho; Kim, Jong-Hyuk; Im, Keum-Soon; Chon, Seung-Ki

2010-01-01

Renal disease includes conditions affecting the glomeruli, tubules, interstitium, pelvis, and vasculature. Diseases of the kidney include glomerular diseases, diseases of the tubules and interstitium, diseases of renal pelvis, and developmental abnormalities. Renal tissue samples (n = 70) submitted to the Department of Veterinary Pathology of Konkuk University from 2003 to 2008 were included in this study. Tissue histopathology was performed using light microscopy with hematoxylin and eosin stains. Masson's trichrome, Congo Red, and Warthin starry silver staining were applied in several individual cases. Glomerular diseases (22.9%), tubulointerstitial diseases (8.6%), neoplastic diseases (8.6%), conditions secondary to urinary obstruction (24.3%), and other diseases (35.7%) were identified. Glomerulonephritis (GN) cases were classified as acute proliferative GN (5.7%), membranous GN (4.3%), membranoproliferative GN (4.3%), focal segmental GN (2.9%), and other GN (4.2%). The proportion of canine GN cases presently identified was not as high as the proportions identified in human studies. Conversely, urinary obstruction and end-stage renal disease cases were relatively higher in dogs than in human populations. PMID:21113095

Trichloroethylene and trichloroethanol-induced formic aciduria and renal injury in male F-344 rats following 12 weeks exposure.

Science.gov (United States)

Yaqoob, Noreen; Evans, Andrew; Foster, John R; Lock, Edward A

2014-09-02

Trichloroethylene (TCE) is widely used as a cleaning and decreasing agent and has been shown to cause liver tumours in rodents and a small incidence of renal tubule tumours in male rats. The basis for the renal tubule injury is believed to be related to metabolism of TCE via glutathione conjugation to yield the cysteine conjugate that can be activated by the enzyme cysteine conjugate β-lyase in the kidney. More recently TCE and its major metabolite trichloroethanol (TCE-OH) have been shown to cause formic aciduria which can cause renal injury after chronic exposure in rats. In this study we have compared the renal toxicity of TCE and TCE-OH in rats to try and ascertain whether the glutathione pathway or formic aciduria can account for the toxicity. Male rats were given TCE (500mg/kg/day) or TCE-OH at (100mg/kg/day) for 12 weeks and the extent of renal injury measured at several time points using biomarkers of nephrotoxicity and prior to termination assessing renal tubule cell proliferation. The extent of formic aciduria was also determined at several time points, while renal pathology and plasma urea and creatinine were determined at the end of the study. TCE produced a very mild increase in biomarkers of renal injury, total protein, and glucose over the first two weeks of exposure and increased Kim-1 and NAG in urine after 1 and 5 weeks exposure, while TCE-OH did not produce a consistent increase in these biomarkers in urine. However, both chemicals produced a marked and sustained increase in the excretion of formic acid in urine to a very similar extent. The activity of methionine synthase in the liver of TCE and TCE-OH treated rats was inhibited by about 50% indicative of a block in folate synthesis. Both renal pathology and renal tubule cell proliferation were reduced after TCE and TCE-OH treatment compared to controls. Our findings do not clearly identify the pathway which is responsible for the renal toxicity of TCE but do provide some support for metabolism

Trichloroethylene and trichloroethanol-induced formic aciduria and renal injury in male F-344 rats following 12 weeks exposure

International Nuclear Information System (INIS)

Yaqoob, Noreen; Evans, Andrew; Foster, John R.; Lock, Edward A.

2014-01-01

Trichloroethylene (TCE) is widely used as a cleaning and decreasing agent and has been shown to cause liver tumours in rodents and a small incidence of renal tubule tumours in male rats. The basis for the renal tubule injury is believed to be related to metabolism of TCE via glutathione conjugation to yield the cysteine conjugate that can be activated by the enzyme cysteine conjugate β-lyase in the kidney. More recently TCE and its major metabolite trichloroethanol (TCE-OH) have been shown to cause formic aciduria which can cause renal injury after chronic exposure in rats. In this study we have compared the renal toxicity of TCE and TCE-OH in rats to try and ascertain whether the glutathione pathway or formic aciduria can account for the toxicity. Male rats were given TCE (500 mg/kg/day) or TCE-OH at (100 mg/kg/day) for 12 weeks and the extent of renal injury measured at several time points using biomarkers of nephrotoxicity and prior to termination assessing renal tubule cell proliferation. The extent of formic aciduria was also determined at several time points, while renal pathology and plasma urea and creatinine were determined at the end of the study. TCE produced a very mild increase in biomarkers of renal injury, total protein, and glucose over the first two weeks of exposure and increased Kim-1 and NAG in urine after 1 and 5 weeks exposure, while TCE-OH did not produce a consistent increase in these biomarkers in urine. However, both chemicals produced a marked and sustained increase in the excretion of formic acid in urine to a very similar extent. The activity of methionine synthase in the liver of TCE and TCE-OH treated rats was inhibited by about 50% indicative of a block in folate synthesis. Both renal pathology and renal tubule cell proliferation were reduced after TCE and TCE-OH treatment compared to controls. Our findings do not clearly identify the pathway which is responsible for the renal toxicity of TCE but do provide some support for

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

Science.gov (United States)

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

Cordyceps sinensis protects against renal ischemia/reperfusion injury in rats.

Science.gov (United States)

Wang, Hua-Pin; Liu, Ching-Wen; Chang, Hsueh-Wen; Tsai, Jen-Wei; Sung, Ya-Zhu; Chang, Li-Ching

2013-03-01

Cordyceps sinensis (CS) is an entomogenous fungus used as a tonic food and Chinese medicine to replenish health. This study investigated the protective effects of CS in rats post-renal ischemia-reperfusion (I/R) sequence by analyzing the influence on stromal cell-derived factor-1α (SDF-1α and chemokine (C-X-C motif) receptor 4 (CXCR4) expressions and senescence during recovery. Chemokine SDF-1 [now called chemokine C-X-C motif ligand 12 (CXCL12)] and its receptor CXCR4 are crucial in kidney repair after ischemic acute renal failure. CS treatment significantly alleviated I/R-induced renal damage assessed by creatinine levels (p < 0.05) and abated renal tubular damages assessed by periodic acid-Schiff with diastase (PASD) staining. CS induced early SDF-1α expression and increased CXCR4 expression 1-6 h post-reperfusion. Histology studies have revealed that CS induced SDF-1α in squamous cells of Bowman's capsule, mesangial cells, distal convoluted tubules (DCT), and proximal convoluted tubules (PCT). CS also improved renal repair in I/R-induced injury by increasing Ki-67 staining. I/R induced renal senescence after 3 and 6 h of reperfusion. However, CS alleviated I/R-induced senescence at early stage (1 and 3 h). We conclude that CS protects against I/R injury via the SDF-1/CXCR4-signaling axis and alleviates senescence.

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

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)

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

Directory of Open Access Journals (Sweden)

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.

Renal dysfunction and barttin expression in Bartter syndrome Type IV associated with a G47R mutation in BSND in a family.

Science.gov (United States)

Park, C W; Lim, J H; Youn, D-Y; Chung, S; Lim, M-H; Kim, Y K; Chang, Y S; Lee, J-H

2011-02-01

Bartter syndrome (BS) Type IV, associated with a G47R mutation in the BSND gene, is known to result in a mild renal phenotype. However, we report here on three brothers with varying degrees of renal dysfunction from mild to end-stage renal disease associated with renal barttin and ClC-K expression. The brothers had histories of polyhydramnios, prematurity, polyuria, deafness, and small body size. Laboratory findings showed hypokalemic metabolic alkalosis, normotensive hyperreninemic hyperaldosteronism, and an increased urinary excretion of sodium, potassium and chloride, consistent with BS Type IV. Microscopic examination of renal tissue showed hyperplasia of cells at the juxtaglomerular apparatus with dilated atrophic tubules and tubulointerstitial fibrosis. A weak barttin signal related to CIC-K expression in the cytoplasm of tubule cells, but not the basement membrane, was noted. A sequence analysis of the BSND gene showed that the affected males were homozygous for a missense G47R mutation in exon 1 of BSND. These findings suggest that the G47R mutation results in a dramatic decrease in barttin expression, which appears to be related to the location of CIC-K being changed from the basement membrane to the cytoplasm in the tubule and might have varying effects on renal function associated with factors other than this gene.

Sorting Tubules Regulate Blood-Brain Barrier Transcytosis

Directory of Open Access Journals (Sweden)

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

Science.gov (United States)

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.

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

Science.gov (United States)

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

Computer-assisted static/dynamic renal imaging: a screening test for renovascular hypertension

International Nuclear Information System (INIS)

Keim, H.J.; Johnson, P.M.; Vaughan, E.D. Jr.; Beg, K.; Follett, D.A.; Freeman, L.M.; Laragh, J.H.

1979-01-01

Computer-assisted static/dynamic renal imaging with [ 197 Hg] chlormerodrin and [/sup 99m/Tc] pertechnetate was evaluated prospectively as a screening test for renovascular hypertension. Results are reported for 51 patients: 33 with benign essential hypertension and 18 with renovascular hypertension, and for 21 normal controls. All patients underwent renal arteriography. Patients with significant obesity, renal insufficiency, or renoparenchymal disease were excluded from this study. Independent visual analyses of renal gamma images and time-activity transit curves identified 17 of the 18 patients with renovascular hypertension; one study was equivocal. There were five equivocal and three false-positive results in the essential hypertension and normal control groups. The sensitivity of the method was 94% and the specificity 85%. Since the prevalence of the renovascular subset of hypertension is approximately 5%, the predictive value is only 25%. Inclusion of computer-generated data did not improve this result. Accordingly, this method is not recommended as a primary screening test for renovascular hypertension

Dentinal tubules revealed with X-ray tensor tomography.

Science.gov (United States)

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.

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

Directory of Open Access Journals (Sweden)

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.

Renal cell carcinoma as a cause of iron deficiency anemia

African Journals Online (AJOL)

Amar A. Dowd

derived from the various parts of the nephron (epithelium or renal tubules) and possessing ... [3] is hematuria, flank pain, and an abdominal mass, similar to bloat- ... mass in the right kidney implicating its anterior aspect, measuring 62 × 48 mm.

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.

Is the renal kallikrein-kinin system a factor that modulates hypercalciuria?

Directory of Open Access Journals (Sweden)

Armando Luis Negri

2017-01-01

Full Text Available Renal tubular calcium reabsorption is one of the principal factors that determine serum calcium concentration and calcium excretion. Calcium excretion is regulated by the distal convoluted tubule and connecting tubule, where the epithelial calcium channel TRPV5 can be found, which limits the rate of transcellular calcium transport. The dynamic presence of the TRPV5 channel on the surface of the tubular cell is mediated by an endosomal recycling process. Different intrarenal factors are involved in calcium channel fixation in the apical membrane, including the anti-ageing hormone klotho and tissue kallikrein (TK. Both proteins are synthesised in the distal tubule and secreted in the tubular fluid. TK stimulates active calcium reabsorption through the bradykinin receptor B2 that compromises TRPV5 activation through the protein kinase C pathway. TK-deficient mice show hypercalciuria of renal origin comparable to that seen in TRPV5 knockout mice. There is a polymorphism with loss of function of the human TK gene R53H (allele H that causes a marked decrease in enzymatic activity. The presence of the allele H seems to be common at least in the Japanese population (24%. These individuals have a tendency to greater calcium and sodium excretion in urine that is more evident during furosemide infusion. Future studies should analyse if manipulating the renal kallikrein-kinin system can correct idiopathic hypercalciuria with drugs other than thiazide diuretics.

Localisation and mechanism of renal retention of radiolabelled somatostatin analogues

Energy Technology Data Exchange (ETDEWEB)

Melis, Marleen; Krenning, Eric P.; Bernard, Bert F.; Jong, Marion de [Erasmus MC, Department of Nuclear Medicine, Rotterdam (Netherlands); Barone, Raffaella [UCL, Centre of Nuclear Medicine and Laboratory of PET, Brussels (Belgium); Visser, Theo J. [Erasmus MC, Department of Internal Medicine, Rotterdam (Netherlands)

2005-10-01

Radiolabelled somatostatin analogues, such as octreotide and octreotate, are used for tumour scintigraphy and radionuclide therapy. The kidney is the most important critical organ during such therapy owing to the reabsorption and retention of radiolabelled peptides. The aim of this study was to investigate in a rat model both the localisation and the mechanism of renal uptake after intravenous injection of radiolabelled somatostatin analogues. The multi-ligand megalin/cubilin receptor complex, responsible for reabsorption of many peptides and proteins in the kidney, is an interesting candidate for renal endocytosis of these peptide analogues. For localisation studies, ex vivo autoradiography and micro-autoradiography of rat kidneys were performed 1-24 h after injection of radiolabelled somatostatin analogues and compared with the renal anti-megalin immunohistochemical staining pattern. To confirm a role of megalin in the mechanism of renal retention of [{sup 111}In-DTPA]octreotide, the effects of three inhibitory substances were explored in rats. Renal ex vivo autoradiography showed high cortical radioactivity and lower radioactivity in the outer medulla. The distribution of cortical radioactivity was inhomogeneous. Micro-autoradiography indicated that radioactivity was only retained in the proximal tubules. The anti-megalin immunohistochemical staining pattern showed a strong similarity with the renal [{sup 111}In-DTPA]octreotide ex vivo autoradiograms. Biodistribution studies showed that co-injection of positively charged d-lysine reduced renal uptake to 60% of control. Sodium maleate reduced renal [{sup 111}In-DTPA]octreotide uptake to 15% of control. Finally, cisplatin pre-treatment of rats reduced kidney uptake to 70% of control. Renal retention of [{sup 111}In-DTPA]octreotide is confined to proximal tubules in the rat kidney, in which megalin-mediated endocytosis may play an important part. (orig.)

Solo and keratin filaments regulate epithelial tubule morphology.

Science.gov (United States)

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.

The renal effects and initial characterization of venom from Philodryas nattereri Steindachner, 1870

Directory of Open Access Journals (Sweden)

Marinetes Dantas de Aquino Nery

2014-01-01

Full Text Available The venom of the snake Philodryas nattereri is a mixture of proteins and toxic peptides with several important local and systemic actions, which are similar to those occurring in Bothrops snake bites. The mechanisms involved in the local and systemic actions of this venom are unknown. The aims of the work were to initial characterization of P. nattereri venom and investigate the effects of the poison in the renal perfusion system and in cultured renal tubular cells of the type MDCK (Madin–Darby canine kidney. The P. nattereri venom is composed majority of proteins (86.3% and this poison promoted changes in all the evaluated renal parameters, mainly decreasing renal perfusion pressure (PP and renal vascular resistance (RVR and increasing urine flow (UF and glomerular filtration rate (GFR. The most relevant result was that this venom was highly detrimental to the renal tubules independent of the PP reduction, which was shown by a decrease in sodium (Na+, potassium (K+ and chloride (Cl− electrolyte transport in the studied concentrations. The glomeruli and tubules contain protein bodies and blood extravasation, which were observed by histological analysis. The venom of P. nattereri reduced viability of the MDCK cells only at high concentrations (50 and 100 μg/mL with an IC50 of 169.5 μg/mL.

Renal type a intercalated cells contain albumin in organelles with aldosterone-regulated abundance.

Directory of Open Access Journals (Sweden)

Thomas Buus Jensen

Full Text Available Albumin has been identified in preparations of renal distal tubules and collecting ducts by mass spectrometry. This study aimed to establish whether albumin was a contaminant in those studies or actually present in the tubular cells, and if so, identify the albumin containing cells and commence exploration of the origin of the intracellular albumin. In addition to the expected proximal tubular albumin immunoreactivity, albumin was localized to mouse renal type-A intercalated cells and cells in the interstitium by three anti-albumin antibodies. Albumin did not colocalize with markers for early endosomes (EEA1, late endosomes/lysosomes (cathepsin D or recycling endosomes (Rab11. Immuno-gold electron microscopy confirmed the presence of albumin-containing large spherical membrane associated bodies in the basal parts of intercalated cells. Message for albumin was detected in mouse renal cortex as well as in a wide variety of other tissues by RT-PCR, but was absent from isolated connecting tubules and cortical collecting ducts. Wild type I MDCK cells showed robust uptake of fluorescein-albumin from the basolateral side but not from the apical side when grown on permeable support. Only a subset of cells with low peanut agglutinin binding took up albumin. Albumin-aldosterone conjugates were also internalized from the basolateral side by MDCK cells. Aldosterone administration for 24 and 48 hours decreased albumin abundance in connecting tubules and cortical collecting ducts from mouse kidneys. We suggest that albumin is produced within the renal interstitium and taken up from the basolateral side by type-A intercalated cells by clathrin and dynamin independent pathways and speculate that the protein might act as a carrier of less water-soluble substances across the renal interstitium from the capillaries to the tubular cells.

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

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...

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 (

Effect of diuretics on renal tubular transport of calcium and magnesium.

Science.gov (United States)

Alexander, R Todd; Dimke, Henrik

2017-06-01

Calcium (Ca 2+ ) and Magnesium (Mg 2+ ) reabsorption along the renal tubule is dependent on distinct trans- and paracellular pathways. Our understanding of the molecular machinery involved is increasing. Ca 2+ and Mg 2+ reclamation in kidney is dependent on a diverse array of proteins, which are important for both forming divalent cation-permeable pores and channels, but also for generating the necessary driving forces for Ca 2+ and Mg 2+ transport. Alterations in these molecular constituents can have profound effects on tubular Ca 2+ and Mg 2+ handling. Diuretics are used to treat a large range of clinical conditions, but most commonly for the management of blood pressure and fluid balance. The pharmacological targets of diuretics generally directly facilitate sodium (Na + ) transport, but also indirectly affect renal Ca 2+ and Mg 2+ handling, i.e., by establishing a prerequisite electrochemical gradient. It is therefore not surprising that substantial alterations in divalent cation handling can be observed following diuretic treatment. The effects of diuretics on renal Ca 2+ and Mg 2+ handling are reviewed in the context of the present understanding of basal molecular mechanisms of Ca 2+ and Mg 2+ transport. Acetazolamide, osmotic diuretics, Na + /H + exchanger (NHE3) inhibitors, and antidiabetic Na + /glucose cotransporter type 2 (SGLT) blocking compounds, target the proximal tubule, where paracellular Ca 2+ transport predominates. Loop diuretics and renal outer medullary K + (ROMK) inhibitors block thick ascending limb transport, a segment with significant paracellular Ca 2+ and Mg 2+ transport. Thiazides target the distal convoluted tubule; however, their effect on divalent cation transport is not limited to that segment. Finally, potassium-sparing diuretics, which inhibit electrogenic Na + transport at distal sites, can also affect divalent cation transport. Copyright © 2017 the American Physiological Society.

Megalin and cubilin are endocytic receptors involved in renal clearance of hemoglobin

DEFF Research Database (Denmark)

Gburek, Jakub; Verroust, Pierre J; Willnow, Thomas E

2002-01-01

-Sepharose affinity chromatography of solubilized renal brush-border membranes. Apparent dissociation constants of 1.7 microM for megalin and 4.1 microM for cubilin were determined by surface plasmon resonance analysis. The binding was calcium dependent in both cases. Uptake of fluorescence-labeled hemoglobin by BN......The kidney is the main site of hemoglobin clearance and degradation in conditions of severe hemolysis. Herein it is reported that megalin and cubilin, two epithelial endocytic receptors, mediate the uptake of hemoglobin in renal proximal tubules. Both receptors were purified by use of hemoglobin...... not affect the uptake. By use of immunohistochemistry, it was demonstrated that uptake of hemoglobin in proximal tubules of rat, mouse, and dog kidneys occurs under physiologic conditions. Studies on normal and megalin knockout mouse kidney sections showed that megalin is responsible for physiologic...

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

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...

Regulation of transport in the connecting tubule and cortical collecting duct

Science.gov (United States)

Staruschenko, Alexander

2012-01-01

The central goal of this overview article is to summarize recent findings in renal epithelial transport, focusing chiefly on the connecting tubule (CNT) and the cortical collecting duct (CCD). Mammalian CCD and CNT are involved in fine tuning of electrolyte and fluid balance through reabsorption and secretion. Specific transporters and channels mediate vectorial movements of water and solutes in these segments. Although only a small percent of the glomerular filtrate reaches the CNT and CCD, these segments are critical for water and electrolyte homeostasis since several hormones, e.g. aldosterone and arginine vasopressin, exert their main effects in these nephron sites. Importantly, hormones regulate the function of the entire nephron and kidney by affecting channels and transporters in the CNT and CCD. Knowledge about the physiological and pathophysiological regulation of transport in the CNT and CCD and particular roles of specific channels/transporters has increased tremendously over the last two decades. Recent studies shed new light on several key questions concerning the regulation of renal transport. Precise distribution patterns of transport proteins in the CCD and CNT will be reviewed, and their physiological roles and mechanisms mediating ion transport in these segments will be also covered. Special emphasis will be given to pathophysiological conditions appearing as a result of abnormalities in renal transport in the CNT and CCD. PMID:23227301

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

Directory of Open Access Journals (Sweden)

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.

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.

The cellular basis of renal injury by radiation

International Nuclear Information System (INIS)

Williams, M.V.

1986-01-01

This review with substantial bibliography summarises renal assay techniques available and discusses the histological and functional studies leading to differing opinions between the belief that vascular injury provides a general explanation of the late effects of radiotherapy and the opposing view that parenchymal cell damage is more important. It is proposed that the link between glomerular and tubular function obscures the primary site of injury and that radiation injury will result in a reduction of functioning nephron mass by primary damage to the tubules or glomeruli. Compensatory renal vasodilation would close a positive feedback loop. Radiation could also cause direct vascular injury; decreased renal perfusion and hypertension would result. Again sensitisation to hypertensive vascular damage would close a feedback loop. (UK)

[Autosomal-recessive renal cystic disease and congenital hepatic fibrosis: clinico-anatomic case].

Science.gov (United States)

Rostol'tsev, K V; Burenkov, R A; Kuz'micheva, I A

2012-01-01

Clinico-anatomic observation of autosomal-recessive renal cystic disease and congenital hepatic fibrosis at two fetuses from the same family was done. Mutation of His3124Tyr in 58 exon of PKHD1 gene in heterozygous state was found out. The same pathomorphological changes in the epithelium of cystic renal tubules and bile ducts of the liver were noted. We suggest that the autopsy research of fetuses with congenital abnormalities, detected after prenatal ultrasonic screening, has high diagnostic importance.

Role of NH3 and NH4+ transporters in renal acid-base transport.

Science.gov (United States)

Weiner, I David; Verlander, Jill W

2011-01-01

Renal ammonia excretion is the predominant component of renal net acid excretion. The majority of ammonia excretion is produced in the kidney and then undergoes regulated transport in a number of renal epithelial segments. Recent findings have substantially altered our understanding of renal ammonia transport. In particular, the classic model of passive, diffusive NH3 movement coupled with NH4+ "trapping" is being replaced by a model in which specific proteins mediate regulated transport of NH3 and NH4+ across plasma membranes. In the proximal tubule, the apical Na+/H+ exchanger, NHE-3, is a major mechanism of preferential NH4+ secretion. In the thick ascending limb of Henle's loop, the apical Na+-K+-2Cl- cotransporter, NKCC2, is a major contributor to ammonia reabsorption and the basolateral Na+/H+ exchanger, NHE-4, appears to be important for basolateral NH4+ exit. The collecting duct is a major site for renal ammonia secretion, involving parallel H+ secretion and NH3 secretion. The Rhesus glycoproteins, Rh B Glycoprotein (Rhbg) and Rh C Glycoprotein (Rhcg), are recently recognized ammonia transporters in the distal tubule and collecting duct. Rhcg is present in both the apical and basolateral plasma membrane, is expressed in parallel with renal ammonia excretion, and mediates a critical role in renal ammonia excretion and collecting duct ammonia transport. Rhbg is expressed specifically in the basolateral plasma membrane, and its role in renal acid-base homeostasis is controversial. In the inner medullary collecting duct (IMCD), basolateral Na+-K+-ATPase enables active basolateral NH4+ uptake. In addition to these proteins, several other proteins also contribute to renal NH3/NH4+ transport. The role and mechanisms of these proteins are discussed in depth in this review.

Ectopic germinal center and megalin defect in primary Sjogren syndrome with renal Fanconi syndrome.

Science.gov (United States)

Wang, Jing; Wen, Yubing; Zhou, Mengyu; Shi, Xiaoxiao; Jiang, Lanping; Li, Mingxi; Yu, Yang; Li, Xuemei; Li, Xuewang; Zhang, Wen; Lundquist, Andrew L; Chen, Limeng

2017-06-02

This study reports the clinical and pathological features of 12 cases of primary Sjogren syndrome (pSS) with renal involvement presenting with proximal tubular dysfunction in a single center, and investigates the possible correlation of ectopic germinal center formation and megalin/cubilin down-expression. Clinical and pathological records were reviewed. Immunohistochemistry was carried out to detect megalin, cubilin, CD21 and IL-17 expression. Patients presented with different degrees of proximal renal tubule lesion and decreased estimated glomerular filtration rate (eGFR). Renal biopsy revealed tubulointerstitial nephritis, with tubular epithelial cell degeneration, tubular atrophy, interstitial inflammation and focal fibrosis. Immunohistochemistry revealed decreased expression of megalin and cubilin, two important multiligand protein receptors on the brush border of proximal tubular epithelial cells. IL-17 secreted by Th17 subtype effector T cells was diffusely detected in the renal proximal tubule, with a negative correlation of IL-17 and megalin expression. In addition, ectopic germinal centers characterized by CD21 + follicular dendritic cells were present in the renal interstitium. In patients with a decreased eGFR, treatment with 4 weeks of glucocorticoid therapy resulted in an improved eGFR in 75% of patients. We report 12 cases of pSS characterized by Fanconi syndrome. The decreased megalin and cubilin expression may contribute to the proximal tubular reabsorption defect, possibly secondary to Th17 infiltration and formation of ectopic germinal centers.

Renal denervation prevents long-term sequelae of ischemic renal injury

Science.gov (United States)

Kim, Jinu; Padanilam, Babu J.

2014-01-01

Signals that drive interstitial fibrogenesis after renal ischemia reperfusion injury remain undefined. Sympathetic activation is manifest even in the early clinical stages of chronic kidney disease and is directly related to disease severity. A role for renal nerves in renal interstitial fibrogenesis in the setting of ischemia reperfusion injury has not been studied. In male 129S1/SvImJ mice, ischemia reperfusion injury induced tubulointerstitial fibrosis as indicated by collagen deposition and profibrotic protein expression 4 to 16 days after the injury.. Leukocyte influx, proinflammatory protein expression, oxidative stress, apoptosis, and cell cycle arrest at G2/M phase were enhanced after ischemia reperfusion injury. Renal denervation at the time of injury or up to 1 day post-injury improved histology, decreased proinflammatory/profibrotic responses and apoptosis, and prevented G2/M cell cycle arrest in the kidney. Treatment with afferent nerve-derived calcitonin gene-related peptide (CGRP) or efferent nerve-derived norepinephrine in denervated and ischemia reperfusion injury-induced kidneys mimicked innervation, restored inflammation and fibrosis, induced G2/M arrest, and enhanced TGF-β1 activation. Blocking norepinephrine or CGRP function using respective receptor blockers prevented these effects. Consistent with the in vivo study, treatment with either norepinephrine or CGRP induced G2/M cell cycle arrest in HK-2 proximal tubule cells, whereas antagonists against their respective receptors prevented G2/M arrest. Thus, renal nerve stimulation is a primary mechanism and renal nerve-derived factors drive epithelial cell cycle arrest and the inflammatory cascade causing interstitial fibrogenesis after ischemia reperfusion injury. PMID:25207878

Proximal Tubule Cell Hypothesis for Cardiorenal Syndrome in Diabetes

Directory of Open Access Journals (Sweden)

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.

Renal Tubule Repair: Is Wnt/β-Catenin a Friend or Foe?

Science.gov (United States)

Gewin, Leslie S

2018-01-24

Wnt/β-catenin signaling is extremely important for proper kidney development. This pathway is also upregulated in injured renal tubular epithelia, both in acute kidney injury and chronic kidney disease. The renal tubular epithelium is an important target of kidney injury, and its response (repair versus persistent injury) is critical for determining whether tubulointerstitial fibrosis, the hallmark of chronic kidney disease, develops. This review discusses how Wnt/β-catenin signaling in the injured tubular epithelia promotes either repair or fibrosis after kidney injury. There is data suggesting that epithelial Wnt/β-catenin signaling is beneficial in acute kidney injury and important in tubular progenitors responsible for epithelial repair. The role of Wnt/β-catenin signaling in chronically injured epithelia is less clear. There is convincing data that Wnt/β-catenin signaling in interstitial fibroblasts and pericytes contributes to the extracellular matrix accumulation that defines fibrosis. However, some recent studies question whether Wnt/β-catenin signaling in chronically injured epithelia actually promotes fibrosis or repair.

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

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.

Soluble CD30 correlates with clinical but not subclinical renal allograft rejection.

Science.gov (United States)

Hirt-Minkowski, Patricia; Roth, Michèle; Hönger, Gideon; Amico, Patrizia; Hopfer, Helmut; Schaub, Stefan

2013-01-01

Soluble CD30 (sCD30) has been proposed as a promising noninvasive biomarker for clinical renal allograft rejection, but its diagnostic characteristics regarding detection of subclinical rejection have not been assessed. We investigated sCD30 in 146 consecutive kidney allograft recipients under tacrolimus-mycophenolate-based immunosuppression having 250 surveillance biopsies at 3 and 6 months as well as 52 indication biopsies within the first year post-transplant. Allograft histology results were classified as (i) acute Banff score zero or interstitial infiltrates only, (ii) tubulitis t1, (iii) tubulitis t2-3 and (iv) isolated vascular compartment inflammation. sCD30 correlated well with the extent of clinical (P sCD30, histological groups were assigned to two categories: no relevant inflammation (i.e. acute Banff score zero and interstitial infiltrates only) versus all other pathologies (tubulitis t1-3 and isolated vascular compartment inflammation). For clinical allograft inflammation, AUC was 0.87 (sensitivity 89%, specificity 79%; P = 0.0006); however, for subclinical inflammation, AUC was only 0.59 (sensitivity 50%, specificity 69%; P = 0.47). In conclusion, sCD30 correlated with clinical, but not subclinical renal allograft rejection limiting its clinical utility as a noninvasive rejection screening biomarker in patients with stable allograft function receiving tacrolimus-mycophenolate-based immunosuppression. © 2012 The Authors Transplant International © 2012 European Society for Organ Transplantation.

Angiopoietin-like protein 2 increases renal fibrosis by accelerating transforming growth factor-β signaling in chronic kidney disease.

Science.gov (United States)

Morinaga, Jun; Kadomatsu, Tsuyoshi; Miyata, Keishi; Endo, Motoyoshi; Terada, Kazutoyo; Tian, Zhe; Sugizaki, Taichi; Tanigawa, Hiroki; Zhao, Jiabin; Zhu, Shunshun; Sato, Michio; Araki, Kimi; Iyama, Ken-ichi; Tomita, Kengo; Mukoyama, Masashi; Tomita, Kimio; Kitamura, Kenichiro; Oike, Yuichi

2016-02-01

Renal fibrosis is a common pathological consequence of chronic kidney disease (CKD) with tissue fibrosis closely associated with chronic inflammation in numerous pathologies. However, molecular mechanisms underlying that association, particularly in the kidney, remain unclear. Here, we determine whether there is a molecular link between chronic inflammation and tissue fibrosis in CKD progression. Histological analysis of human kidneys indicated abundant expression of angiopoietin-like protein 2 (ANGPTL2) in renal tubule epithelial cells during progression of renal fibrosis. Numerous ANGPTL2-positive renal tubule epithelial cells colocalized with cells positive for transforming growth factor (TGF)-β1, a critical mediator of tissue fibrosis. Analysis of M1 collecting duct cells in culture showed that TGF-β1 increases ANGPTL2 expression by attenuating its repression through microRNA-221. Conversely, ANGPTL2 increased TGF-β1 expression through α5β1 integrin-mediated activation of extracellular signal-regulated kinase. Furthermore, ANGPTL2 deficiency in a mouse unilateral ureteral obstruction model significantly reduced renal fibrosis by decreasing TGF-β1 signal amplification in kidney. Thus, ANGPTL2 and TGF-β1 positively regulate each other as renal fibrosis progresses. Our study provides insight into molecular mechanisms underlying chronic inflammation and tissue fibrosis and identifies potential therapeutic targets for CKD treatment. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Tubuloglomerular feedback dynamics and renal blood flow autoregulation in rats

DEFF Research Database (Denmark)

Holstein-Rathlou, N H; Wagner, A J; Marsh, D J

1991-01-01

To decide whether tubuloglomerular feedback (TGF) can account for renal autoregulation, we tested predictions of a TGF simulation. Broad-band and single-frequency perturbations were applied to arterial pressure; arterial blood pressure, renal blood flow and proximal tubule pressure were measured....... Data were analyzed by linear systems analysis. Broad-band forcings of arterial pressure were also applied to the model to compare experimental results with simulations. With arterial pressure as the input and tubular pressure, renal blood flow, or renal vascular resistance as outputs, the model...... correctly predicted gain and phase only in the low-frequency range. Experimental results revealed a second component of vascular control active at 100-150 mHz that was not predicted by the simulation. Forcings at single frequencies showed that the system behaves linearly except in the band of 33-50 m...

Renal Ammonia Metabolism and Transport

Science.gov (United States)

Weiner, I. David; Verlander, Jill W.

2015-01-01

Renal ammonia metabolism and transport mediates a central role in acid-base homeostasis. In contrast to most renal solutes, the majority of renal ammonia excretion derives from intrarenal production, not from glomerular filtration. Renal ammoniagenesis predominantly results from glutamine metabolism, which produces 2 NH4+ and 2 HCO3− for each glutamine metabolized. The proximal tubule is the primary site for ammoniagenesis, but there is evidence for ammoniagenesis by most renal epithelial cells. Ammonia produced in the kidney is either excreted into the urine or returned to the systemic circulation through the renal veins. Ammonia excreted in the urine promotes acid excretion; ammonia returned to the systemic circulation is metabolized in the liver in a HCO3−-consuming process, resulting in no net benefit to acid-base homeostasis. Highly regulated ammonia transport by renal epithelial cells determines the proportion of ammonia excreted in the urine versus returned to the systemic circulation. The traditional paradigm of ammonia transport involving passive NH3 diffusion, protonation in the lumen and NH4+ trapping due to an inability to cross plasma membranes is being replaced by the recognition of limited plasma membrane NH3 permeability in combination with the presence of specific NH3-transporting and NH4+-transporting proteins in specific renal epithelial cells. Ammonia production and transport are regulated by a variety of factors, including extracellular pH and K+, and by several hormones, such as mineralocorticoids, glucocorticoids and angiotensin II. This coordinated process of regulated ammonia production and transport is critical for the effective maintenance of acid-base homeostasis. PMID:23720285

Urinary cystatin C as a renal biomarker and its immunohistochemical localization in anti-GBM glomerulonephritis rats.

Science.gov (United States)

Togashi, Yuko; Imura, Naoko; Miyamoto, Yohei

2013-11-01

The usefulness of urinary cystatin C for the early detection of renal damage in anti-glomerular basement membrane (GBM) glomerulonephritis rats was investigated and compared to other biomarkers (β2-microglobulin, calbindin, clusterin, epidermal growth factor (EGF), alpha-glutathione S-transferase (GST-α), mu-glutathione S-transferase (GST-μ), kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), osteopontin, tissue inhibitor of metalloprotease-1 (TIMP-1), and vascular endothelial growth factor (VEGF)). Urinary levels of cystatin C increased in anti-GBM glomerulonephritis rats, whereas the conventional markers, plasma creatinine and UN did not, demonstrating its usefulness for the early detection of renal damage associated with anti-GBM glomerulonephritis. As well as cystatin C, urinary β2-microglobulin, clusterin, GST-α, GST-μ, KIM-1, and NGAL also had the potential to detect renal damage associated with anti-GBM glomerulonephritis. Furthermore, the immunohistochemical localization of cystatin C in the kidney was examined. Cystatin C expression was mainly observed in the proximal renal tubules in anti-GBM glomerulonephritis rats, and its expression barely changed with the progression of glomerulonephritis. Cystatin C expression was also observed in the tubular lumen of the cortex and medulla when glomerulonephritis was marked, which was considered to be characteristic of renal damage. In conclusion, urinary cystatin C, β2-microglobulin, clusterin, GST-α, GST-μ, KIM-1, and NGAL could be useful biomarkers of renal damage in anti-GBM glomerulonephritis rats. Immunohistochemical cystatin C expression in the proximal renal tubules was barely changed by the progression of glomerulonephritis, but it was newly observed in the tubular lumen when renal damage was apparent. Crown Copyright © 2013. Published by Elsevier GmbH. 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.

Study of acute renal insufficiency and chronic renal insufficiency using radioisotopes

International Nuclear Information System (INIS)

Raynaud, C.

1976-01-01

Radioisotopic renal function tests are of assistance to diagnose and follow-up the course of renal insufficiency. The radioisotopic renogram is useful in assessing the response to therapy of child obstructive uropathies and evaluating renal transplant function. The renal scan is helpful, in an emergency service, to differenciate chronic renal insufficiency from acute renal insufficiency. Hg renal uptake test provides informations on physiopathological problems. Among them, the following problems are emphasized: evolution of a nonfunctioning kidney, control of the success of a reparative surgery and of bilateral obstructive uropathies with unilateral symptoms [fr

Does injection of metanephric mesenchymal cells improve renal function in rats?

Directory of Open Access Journals (Sweden)

Yu-qing Jiao

2011-01-01

Full Text Available Chronic kidney disease (CKD is a massive global health-care problem. Cell therapy offers a potential treatment for CKD. The aim of this study was to investigate whether the administration of a population of stem cells could be used to treat adriamycin (ADR-induced glomerulopathy in rats, a form of CKD. We intravenously transplanted metanephric mesenchymal cells (MMCs into rats treated with ADR. We also induced MMC differentiation in vitro using a medium derived from serum and homogenates of ADR-induced glomerulopathy rats. We detected the induction of an early epithelial phenotype (cytokeratin-18 expression and a proximal tubule phenotype (vitamin D receptor expression in vitro, and MMC-derived epithelial cells corresponding to the proximal tubule and glomeruli in vivo. Transplantation of MMCs after induction of glomerulopathy significantly increased the creatinine clearance rate (Ccr, a marker for glomerular filtration rate, but had no significant effect on other parameters (24-hour urinary protein excretion, serum albumin, total cholesterol. In addition, there was no significant difference in blood urea nitrogen or serum creatinine levels in rats with and without ADR administration. Our results indicate that MMCs might survive, engraft and differentiate into renal epithelia in vivo when transplanted into ADR-treated rats. However, further studies are needed to determine whether MMC transplantation improves renal function and causes renal repair in this model.

Spontaneous renal tumors suspected of being familial in sprague-dawley rats.

Science.gov (United States)

Kudo, Kayoko; Hoshiya, Toru; Nakazawa, Tomomi; Saito, Tsubasa; Shimoyama, Natsumi; Suzuki, Isamu; Tamura, Kazutoshi; Seely, John Curtis

2012-12-01

Spontaneous renal tubule tumors (RTTs), with a distinctive morphological phenotype, were present in three Sprague-Dawley rats, 1 male and 2 females, out a total of 120 animals of each sex from untreated and placebo control groups in a 2-year carcinogenicity study. One female had one carcinoma, adenoma and hyperplasia, and the other female had five adenomas and many hyperplastic lesions; the male case had one carcinoma. From these cases, a biological continuum of hyperplasia, adenoma and carcinoma could be recognized. The tumors were present in the renal cortex and appeared as solid lobulated growths with occasional central necrosis. The lobules were divided by a small amount of fibrovascular tissue. Occasionally the larger tumors contained a cystic area. Tumor cells appeared distinctive and exhibited variable amounts of eosinophilic/amphophilic and vacuolated cytoplasm. Nuclei were round to oval with a prominent nucleolus. Mitotic figures were uncommon, and no distant metastasis was noted. The tumors were seen as multiple and bilateral lesions in two animals and had no apparent relationship to chronic progressive nephropathy (CPN). Foci of tubule hyperplasia were also noted to contain the same type of cellular morphology. The morphological and biological features of these 3 cases resembled the amphophilic-vacuolar (AV) variant of RTT that has been posited to be of familial origin. This is a report of spontaneous familial renal tumors in Sprague-Dawley rats from Japan.

RENAL CLEARANCE AND URINARY EXCRETION OF KANAMYCIN IN DOMESTIC RUMINANT SPECIES

Directory of Open Access Journals (Sweden)

I. JAVED, Z. U. RAHMAN, F. H. KHAN, F. MUHAMMAD, Z. IQBAL AND B. ASLAM

2006-01-01

Full Text Available Species dependent geonetical differences in renal clearance and urinary excretion of kanamycin were investigated in adult female buffaloes, cows, sheep and goats. The drug was administered as a single intravenous dose (5 mg/kg b.wt. Blood and urine samples were collected at various time intervals after drug administration. The plasma and urine concentrations of the drug were determined using the microbiological assay. The mean (± SE values for endogenous creatinine clearance (an index of glomerular filtration rate were 0.77 ± 0.05, 0.49 ± 0.07, 0.81 ± 0.07 and 0.98 ± 0.13 ml/min.kg in buffaloes, cows, sheep and goats, respectively. Experiments regarding kidney handling of kanamycin in these ruminant species revealed respective values of renal clearance as 0.08 ± 0.01, 0.07 ± 0.01, 0.19 ± 0.02 and 0.23 ± 0.04 ml/min.kg. Besides glomerular filtration, kanamycin was reabsorbed from the renal tubules of all ruminant species and actively secreted into the renal tubules of buffaloes and goats. The cumulative percentages of intravenous dose of kanamycin excreted through urine during 12 hours in buffaloes, cows, sheep and goats were 4.31 ± 0.37, 2.53 ± 0.30, 11.0 ± 1.04 and 15.8 ± 2.22, respectively. This species variation in the percentage of urinary excretion in these domestic ruminants coincides with their respective glomerular filtration rates, being the highest in goats, lowest in cows and intermediate in sheep and buffaloes.

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

Directory of Open Access Journals (Sweden)

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.

The renal metallothionein expression profile is altered in human lupus nephritis

DEFF Research Database (Denmark)

Faurschou, Mikkel; Penkowa, Milena; Andersen, Claus Bøgelund

2008-01-01

of standard statistical methods. RESULTS: Proximal tubules displaying epithelial cell MT-I+II depletion in combination with luminal MT-I+II expression were observed in 31 out of 37 of the lupus nephritis specimens, but not in any of the control sections (P = 0.006). The tubular MT score, defined as the median......INTRODUCTION: Metallothionein (MT) isoforms I + II are polypeptides with potent antioxidative and anti-inflammatory properties. In healthy kidneys, MT-I+II have been described as intracellular proteins of proximal tubular cells. The aim of the present study was to investigate whether the renal MT......-I+II expression profile is altered during lupus nephritis. METHODS: Immunohistochemistry was performed on renal biopsies from 37 patients with lupus nephritis. Four specimens of healthy renal tissue served as controls. Clinicopathological correlation studies and renal survival analyses were performed by means...

Experimental study on irradiation injury of the kidneys. II. Cardiovascular changes following renal irradiation

Energy Technology Data Exchange (ETDEWEB)

Tomita, S; Fuzikawa, K; Nishimori, I; Tsuda, N; Miyagawa, N [Nagasaki Univ. (Japan). School of Medicine

1976-09-01

In order to investigate irradiation injury of the kidney and effect of injured kidney on the whole body, especially cardiovascular changes, a single kidney was extracted from Wistar female rats and only the remaining kidney was irradiated with a great amount of radiation in 4000 R dose experimentally. After seven weeks of irradiation, atrophy and involution of the highest region of the kidney were found. Histologically, fibrous proliferation of interstice accompanied with atrophy of the renal tubule, and slightly increased nuclei and lobulation of the glomerulus were recognized. After 15 weeks of irradiation, atrophy and involution of the whole kidney were found. Histologically, fibrous proliferation of interstice in the kidney accompanied with a high degree of atrophy of the renal tubule, marked increase and lobulation of mesangium ground substance of the glomerulus and mild hypertrophy of arteriole were recognized. Mild degeneration of myocardium was recognized. In the long-term cases passing 29 and 34 weeks after irradiation, blood pressure just before slaughter rose to 250 mmHg. The kidney showed malignant nephrosclerosis-like lesion, and panarteritis was found in the mesentery and peri-pancreatic artery. In the heart, hypertonic myocardosis was recognized. A rise of blood pressure which was observed in this experiment occurred in circulation degenerations resulted from the secondary hypertrophy of the blood vessels accompanied with fibrous proliferation of the interstice which appeared after degeneration of renal tubule. It was thought that panarteritis of cardiovascular system of the whole body, especially mesentery and peri-pancreatic artery, and fibrinoid degeneration of arteriole of the kidney were due to hypertension and angiopathic factors (non-vasopressor extracts from the injured kidney).

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

Digital three-dimensional reconstruction and ultrastructure of the mouse proximal tubule

DEFF Research Database (Denmark)

Zhai, X.Y.; Birn, H.; Jensen, K.B.

2003-01-01

. In the medullary rays, these are arranged in layers outside the clusters of more superficial tubules. In contrast to rat and human kidney, no major segmental variation in the ultrastructure of the proximal tubule was identified, and no parameters enabled definition of distinct segments in this strain of mice......, detailed analyses of normal mouse kidney structure and organization are lacking. This study describes the 3D organization and ultrastructural, segmental variation of the mouse kidney proximal tubule. A total of 160 proximal tubules in three C57/BL/6J mouse kidneys were analyzed on 800 serial sections from...

DIAGNOSIS AND TREATMENT OF A UNILATERAL RENAL CYSTADENOMA IN AN AFRICAN LION (PANTHERA LEO).

Science.gov (United States)

Eustace, Ronan; Rubin, Jacob; Thompson, Kimberly A; Snowdon, Kyle; Sikarskie, James G; Monahan, Colleen; Smedley, Rebecca C

2017-09-01

A renal tubular cystadenoma was diagnosed in a 14-yr-old male African lion (Panthera leo). During a routine health evaluation, a left renal mass was identified via physical examination, radiographs, and abdominal ultrasonography. The mass was 30 × 15 cm in size and had a thin capsule with central hypoechoic fluid, suggestive of a perirenal cyst. An exploratory celiotomy with partial nephrectomy was performed without complications. Histologically, the tumor was characterized by a thick fibrous capsule surrounding multiple, variable-sized cysts that markedly compressed the adjacent fibrotic and atrophied renal cortex. Immunohistochemical labeling for Aquaporin-1 and Tamm-Horsfall protein was consistent with a renal tubular cystadenoma of proximal tubule origin. Renal cystadenomas are an uncommon benign epithelial neoplasm. There are only two documented case reports in domestic cats. This report represents the first documentation, to the authors' knowledge, of a renal cystadenoma in a lion.

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

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.

The renal handling of sodium and water is not affected by the standard-dose cisplatin treatment for testicular cancer

DEFF Research Database (Denmark)

Daugaard, G; Strandgaard, S; Holstein-Rathlou, N H

1987-01-01

Renal clearances of 51Cr-EDTA, lithium, sodium and potassium were measured before and after each of four consecutive treatment series with cisplatin in 15 men with testicular cancer. Since lithium is reabsorbed like sodium and water in the proximal tubules, but not reabsorbed to any measurable...... and all other parameters of glomerular filtration and renal sodium handling remained normal throughout the study (with the exception of a fall in fractional sodium excretion after the first treatment series). Plasma magnesium declined during all four treatment periods, signifying renal magnesium wasting....

17β-estradiol induces non-genomic effects in renal intercalated cells through the G-protein coupled estrogen receptor 1

DEFF Research Database (Denmark)

Hofmeister, Marlene Vind; Damkier, Helle Hasager; Christensen, Birgitte Mønster

2012-01-01

Steroid hormones such as 17β-estradiol (E2) are known to modulate ion transporter expression in the kidney through classic intracellular receptors. Steroid hormones are also known to cause rapid nongenomic responses in a variety of nonrenal tissues. However, little is known about renal short......-term effects of steroid hormones. Here, we studied the acute actions of E2 on intracellular Ca(2+) signaling in isolated distal convoluted tubules (DCT2), connecting tubules (CNT), and initial cortical collecting ducts (iCCD) by fluo 4 fluorometry. Physiological concentrations of E2 induced transient increases...

Effects of vasopressin on the isolated perfused human collecting tubule.

Science.gov (United States)

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.

Renal expression of FGF23 in progressive renal disease of diabetes and the effect of ACE inhibitor.

Directory of Open Access Journals (Sweden)

Cristina Zanchi

Full Text Available Fibroblast growth factor 23 (FGF23 is a phosphaturic hormone mainly produced by bone that acts in the kidney through FGF receptors and Klotho. Here we investigated whether the kidney was an additional source of FGF23 during renal disease using a model of type 2 diabetic nephropathy. Renal expression of FGF23 and Klotho was assessed in Zucker diabetic fatty (ZDF and control lean rats at 2, 4, 6, 8 months of age. To evaluate whether the renoprotective effect of angiotensin converting enzyme (ACE inhibitor in this model was associated with changes in FGF23 and Klotho, ZDF rats received ramipril from 4, when proteinuric, to 8 months of age. FGF23 mRNA was not detectable in the kidney of lean rats, nor of ZDF rats at 2 months of age. FGF23 became measurable in the kidney of diabetic rats at 4 months and significantly increased thereafter. FGF23 protein localized in proximal and distal tubules. Renal Klotho mRNA and protein decreased during time in ZDF rats. As renal disease progressed, serum phosphate levels increased in parallel with decline of fractional phosphorus excretion. Ramipril limited proteinuria and renal injury, attenuated renal FGF23 upregulation and ameliorated Klotho expression. Ramipril normalized serum phosphate levels and tended to increase fractional phosphorus excretion. These data indicate that during progressive renal disease the kidney is a site of FGF23 production which is limited by ACE inhibition. Interfering pharmacologically with the delicate balance of FGF23 and phosphorus in diabetes may have implications in clinics.

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

Science.gov (United States)

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

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

The normal and pathologic renal medulla: a comprehensive overview.

Science.gov (United States)

López, José I; Larrinaga, Gorka; Kuroda, Naoto; Angulo, Javier C

2015-04-01

The renal medulla comprises an intricate system of tubules, blood vessels and interstitium that is not well understood by most general pathologists. We conducted an extensive review of the literature on the renal medulla, in both normal and pathologic conditions. We set out in detail the points of key interest to pathologists: normal and pathological development, physiology, microscopic anatomy, histology and immunohistochemistry; and the specific and most common other types of disease associated with this part of the kidney: developmental abnormalities, (multicystic dysplastic kidney, autosomal dominant and recessive polycystic kidney diseases, medullary cystic kidney disease), inflammatory conditions (xanthogranulomatous pyelonephritis, malakoplakia), hyperplasia and dysplasia, and neoplastic processes (oncocytoma, atypical oncocytic tumors, chromophobe cell carcinoma, collecting duct carcinoma, urothelial carcinoma, other carcinomas, renal medullary fibroma and metastatic tumors). This condensed overview of the origin, function and pathology of the renal medulla, both in terms of development, inflammation and neoplastic processes, should help focus the interest of clinical pathologists on this widely overlooked part of the kidney. Copyright © 2014 Elsevier GmbH. All rights reserved.

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....

The Role of Compounds Derived from Natural Supplement as Anticancer Agents in Renal Cell Carcinoma: A Review

OpenAIRE

Haque, Inamul; Subramanian, Arvind; Huang, Chao H.; Godwin, Andrew K.; Van Veldhuizen, Peter J.; Banerjee, Snigdha; Banerjee, Sushanta K.

2017-01-01

Renal Cell Carcinoma (RCC) is the most prominent kidney cancer derived from renal tubules and accounts for roughly 85% of all malignant kidney cancer. Every year, over 60,000 new cases are registered, and about 14,000 people die from RCC. The incidence of this has been increasing significantly in the U.S. and other countries. An increased understanding of molecular biology and the genomics of RCC has uncovered several signaling pathways involved in the progression of this cancer. Significant ...

In vivo model for microbial invasion of tooth root dentinal tubules

Directory of Open Access Journals (Sweden)

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.

Intra-Abdominal Cooling System Limits Ischemia-Reperfusion Injury During Robot-Assisted Renal Transplantation.

Science.gov (United States)

Meier, R P H; Piller, V; Hagen, M E; Joliat, C; Buchs, J-B; Nastasi, A; Ruttimann, R; Buchs, N C; Moll, S; Vallée, J-P; Lazeyras, F; Morel, P; Bühler, L

2018-01-01

Robot-assisted kidney transplantation is feasible; however, concerns have been raised about possible increases in warm ischemia times. We describe a novel intra-abdominal cooling system to continuously cool the kidney during the procedure. Porcine kidneys were procured by standard open technique. Groups were as follows: Robotic renal transplantation with (n = 11) and without (n = 6) continuous intra-abdominal cooling and conventional open technique with intermittent 4°C saline cooling (n = 6). Renal cortex temperature, magnetic resonance imaging, and histology were analyzed. Robotic renal transplantation required a longer anastomosis time, either with or without the cooling system, compared to the open approach (70.4 ± 17.7 min and 74.0 ± 21.5 min vs. 48.7 ± 11.2 min, p-values system compared to the open approach group (6.5 ± 3.1°C vs. 22.5 ± 6.5°C; p = 0.001) or compared to the robotic group without the cooling system (28.7 ± 3.3°C; p system that suppresses the noncontrolled rewarming of donor kidneys during the transplant procedure and prevents ischemia-reperfusion injuries. © 2017 The Authors. American Journal of Transplantation published by Wiley Periodicals, Inc. on behalf of American Society of Transplant Surgeons.

Studies of the mechanism of contralateral polyuria after renal artery stenosis.

Science.gov (United States)

Galvez, O G; Roberts, B W; Mishkind, M H; Bay, W H; Ferris, T F

1977-01-01

Acute renal artery stenosis in hydropenic dogs caused a contralateral increase in urine volume and free water clearance without change in glomerular filtration, renal blood flow, or osmolar clearance. The increase in urine volume was not dependent on the development of hypertension since it occurred in animals pretreated with trimethaphan but was dependent upon angiotensin since it was presented with angiotensin blockade with Saralasin. The effect was not caused by angiotensin inhibiting antidiuretic hormone release since the polyuria occurred in hypophysectomized animals receiving a constant infusion of 10 muU/kg per min of aqueous Pitressin. Since the rise in urine volume was associated with an increase in renal vein prostaglandin E concentration and was prevented by pretreatment with indomethacin (5 mg/kg) the results suggest that the rise in plasma angiotensin after renal artery stenosis causes an increase in contralateral prostaglandin E synthesis with resultant antagonism to antidiuretic hormone at the collecting tubule. PMID:845253

Histochemical Study of the Progenetic Trematode Alloglossidium renale

Directory of Open Access Journals (Sweden)

Craig A. Schimmer

2014-01-01

Full Text Available A histochemical study of the progenetic trematode Alloglossidium renale has demonstrated the absence of any secreted material between the adult worm and the host (freshwater shrimp antennal gland tubules. Host tissue is affected only by the compression, abrasion, and ingestion by the parasite, and host tubule cells near the worm have the same staining patterns as those distant from the parasite. The trematode sometimes dies within the host, leaving a necrotic mass whose histochemical staining differs significantly from the living organism. In the necrotic mass, the only recognizable features were the ova and the vitellarium, which atrophied and resulted in tyrosine-positive staining within the mass. A melanin reaction was not observed in the host using a specialized ferro-ferricyanide stain. The only apparent host response to infection was a layer of damaged squamous host cells adhering to the necrotic worm. The results confirm benign host-parasite effects and a highly evolved relationship between the host and parasite, perhaps bordering on commensalism.

Impact of ventricular assist device placement on longitudinal renal function in children with end-stage heart failure.

Science.gov (United States)

May, Lindsay J; Montez-Rath, Maria E; Yeh, Justin; Axelrod, David M; Chen, Sharon; Maeda, Katsuhide; Almond, Christopher S D; Rosenthal, David N; Hollander, Seth A; Sutherland, Scott M

2016-04-01

Although ventricular assist devices (VADs) restore hemodynamics in those with heart failure, reversibility of end-organ dysfunction with VAD support is not well characterized. Renal function often improves in adults after VAD placement, but this has not been comprehensively explored in children. Sixty-three children on VAD support were studied. Acute kidney injury (AKI) was defined by Kidney Disease: Improving Global Outcomes criteria. Estimated glomerular filtration rate (eGFR) was determined by the Schwartz method. Generalized linear mixed-effects models compared the pre-VAD and post-VAD eGFR for the cohort and sub-groups with and without pre-VAD renal dysfunction (pre-VAD eGFR renal dysfunction. AKI affected 60.3% (38 of 63), with similar rates in those with and without pre-existing renal dysfunction. Within the cohort, the nadir eGFR occurred 1 day post-operatively (62.9 ml/min/1.73 m(2); IQR, 51.2-88.9 ml/min/1.73 m(2); p renal dysfunction experienced the greatest improvement in the eGFR (β = 0.0051 vs β = 0.0013, p Renal dysfunction is prevalent in children with heart failure undergoing VAD placement. Although peri-operative AKI is common, renal function improves substantially in the first post-operative week and for months thereafter. This is particularly pronounced in those with pre-VAD renal impairment, suggesting that VADs may facilitate recovery and maintenance of kidney function in children with advanced heart failure. Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Effects of sirolimus alone or in combination with cyclosporine A on renal ischemia/reperfusion injury

Directory of Open Access Journals (Sweden)

B.J. Pereira

2010-08-01

Full Text Available Calcineurin inhibitors exacerbate ischemic injury in transplanted kidneys, but it is not known if sirolimus protects or exacerbates the transplanted kidney from ischemic injury. We determined the effects of sirolimus alone or in combination with cyclosporin A (CsA on oxygenated and hypoxic/reoxygenated rat proximal tubules in the following in vitro groups containing 6-9 rats per group: sirolimus (10, 50, 100, 250, 500, and 1000 ηg/mL; CsA (100 µg/mL; sirolimus (50 and 250 ηg/mL + CsA (100 µg/mL; control; vehicle (20% ethanol. For in vivo studies, 3-week-old Wistar rats (150-250 g were submitted to left nephrectomy and 30-min renal artery clamping. Renal function and histological evaluation were performed 24 h and 7 days after ischemia (I in five groups: sham, I, I + SRL (3 mg·kg-1·day-1, po, I + CsA (3 mg·kg-1·day-1, sc, I + SRL + CsA. Sirolimus did not injure oxygenated or hypoxic/reoxygenated proximal tubules and did not potentiate the tubular toxic effects of CsA. Neither drug affected the glomerular filtration rate (GFR at 24 h. GFR was reduced in CsA-treated rats on day 7 (0.5 ± 0.1 mL/min but not in rats receiving sirolimus + CsA (0.8 ± 0.1 mL/min despite the reduction in renal blood flow (3.9 ± 0.5 mL/min. Acute tubular necrosis regeneration was similar for all groups. Sirolimus alone was not toxic and did not enhance hypoxia/reoxygenation injury or CsA toxicity to proximal tubules. Despite its hemodynamic effects, sirolimus protected post-ischemic kidneys against CsA toxicity.

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

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

Directory of Open Access Journals (Sweden)

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.

Calpastatin overexpression prevents progression of S-1,2-dichlorovinyl-L-cysteine (DCVC)-initiated acute renal injury and renal failure (ARF) in diabetes

International Nuclear Information System (INIS)

Dnyanmote, Ankur V.; Sawant, Sharmilee P.; Lock, Edward A.; Latendresse, John R.; Warbritton, Alan A.; Mehendale, Harihara M.

2006-01-01

Previously we have shown that 90% of streptozotocin (STZ)-induced type-1 diabetic (DB) mice survive from acute renal failure (ARF) and death induced by a normally LD 9 dose (75 mg/kg, i.p.) of the nephrotoxicant S-1,2-dichlorovinyl-L-cysteine (DCVC). This remarkable protection is due to a combination of slower progression of DCVC-initiated renal injury and increased compensatory nephrogenic tissue repair in the DB kidneys. BRDU immunohistochemistry revealed that the DB condition led to 4-fold higher number of proximal tubular cells (PTC) entering S-phase of cell cycle. In the present study, we tested the hypothesis that DB-induced augmentation of PTC into S-phase is accompanied by overexpression of the calpain-inhibitor calpastatin, which endogenously prevents the progression of DCVC-initiated renal injury mediated by the calpain escaping out of damaged PTCs. Immunohistochemical detection of renal calpain and its activity in the urine, over a time course after treatment with the LD 9 dose of DCVC, indicated progressive increase in leakage of calpain into the extracellular spaces of the injured PTCs of the non-diabetic (NDB) kidneys as compared to the DB kidneys. Calpastatin expression was minimally detected in the NDB kidneys, using immunohistochemistry, over the time course. On the other hand, consistently higher number of tubules in the DB kidney showed calpastatin expression over the time course. The lower leakage of calpain in the DB kidneys was commensurate with constitutively higher expression of calpastatin in the S-phase-laden PTCs of these mice. To test the protective role of newly divided/dividing PTCs, DB mice were given the anti-mitotic agent colchicine (CLC) (2 mg/kg and 1.5 mg/kg, i.p., on days 8 and 10 after STZ injection) prior to challenge with a LD 9 dose of DCVC, which led to 100% mortality by 48 h. Mortality was due to rapid progression of DCVC-initiated renal injury, suggesting that newly divided/dividing cells are instrumental in mitigating

Homer W. Smith's contribution to renal physiology.

Science.gov (United States)

Giebisch, Gerhard

2004-01-01

Homer Smith was, for three decades, from the 1930s until his death in 1962, one of the leaders in the field of renal physiology. His contributions were many: he played a major role in introducing and popularizing renal clearance methods, introduced non-invasive methods for the measurement of glomerular filtration rate, of renal blood flow and tubular transport capacity, and provided novel insights into the mechanisms of excretion of water and electrolytes. Homer Smith's contributions went far beyond his personal investigations. He was a superb writer of several inspiring textbooks of renal physiology that exerted great and lasting influence on the development of renal physiology. Smith's intellectual insights and ability for critical analysis of data allowed him to create broad concepts that defined the functional properties of glomeruli, tubules and the renal circulation. A distinguishing feature of Homer Smith's career was his close contact and collaboration, over many years, with several clinicians of his alma mater, New York University. For initiating these pathophysiological investigations, he is justly credited to have advanced, in a major way, our understanding of altered renal function in disease. Smith's lasting scientific impact is also reflected by a whole school of investigators that trained with him and who applied his methods, analyses and concepts to the study of renal function all over the world. So great was his influence and preeminence that Robert Pitts, in his excellent tribute to Homer Smith in the Memoirs of the National Academy of Science states that his death brought an end to what might be aptly called the Smithian Era of renal physiology.

Metrizamide in experimental selective renal angiography

International Nuclear Information System (INIS)

Pokorny, L.; Kelemen, J.

1981-01-01

Forty-seven dogs or seventy-four kidneys, respectively, were used in studies into the activity of metrizamide (Amipaque). The angiograms were of good quality; as compared with contrast media tested before, the incidence of abnormalities was somewhat lower, and the symptoms (spasm, inhomogeneous nephrogram) were less important. Histological examination showed that plenty of homogeneous pink proteinlike substance had accumulated in many tubules as well as in the lumen of the Bowman's capsules; fibroses were seen in several parts after 7 and 28 days, respectively. However, the evaluation of the renal function showed no considerable changes in the laboratory values. (orig.) [de

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

Science.gov (United States)

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.

Comparative study of unilateral renal tubule function using 131I-o-hippuran and sup(99m)Tc-dimercaptosuccinic acid with regard to renal depth and excretion relations

International Nuclear Information System (INIS)

Moser, E.A.

1980-01-01

Good agreement was found between sonographic and nuclear renal depth data. In patients with undisturbed postrenal urodynamics, the data of unilateral renal clearance obtained by DMSA and OIH are in good agreement after depth correction. With OIH, the activity measured for unilateral congestion kidneys was higher than with DMSA. However, both methods may overestimate unilateral congestion kidneys. The OIH method should be favoured in nuclear renal diagnostics. In patients with mobile kidneys, the lower function calculated for the ptotic kidney can be evaluated only after depth correction. To reduce the radiation exposure, renal depth data required for depth correction should be determined by sonographic methods. The peak/scatter method of renal depth determination cannot be employed in practice in the 131 J hippurane test; in the sup(99m)Tc-DMSA test, sufficient agreement between peak/scatter quotient and renal depth is only obtained after background correction. The result does not warrant the tedious procedure. DMSA studies of the kidneys are appropriate in the following cases: 1. Emergency studies of unilateral renal function in cases of acute anuria due to postrenal stoppage. 2. Assessment of unilateral parenchymal function in patients with mobile kidneys if the ptotic kidney cannot be imaged by sonographic processes. 3. Search for extremely displaced renal tissue. 4. Unilateral renal function studies in patients with unilateral kidney diseases if the postrenal situation and the global renal function can be assessed by other methods. (orig./MG) [de

Renal 99M-technetium dimercaptosuccinic acid scintigraphy

International Nuclear Information System (INIS)

Ajdinovic, B.; Jaukovic, L.; Jankovic, Z.; Krstic, Z.

2004-01-01

99m-Technetium dimercaptosuccinic acid (99mTc-DMSA) whose ligand was used as a radioprotective agent and as a chelating compound for metal poisoning was reported to be an excellent renal imaging agent. As 99mTc-DMSA concentrates actively in the proximal convoluted tubule, it gives an image functional renal mass. Its integrity is dependent upon several factors, predominently intrarenal blood flow and intact enzyme function.Considering low radiation dose delivered by 99mTc DMSA and wide pediatric use of this radiopharmaceutical we calculate abnormal findings incidence (%).Results of 592 99m Tc-DMSA renal scintigraphy (348 children), which were classified as: 1. normal, 2. probably normal, 3. equivocal, 4. probably abnormal, 5. abnormal, are presented.Normal results were found in 269 patients (45,4%), 25% of whom was normal and 75% probably normal. Equivocal findings were found in 47 patients (7,9%). Abnormal results were presented in 276 patients (82% abnormal, 18% probably abnormal).The highest abnormal findings incidence was found in patients with congenital anomaly (88%), calculosis (87%) and policystic renal disease (79,3%). The lowest abnormal findings percentage was present in patients with urinary tract infection (12,9%) and arterial hypertension (17,3%)The role 99mTc-DMSA renal scintigraphy in pathology is clear in pyelonephrifis, hydronephrotic kidneys, and pediatric disease (urinary tract infections, congenital anomalies) and is confirmed by our results. (authors)

Mechanism of renal excretion of creatinine by the pony

International Nuclear Information System (INIS)

Finco, D.R.; Groves, C.

1985-01-01

Free-flow and stop-flow procedures conducted on 2 female and 2 testosterone-treated castrated male ponies indicated that [ 14 C]inulin and exogenous creatinine clearance values were the same. These results indicated that creatinine was neither reabsorbed nor secreted by the renal tubules and that exogenous creatinine clearance was an accurate method for determining glomerular filtration rate. As in other species which have been studied, endogenous creatinine clearance probably underestimated glomerular filtration rate because of the presence of noncreatinine chromogens in plasma

Differences in dynamic autoregulation of renal blood flow between SHR and WKY rats

DEFF Research Database (Denmark)

Chen, Y M; Holstein-Rathlou, N H

1993-01-01

by chaotic fluctuations. We sought to determine whether this change was associated with a change in the dynamic autoregulation of renal blood flow. In halothane-anesthetized 250- to 320-g SHR and WKY rats, renal blood flow was measured during "white noise" forcing of arterial blood pressure. The frequency...... conclude that the change in the dynamics of TGF leads to a change in the dynamic autoregulation of renal blood flow between SHR and WKY rats. This change results in a more efficient dynamic autoregulation of renal blood flow in the SHR compared with the WKY rats. The functional consequences of this......In halothane-anesthetized Wistar-Kyoto (WKY) rats the single-nephron blood flow and the proximal tubule pressure oscillate at a frequency of 35-50 mHz because of the operation of the tubuloglomerular feedback (TGF) mechanism. In spontaneously hypertensive rats (SHR) the oscillations are replaced...

76 FR 36349 - Diethylene Glycol MonoEthyl Ether (DEGEE); Exemption From the Requirement of a Tolerance

Science.gov (United States)

2011-06-22

..., based on decreased growth, epithelial necrosis of renal tubules and cloudy swelling of hepatic tissue... growth, FQPA SF = 1x epithelial necrosis of renal tubules and cloudy swelling of hepatic tissue... calculi, epithelial necrosis of the renal tubules and cloudy swelling of hepatic tissue were observed in...

Sistematização da Assistência de Enfermagem ao portador de Diabetes Mellitus e Insuficiência Renal Crônica Sistematización de la Asistencia de Enfermería al portador de Diabetes Mellitus y Insuficiencia Renal Systematization of Nursing Assistance to patients with Diabetes Mellitus and Chronic Renal

Directory of Open Access Journals (Sweden)

Nildo Batista Mascarenhas

2011-02-01

Full Text Available Tratou-se de um estudo de caso clínico desenvolvido durante as atividades práticas da disciplina Enfermagem Clínico-Cirúrgica I, do curso de Graduação em Enfermagem de uma universidade pública do Estado da Bahia, que objetivou relatar a aplicação da Sistematização da Assistência de Enfermagem na assistência a um paciente portador de Diabetes Mellitus e Insuficiência Renal Crônica. Com o desenvolvimento do estudo, em especial após a melhora positiva da paciente face às condutas planejadas e implementadas e, considerando as reflexões que emergiram, foi possível constatar a necessidade da interface entre a Sistematização da Assistência de Enfermagem, equipe de enfermagem e paciente no processo do cuidar, frente à excelência e singularidade dos cuidados de enfermagemEste es un estudio de caso desarrollado durante las actividades prácticas de la disciplina de Enfermería Clínica Quirúrgica I, del curso de Grado en Enfermería en una universidad pública del Estado de Bahía, que tuvo por objetivo relatar la aplicación de la Sistematización de la Asistencia de Enfermería (SAE en asistencia a un paciente conducir a la Diabetes Mellitus y la Insuficiencia Renal Crónica. Con el desarrollo del estudio, sobre todo después de la mejora positiva del paciente, se enfrentan para llevar a cabo y planifiquen y ejecuten teniendo en cuenta las ideas que surgieron, es posible ver la necesidad de interfaz entre la Sistematización de la Asistencia de Enfermería y el personal de enfermería y el paciente en el proceso de atención, en la excelencia y la singularidad de los cuidados de enfermeríaThis is a clinical case study developed during the practical activities of the discipline Surgical Clinical Nursing I, of course of Graduation in Nursing of a public university of Bahia State, that aimed to report the application of the Systematization of Nursing Assistance in the assistance to a client whit Diabetes Mellitus and Chronic Renal

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.

Manifestations of Renal Impairment in Fructose-induced Metabolic Syndrome.

Science.gov (United States)

Bratoeva, Kameliya; Stoyanov, George S; Merdzhanova, Albena; Radanova, Mariya

2017-11-07

Introduction International studies show an increased incidence of chronic kidney disease (CKD) in patients with metabolic syndrome (MS). It is assumed that the major components of MS - obesity, insulin resistance, dyslipidemia, and hypertension - are linked to renal damage through the systemic release of several pro-inflammatory mediators, such as uric acid (UA), C-reactive protein (CRP), and generalized oxidative stress. The aim of the present study was to investigate the extent of kidney impairment and manifestations of dysfunction in rats with fructose-induced MS. Methods We used a model of high-fructose diet in male Wistar rats with 35% glucose-fructose corn syrup in drinking water over a duration of 16 weeks. The experimental animals were divided into two groups: control and high-fructose drinking (HFD). Serum samples were obtained from both groups for laboratory study, and the kidneys were extracted for observation via light microscopy examination. Results All HFD rats developed obesity, hyperglycemia, hypertriglyceridemia, increased levels of CRP and UA (when compared to the control group), and oxidative stress with high levels of malondialdehyde and low levels of reduced glutathione. The kidneys of the HFD group revealed a significant increase in kidney weight in the absence of evidence of renal dysfunction and electrolyte disturbances. Under light microscopy, the kidneys of the HFD group revealed amyloid deposits in Kimmelstiel-Wilson-like nodules and the walls of the large caliber blood vessels, early-stage atherosclerosis with visible ruptures and scarring, hydropic change (vacuolar degeneration) in the epithelial cells covering the proximal tubules, and increased eosinophilia in the distant tubules when compared to the control group. Conclusion Under the conditions of a fructose-induced metabolic syndrome, high serum UA and CRP correlate to the development of early renal disorders without a clinical manifestation of renal dysfunction. These

MAP17 Is a Necessary Activator of Renal Na+/Glucose Cotransporter SGLT2

Science.gov (United States)

Coady, Michael J.; El Tarazi, Abdulah; Santer, René; Bissonnette, Pierre; Sasseville, Louis J.; Calado, Joaquim; Lussier, Yoann; Dumayne, Christopher; Bichet, Daniel G.

2017-01-01

The renal proximal tubule reabsorbs 90% of the filtered glucose load through the Na+-coupled glucose transporter SGLT2, and specific inhibitors of SGLT2 are now available to patients with diabetes to increase urinary glucose excretion. Using expression cloning, we identified an accessory protein, 17 kDa membrane-associated protein (MAP17), that increased SGLT2 activity in RNA-injected Xenopus oocytes by two orders of magnitude. Significant stimulation of SGLT2 activity also occurred in opossum kidney cells cotransfected with SGLT2 and MAP17. Notably, transfection with MAP17 did not change the quantity of SGLT2 protein at the cell surface in either cell type. To confirm the physiologic relevance of the MAP17–SGLT2 interaction, we studied a cohort of 60 individuals with familial renal glucosuria. One patient without any identifiable mutation in the SGLT2 coding gene (SLC5A2) displayed homozygosity for a splicing mutation (c.176+1G>A) in the MAP17 coding gene (PDZK1IP1). In the proximal tubule and in other tissues, MAP17 is known to interact with PDZK1, a scaffolding protein linked to other transporters, including Na+/H+ exchanger 3, and to signaling pathways, such as the A-kinase anchor protein 2/protein kinase A pathway. Thus, these results provide the basis for a more thorough characterization of SGLT2 which would include the possible effects of its inhibition on colocalized renal transporters. PMID:27288013

Computer tomography urography assisted real-time ultrasound-guided percutaneous nephrolithotomy on renal calculus.

Science.gov (United States)

Fang, You-Qiang; Wu, Jie-Ying; Li, Teng-Cheng; Zheng, Hao-Feng; Liang, Guan-Can; Chen, Yan-Xiong; Hong, Xiao-Bin; Cai, Wei-Zhong; Zang, Zhi-Jun; Di, Jin-Ming

2017-06-01

This study aimed to assess the role of pre-designed route on computer tomography urography (CTU) in the ultrasound-guided percutaneous nephrolithotomy (PCNL) for renal calculus.From August 2013 to May 2016, a total of 100 patients diagnosed with complex renal calculus in our hospital were randomly divided into CTU group and control group (without CTU assistance). CTU was used to design a rational route for puncturing in CTU group. Ultrasound was used in both groups to establish a working trace in the operation areas. Patients' perioperative parameters and postoperative complications were recorded.All operations were successfully performed, without transferring to open surgery. Time of channel establishment in CTU group (6.5 ± 4.3 minutes) was shorter than the control group (10.0 ± 6.7 minutes) (P = .002). In addition, there was shorter operation time, lower rates of blood transfusion, secondary operation, and less establishing channels. The incidence of postoperative complications including residual stones, sepsis, severe hemorrhage, and perirenal hematoma was lower in CTU group than in control group.Pre-designing puncture route on CTU images would improve the puncturing accuracy, lessen establishing channels as well as improve the security in the ultrasound-guided PCNL for complex renal calculus, but at the cost of increased radiation exposure.

Mechanisms of adaptation to chronic respiratory acidosis in the rabbit proximal tubule.

OpenAIRE

Krapf, R

1989-01-01

The hyperbicarbonatemia of chronic respiratory acidosis is maintained by enhanced bicarbonate reabsorption in the proximal tubule. To investigate the cellular mechanisms involved in this adaptation, cell and luminal pH were measured microfluorometrically using (2",7')-bis(carboxyethyl)-(5,6)-carboxyfluorescein in isolated, microperfused S2 proximal convoluted tubules from control and acidotic rabbits. Chronic respiratory acidosis was induced by exposure to 10% CO2 for 52-56 h. Tubules from ac...

Characterization of Organic Anion Transporter 2 (SLC22A7): A Highly Efficient Transporter for Creatinine and Species-Dependent Renal Tubular Expression.

Science.gov (United States)

Shen, Hong; Liu, Tongtong; Morse, Bridget L; Zhao, Yue; Zhang, Yueping; Qiu, Xi; Chen, Cliff; Lewin, Anne C; Wang, Xi-Tao; Liu, Guowen; Christopher, Lisa J; Marathe, Punit; Lai, Yurong

2015-07-01

The contribution of organic anion transporter OAT2 (SLC22A7) to the renal tubular secretion of creatinine and its exact localization in the kidney are reportedly controversial. In the present investigation, the transport of creatinine was assessed in human embryonic kidney (HEK) cells that stably expressed human OAT2 (OAT2-HEK) and isolated human renal proximal tubule cells (HRPTCs). The tubular localization of OAT2 in human, monkey, and rat kidney was characterized. The overexpression of OAT2 significantly enhanced the uptake of creatinine in OAT2-HEK cells. Under physiologic conditions (creatinine concentrations of 41.2 and 123.5 µM), the initial rate of OAT2-mediated creatinine transport was approximately 11-, 80-, and 80-fold higher than OCT2, multidrug and toxin extrusion protein (MATE)1, and MATE2K, respectively, resulting in approximately 37-, 1850-, and 80-fold increase of the intrinsic transport clearance when normalized to the transporter protein concentrations. Creatinine intracellular uptake and transcellular transport in HRPTCs were decreased in the presence of 50 µM bromosulfophthalein and 100 µM indomethacin, which inhibited OAT2 more potently than other known creatinine transporters, OCT2 and multidrug and toxin extrusion proteins MATE1 and MATE2K (IC50: 1.3 µM vs. > 100 µM and 2.1 µM vs. > 200 µM for bromosulfophthalein and indomethacin, respectively) Immunohistochemistry analysis showed that OAT2 protein was localized to both basolateral and apical membranes of human and cynomolgus monkey renal proximal tubules, but appeared only on the apical membrane of rat proximal tubules. Collectively, the findings revealed the important role of OAT2 in renal secretion and possible reabsorption of creatinine and suggested a molecular basis for potential species difference in the transporter handling of creatinine. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

DHEA-induced modulation of renal gluconeogenesis, insulin sensitivity and plasma lipid profile in the control- and dexamethasone-treated rabbits. Metabolic studies.

Science.gov (United States)

Kiersztan, Anna; Nagalski, Andrzej; Nalepa, Paweł; Tempes, Aleksandra; Trojan, Nina; Usarek, Michał; Jagielski, Adam K

2016-02-01

In view of antidiabetic and antiglucocorticoid effects of dehydroepiandrosterone (DHEA) both in vitro and in vivo studies were undertaken: (i) to elucidate the mechanism of action of both dexamethasone phosphate (dexP) and DHEA on glucose synthesis in primary cultured rabbit kidney-cortex tubules and (ii) to investigate the influence of DHEA on glucose synthesis, insulin sensitivity and plasma lipid profile in the control- and dexP-treated rabbits. Data show, that in cultured kidney-cortex tubules dexP significantly stimulated gluconeogenesis by increasing flux through fructose-1,6-bisphosphatase (FBPase). DexP-induced effects were dependent only upon glucocorticoid receptor. DHEA decreased glucose synthesis via inhibition of glucose-6-phosphatase (G6Pase) and suppressed the dexP-induced stimulation of renal gluconeogenesis. Studies with the use of inhibitors of DHEA metabolism in cultured renal tubules showed for the first time that DHEA directly affects renal gluconeogenesis. However, in view of analysis of glucocorticoids and DHEA metabolites levels in urine, it seems likely, that testosterone may also contribute to DHEA-evoked effects. In dexP-treated rabbits, plasma glucose level was not altered despite increased renal and hepatic FBPase and G6Pase activities, while a significant elevation of both plasma insulin and HOMA-IR was accompanied by a decline of ISI index. It thus appears that increased insulin levels were required to maintain normoglycaemia and to compensate the insulin resistance. DHEA alone affected neither plasma glucose nor lipid levels, while it increased insulin sensitivity and diminished both renal and hepatic G6Pase activities. Surprisingly, DHEA co-administrated with dexP did not alter insulin sensitivity, while it partially suppressed the dexP-induced elevation of renal G6Pase activity and plasma cholesterol and triglyceride contents. As (i) gluconeogenic pathway in rabbit is similar to that in human, and (ii) DHEA counteracts several

Thiazolidinediones and Edema: Recent Advances in the Pathogenesis of Thiazolidinediones-Induced Renal Sodium Retention.

Science.gov (United States)

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

2015-01-01

Thiazolidinediones (TZDs) are one of the major classes of antidiabetic drugs that are used widely. TZDs improve insulin resistance by activating peroxisome proliferator-activated receptor gamma (PPARγ) and ameliorate diabetic and other nephropathies, at least, in experimental animals. However, TZDs have side effects, such as edema, congestive heart failure, and bone fracture, and may increase bladder cancer risk. Edema and heart failure, which both probably originate from renal sodium retention, are of great importance because these side effects make it difficult to continue the use of TZDs. However, the pathogenesis of edema remains a matter of controversy. Initially, upregulation of the epithelial sodium channel (ENaC) in the collecting ducts by TZDs was thought to be the primary cause of edema. However, the results of other studies do not support this view. Recent data suggest the involvement of transporters in the proximal tubule, such as sodium-bicarbonate cotransporter and sodium-proton exchanger. Other studies have suggested that sodium-potassium-chloride cotransporter 2 in the thick ascending limb of Henle and aquaporins are also possible targets for TZDs. This paper will discuss the recent advances in the pathogenesis of TZD-induced sodium reabsorption in the renal tubules and edema.

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

Directory of Open Access Journals (Sweden)

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.

Endovascular MR-guided Renal Embolization by Using a Magnetically Assisted Remote-controlled Catheter System.

Science.gov (United States)

Lillaney, Prasheel V; Yang, Jeffrey K; Losey, Aaron D; Martin, Alastair J; Cooke, Daniel L; Thorne, Bradford R H; Barry, David C; Chu, Andrew; Stillson, Carol; Do, Loi; Arenson, Ronald L; Saeed, Maythem; Wilson, Mark W; Hetts, Steven W

2016-10-01

Purpose To assess the feasibility of a magnetically assisted remote-controlled (MARC) catheter system under magnetic resonance (MR) imaging guidance for performing a simple endovascular procedure (ie, renal artery embolization) in vivo and to compare with x-ray guidance to determine the value of MR imaging guidance and the specific areas where the MARC system can be improved. Materials and Methods In concordance with the Institutional Animal Care and Use Committee protocol, in vivo renal artery navigation and embolization were tested in three farm pigs (mean weight 43 kg ± 2 [standard deviation]) under real-time MR imaging at 1.5 T. The MARC catheter device was constructed by using an intramural copper-braided catheter connected to a laser-lithographed saddle coil at the distal tip. Interventionalists controlled an in-room cart that delivered electrical current to deflect the catheter in the MR imager. Contralateral kidneys were similarly embolized under x-ray guidance by using standard clinical catheters and guidewires. Changes in renal artery flow and perfusion were measured before and after embolization by using velocity-encoded and perfusion MR imaging. Catheter navigation times, renal parenchymal perfusion, and renal artery flow rates were measured for MR-guided and x-ray-guided embolization procedures and are presented as means ± standard deviation in this pilot study. Results Embolization was successful in all six kidneys under both x-ray and MR imaging guidance. Mean catheterization time with MR guidance was 93 seconds ± 56, compared with 60 seconds ± 22 for x-ray guidance. Mean changes in perfusion rates were 4.9 au/sec ± 0.8 versus 4.6 au/sec ± 0.6, and mean changes in renal flow rate were 2.1 mL/min/g ± 0.2 versus 1.9 mL/min/g ± 0.2 with MR imaging and x-ray guidance, respectively. Conclusion The MARC catheter system is feasible for renal artery catheterization and embolization under real-time MR imaging in vivo, and quantitative physiologic

Diminished renal urea excretion in the llama at reduced food intake

International Nuclear Information System (INIS)

Engelhardt, W.; Engelhardt, W. von

1976-01-01

Renal urea excretion was studied in three llamas under various feeding conditions. Glomerular filtration rate (GFR) was estimated from inulin clearance. Tubular reabsorbed urea was the difference between glomerular filtered and renal excreted urea. Plasma urea concentration increased significantly when feeding was reduced by 40% and 60%, not applicable to a straw diet. With reduced hay feeding and on a straw diet only a slight and insignificant decrease was observed in renal urea excretion, with only a 3% lowering in GFR and glomerular filtered urea. With a straw diet, the glomerular filtered urea was significantly below the controls. The fraction of filtered urea reabsorbed in the tubules was constant (36%-47%). Very high reabsorption (87%) on a supplemented straw dietwas observed in one llama which after nearly 6 months on this low protein diet - could be shown to have lost only 5% of its body weight

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

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.

Unilateral Renal Ischemia as a Model of Acute Kidney Injury and Renal Fibrosis in Cats.

Science.gov (United States)

Schmiedt, C W; Brainard, B M; Hinson, W; Brown, S A; Brown, C A

2016-01-01

The objectives of this study were to define the acute and chronic effects of 1-hour unilateral in vivo renal ischemia on renal function and histology in cats. Twenty-one adult purpose-bred research cats were anesthetized, and 1 kidney underwent renal artery and vein occlusion for 1 hour. Serum creatinine and urea concentrations, urine protein:creatinine ratio, urine-specific gravity, glomerular filtration rate, hematocrit, platelet concentration and function, and white blood cell count were measured at baseline and variable time points after ischemia. Renal histopathology was evaluated on days 3, 6, 12, 21, 42, and 70 postischemia; changes in smooth muscle actin and interstitial collagen were examined. Following ischemia, whole animal glomerular filtration rate was significantly reduced (57% of baseline on day 6; P < .05). At the early time points, the ischemic kidneys exhibited severe acute epithelial necrosis accompanied by evidence of regeneration of tubules predominantly within the corticomedullary junction. At later periods, postischemic kidneys had evidence of tubular atrophy and interstitial inflammation with significantly more smooth muscle actin and interstitial collagen staining and interstitial fibrosis when compared with the contralateral control kidneys. This study characterizes the course of ischemic acute kidney injury in cats and demonstrates that ischemic acute kidney injury triggers chronic fibrosis, interstitial inflammation, and tubular atrophy in feline kidneys. These late changes are typical of those observed in cats with naturally occurring chronic kidney disease. © The Author(s) 2015.

Perioperative outcomes of zero ischemia radiofrequency ablation-assisted tumor enucleation for renal cell carcinoma: results of 182 patients.

Science.gov (United States)

Zhang, Chengwei; Zhao, Xiaozhi; Guo, Suhan; Ji, Changwei; Wang, Wei; Guo, Hongqian

2018-05-15

To evaluate the perioperative outcomes of zero ischemia radiofrequency ablation-assisted tumor enucleation. Patients undergoing zero ischemia radiofrequency ablation-assisted tumor enucleation were retrospectively identified from July 2008 to March 2013. The tumor was enucleated after RFA treatment. R.E.N.A.L., PADUA and centrality index (C-index) score systems were used to assess each tumor case. We analyzed the correlation of perioperative outcomes with these scores. Postoperative complications were graded with Clavien-Dindo system. Multivariate logistic regression analyses were used to assess risk of complications. Among 182 patients assessed, median tumor size, estimated blood loss, hospital stay and operative time were 3.2 cm (IQR 2.8-3.4), 80 ml (IQR 50-120), 7 days (IQR 6-8) and 100 min (IQR 90-120), respectively. All three scoring systems were strongly correlated with estimated blood loss, hospital stay and operative time. We found 3 (1.6%) intraoperative and 23 (12.6%, 13 [7.1%] Grade 1 and 10 [5.5%] Grade 2 & 3a) postoperative complications. The median follow-up was 55.5 months (IQR 45-70). Additionally, the complexities of R.E.N.A.L., PADUA and C-index scores were significantly correlated with complication grades (P radiofrequency ablation-assisted tumor enucleation is considered an effective nephron-sparing treatment. Scoring systems could be useful for predicting perioperative outcomes of radiofrequency ablation-assisted tumor enucleation.

Acute Alcohol Intoxication Exacerbates Rhabdomyolysis-Induced Acute Renal Failure in Rats.

Science.gov (United States)

Tsai, Jen-Pi; Lee, Chung-Jen; Subeq, Yi-Maun; Lee, Ru-Ping; Hsu, Bang-Gee

2017-01-01

Traumatic and nontraumatic rhabdomyolysis can lead to acute renal failure (ARF), and acute alcohol intoxication can lead to multiple abnormalities of the renal tubules. We examined the effect of acute alcohol intoxication in a rat model of rhabdomyolysis and ARF. Intravenous injections of 5 g/kg ethanol were given to rats over 3 h, followed by glycerol-induced rhabdomyolysis. Biochemical parameters, including blood urea nitrogen (BUN), creatinine (Cre), glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), and creatine phosphokinase (CPK), were measured before and after induction of rhabdomyolysis. Renal tissue injury score, renal tubular cell expression of E-cadherin, nuclear factor-κB (NF-κB), and inducible nitric oxide synthase (iNOS) were determined. Relative to rats in the vehicle group, rats in the glycerol-induced rhabdomyolysis group had significantly increased serum levels of BUN, Cre, GOT, GPT, and CPK, elevated renal tissue injury scores, increased expression of NF-κB and iNOS, and decreased expression of E-cadherin. Ethanol exacerbated all of these pathological responses. Our results suggest that acute alcohol intoxication exacerbates rhabdomyolysis-induced ARF through its pro-oxidant and inflammatory effects.

Spontaneous Renal Tumors Suspected of Being Familial in Sprague-Dawley Rats

OpenAIRE

Kudo, Kayoko; Hoshiya, Toru; Nakazawa, Tomomi; Saito, Tsubasa; Shimoyama, Natsumi; Suzuki, Isamu; Tamura, Kazutoshi; Seely, John Curtis

2012-01-01

Spontaneous renal tubule tumors (RTTs), with a distinctive morphological phenotype, were present in three Sprague-Dawley rats, 1 male and 2 females, out a total of 120 animals of each sex from untreated and placebo control groups in a 2-year carcinogenicity study. One female had one carcinoma, adenoma and hyperplasia, and the other female had five adenomas and many hyperplastic lesions; the male case had one carcinoma. From these cases, a biological continuum of hyperplasia, adenoma and carci...

Role of Bone Marrow Derived Mesenchymal Stem Cells and the Protective Effect of Silymarin in Cisplatin-Induced Acute Renal Failure in Rats.

Science.gov (United States)

Ibrahim, Mohamed El-Tantawy; Bana, Eman El; El-Kerdasy, Hanan I

2018-01-01

Cisplatin is a highly effective antitumor agent whose clinical application is limited by its nephrotoxicity, which is associated with high mortality and morbidity rates. We aimed to study the protective role of silymarin and mesenchymal stem cells as a therapeutic tool of cisplatin nephrotoxicity. We injected rats with cisplatin in a dose of 5mg/kg body weight for 5 days to induce acute renal failure (ARF). Silymarin was administrated 6 hours before cisplatin injection and mesenchymal stem cells were injected 24 hours after cisplatin-induced ARF. We assessed the ARF biochemically by elevation of kidney function tests and histopathologically by an alteration of the histological architecture of the renal cortex in the form of shrinkage of glomeruli, lobulated tufts and glomerular hypertrophy with narrowing capsular space. The tubules showed extensive tubular degeneration with cellular hyaline materials and debris in the lumen of the renal tubules. The renal blood vessels appeared sclerotic with marked thickened walls. When silymarin was given in different doses before cisplatin, it decreased the toxic effect of cisplatin in the kidney but sclerotic blood vessels remained. Injection of mesenchymal stem cells in rats with cisplatin-induced ARF improved the histopathological effects of cisplatin in renal tissues and kidney function tests were significantly improved. There was a significant improvement in kidney function tests and renal histopathology by using silymarin as protective mechanism in cisplatin-induced ARF. Administration of mesenchymal stem cells denoted a more remarkable therapeutic effect in ARF. Copyright © 2018 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

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

Engineering kidney cells: reprogramming and directed differentiation to renal tissues.

Science.gov (United States)

Kaminski, Michael M; Tosic, Jelena; Pichler, Roman; Arnold, Sebastian J; Lienkamp, Soeren S

2017-07-01

Growing knowledge of how cell identity is determined at the molecular level has enabled the generation of diverse tissue types, including renal cells from pluripotent or somatic cells. Recently, several in vitro protocols involving either directed differentiation or transcription-factor-based reprogramming to kidney cells have been established. Embryonic stem cells or induced pluripotent stem cells can be guided towards a kidney fate by exposing them to combinations of growth factors or small molecules. Here, renal development is recapitulated in vitro resulting in kidney cells or organoids that show striking similarities to mammalian embryonic nephrons. In addition, culture conditions are also defined that allow the expansion of renal progenitor cells in vitro. Another route towards the generation of kidney cells is direct reprogramming. Key transcription factors are used to directly impose renal cell identity on somatic cells, thus circumventing the pluripotent stage. This complementary approach to stem-cell-based differentiation has been demonstrated to generate renal tubule cells and nephron progenitors. In-vitro-generated renal cells offer new opportunities for modelling inherited and acquired renal diseases on a patient-specific genetic background. These cells represent a potential source for developing novel models for kidney diseases, drug screening and nephrotoxicity testing and might represent the first steps towards kidney cell replacement therapies. In this review, we summarize current approaches for the generation of renal cells in vitro and discuss the advantages of each approach and their potential applications.

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...

Endolymphatic Sac Enlargement in a Girl with a Novel Mutation for Distal Renal Tubular Acidosis and Severe Deafness

Directory of Open Access Journals (Sweden)

Rink Nikki

2012-01-01

Full Text Available Hereditary distal renal tubular acidosis (dRTA is caused by mutations of genes encoding subunits of the H+-ATPase (ATP6V0A4 and ATP6V1B1 expressed in α-intercalated cells of the distal renal tubule and in the cochlea. We report on a 2-year-old girl with distal RTA and profound speech delay which was initially misdiagnosed as autism. Genetic analysis showed compound heterozygous mutations with one known and one novel mutation of the ATP6V1B1 gene; cerebral magnetic resonance imaging (MRI revealed bilateral enlargement of the endolymphatic sacs of the inner ear. With improved cooperation, audiometric testing showed that hearing loss was most profound on the right, where endolymphatic sac enlargement was greatest, demonstrating a clear link between the degree of deafness and the degree of inner ear abnormality. This case indicates the value of MRI for diagnosis of inner ear involvement in very young children with distal RTA. Although citrate therapy quickly corrects the acidosis and restores growth, early diagnosis of deafness is crucial so that hearing aids can be used to assist acquisition of speech and to provide enough auditory nerve stimulation to assure the affected infants remain candidates for cochlear implantation.

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.

Renal tissue damage induced by focused shock waves

Science.gov (United States)

Ioritani, N.; Kuwahara, M.; Kambe, K.; Taguchi, K.; Saitoh, T.; Shirai, S.; Orikasa, S.; Takayama, K.; Lush, P. A.

1990-07-01

Biological evidence of renal arterial wall damage induced by the microjet due to shock wave-cavitation bubble interaction was demonstrated in living dog kidneys. We also intended to clarify the mechanism of renal tissue damage and the effects of different conditions of shock wave exposure (peak pressure of focused area, number of shots, exposure rate) on the renal tissue damage in comparison to stone disintegration. Disruption of arterial wall was the most remarkable histological change in the focused area of the kidneys. This lesion appeared as if the wall had been punctured by a needle. Large hematoma formation in the renal parenchym, and interstitial hemorrhage seemed to be the results of the arterial lesion. This arterial disorder also led to ischemic necrosis of the tubules surrounding the hematoma. Micro-angiographic examination of extracted kidneys also proved such arterial puncture lesions and ischemic lesions. The number of shots required for model stone disintegration was not inversely proportional to peak pressure. It decreased markedly when peak pressure was above 700 bar. Similarly thenumber of shots for hematoma formation was not inversely proportional to peak pressure, however, this decreased markedly above 500 bar. These results suggested that a hematoma could be formed under a lower peak pressure than that required for stone disintegration.

Role of the Sympathetic Nervous System and Its Modulation in Renal Hypertension.

Science.gov (United States)

Sata, Yusuke; Head, Geoffrey A; Denton, Kate; May, Clive N; Schlaich, Markus P

2018-01-01

The kidneys are densely innervated with renal efferent and afferent nerves to communicate with the central nervous system. Innervation of major structural components of the kidneys, such as blood vessels, tubules, the pelvis, and glomeruli, forms a bidirectional neural network to relay sensory and sympathetic signals to and from the brain. Renal efferent nerves regulate renal blood flow, glomerular filtration rate, tubular reabsorption of sodium and water, as well as release of renin and prostaglandins, all of which contribute to cardiovascular and renal regulation. Renal afferent nerves complete the feedback loop via central autonomic nuclei where the signals are integrated and modulate central sympathetic outflow; thus both types of nerves form integral parts of the self-regulated renorenal reflex loop. Renal sympathetic nerve activity (RSNA) is commonly increased in pathophysiological conditions such as hypertension and chronic- and end-stage renal disease. Increased RSNA raises blood pressure and can contribute to the deterioration of renal function. Attempts have been made to eliminate or interfere with this important link between the brain and the kidneys as a neuromodulatory treatment for these conditions. Catheter-based renal sympathetic denervation has been successfully applied in patients with resistant hypertension and was associated with significant falls in blood pressure and renal protection in most studies performed. The focus of this review is the neural contribution to the control of renal and cardiovascular hemodynamics and renal function in the setting of hypertension and chronic kidney disease, as well as the specific roles of renal efferent and afferent nerves in this scenario and their utility as a therapeutic target.

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.

The perioperative outcomes between renal hilar and non-hilar tumors following robotic-assisted partial nephrectomy (RAPN).

Science.gov (United States)

Lu, Shih-Yen; Chung, Hsiao-Jen; Huang, Eric Yi-Hsiu; Lin, Tzu-Pin; Lin, Alex T L

2018-03-15

The aim of this study was to compare the perioperative outcomes between renal hilar tumors and non-hilar tumors after robotic-assisted partial nephrectomy (RAPN). A retrospective review of consecutive patients who underwent RAPN from December 2009 to September 2015 at our institution was recruited. Perioperative outcomes including demographic characteristics, perioperative, pathological and renal function outcomes were compared between the hilar group (n = 30) and non-hilar group (n = 170). In characteristics, hilar group was younger (52.4 vs. 58 years, p = 0.04) and had less body mass index (23.7 vs. 25.4 kg/m 2 , p = 0.018). Hilar group had larger tumor size (4.8 vs. 3.7 cm, p = 0.009), higher Preoperative Aspects and Dimensions Used for an Anatomical (PADUA) score (10.7 vs. 8.5, p Hilar tumor was associated with longer operative time (293.6 vs. 240.5 min, p = 0.001) and warm ischemia time (39.9 vs. 21.8 min, p hilar tumor patients had no difference of the change of creatinine and estimated glomerular filtration rate (eGFR) at postoperative 6 and 12 month as compared with non-hilar tumor patients. For renal hilar tumor, RAPN could provide acceptable results of perioperative, pathological and renal function outcome as compared with non-hilar tumor group. Thus RAPN is a safe and effective nephron-sparing surgery technique for renal hilar tumors. Copyright © 2018. Published by Elsevier Taiwan LLC.

An experimental study on renal damage induced by ionic contrast media in relation to iodine concentration

International Nuclear Information System (INIS)

Sung, Dong Wook; Yoon, Yup; Lim, Jae Hoon; Yang, Moon Ho

1990-01-01

Renal injury caused by iodinated contrast media has been widely known, but there has been few papers regarding the pathological change. A series of kidneys after injection of iodinated contrast media was examined to document pathological change. A total of 80 rats was divided into two groups; those given Urografin-60% by 5ml/kg; those given Urografin-76% by 5ml/kg. The kidneys were removed out 1, 2, 3, 5, 7, 10, 14 and 21 days after injection of contrast media and microscopically examined. The resulted were as follows: 1. Pathological changes induced by ionic contrast media were deposition of proteinaceous materials in the proximal convoluted tubules, congestion of interstitial vessels, and vasa rectae, and epithelial degeneration of collecting ducts. There was no detectable pathological changes in the glomerulus, loop of Henle, and distal convoluted tubules. 2. All pathological changes were severe, as the concentration of contrast media increased. 3. These pathologic changes appeared 1 day after injection of contrast media and persisted at least 3 weeks without improvement. Author concludes that the renal damage induced by ionic contrast media becomes severe with increase in concentration, and pathologic changes are not influence with time interval

Role of CAP350 in centriolar tubule stability and centriole assembly.

Directory of Open Access Journals (Sweden)

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)

Thiazolidinediones and Edema: Recent Advances in the Pathogenesis of Thiazolidinediones-Induced Renal Sodium Retention

Directory of Open Access Journals (Sweden)

Shoko Horita

2015-01-01

Full Text Available Thiazolidinediones (TZDs are one of the major classes of antidiabetic drugs that are used widely. TZDs improve insulin resistance by activating peroxisome proliferator-activated receptor gamma (PPARγ and ameliorate diabetic and other nephropathies, at least, in experimental animals. However, TZDs have side effects, such as edema, congestive heart failure, and bone fracture, and may increase bladder cancer risk. Edema and heart failure, which both probably originate from renal sodium retention, are of great importance because these side effects make it difficult to continue the use of TZDs. However, the pathogenesis of edema remains a matter of controversy. Initially, upregulation of the epithelial sodium channel (ENaC in the collecting ducts by TZDs was thought to be the primary cause of edema. However, the results of other studies do not support this view. Recent data suggest the involvement of transporters in the proximal tubule, such as sodium-bicarbonate cotransporter and sodium-proton exchanger. Other studies have suggested that sodium-potassium-chloride cotransporter 2 in the thick ascending limb of Henle and aquaporins are also possible targets for TZDs. This paper will discuss the recent advances in the pathogenesis of TZD-induced sodium reabsorption in the renal tubules and edema.

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

Science.gov (United States)

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

Vacuum-assisted closure (VAC) therapy in the management of wound infection following renal transplantation.

Science.gov (United States)

Shrestha, B M; Nathan, V C; Delbridge, M C; Parker, K; Throssell, D; McKane, W S; Karim, M S; Raftery, A T

2007-01-01

Wound infection in the setting of immunosuppressed state such as renal transplantation (RT) causes significant morbidity from sepsis, prolongs hospital stay and is expensive. Vacuum-assisted closure (VAC) therapy is a new technique of management of wound based on the principle of application of controlled negative pressure. The aim of this study was to assess the efficacy of VAC therapy in the management of wound infection following RT. This is a prospective study of a cohort of 180 consecutive RTs performed over a period of 4 years, where the data were retrieved from a prospectively maintained computerised database and case-notes. 9 of 180 (5%) patients developed wound infection following RT which led to cavitations and dehiscence with copious discharge, and refused to heal with conventional treatment. All 9 cases were treated with VAC therapy. The VAC system was removed after a median of 9 (range 3-30) days when discharge from the wound ceased. Four patients were discharged home with portable VAC device and managed on an outpatient basis, where the system was removed after a median 5.5 (range 3-7) days. The median hospital stay after initiation of VAC therapy was significantly shorter (5, range 2-12 days) than on conventional treatment prior to VAC therapy (11, range, 5-20 days) (p=0.003). Complete healing was achieved in all cases. The use of VAC therapy is an effective and safe adjunct to conventional and established treatment modalities for the management of wound infection and dehiscence following RT. Key words: Renal transplantation, wound infection, vacuum-assisted closure therapy.

Role of the Sympathetic Nervous System and Its Modulation in Renal Hypertension

Directory of Open Access Journals (Sweden)

Yusuke Sata

2018-03-01

Full Text Available The kidneys are densely innervated with renal efferent and afferent nerves to communicate with the central nervous system. Innervation of major structural components of the kidneys, such as blood vessels, tubules, the pelvis, and glomeruli, forms a bidirectional neural network to relay sensory and sympathetic signals to and from the brain. Renal efferent nerves regulate renal blood flow, glomerular filtration rate, tubular reabsorption of sodium and water, as well as release of renin and prostaglandins, all of which contribute to cardiovascular and renal regulation. Renal afferent nerves complete the feedback loop via central autonomic nuclei where the signals are integrated and modulate central sympathetic outflow; thus both types of nerves form integral parts of the self-regulated renorenal reflex loop. Renal sympathetic nerve activity (RSNA is commonly increased in pathophysiological conditions such as hypertension and chronic- and end-stage renal disease. Increased RSNA raises blood pressure and can contribute to the deterioration of renal function. Attempts have been made to eliminate or interfere with this important link between the brain and the kidneys as a neuromodulatory treatment for these conditions. Catheter-based renal sympathetic denervation has been successfully applied in patients with resistant hypertension and was associated with significant falls in blood pressure and renal protection in most studies performed. The focus of this review is the neural contribution to the control of renal and cardiovascular hemodynamics and renal function in the setting of hypertension and chronic kidney disease, as well as the specific roles of renal efferent and afferent nerves in this scenario and their utility as a therapeutic target.

Tick-Tock Chimes the Kidney Clock – from Biology of Renal Ageing to Clinical Applications

Directory of Open Access Journals (Sweden)

Joshua Rowland

2018-01-01

Full Text Available Ageing of the kidney is a multi-dimensional process that occurs simultaneously at the molecular, cellular, histological, anatomical and physiological level. Nephron number and renal cortical volume decline, renal tubules become atrophic and glomeruli become sclerotic with age. These structural changes are accompanied by a decline in glomerular filtration rate, decreased sodium reabsorption and potassium excretion, reduced urinary concentrating capacity and alterations in the endocrine activity of the kidney. However, the pace of progression of these changes is not identical in everyone - individuals of the same age and seemingly similar clinical profile often exhibit stark differences in the age-related decline in renal health. Thus, chronological age poorly reflects the time-dependent changes that occur in the kidney. An ideal measure of renal vitality is biological kidney age – a measure of the age-related changes in physiological function. Replacing chronological age with biological age could provide numerous clinical benefits including improved prognostic accuracy in renal transplantation, better stratification of risk and identification of those who are on a fast trajectory to an age-related drop in kidney health.

A Mathematical Model of Renal Blood Distribution Coupling TGF, MR and Tubular System

Institute of Scientific and Technical Information of China (English)

GAO Ci-xiu; YANG Lin; WANG Ke-qiang; XU Shi-xiong; DAI Pei-dong

2009-01-01

Objective:To investigate the relationship between renal blood distribution and the physiological activities of the kidney. Methods:A mathematical model is developed based on Hagan-Poiseuille law and mass transport, coupling mechanics of myogenic response (MR), tubuloglomerular feedback (TGF) and the tubular system in the renal medulla. The model parameters, including the permeability coefficients, the vascular lumen radius and the solute concentration at the inlet of the tubes, are derived from the experimental results. Simulations of the blood and water flow in the loop of Henel, the collecting duct and vas rectum, are carried out by the model of the tubular system in the renal medulla, based on conservations of water and solutes for transmural transport. Then the tubular model is coupled with MR and TGF mechanics. Results:The results predict the dynamics of renal autoregulation on its blood pressure and flow,and the distributions are 88.5% in the cortex, 10.3% in the medulla, and 1.2% at papilla,respectively. The fluid flow and solute concentrations along the tubules and vasa recta are obtained. Conclusion:The present model could assess renal functions qualitatively and quantitatively and provide a methodological approach for clinical research.

Reduced kidney lipoprotein lipase and renal tubule triglyceride accumulation in cisplatin-mediated acute kidney injury

NARCIS (Netherlands)

Li, Shenyang; Nagothu, K.; Ranganathan, G.; Ali, S.M.; Shank, B.; Gokden, N.; Ayyadevara, S.; Megysi, J.; Olivecrona, G.; Chugh, S.S.; Kersten, A.H.; Portilla, D.

2012-01-01

Peroxisome proliferator-activated receptor-a (PPARa) activation attenuates cisplatin (CP)-mediated acute kidney injury by increasing fatty acid oxidation, but mechanisms leading to reduced renal triglyceride (TG) accumulation could also contribute. Here, we investigated the effects of PPARa and CP

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

Directory of Open Access Journals (Sweden)

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.

Stent-Assisted Coil Embolization of a Mycotic Renal Artery Aneurysm by Use of a Self-Expanding Neurointerventional Stent

International Nuclear Information System (INIS)

Rabellino, Martin; García-Nielsen, Luis; Zander, Tobias; Baldi, Sebastián; Llorens, Rafael; Maynar, Manuel

2011-01-01

Mycotic aneurysms are uncommon, especially those located in visceral arteries. We present a case of a patient with two visceral mycotic aneurysms due to bacterial endocarditis, one located in right upper pole renal artery and the second in the splenic artery. Both aneurysms were treated as endovascular embolization using microcoils. In the aneurysm located at the renal artery, the technique of stent-assisted coils embolization was preferred to avoid coils migration due to its wide neck. The stent used was the Solitaire AB, which was designed for the treatment of intracranial aneurysms and was used recently in acute stroke as a mechanical thrombectomy device. Complete embolization of the aneurysm was achieved, preserving all the arterial branches without nephrogram defects in the final angiogram.

Reduced Insulin Receptor Expression Enhances Proximal Tubule Gluconeogenesis.

Science.gov (United States)

Pandey, Gaurav; Shankar, Kripa; Makhija, Ekta; Gaikwad, Anil; Ecelbarger, Carolyn; Mandhani, Anil; Srivastava, Aneesh; Tiwari, Swasti

2017-02-01

Reduced insulin receptor protein levels have been reported in the kidney cortex from diabetic humans and animals. We recently reported that, targeted deletion of insulin receptor (IR) from proximal tubules (PT) resulted in hyperglycemia in non-obese mice. To elucidate the mechanism, we examined human proximal tubule cells (hPTC) and C57BL/6 mice fed with high-fat diet (HFD, 60% fat for 20 weeks). Immunoblotting revealed a significantly lower protein level of IR in HFD compare to normal chow diet (NCD). Furthermore, a blunted rise in p-AKT 308 levels in the kidney cortex of HFD mice was observed in response to acute insulin (0.75 IU/kg body weight, i.p) relative to NCD n = 8/group, P gluconeogenesis. Transcript levels of the gluconeogenic enzyme PEPCK were significantly increased in cAMP/DEXA-stimulated hPTC cells (n = 3, P gluconeogenesis and PEPCK induction was significantly attenuated in IR (siRNA) silenced hPTC (n = 3, P gluconeogenesis. Thus reduced insulin signaling of the proximal tubule may contribute to hyperglycemia in the metabolic syndrome via elevated gluconeogenesis. J. Cell. Biochem. 118: 276-285, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Renal morphology of Bradypus torquatus

Directory of Open Access Journals (Sweden)

Pedro Kastein Faria da Cunha Bianchi

2012-11-01

Full Text Available Among the Xenarthras, sloths present a hydric ingestion restricted to water from leaves, fruits, and vegetables. As a first approach to verify whether these animals have some morphophysiological difference which could justify or compensate this low hydric ingestion, the renal anatomy of these animals was investigated, particularly that of maned sloth (Bradypus torquatus. Kidneys from these animals were macroscopically analyzed, through light microscopy and scanning electron microscopy. The Bradypus torquatus kidneys are bean-shaped paired organs, located dorso-cranially to the pelvic girdle, between the peritoneum and the posterior abdominal wall. The use of histological techniques allowed us to identify, in the cortical region, the renal corpuscles and tubules, and, in the medullary region, a significant amount of interstitial tissue with a collecting duct. The results of this study showed that, although Bradypus torquatus doesn’t drink water directly, its kidneys doesn’t differ from that of most mammals, presenting the same anatomical structure, suggesting that these animals fully reach their hydric needs, basically by consuming leaves, fruits, and sprouts. Nevertheless, in order to confirm this hypothesis, studies on the effectiveness of water reabsorption, such as the renin-angiotensin-aldosterone system, must be carried out.

Dentine tubule infection and endodontic therapy implications.

Science.gov (United States)

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.

Inhibition of renal Na+/H+ exchange in cadmium-intoxicated rats

International Nuclear Information System (INIS)

Ahn, Do Whan; Chung, Jin Mo; Kim, Jee Yeun; Kim, Kyoung Ryong; Park, Yang Saeng

2005-01-01

Chronic exposure to cadmium (Cd) results in bicarbonaturia, leading to metabolic acidosis. To elucidate the mechanism(s) by which renal bicarbonate reabsorption is inhibited, we investigated changes in renal transporters and enzymes associated with bicarbonate reabsorption in Cd-intoxicated rats. Cd intoxication was induced by subcutaneous injections of CdCl 2 (2 mg Cd/kg per day) for 3 weeks. Cd intoxication resulted in a significant reduction in V max of Na + /H + antiport with no changes in K Na in the renal cortical brush-border membrane vesicles (BBMV). Western blotting of BBM proteins and indirect immunohistochemistry in renal tissue sections, using an antibody against Na + /H + exchange-3 (NHE3), showed a diminished expression of NHE3 protein in the BBM. Reverse transcription-polymerase chain reaction (RT-PCR) analysis revealed that NHE3 mRNA expression was reduced in the renal cortex. The activity of carbonic anhydrase IV (CA IV) in BBM was not changed. The protein abundance of Na + -HCO 3 - cotransporter-1 (NBC1) in whole kidney membrane fractions was slightly attenuated, whereas that of the Na + -K + -ATPase α-subunit was markedly elevated in Cd-intoxicated animals. These results indicate that Cd intoxication impairs NHE3 expression in the proximal tubule, thereby reducing the capacity for bicarbonate reabsorption, leading to bicarbonaturia in an intact animal

Evaluation of radioimmunoassay for renal functions in senile patients with cor pulmonale without respiratory failure

International Nuclear Information System (INIS)

Fu Benqi; Chen Mingxi; Zhou Gangyi; Zhang Zhengzhong

1995-01-01

The results of RIA about serum β 2 -MG and urine β 2 -MG, Alb, IgG in the senile patients with cor pulmonale are reported. The contents of sβ 2 -MG, uβ 2 -MG, uAlb in non-respiratory failure group are higher than that of the control group. The contents of sβ 2 -MG, uβ 2 -MG, uAlb and uIgG in the respiratory failure group are higher than that of the non-respiratory failure group. The results show that the renal glamorous and renal tubules functions are slightly damaged in non-respiratory failure group, while functions of the respiratory failure group become worse

Sistematização da assistência de enfermagem ao idoso, portador de insuficiência renal crônica, hospitalizado

OpenAIRE

Santos, Reginaldo Passoni dos; Pontifícia Universidade Católica do Paraná (PUC-SP). Departamento de Enfermagem.; Rocha, Daniele Lais Brandalize; Pontifícia Universidade Católica do Paraná (PUC-SP). Departamento de Enfermagem.

2014-01-01

O presente artigo relata a experiência de acadêmicos de enfermagem no processo de elaboração do plano de cuidados à saúde do idoso, portador de Insuficiência Renal Crônica, hospitalizado. A elaboração do planejamento da assistência buscou abarcar o cuidado ao sujeito na sua integralidade. A vivência acadêmica, junto à realidade profissional, fortalecem a habilidade para a aplicação prática do aprendizado teórico relativo às metodologias da assistência de enfermagem. This paper reports the ...

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.

Renal and urinary levels of endothelial protein C receptor correlate with acute renal allograft rejection.

Directory of Open Access Journals (Sweden)

Lionel Lattenist

Full Text Available The Endothelial Protein C Receptor (EPCR is expressed on leukocytes, on endothelium of large blood vessels and to a lesser extent on capillaries. Membrane bound EPCR plays an important role in the activation of protein C which has anticoagulant, anti-inflammatory and cytoprotective effects. After cleavage by a protease EPCR is also found as a soluble protein. Acute rejection of kidney allografts can be divided in T-cell-mediated rejection (TCMR and antibody-mediated (ABMR rejection. The latter is characterized by strong activation of coagulation. Currently no reliable non-invasive biomarkers are available to monitor rejection. Renal biopsies were available from 81 renal transplant patients (33 without rejection, 26 TCMR and 22 ABMR, we had access to mRNA material, matched plasma and urine samples for a portion of this cohort. Renal EPCR expression was assessed by RT-PCR and immunostaining. Plasma and urine sEPCR levels were measured by ELISA. ABMR patients showed higher levels of EPCR mRNA than TCMR patients. EPCR expression on glomeruli was significantly elevated in ABMR patients than in TCMR or control patients. In the peritubular capillaries EPCR expression was higher in ABMR patients than in control patients. EPCR expression was higher in tubules and arteries of rejection patients than in control patients. Plasma sEPCR levels did not differ. Urine sEPCR levels were more elevated in the ABMR group than in patients with TCMR or without rejection. ROC analysis demonstrated that urinary sEPCR is appropriate to discriminate between ABMR patients and TCMR or control patients. We conclude that urinary sEPCR could be a novel non-invasive biomarker of antibody mediated rejection in renal transplantation.

Loss of renal SNX5 results in impaired IDE activity and insulin resistance in mice.

Science.gov (United States)

Li, Fengmin; Yang, Jian; Villar, Van Anthony M; Asico, Laureano D; Ma, Xiaobo; Armando, Ines; Sanada, Hironobu; Yoneda, Minoru; Felder, Robin A; Jose, Pedro A; Wang, Xiaoyan

2018-03-01

We hypothesised that renal sorting nexin 5 (SNX5) regulates the insulin-degrading enzyme (IDE) and, thus, circulating insulin levels. We therefore studied the dynamic interaction between SNX5 and IDE in human renal proximal tubule cells (hRPTCs), as well as in rat and mouse kidneys. The regulation of IDE by SNX5 expressed in the kidney was studied in vitro and in vivo. Snx5 or mock siRNA was added to immortalised hRPTCs (passage <20) in culture or selectively infused, via osmotic mini-pump, into the remnant kidney of uninephrectomised mice and rats. SNX5 co-localised with IDE at the plasma membrane and perinuclear area of hRPTCs and in the brush border membrane of proximal tubules of human, rat, and mouse kidneys. Insulin increased the co-localisation and co-immunoprecipitation of SNX5 and IDE in hRPTCs. Silencing SNX5 in hRPTCs decreased IDE expression and activity. Renal-selective silencing of Snx5 (SNX5 protein: 100 ± 25 vs 29 ± 10, p < 0.05 [% of control]) in C57Bl/6J mice decreased IDE protein (100 ± 13 vs 57 ± 6, p < 0.05 [% of control]) and urinary insulin excretion, impaired the responses to insulin and glucose, and increased blood insulin and glucose levels. Spontaneously hypertensive rats (SHRs) had increased blood insulin and glucose levels and decreased renal SNX5 (100 ± 27 vs 29 ± 6, p < 0.05 [% of control]) and IDE (100 ± 5 vs 75 ± 4, p < 0.05 [% of control]) proteins, compared with normotensive Wistar-Kyoto (WKY) rats. Kidney Snx5-depleted WKY rats also had increased blood insulin and glucose levels. The expression of SNX5 and IDE was decreased in RPTCs from SHRs and hypertensive humans compared with cells from normotensive volunteers, indicating a common cause for hyperinsulinaemia and hypertension. Renal SNX5 positively regulates IDE expression and function. This study is the first to demonstrate the novel and crucial role of renal SNX5 in insulin and glucose metabolism.

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).

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...

Robot-assisted partial nephrectomy in contemporary practice

Directory of Open Access Journals (Sweden)

Youssef S. Tanagho

2013-01-01

Full Text Available Laparoscopic renal surgery is associated with reduced blood loss, shorter hospital stay, enhanced cosmesis, and more rapid convalescence relative to open renal surgery. Laparoscopic partial nephrectomy is a minimally invasive, nephron-sparing alternative to laparoscopic radical nephrectomy for the management of small renal masses. While offering similar oncological outcomes to laparoscopic radical nephrectomy, the technical challenges and prolonged learning curve associated with laparoscopic partial nephrectomy limit its wider dissemination. Robot-assisted partial nephrectomy, although still an evolving procedure with no long-term data, has emerged as a viable alternative to laparoscopic partial nephrectomy, with favorable preliminary outcomes. This article provides an overview of the role of robot-assisted partial nephrectomy in the management of renal cell carcinoma. The clinical indications and principles of surgical technique for this procedure are discussed. The oncological, renal functional, and perioperative outcomes of robot-assisted partial nephrectomy are also evaluated, as are complication rates.

Roles of renal ammonia metabolism other than in acid-base homeostasis.

Science.gov (United States)

Weiner, I David

2017-06-01

The importance of renal ammonia metabolism in acid-base homeostasis is well known. However, the effects of renal ammonia metabolism other than in acid-base homeostasis are not as widely recognized. First, ammonia differs from almost all other solutes in the urine in that it does not result from arterial delivery. Instead, ammonia is produced by the kidney, and only a portion of the ammonia produced is excreted in the urine, with the remainder returned to the systemic circulation through the renal veins. In normal individuals, systemic ammonia addition is metabolized efficiently by the liver, but in patients with either acute or chronic liver disease, conditions that increase the addition of ammonia of renal origin to the systemic circulation can result in precipitation and/or worsening of hyperammonemia. Second, ammonia appears to serve as an intrarenal paracrine signaling molecule. Hypokalemia increases proximal tubule ammonia production and secretion as well as reabsorption in the thick ascending limb of the loop of Henle, thereby increasing delivery to the renal interstitium and the collecting duct. In the collecting duct, ammonia decreases potassium secretion and stimulates potassium reabsorption, thereby decreasing urinary potassium excretion and enabling feedback correction of the initiating hypokalemia. Finally, the stimulation of renal ammonia metabolism by hypokalemia may contribute to the development of metabolic alkalosis, which in turn can stimulate NaCl reabsorption and contribute to the intravascular volume expansion, increased blood pressure and diuretic resistance that can develop with hypokalemia. The evidence supporting these novel non-acid-base roles of renal ammonia metabolism is discussed in this review.

Computer assisted diagnosis in renal nuclear medicine: rationale, methodology and interpretative criteria for diuretic renography

Science.gov (United States)

Taylor, Andrew T; Garcia, Ernest V

2014-01-01

The goal of artificial intelligence, expert systems, decision support systems and computer assisted diagnosis (CAD) in imaging is the development and implementation of software to assist in the detection and evaluation of abnormalities, to alert physicians to cognitive biases, to reduce intra and inter-observer variability and to facilitate the interpretation of studies at a faster rate and with a higher level of accuracy. These developments are needed to meet the challenges resulting from a rapid increase in the volume of diagnostic imaging studies coupled with a concurrent increase in the number and complexity of images in each patient data. The convergence of an expanding knowledge base and escalating time constraints increases the likelihood of physician errors. Errors are even more likely when physicians interpret low volume studies such as 99mTc-MAG3 diuretic scans where imagers may have had limited training or experience. Decision support systems include neural networks, case-based reasoning, expert systems and statistical systems. iRENEX (renal expert) is an expert system for diuretic renography that uses a set of rules obtained from human experts to analyze a knowledge base of both clinical parameters and quantitative parameters derived from the renogram. Initial studies have shown that the interpretations provided by iRENEX are comparable to the interpretations of a panel of experts. iRENEX provides immediate patient specific feedback at the time of scan interpretation, can be queried to provide the reasons for its conclusions and can be used as an educational tool to teach trainees to better interpret renal scans. iRENEX also has the capacity to populate a structured reporting module and generate a clear and concise impression based on the elements contained in the report; adherence to the procedural and data entry components of the structured reporting module assures and documents procedural competency. Finally, although the focus is CAD applied to

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

The Putative Role of the Antiageing Protein Klotho in Cardiovascular and Renal Disease

Directory of Open Access Journals (Sweden)

Giuseppe Maltese

2012-01-01

Full Text Available Ageing is a multifactorial process often characterized by a progressive decline in physiological function(s. Ageing can and is often associated with an increased incidence of cardiovascular and renal disease. Klotho is a novel antiageing gene that encodes a protein with multiple pleiotropic functions including an emerging role in cardiorenal disease. Mice deficient for this gene display a phenotype of premature human ageing characterized by diffuse vascular calcification, altered calcium/phosphate metabolism, and shortened lifespan. Klotho is mainly expressed in the renal tubules but it also exists as circulating soluble form detectable in the blood, with systemic effects. Reduction in soluble Klotho has been associated with renal disease, hyperphosphataemia, increased oxidative stress, endothelial dysfunction, and diffuse vascular calcification. Conversely, overexpression of Klotho promotes cardiovascular-renal protection. The majority of the research on Klotho has been conducted in vitro and in animal studies but there is emerging data from human studies which suggest that Klotho may be a modifiable factor involved in the pathogenesis of cardiovascular and renal disease in at-risk populations. Further data is required to confirm if this novel protein can emerge as therapeutic tool that may be used to prevent or slow progression of cardiorenal disease.

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

Science.gov (United States)

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.

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

Strontium effects on root dentin tubule occlusion and nanomechanical properties.

Science.gov (United States)

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.

Renal tissue alterations were size-dependent with smaller ones induced more effects and related with time exposure of gold nanoparticles

Directory of Open Access Journals (Sweden)

Jarrar Bashir M

2011-09-01

Full Text Available Abstract Background Gold nanoparticles (GNPs have important application for cell labeling and imaging, drug delivery, diagnostic and therapeutic purposes mainly in cancer. Nanoparticles (NPs are being increasingly exploited for medical applications. The aim of the present study was to investigate the particle-size and period effects of administration of GNPs on the renal tissue in an attempt to address their potential toxicity. Methods A total of 70 healthy male Wistar-Kyoto rats were exposed to GNPs received 50 or 100 μl of GNPs infusion of size (10, 20 and 50 nm for 3 or 7 days to investigate particle-size effect of GNPs on the renal tissue. Animals were randomly divided into groups, 6 GNPs-treated rats groups and one control group. Groups 1, 2 and 3 received infusion of 50 μl GNPs of size 10 nm (3 or 7 days, size 20 nm (3 or 7 days and 50 nm (3 or 7 days, respectively; while groups 4, 5 and 6 received infusion of 100 μl GNPs of size 10 nm, size 20 nm and 50 nm, respectively. Stained sections of control and treated rats kidneys were examined for renal tissue alterations induced by GNPs. Results In comparison with respective control rats, exposure to GNPs doses has produced the following renal tubular alterations: cloudy swelling, vacuolar degeneration, hyaline droplets and casts, anisokaryosis, karopyknosis, karyorrhexis and karyolysis. The glomeruli showed moderate congestion with no hypercelluraity, mesangial proliferation or basement membrane thickening. The histological alterations were mainly seen in the cortex and the proximal renal convoluted tubules were more affected than the distal ones. Conclusions The induced histological alterations might be an indication of injured renal tubules due to GNPs toxicity that became unable to deal with the accumulated residues resulting from metabolic and structural disturbances caused by these NPs. The findings may suggest that GNPs interact with proteins and enzymes of the renal tissue

Effect of Dietary Countermeasures and Impact of Gravity on Renal Calculi Size Distributions Predicted by PBE-System and PBE-CFD Models

Science.gov (United States)

Kassemi, M.; Thompson, D.; Goodenow, D.; Gokoglu, S.; Myers, J.

2016-01-01

Renal stone disease is not only a concern on earth but can conceivably pose a serious risk to the astronauts health and safety in Space. In this work, two different deterministic models based on a Population Balance Equation (PBE) analysis of renal stone formation are developed to assess the risks of critical renal stone incidence for astronauts during space travel. In the first model, the nephron is treated as a continuous mixed suspension mixed product removal crystallizer and the PBE for the nucleating, growing and agglomerating renal calculi is coupled to speciation calculations performed by JESS. Predictions of stone size distributions in the kidney using this model indicate that the astronaut in microgravity is at noticeably greater but still subcritical risk and recommend administration of citrate and augmented hydration as effective means of minimizing and containing this risk. In the second model, the PBE analysis is coupled to a Computational Fluid Dynamics (CFD) model for flow of urine and transport of Calcium and Oxalate in the nephron to predict the impact of gravity on the stone size distributions. Results presented for realistic 3D tubule and collecting duct geometries, clearly indicate that agglomeration is the primary mode of size enhancement in both 1g and microgravity. 3D numerical simulations seem to further indicate that there will be an increased number of smaller stones developed in microgravity that will likely pass through the nephron in the absence of wall adhesion. However, upon reentry to a 1g (Earth) or 38g (Mars) partial gravitational fields, the renal calculi can lag behind the urinary flow in tubules that are adversely oriented with respect to the gravitational field and grow agglomerate to large sizes that are sedimented near the wall with increased propensity for wall adhesion, plaque formation, and risk to the astronauts.

Hepatic and renal function with successful long-term support on a continuous flow left ventricular assist device.

Science.gov (United States)

Deo, Salil V; Sharma, Vikas; Altarabsheh, Salah E; Hasin, Tal; Dillon, John; Shah, Ishan K; Durham, Lucian A; Stulak, John M; Daly, Richard C; Joyce, Lyle D; Park, Soon J

2014-03-01

Data regarding the long-term clinical effects of a continuous flow left ventricular assist device (CF-LVAD) on hepato-renal function is limited. Hence our aim was to assess changes in hepato-renal function over a one-year period in patients supported on a CF-LVAD. During the study period 126 patients underwent CF-LVAD implant. Changes in hepato-renal laboratory parameters were studied in 61/126 patients successfully supported on a CF-LVAD for period of one year. A separate cohort of a high-risk group (HCrB) of patients (56/126) with a serum creat>1.9 mg/dL (168 μmol/L) (75th percentile) or a serum bil>1.5 mg/dL (25.65 μmol/L) (75th percentile) was created. Changes in serum creatinine and bilirubin were analysed at regular intervals for this group along with the need for renal replacement therapy. Baseline creatinine and blood urea nitrogen (BUN) for the entire cohort was 1.4[1.2,1.9 mg/dL] [123.7(106,168) μmol/L) and 27[20,39.5 mg/dL] [9.6(7.1,14.1) mmol/L] respectively. After an initial reduction at the end of one month [1(0.8,1.2) mg/dL; 88(70,105) μmol/L] (passist device support for one year. High-risk patients demonstrate a higher 30-day mortality and temporary need for renal replacement therapy. Yet even in this cohort, improvement is present over a period of one year on the device, with a minimal need for permanent haemodialysis. Copyright © 2013 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

Mini-review: regulation of the renal NaCl cotransporter by hormones.

Science.gov (United States)

Rojas-Vega, Lorena; Gamba, Gerardo

2016-01-01

The renal thiazide-sensitive NaCl cotransporter, NCC, is the major pathway for salt reabsorption in the distal convoluted tubule. The activity of this cotransporter is critical for regulation of several physiological variables such as blood pressure, serum potassium, acid base metabolism, and urinary calcium excretion. Therefore, it is not surprising that numerous hormone-signaling pathways regulate NCC activity to maintain homeostasis. In this review, we will provide an overview of the most recent evidence on NCC modulation by aldosterone, angiotensin II, vasopressin, glucocorticoids, insulin, norepinephrine, estradiol, progesterone, prolactin, and parathyroid hormone. Copyright © 2016 the American Physiological Society.

A new perspective on the pathogenesis of chronic renal disease in captive cheetahs (Acinonyx jubatus).

Science.gov (United States)

Mitchell, Emily P; Prozesky, Leon; Lawrence, John

2018-01-01

The sustainability of captive cheetah populations is limited by high mortality due to chronic renal disease. This necropsy study, conducted on 243 captive cheetahs from one institution, investigated the relationships between focal palatine erosions, gastritis, enterocolitis, glomerulosclerosis, chronic renal infarcts, renal cortical and medullary fibrosis, and renal medullary amyloidosis at death. Associations between the individual renal lesions and death due to chronic renal disease and comparisons of lesion prevalence between captive bred and wild born and between normal and king coated cheetahs were also assessed. All lesions were significantly positively correlated with age at death. Renal medullary fibrosis was the only lesion associated with the likelihood of death being due to chronic renal disease, and cheetahs with this lesion were younger, on average, than cheetahs with other renal lesions. Alimentary tract lesions were not associated with amyloidosis. All lesions, except for palatine erosions, were more common in wild born than in captive bred cheetahs; the former were older at death than the latter. Having a king coat had no clear effect on disease prevalence. These results suggest that age and renal medullary fibrosis are the primary factors influencing the pathogenesis of chronic renal disease in captive cheetahs. Apart from amyloidosis, these findings are analogous to those described in chronic renal disease in domestic cats, which is postulated to result primarily from repetitive hypoxic injury of renal tubules, mediated by age and stress. Cheetahs may be particularly susceptible to acute renal tubular injury due to their propensity for stress and their extended life span in captivity, as well as their adaptation for fecundity (rather than longevity) and adrenaline-mediated high speed prey chases. The presence of chronic renal disease in subadult cheetahs suggests that prevention, identification and mitigation of stress are critical to the

The Renal Sodium Bicarbonate Cotransporter NBCe2: Is It a Major Contributor to Sodium and pH Homeostasis?

Science.gov (United States)

Felder, Robin A; Jose, Pedro A; Xu, Peng; Gildea, John J

2016-09-01

The sodium bicarbonate cotransporter (NBCe2, aka NBC4) was originally isolated from the human testis and heart (Pushkin et al. IUBMB Life 50:13-19, 2000). Subsequently, NBCe2 was found in diverse locations where it plays a role in regulating sodium and bicarbonate transport, influencing intracellular, extracellular, interstitial, and ultimately plasma pH (Boron et al. J Exp Biol. 212:1697-1706, 2009; Parker and Boron, Physiol Rev. 93:803-959, 2013; Romero et al. Mol Asp Med. 34:159-182, 2013). NBCe2 is located in human and rodent renal-collecting duct and proximal tubule. While much is known about the two electrogenic sodium bicarbonate cotransporters, NBCe1 and NBCe2, in the regulation of sodium homeostasis and pH balance in the rodent kidney, little is known about their roles in human renal physiology. NBCe2 is located in the proximal tubule Golgi apparatus under basal conditions and then disperses throughout the cell, but particularly into the apical membrane microvilli, during various maneuvers that increase intracellular sodium. This review will summarize our current understanding of the distribution and function of NBCe2 in the human kidney and how genetic variants of its gene, SLC4A5, contribute to salt sensitivity of blood pressure.

Tubular overexpression of gremlin induces renal damage susceptibility in mice.

Directory of Open Access Journals (Sweden)

Alejandra Droguett

Full Text Available A growing number of patients are recognized worldwide to have chronic kidney disease. Glomerular and interstitial fibrosis are hallmarks of renal progression. However, fibrosis of the kidney remains an unresolved challenge, and its molecular mechanisms are still not fully understood. Gremlin is an embryogenic gene that has been shown to play a key role in nephrogenesis, and its expression is generally low in the normal adult kidney. However, gremlin expression is elevated in many human renal diseases, including diabetic nephropathy, pauci-immune glomerulonephritis and chronic allograft nephropathy. Several studies have proposed that gremlin may be involved in renal damage by acting as a downstream mediator of TGF-β. To examine the in vivo role of gremlin in kidney pathophysiology, we generated seven viable transgenic mouse lines expressing human gremlin (GREM1 specifically in renal proximal tubular epithelial cells under the control of an androgen-regulated promoter. These lines demonstrated 1.2- to 200-fold increased GREM1 expression. GREM1 transgenic mice presented a normal phenotype and were without proteinuria and renal function involvement. In response to the acute renal damage cause by folic acid nephrotoxicity, tubule-specific GREM1 transgenic mice developed increased proteinuria after 7 and 14 days compared with wild-type treated mice. At 14 days tubular lesions, such as dilatation, epithelium flattening and hyaline casts, with interstitial cell infiltration and mild fibrosis were significantly more prominent in transgenic mice than wild-type mice. Tubular GREM1 overexpression was correlated with the renal upregulation of profibrotic factors, such as TGF-β and αSMA, and with increased numbers of monocytes/macrophages and lymphocytes compared to wild-type mice. Taken together, our results suggest that GREM1-overexpressing mice have an increased susceptibility to renal damage, supporting the involvement of gremlin in renal damage

Short- and Mid-term Effects of Irreversible Electroporation on Normal Renal Tissue: An Animal Model

Energy Technology Data Exchange (ETDEWEB)

Wendler, J. J., E-mail: johann.wendler@med.ovgu.de; Porsch, M.; Huehne, S.; Baumunk, D. [University of Magdeburg, Department of Urology (Germany); Buhtz, P. [Institute of Pathology, University of Magdeburg (Germany); Fischbach, F.; Pech, M. [University of Magdeburg, Department of Radiology (Germany); Mahnkopf, D. [Institute of Medical Technology and Research (Germany); Kropf, S. [Institute of Biometry, University of Magdeburg (Germany); Roessner, A. [Institute of Pathology, University of Magdeburg (Germany); Ricke, J. [University of Magdeburg, Department of Radiology (Germany); Schostak, M.; Liehr, U.-B. [University of Magdeburg, Department of Urology (Germany)

2013-04-15

Irreversible electroporation (IRE) is a novel nonthermal tissue ablation technique by high current application leading to apoptosis without affecting extracellular matrix. Previous results of renal IRE shall be supplemented by functional MRI and differentiated histological analysis of renal parenchyma in a chronic treatment setting. Three swine were treated with two to three multifocal percutaneous IRE of the right kidney. MRI was performed before, 30 min (immediate-term), 7 days (short-term), and 28 days (mid-term) after IRE. A statistical analysis of the lesion surrounded renal parenchyma intensities was made to analyze functional differences depending on renal part, side and posttreatment time. Histological follow-up of cortex and medulla was performed after 28 days. A total of eight ablations were created. MRI showed no collateral damage of surrounded tissue. The highest visual contrast between lesions and normal parenchyma was obtained by T2-HR-SPIR-TSE-w sequence of DCE-MRI. Ablation zones showed inhomogeneous necroses with small perifocal edema in the short-term and sharp delimitable scars in the mid-term. MRI showed no significant differences between adjoined renal parenchyma around ablations and parenchyma of untreated kidney. Histological analysis demonstrated complete destruction of cortical glomeruli and tubules, while collecting ducts, renal calyxes, and pelvis of medulla were preserved. Adjoined kidney parenchyma around IRE lesions showed no qualitative differences to normal parenchyma of untreated kidney. This porcine IRE study reveals a multifocal renal ablation, while protecting surrounded renal parenchyma and collecting system over a mid-term period. That offers prevention of renal function ablating centrally located or multifocal renal masses.

Short- and Mid-term Effects of Irreversible Electroporation on Normal Renal Tissue: An Animal Model

International Nuclear Information System (INIS)

Wendler, J. J.; Porsch, M.; Hühne, S.; Baumunk, D.; Buhtz, P.; Fischbach, F.; Pech, M.; Mahnkopf, D.; Kropf, S.; Roessner, A.; Ricke, J.; Schostak, M.; Liehr, U.-B.

2013-01-01

Irreversible electroporation (IRE) is a novel nonthermal tissue ablation technique by high current application leading to apoptosis without affecting extracellular matrix. Previous results of renal IRE shall be supplemented by functional MRI and differentiated histological analysis of renal parenchyma in a chronic treatment setting. Three swine were treated with two to three multifocal percutaneous IRE of the right kidney. MRI was performed before, 30 min (immediate-term), 7 days (short-term), and 28 days (mid-term) after IRE. A statistical analysis of the lesion surrounded renal parenchyma intensities was made to analyze functional differences depending on renal part, side and posttreatment time. Histological follow-up of cortex and medulla was performed after 28 days. A total of eight ablations were created. MRI showed no collateral damage of surrounded tissue. The highest visual contrast between lesions and normal parenchyma was obtained by T2-HR-SPIR-TSE-w sequence of DCE-MRI. Ablation zones showed inhomogeneous necroses with small perifocal edema in the short-term and sharp delimitable scars in the mid-term. MRI showed no significant differences between adjoined renal parenchyma around ablations and parenchyma of untreated kidney. Histological analysis demonstrated complete destruction of cortical glomeruli and tubules, while collecting ducts, renal calyxes, and pelvis of medulla were preserved. Adjoined kidney parenchyma around IRE lesions showed no qualitative differences to normal parenchyma of untreated kidney. This porcine IRE study reveals a multifocal renal ablation, while protecting surrounded renal parenchyma and collecting system over a mid-term period. That offers prevention of renal function ablating centrally located or multifocal renal masses.

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

Science.gov (United States)

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

Renal dysfunction induced by long-term exposure to depleted uranium in rats

Energy Technology Data Exchange (ETDEWEB)

Zhu, Guoying; Xiang, Xiqiao; Chen, Xiao; Wang, Lihua; Hu, Heping; Weng, Shifang [Fudan University, Institute of Radiation Medicine, Shanghai (China)

2009-01-15

Depleted uranium (DU) is a kind of radioactive heavy metal which can enter into the body via inhalation (aerosols), ingestion (drinking and eating) and wounds (embedded), and causes chemical and/or radiation-induced toxicities. In this study, male Sprague Dawley rats were surgically implanted in gastrocnemius muscle with DU fragments at three dose levels (low-dose, medium-dose and high-dose), with biologically inert tantalum (Ta) fragments served as controls. At 1 day, 7 days, and 3, 6, and 12 months after implantation, the rats were euthanized and tissue samples were collected, and uranium levels were measured in a variety of tissues by inductively coupled plasma-mass spectrometry (ICP-MS) to analyze the dynamic changes and distribution of uranium in rats. Thereafter, at 3, 6 and 12 months after implantation, the rats were euthanized after the collection of 24 h urine, blood and kidney samples were collected for analysis of DU-induced renal histopathologic changes and renal dysfunction. It was observed that DU concentrations in all the DU implanted groups were higher than that in Ta control group, and DU concentrations in the kidney increased with the implanted times, peaked at the 90 days after implantation, with a high correlation to the implanted DU doses, and then began to decrease gradually and slowly, and the DU concentrations in kidney still maintained at a relatively high level even at the 360 days after implantation. Otherwise, chronic DU contamination could induce the pathological changes of renal glomeruli, tubules and mesenchyme, such as interstitial fibrosis, enlarged interstice of renal tubular epithelial cells, tumefactions and necrosis of epithelial cells, shrinkage and disappearance of cavity of Bowman's capsule. By TEM, it was shown that the basement membrane of glomerulus was incrassated, mitochondrial of kidney proximal tubule had visible tumefaction and became bigger, and the mitochondrial cristae became shorter and disorderly in

Renal dysfunction induced by long-term exposure to depleted uranium in rats

International Nuclear Information System (INIS)

Zhu, Guoying; Xiang, Xiqiao; Chen, Xiao; Wang, Lihua; Hu, Heping; Weng, Shifang

2009-01-01

Depleted uranium (DU) is a kind of radioactive heavy metal which can enter into the body via inhalation (aerosols), ingestion (drinking and eating) and wounds (embedded), and causes chemical and/or radiation-induced toxicities. In this study, male Sprague Dawley rats were surgically implanted in gastrocnemius muscle with DU fragments at three dose levels (low-dose, medium-dose and high-dose), with biologically inert tantalum (Ta) fragments served as controls. At 1 day, 7 days, and 3, 6, and 12 months after implantation, the rats were euthanized and tissue samples were collected, and uranium levels were measured in a variety of tissues by inductively coupled plasma-mass spectrometry (ICP-MS) to analyze the dynamic changes and distribution of uranium in rats. Thereafter, at 3, 6 and 12 months after implantation, the rats were euthanized after the collection of 24 h urine, blood and kidney samples were collected for analysis of DU-induced renal histopathologic changes and renal dysfunction. It was observed that DU concentrations in all the DU implanted groups were higher than that in Ta control group, and DU concentrations in the kidney increased with the implanted times, peaked at the 90 days after implantation, with a high correlation to the implanted DU doses, and then began to decrease gradually and slowly, and the DU concentrations in kidney still maintained at a relatively high level even at the 360 days after implantation. Otherwise, chronic DU contamination could induce the pathological changes of renal glomeruli, tubules and mesenchyme, such as interstitial fibrosis, enlarged interstice of renal tubular epithelial cells, tumefactions and necrosis of epithelial cells, shrinkage and disappearance of cavity of Bowman's capsule. By TEM, it was shown that the basement membrane of glomerulus was incrassated, mitochondrial of kidney proximal tubule had visible tumefaction and became bigger, and the mitochondrial cristae became shorter and disorderly in alignment

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

Science.gov (United States)

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.

Advanced glycation end products overload might explain intracellular cobalamin deficiency in renal dysfunction, diabetes and aging.

Science.gov (United States)

Obeid, Rima; Shannan, Batool; Herrmann, Wolfgang

2011-11-01

Advanced glycation end products (AGEs) contribute to aging. Cobalamin (Cbl) is required for cell growth and functions, and its deficiency causes serious complications. Diabetics and renal patients show high concentrations of Cbl, but metabolic evidence of Cbl deficiency that is reversible after Cbl treatment. Cbl might be sequestered in blood and cannot be delivered to the cell. Megalin mediates the uptake of transcobalamin-Cbl complex into the proximal tubule cells. Megalin is involved in the uptake and degradation of AGEs. In aging, diabetes or renal dysfunction, AGEs might overload megalin thus lowering Cbl uptake. Transcobalamin-Cbl might retain in blood. Shedding of megalin and transcobalamin receptor under glycation conditions is also a possible mechanism of this phenomenon. Copyright © 2011 Elsevier Ltd. All rights reserved.

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

Directory of Open Access Journals (Sweden)

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.

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

Directory of Open Access Journals (Sweden)

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.

Technetium-99m DTPA renal flow studies in Goldblatt hypertension

International Nuclear Information System (INIS)

Nally, J.V.; Clarke, H.S.; Windham, J.P.; Grecos, G.P.; Gross, M.L.; Potvin, W.J.

1985-01-01

Computer-assisted dynamic renal studies were performed on a group of 14 mongrel dogs before and after the induction of unilateral renal artery stenosis. Ninety-second technetium-99m diethylenetriaminepentaacetic acid ([/sup 99m/Tc]DTPA), 15-min [/sup 99m/Tc]DTPA, and 30-min iodine-131 orthoiodohippurate ([ 131 I]hippuran) time-activity curves were analyzed and correlated with reduction of renal blood flow as measured by electromagnetic flow probe and PAH clearance techniques. For blood flow reductions greater than 33%, the [/sup 99m/Tc]DTPA studies were judged diagnostic of unilateral renal artery stenosis in all cases, whereas the [ 131 I]hippuran time-activity curves were indicative of stenosis in only six of ten studies. Thus, in this model we find the computer-assisted 90-sec [/sup 99m/Tc]DTPA renal flow study to be superior to conventional [ 131 I]hippuran renography in the diagnosis of moderate-to-serve unilateral renal artery stenosis

Functionally induced changes in water transport in the proximal tubule segment of rat kidneys

DEFF Research Database (Denmark)

Faarup, Poul; von Holstein-Rathlou, Niels-Henrik; Nørgaard, Tove

2011-01-01

To eliminate freezing artifacts in the proximal tubule cells, two cryotechniques were applied to normal rat kidneys, ie, freeze substitution and special freeze drying. In addition, salt depletion and salt loading were applied to groups of rats to evaluate whether the segmental structure of the pr......To eliminate freezing artifacts in the proximal tubule cells, two cryotechniques were applied to normal rat kidneys, ie, freeze substitution and special freeze drying. In addition, salt depletion and salt loading were applied to groups of rats to evaluate whether the segmental structure...... segment, representing a structural background for the essential transport of water from the proximal tubules to the peritubular capillaries....

Masonry structures built with fictile tubules: Experimental and numerical analyses

Science.gov (United States)

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.

Science.gov (United States)

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.

Monoclonal antibodies that bind the renal Na+/glucose symport system. 1. Identification

International Nuclear Information System (INIS)

Wu, J.S.R.; Lever, J.E.

1987-01-01

Phlorizin is a specific, high-affinity ligand that binds the active site of the Na + /glucose symporter by a Na + -dependent mechanism but is not itself transported across the membrane. The authors have isolated a panel of monoclonal antibodies that influence high-affinity, Na + -dependent phlorizin binding to pig renal brush border membranes. Antibodies were derived after immunization of mice either with highly purified renal brush border membranes or with apical membranes purified from LLC-PK 1 , a cell line of pig renal proximal tubule origin. Antibody 11A3D6, an IgG/sub 2b/, reproducibly stimulated Na + -dependent phlorizin binding whereas antibody 18H10B12, an IgM, strongly inhibited specific binding. These effects were maximal after 30-min incubation and exhibited saturation at increased antibody concentrations. Antibodies did not affect Na + -dependent sugar uptake in vesicles but significantly prevented transport inhibition by bound phlorizin. Antibodies recognized a 75-kDa antigen identified by Western blot analysis of brush border membranes, and a 75-kDa membrane protein could be immunoprecipitated by 18H10B12. These properties, provide compelling evidence that the 75-kDa antigen recognized by these antibodies is a component of the renal Na + /glucose symporter

Selenium intoxication with selenite broth resulting in acute renal failure and severe gastritis

Directory of Open Access Journals (Sweden)

Kamble P

2009-01-01

Full Text Available Selenium (Se is an essential trace element in human and animal nutrition. It is also widely utilized in industrial processes. Reports of acute selenium toxicity in humans are rare. We report a case of a 23-year-old female who consumed about 100 mL of liquid selenite broth and presented with severe nausea, vomiting, abdominal pain, hematemesis and acute renal failure (ARF. The serum selenium level was significantly increased. Gastro-duodenoscopy revealed severe corrosive gastritis. Renal biopsy showed features of acute tubular necrosis (ATN, affecting primarily the proximal tubules. The patient was managed with gastric lavage, blood transfusions, infusion of fresh frozen plasma (FFP and platelet concentrates and hemo-dialysis. The patient was discharged five weeks after admission and her renal functions reco-vered completely by eight weeks after admission. She continues to be on regular follow-up for any possible sequelae of mucosal corrosive damage. This case highlights a case of selenium intoxication from selenite broth resulting in ARF and corrosive gastritis. The recovery was complete.

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

Directory of Open Access Journals (Sweden)

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.

Renal aging in WKY rats: changes in Na+,K+ -ATPase function and oxidative stress.

Science.gov (United States)

Silva, E; Pinto, V; Simão, S; Serrão, M P; Afonso, J; Amaral, J; Pinho, M J; Gomes, P; Soares-da-Silva, P

2010-12-01

It has been suggested that alterations in Na(+),K(+)-ATPase mediate the development of several aging-related pathologies, such as hypertension and diabetes. Thus, we evaluated Na(+),K(+)-ATPase function and H(2)O(2) production in the renal cortex and medulla of Wistar Kyoto (WKY) rats at 13, 52 and 91 weeks of age. Creatinine clearance, proteinuria, urinary excretion of Na(+) and K(+) and fractional excretion of Na(+) were also determined. The results show that at 91 weeks old WKY rats had increased creatinine clearance and did not have proteinuria. Despite aging having had no effect on urinary Na(+) excretion, urinary K(+) excretion was increased and fractional Na(+) excretion was decreased with age. In renal proximal tubules and isolated renal cortical cells, 91 week old rats had decreased Na(+),K(+)-ATPase activity when compared to 13 and 52 week old rats. In renal medulla, 91 week old rats had increased Na(+),K(+)-ATPase activity, paralleled by an increase in protein expression of α(1)-subunit of Na(+),K(+)-ATPase. In addition, renal H(2)O(2) production increased with age and at 91 weeks of age renal medulla H(2)O(2) production was significantly higher than renal cortex production. The present work demonstrates that although at 91 weeks of age WKY rats were able to maintain Na(+) homeostasis, aging was accompanied by alterations in renal Na(+),K(+)-ATPase function. The observed increase in oxidative stress may account, in part, for the observed changes. Possibly, altered Na(+),K(+)-ATPase renal function may precede the development of age-related pathologies and loss of renal function. Copyright © 2010 Elsevier Inc. All rights reserved.

Targeting renal glucose reabsorption to treat hyperglycaemia: the pleiotropic effects of SGLT2 inhibition.

Science.gov (United States)

Vallon, Volker; Thomson, Scott C

2017-02-01

Healthy kidneys filter ∼160 g/day of glucose (∼30% of daily energy intake) under euglycaemic conditions. To prevent valuable energy from being lost in the urine, the proximal tubule avidly reabsorbs filtered glucose up to a limit of ∼450 g/day. When blood glucose levels increase to the point that the filtered load exceeds this limit, the surplus is excreted in the urine. Thus, the kidney provides a safety valve that can prevent extreme hyperglycaemia as long as glomerular filtration is maintained. Most of the capacity for renal glucose reabsorption is provided by sodium glucose cotransporter (SGLT) 2 in the early proximal tubule. In the absence or with inhibition of SGLT2, the renal reabsorptive capacity for glucose declines to ∼80 g/day (the residual capacity of SGLT1), i.e. the safety valve opens at a lower threshold, which makes it relevant to glucose homeostasis from day-to-day. Several SGLT2 inhibitors are now approved glucose lowering agents for individuals with type 2 diabetes and preserved kidney function. By inducing glucosuria, these drugs improve glycaemic control in all stages of type 2 diabetes, while their risk of causing hypoglycaemia is low because they naturally stop working when the filtered glucose load falls below ∼80 g/day and they do not otherwise interfere with metabolic counterregulation. Through glucosuria, SGLT2 inhibitors reduce body weight and body fat, and shift substrate utilisation from carbohydrates to lipids and, possibly, ketone bodies. Because SGLT2 reabsorbs sodium along with glucose, SGLT2 blockers are natriuretic and antihypertensive. Also, because they work in the proximal tubule, SGLT2 inhibitors increase delivery of fluid and electrolytes to the macula densa, thereby activating tubuloglomerular feedback and increasing tubular back pressure. This mitigates glomerular hyperfiltration, reduces the kidney's demand for oxygen and lessens albuminuria. For reasons that are less well understood, SGLT2 inhibitors are

Renal transport and metabolism of nicotinic acid

International Nuclear Information System (INIS)

Schuette, S.; Rose, R.C.

1986-01-01

Renal metabolism and brush-border transport of nicotinic acid were studied in renal cortical slices and brush-border membrane vesicles exposed to a physiological concentration of vitamin (2.2-3.5 microM). Vesicle transport of [ 3 H]nicotinic acid was found to be Na+ dependent and concentrative. The presence of a Na+ gradient resulted in a fivefold increase in the rate of nicotinic acid uptake over that observed with mannitol and caused a transient nicotinic acid accumulation two- to fourfold above the equilibrium value. The effects of membrane potential, pH, and elimination of Na+-H+ exchange were also studied. Cortical slices and isolated tubules exposed to 2.2 microM [ 14 C]nicotinic acid took up vitamin and rapidly metabolized most of it to intermediates in the Preiss-Handler pathway for NAD biosynthesis; little free nicotinic acid was detectable intracellularly. The replacement of Na+ with Li+ in the bathing medium reduced total accumulation of 14 C label primarily as a result of reduced nicotinic acid uptake. Cortical tissue concentrated free nicotinic acid only when the involved metabolic pathways were saturated by levels of nicotinic acid far in excess of what occurs in vivo

Impacts of nitric oxide and superoxide on renal medullary oxygen transport and urine concentration

Science.gov (United States)

Edwards, Aurélie; Layton, Anita T.

2015-01-01

The goal of this study was to investigate the reciprocal interactions among oxygen (O2), nitric oxide (NO), and superoxide (O2−) and their effects on medullary oxygenation and urinary output. To accomplish that goal, we developed a detailed mathematical model of solute transport in the renal medulla of the rat kidney. The model represents the radial organization of the renal tubules and vessels, which centers around the vascular bundles in the outer medulla and around clusters of collecting ducts in the inner medulla. Model simulations yield significant radial gradients in interstitial fluid oxygen tension (Po2) and NO and O2− concentration in the OM and upper IM. In the deep inner medulla, interstitial fluid concentrations become much more homogeneous, as the radial organization of tubules and vessels is not distinguishable. The model further predicts that due to the nonlinear interactions among O2, NO, and O2−, the effects of NO and O2− on sodium transport, osmolality, and medullary oxygenation cannot be gleaned by considering each solute's effect in isolation. An additional simulation suggests that a sufficiently large reduction in tubular transport efficiency may be the key contributing factor, more so than oxidative stress alone, to hypertension-induced medullary hypoxia. Moreover, model predictions suggest that urine Po2 could serve as a biomarker for medullary hypoxia and a predictor of the risk for hospital-acquired acute kidney injury. PMID:25651567

Selective pharmacological modulation of renal peripheral-type benzodiazepine binding by treatment with diuretic drugs

International Nuclear Information System (INIS)

Lukeman, D.S.; Vaughn, D.A.; Fanestil, D.D.

1988-01-01

The authors have assessed the effects of in vivo administration of different classes of diuretic drugs on the expression of the peripheral-type benzodiazepine binding site (PBBS) in crude membranes derived from the cortex and outer medulla of rat kidney by saturation analysis with the PBBS-selective ligands [ 3 H]RO5-4864 and [ 3 H]PH 11195 in cortex and [ 3 H]RO5-4864 in outer medulla. Administration for 14-15 days of furosemide, a drug that blocks NaCl-KCl coupled transport in the thick ascending limb of the loop of Henle, produced a significant doubling in the PBBS density (B/sub max/) in outer medulla, a region of the kidney rich in thick ascending limbs, and produced a lesser but significant increase in PBBS density in the cortex. Conversely, administration for 14-15 days of the carbonic anhydrase inhibitor acetazolamide, which acts predominantly in the proximal tubule, and hydrochlorothiazide, which acts predominantly in the early distal tubule, elicited statistically significant increases in PBBS density in renal cortex but not in renal outer medulla. Furthermore, all drug treatments were without effect on the equilibrium dissociation constants (K/sub d/s) of [ 3 H]RO5-4864 and [ 3 H]PK 11195 binding to cortical and outer medullary membrane preparations. These findings demonstrate that the PBBS can be selectively up-regulated in different regions of the kidney by diuretic drugs with different modes/sites of action. 50 references, 1 table

Biomarkers-a potential route for improved diagnosis and management of ongoing renal damage.

Science.gov (United States)

Oberbauer, R

2008-12-01

Currently, the identification and validation of biomarkers of kidney injury is among the top priorities of many diagnostic biotechnology companies as well as academic research institutes. Specifically, in renal transplantation, validated biomarkers of tissue injury with good discriminatory power between the various renal compartments and the underlying pathophysiology are desired, because sequential allograft biopsies are limited in number and cannot be used as a screening tool. Given the high demands on these markers, it is not surprising that none of those currently under evaluation has been thoroughly validated for a specific entity. Published biomarker candidates for early tubular damage include neutrophil gelatinase-associated lipocalin (NGAL), interleukin (IL)-18, soluble CD30, perforin, and granzyme B. Recently, C4d flow panel reactive antibodies were evaluated as biomarkers for humoral alloimmune responses. Additional biomarkers such as FOXP3 and kidney injury molecule 1 have been studied in the maintenance phase of renal transplantation. Given the complex prerequisites, it is not surprising that no biomarker panel has been sufficiently validated for clinical use. However, in the near future a biomarker for use as an indicator of renal tubule cell injury will be available. Troponin T or transaminase of the kidney may then at least be used to differentiate between functional renal failure (equivalent to a rise in creatinine) and intrinsic kidney injury.

Prolonged Pulmonary Exposure to Diesel Exhaust Particles Exacerbates Renal Oxidative Stress, Inflammation and DNA Damage in Mice with Adenine-Induced Chronic Renal Failure

Directory of Open Access Journals (Sweden)

Abderrahim Nemmar

2016-05-01

Full Text Available Background/Aims: Epidemiological evidence indicates that patients with chronic kidney diseases have increased susceptibility to adverse outcomes related to long-term exposure to particulate air pollution. However, mechanisms underlying these effects are not fully understood. Methods: Presently, we assessed the effect of prolonged exposure to diesel exhaust particles (DEP on chronic renal failure induced by adenine (0.25% w/w in feed for 4 weeks, which is known to involve inflammation and oxidative stress. DEP (0.5m/kg was intratracheally (i.t. instilled every 4th day for 4 weeks (7 i.t. instillation. Four days following the last exposure to either DEP or saline (control, various renal endpoints were measured. Results: While body weight was decreased, kidney weight increased in DEP+adenine versus saline+adenine or DEP. Water intake, urine volume, relative kidney weight were significantly increased in adenine+DEP versus DEP and adenine+saline versus saline. Plasma creatinine and urea increased and creatinine clearance decreased in adenine+DEP versus DEP and adenine+saline versus saline. Tumor necrosis factor α, lipid peroxidation and reactive oxygen species were significantly increased in adenine+DEP compared with either DEP or adenine+saline. The antioxidant calase was significantly decreased in adenine+DEP compared with either adenine+saline or DEP. Notably, renal DNA damage was significantly potentiated in adenine+DEP compared with either adenine+saline or DEP. Similarly, systolic blood pressure was increased in adenine+DEP versus adenine+saline or DEP, and in DEP versus saline. Histological evaluation revealed more collagen deposition, higher number of necrotic cell counts and dilated tubules, cast formation and collapsing glomeruli in adenine+DEP versus adenine+saline or DEP. Conclusion: Prolonged pulmonary exposure to diesel exhaust particles worsen renal oxidative stress, inflammation and DNA damage in mice with adenine-induced chronic

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

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

Recombinant erythropoietin acutely decreases renal perfusion and decouples the renin-angiotensin-aldosterone system.

Science.gov (United States)

Aachmann-Andersen, Niels J; Christensen, Soren J; Lisbjerg, Kristian; Oturai, Peter; Johansson, Pär I; Holstein-Rathlou, Niels-Henrik; Olsen, Niels V

2018-03-01

The effect of recombinant erythropoietin (rhEPO) on renal and systemic hemodynamics was evaluated in a randomized double-blinded, cross-over study. Sixteen healthy subjects were tested with placebo, or low-dose rhEPO for 2 weeks, or high-dose rhEPO for 3 days. Subjects refrained from excessive salt intake, according to instructions from a dietitian. Renal clearance studies were done for measurements of renal plasma flow, glomerular filtration rate (GFR) and the segmentel tubular handling of sodium and water (lithium clearance). rhEPO increased arterial blood pressure, total peripheral resistance, and renal vascular resistance, and decreased renal plasma flow in the high-dose rhEPO intervention and tended to decrease GFR. In spite of the decrease in renal perfusion, rhEPO tended to decrease reabsorption of sodium and water in the proximal tubule and induced a prompt decrease in circulating levels of renin and aldosterone, independent of changes in red blood cell mass, blood volumes, and blood pressure. We also found changes in biomarkers showing evidence that rhEPO induced a prothrombotic state. Our results suggest that rhEPO causes a direct downregulation in proximal tubular reabsorption that seems to decouple the activity of the renin-angiotensin-aldosterone system from changes in renal hemodynamics. This may serve as a negative feed-back mechanism on endogenous synthesis of EPO when circulating levels of EPO are high. These results demonstrates for the first time in humans a direct effect of rhEPO on renal hemodynamics and a decoupling of the renin-angiotensin-aldosterone system. © 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Study to improve the precision of calculation of split renal clearance by gamma camera method using 99mTc-MAG3

International Nuclear Information System (INIS)

Mimura, Hiroaki; Tomomitsu, Tatsushi; Yanagimoto, Shinichi

1999-01-01

Both fundamental and clinical studies were performed to improve the precision with which split renal clearance is calculated from the relation between renal clearance and the total renal uptake rate by using 99m Tc-MAG 3 , which is mainly excreted into the proximal renal tubules. In the fundamental study, the most suitable kidney phantom threshold values for the extracted renal outline were investigated with regard to size, radioactivity, depth of the kidney phantom, and radioactivity in the background. In the clinical study, suitable timing to obtain additional images for making the ROI and the standard point for calculation of renal uptake rate were investigated. The results indicated that, although suitable threshold values were distributed from 25% to 45%, differences in size, solution activity, and the position of the phantom or BG activity did not have significant effects. Comparing 1-3 min with 2-5 min as the time for additional images for ROI, we found that renal areas using the former time showed higher values, and the correlation coefficient of the regression formula improved significantly. Comparison of the timing for the start of data acquisition with the end of the arterial phase as a standard point of calculating renal uptake rate showed improvement in the latter. (author)

Cancer drug troglitazone stimulates the growth and response of renal cells to hypoxia inducible factors

Energy Technology Data Exchange (ETDEWEB)

Taub, Mary, E-mail: biochtau@buffalo.edu

2016-03-11

Troglitazone has been used to suppress the growth of a number of tumors through apoptosis and autophagy. However, previous in vitro studies have employed very high concentrations of troglitazone (≥10{sup −5} M) in order to elicit growth inhibitory effects. In this report, when employing lower concentrations of troglitazone in defined medium, troglitazone was observed to stimulate the growth of primary renal proximal tubule (RPT) cells. Rosiglitazone, like troglitazone, is a thiazolidinedione (TZD) that is known to activate Peroxisome Proliferator Activated Receptor Υ (PPARΥ). Notably, rosiglitazone also stimulates RPT cell growth, as does Υ-linolenic acids, another PPARΥ agonist. The PPARΥ antagonist GW9662 inhibited the growth stimulatory effect of troglitazone. In addition, troglitazone stimulated transcription by a PPAR Response Element/Luciferase construct. These results are consistent with the involvement of PPARΥ as a mediator of the growth stimulatory effect of troglitazone. In a number of tumor cells, the expression of hypoxia inducible factor (HIF) is increased, promoting the expression of HIF inducible genes, and vascularization. Troglitazone was observed to stimulate transcription by a HIF/luciferase construct. These observations indicate that troglitazone not only promotes growth, also the survival of RPT cells under conditions of hypoxia. - Highlights: • Troglitazone and rosiglitazone stimulate renal proximal tubule cell growth. • Troglitazone and linolenic acid stimulate growth via PPARϒ. • Linolenic acid stimulates growth in the presence of fatty acid free serum albumin. • Rosiglitazone stimulates transcription by a HRE luciferase construct.

Cancer drug troglitazone stimulates the growth and response of renal cells to hypoxia inducible factors

International Nuclear Information System (INIS)

Taub, Mary

2016-01-01

Troglitazone has been used to suppress the growth of a number of tumors through apoptosis and autophagy. However, previous in vitro studies have employed very high concentrations of troglitazone (≥10"−"5 M) in order to elicit growth inhibitory effects. In this report, when employing lower concentrations of troglitazone in defined medium, troglitazone was observed to stimulate the growth of primary renal proximal tubule (RPT) cells. Rosiglitazone, like troglitazone, is a thiazolidinedione (TZD) that is known to activate Peroxisome Proliferator Activated Receptor Υ (PPARΥ). Notably, rosiglitazone also stimulates RPT cell growth, as does Υ-linolenic acids, another PPARΥ agonist. The PPARΥ antagonist GW9662 inhibited the growth stimulatory effect of troglitazone. In addition, troglitazone stimulated transcription by a PPAR Response Element/Luciferase construct. These results are consistent with the involvement of PPARΥ as a mediator of the growth stimulatory effect of troglitazone. In a number of tumor cells, the expression of hypoxia inducible factor (HIF) is increased, promoting the expression of HIF inducible genes, and vascularization. Troglitazone was observed to stimulate transcription by a HIF/luciferase construct. These observations indicate that troglitazone not only promotes growth, also the survival of RPT cells under conditions of hypoxia. - Highlights: • Troglitazone and rosiglitazone stimulate renal proximal tubule cell growth. • Troglitazone and linolenic acid stimulate growth via PPARϒ. • Linolenic acid stimulates growth in the presence of fatty acid free serum albumin. • Rosiglitazone stimulates transcription by a HRE luciferase construct.

Furosemide-caused alterations in the renogram of patients with renal disease and hypertension

International Nuclear Information System (INIS)

Camargo, E.E.; Papaleo Netto, M.; Dias Neto, A.L.; Carvalho, N.

1975-01-01

In 21 patients suffering - separately or simultaneously - from hypertension or nephropathy, the behavior of the differential effective renal plasma flow (ERPF sub(R) and ERPF sub(D)) and of the following time parameters of the renogram: time from point of injection to point of maximum count rate (T sub(max)), time from maximum count rate to point of 1/2 maximum count (T sub(1/2)), 'secretory' (T sub(S)) 'excretory' (T sub(ex)) half-lives of hippuran- 131 I are studied, before and after administration of furosemide. The diuretic markedly shortens all the time parameters studied, but does not change the differential effective renal plasma flow. Results suggest an action of the drug on the proximal tubule and also on loop of Henle. Neither the rate of the supply of the tracer to the tubular cell nor the tracer's pathway are altered by the diuretic [pt

Follistatin, an Activin Antagonist, Ameliorates Renal Interstitial Fibrosis in a Rat Model of Unilateral Ureteral Obstruction

Directory of Open Access Journals (Sweden)

Akito Maeshima

2014-01-01

Full Text Available Activin, a member of the TGF-β superfamily, regulates cell growth and differentiation in various cell types. Activin A acts as a negative regulator of renal development as well as tubular regeneration after renal injury. However, it remains unknown whether activin A is involved in renal fibrosis. To clarify this issue, we utilized a rat model of unilateral ureteral obstruction (UUO. The expression of activin A was significantly increased in the UUO kidneys compared to that in contralateral kidneys. Activin A was detected in glomerular mesangial cells and interstitial fibroblasts in normal kidneys. In UUO kidneys, activin A was abundantly expressed by interstitial α-SMA-positive myofibroblasts. Administration of recombinant follistatin, an activin antagonist, reduced the fibrotic area in the UUO kidneys. The number of proliferating cells in the interstitium, but not in the tubules, was significantly lower in the follistatin-treated kidneys. Expression of α-SMA, deposition of type I collagen and fibronectin, and CD68-positive macrophage infiltration were significantly suppressed in the follistatin-treated kidneys. These data suggest that activin A produced by interstitial fibroblasts acts as a potent profibrotic factor during renal fibrosis. Blockade of activin A action may be a novel approach for the prevention of renal fibrosis progression.

Antioxidant Effects of Selenium on Seminiferous Tubules of Immature Mice Testis

Directory of Open Access Journals (Sweden)

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

Directory of Open Access Journals (Sweden)

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.

MT1-MMP-mediated basement membrane remodeling modulates renal development

International Nuclear Information System (INIS)

Riggins, Karen S.; Mernaugh, Glenda; Su, Yan; Quaranta, Vito; Koshikawa, Naohiko; Seiki, Motoharu; Pozzi, Ambra; Zent, Roy

2010-01-01

Extracellular matrix (ECM) remodeling regulates multiple cellular functions required for normal development and tissue repair. Matrix metalloproteinases (MMPs) are key mediators of this process and membrane targeted MMPs (MT-MMPs) in particular have been shown to be important in normal development of specific organs. In this study we investigated the role of MT1-MMP in kidney development. We demonstrate that loss of MT1-MMP leads to a renal phenotype characterized by a moderate decrease in ureteric bud branching morphogenesis and a severe proliferation defect. The kidneys of MT1-MMP-null mice have increased deposition of collagen IV, laminins, perlecan, and nidogen and the phenotype is independent of the MT-1MMP target, MMP-2. Utilizing in vitro systems we demonstrated that MTI-MMP proteolytic activity is required for renal tubule cells to proliferate in three dimensional matrices and to migrate on collagen IV and laminins. Together these data suggest an important role for MT1-MMP in kidney development, which is mediated by its ability to regulate cell proliferation and migration by proteolytically cleaving kidney basement membrane components.

Autocrine CSF-1 and CSF-1 Receptor Co-expression Promotes Renal Cell Carcinoma Growth

Science.gov (United States)

Menke, Julia; Kriegsmann, Jörg; Schimanski, Carl Christoph; Schwartz, Melvin M.; Schwarting, Andreas; Kelley, Vicki R.

2011-01-01

Renal cell carcinoma is increasing in incidence but the molecular mechanisms regulating its growth remain elusive. Co-expression of the monocytic growth factor CSF-1 and its receptor CSF-1R on renal tubular epithelial cells (TEC) will promote proliferation and anti-apoptosis during regeneration of renal tubules. Here we show that a CSF-1-dependent autocrine pathway is also responsible for the growth of renal cell carcinoma (RCC). CSF-1 and CSF-1R were co-expressed in RCC and TEC proximally adjacent to RCC. CSF-1 engagement of CSF-1R promoted RCC survival and proliferation and reduced apoptosis, in support of the likelihood that CSF-1R effector signals mediate RCC growth. In vivo CSF-1R blockade using a CSF-1R tyrosine kinase inhibitor decreased RCC proliferation and macrophage infiltration in a manner associated with a dramatic reduction in tumor mass. Further mechanistic investigations linked CSF-1 and EGF signaling in RCC. Taken together, our results suggest that budding RCC stimulates the proximal adjacent microenvironment in the kidney to release mediators of CSF-1, CSF-1R and EGF expression in RCC. Further, our findings imply that targeting CSF-1/CSF-1R signaling may be therapeutically effective in RCC. PMID:22052465

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.

Effect of cyclosporine, tacrolimus and sirolimus on cellular senescence in renal epithelial cells.

Science.gov (United States)

Koppelstaetter, Christian; Kern, Georg; Leierer, Gisela; Mair, Sabine Maria; Mayer, Gert; Leierer, Johannes

2018-04-01

In transplantation medicine calcineurin inhibitors (CNI) still represent the backbone of immunosuppressive therapy. The nephrotoxic potential of the CNI Cyclosporine A (CsA) and Tacrolimus (FK506) is well recognized and CNI not only have been linked with toxicity, but also with cellular senescence which hinders parenchymal tissue regeneration and thus may prime kidneys for subsequent insults. To minimize pathological effects on kidney grafts, alternative immunosuppressive agents like mTOR inhibitors or the T-cell co-stimulation blocker Belatacept have been introduced. We compared the effects of CsA, FK506 and Sirolimus on the process of cellular senescence in different human renal tubule cell types (HK2, RPTEC). Telomere length (by real time PCR), DNA synthesis (by BrdU incorporation), cell viability (by Resazurin conversion), gene expression (by RT-PCR), protein (by western blotting), Immuncytochemistry and H 2 O 2 production (by Amplex Red® conversion) were evaluated. DNA synthesis was significantly reduced when cells were treated with cyclosporine but not with tacrolimus and sirolimus. Resazurin conversion was not altered by all three immunosuppressive agents. The gene expression as well as protein production of the cell cycle inhibitor p21 (CDKN1A) but not p16 (CDKN2A) was significantly induced by cyclosporine compared to the other two immunosuppressive agents when determined by western blotting an immuncytochemistry. Relative telomere length was reduced and hydrogen peroxide production increased after treatment with CsA but not with FK506 or sirolimus. In summary, renal tubule cells exposed to CsA show clear signs of cellular senescence where on the contrary the second calcineurin inhibitor FK506 and the mTOR inhibitor sirolimus are not involved in such mechanisms. Chronic renal allograft dysfunction could be in part triggered by cellular senescence induced by immunosuppressive medication and the choice of drug could therefore influence long term outcome

Percutaneous Radiofrequency Ablation Versus Robotic-Assisted Partial Nephrectomy for the Treatment of Small Renal Cell Carcinoma

Energy Technology Data Exchange (ETDEWEB)

Pantelidou, Maria [King’s Health Partners, Department of Interventional Radiology, Guy’s and St. Thomas’ Hospitals, NHS Foundation Trust (United Kingdom); Challacombe, Ben [King’s Health Partners, Department of Urology, Guy’s and St. Thomas’ Hospitals, NHS Foundation Trust (United Kingdom); McGrath, Andrew [King’s Health Partners, Department of Interventional Radiology, Guy’s and St. Thomas’ Hospitals, NHS Foundation Trust (United Kingdom); Brown, Matthew [King’s Health Partners, Department of Urology, Guy’s and St. Thomas’ Hospitals, NHS Foundation Trust (United Kingdom); Ilyas, Shahzad; Katsanos, Konstantinos, E-mail: konstantinos.katsanos@gstt.nhs.uk; Adam, Andreas [King’s Health Partners, Department of Interventional Radiology, Guy’s and St. Thomas’ Hospitals, NHS Foundation Trust (United Kingdom)

2016-11-15

IntroductionThe authors compared the oncologic outcomes of radiofrequency ablation (RFA) with robotic-assisted partial nephrectomy (RPN) for the treatment of T1 stage renal cell carcinoma (RCC).Materials and methodsThis was a retrospective data analysis of a high-volume single tertiary centre. Patients were treated with RFA or RPN following multidisciplinary decision making. Only histologically proven RCCs were included. Baseline demographics were collected, and PADUA scores of tumour features were calculated to standardize baseline anatomy. Peri-operative complications, kidney function and oncological outcomes were compared.ResultsSixty-three cases were included in each group. Baseline renal function was poorer in RFA, and 16/63 RFA patients had tumours in single kidneys compared to 1/63 RPN cases (p < 0.001). Length of stay was shorter in RFA (1 vs. 3 days, p < 0.0001). Post-procedure renal function decline at 30 days was significantly less in RFA [(−0.8) ± 9.6 vs. (−16.1) ± 19.5 mls/min/1.73 m{sup 2}; p < 0.0001]. More minor complications were recorded in RPN (10/63 vs. 4/63, p = 0.15), but local recurrence was numerically higher in RFA (6/63 vs. 1/63, p = 0.11). Disease-free survival (DFS) was not significantly different (adjusted HR = 0.6, 95 % Cl 0.1–3.7; p = 0.60). Increasing tumour size was an independent predictor of local recurrence (adjusted HR = 1.7; 95 % Cl 1.1–2.6 per cm; p = 0.02).ConclusionsBoth RPN and RFA offer very good oncological outcomes for the treatment of T1 RCC with low peri-operative morbidity and similar oncologic outcomes. RFA demonstrated fewer peri-operative complications and better preservation of renal function, whereas RPN had an insignificantly lower local recurrence rate. RFA should be offered alongside RPN for selected cases.

Percutaneous Radiofrequency Ablation Versus Robotic-Assisted Partial Nephrectomy for the Treatment of Small Renal Cell Carcinoma

International Nuclear Information System (INIS)

Pantelidou, Maria; Challacombe, Ben; McGrath, Andrew; Brown, Matthew; Ilyas, Shahzad; Katsanos, Konstantinos; Adam, Andreas

2016-01-01

IntroductionThe authors compared the oncologic outcomes of radiofrequency ablation (RFA) with robotic-assisted partial nephrectomy (RPN) for the treatment of T1 stage renal cell carcinoma (RCC).Materials and methodsThis was a retrospective data analysis of a high-volume single tertiary centre. Patients were treated with RFA or RPN following multidisciplinary decision making. Only histologically proven RCCs were included. Baseline demographics were collected, and PADUA scores of tumour features were calculated to standardize baseline anatomy. Peri-operative complications, kidney function and oncological outcomes were compared.ResultsSixty-three cases were included in each group. Baseline renal function was poorer in RFA, and 16/63 RFA patients had tumours in single kidneys compared to 1/63 RPN cases (p < 0.001). Length of stay was shorter in RFA (1 vs. 3 days, p < 0.0001). Post-procedure renal function decline at 30 days was significantly less in RFA [(−0.8) ± 9.6 vs. (−16.1) ± 19.5 mls/min/1.73 m"2; p < 0.0001]. More minor complications were recorded in RPN (10/63 vs. 4/63, p = 0.15), but local recurrence was numerically higher in RFA (6/63 vs. 1/63, p = 0.11). Disease-free survival (DFS) was not significantly different (adjusted HR = 0.6, 95 % Cl 0.1–3.7; p = 0.60). Increasing tumour size was an independent predictor of local recurrence (adjusted HR = 1.7; 95 % Cl 1.1–2.6 per cm; p = 0.02).ConclusionsBoth RPN and RFA offer very good oncological outcomes for the treatment of T1 RCC with low peri-operative morbidity and similar oncologic outcomes. RFA demonstrated fewer peri-operative complications and better preservation of renal function, whereas RPN had an insignificantly lower local recurrence rate. RFA should be offered alongside RPN for selected cases.

Renal Impairment with Sublethal Tubular Cell Injury in a Chronic Liver Disease Mouse Model.

Directory of Open Access Journals (Sweden)

Tokiko Ishida

Full Text Available The pathogenesis of renal impairment in chronic liver diseases (CLDs has been primarily studied in the advanced stages of hepatic injury. Meanwhile, the pathology of renal impairment in the early phase of CLDs is poorly understood, and animal models to elucidate its mechanisms are needed. Thus, we investigated whether an existing mouse model of CLD induced by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC shows renal impairment in the early phase. Renal injury markers, renal histology (including immunohistochemistry for tubular injury markers and transmission electron microscopy, autophagy, and oxidative stress were studied longitudinally in DDC- and standard diet-fed BALB/c mice. Slight but significant renal dysfunction was evident in DDC-fed mice from the early phase. Meanwhile, histological examinations of the kidneys with routine light microscopy did not show definitive morphological findings, and electron microscopic analyses were required to detect limited injuries such as loss of brush border microvilli and mitochondrial deformities. Limited injuries have been recently designated as sublethal tubular cell injury. As humans with renal impairment, either with or without CLD, often show almost normal tubules, sublethal injury has been of particular interest. In this study, the injuries were associated with mitochondrial aberrations and oxidative stress, a possible mechanism for sublethal injury. Intriguingly, two defense mechanisms were associated with this injury that prevent it from progressing to apparent cell death: autophagy and single-cell extrusion with regeneration. Furthermore, the renal impairment of this model progressed to chronic kidney disease with interstitial fibrosis after long-term DDC feeding. These findings indicated that DDC induces renal impairment with sublethal tubular cell injury from the early phase, leading to chronic kidney disease. Importantly, this CLD mouse model could be useful for studying the

Akt Substrate of 160 kD Regulates Na+,K+-ATPase Trafficking in Response to Energy Depletion and Renal Ischemia

Science.gov (United States)

Alves, Daiane S.; Thulin, Gunilla; Loffing, Johannes; Kashgarian, Michael

2015-01-01

Renal ischemia and reperfusion injury causes loss of renal epithelial cell polarity and perturbations in tubular solute and fluid transport. Na+,K+-ATPase, which is normally found at the basolateral plasma membrane of renal epithelial cells, is internalized and accumulates in intracellular compartments after renal ischemic injury. We previously reported that the subcellular distribution of Na+,K+-ATPase is modulated by direct binding to Akt substrate of 160 kD (AS160), a Rab GTPase-activating protein that regulates the trafficking of glucose transporter 4 in response to insulin and muscle contraction. Here, we investigated the effect of AS160 on Na+,K+-ATPase trafficking in response to energy depletion. We found that AS160 is required for the intracellular accumulation of Na+,K+-ATPase that occurs in response to energy depletion in cultured epithelial cells. Energy depletion led to dephosphorylation of AS160 at S588, which was required for the energy depletion–induced accumulation of Na,K-ATPase in intracellular compartments. In AS160-knockout mice, the effects of renal ischemia on the distribution of Na+,K+-ATPase were substantially reduced in the epithelial cells of distal segments of the renal tubules. These data demonstrate that AS160 has a direct role in linking the trafficking of Na+,K+-ATPase to the energy state of renal epithelial cells. PMID:25788531

Akt Substrate of 160 kD Regulates Na+,K+-ATPase Trafficking in Response to Energy Depletion and Renal Ischemia.

Science.gov (United States)

Alves, Daiane S; Thulin, Gunilla; Loffing, Johannes; Kashgarian, Michael; Caplan, Michael J

2015-11-01

Renal ischemia and reperfusion injury causes loss of renal epithelial cell polarity and perturbations in tubular solute and fluid transport. Na(+),K(+)-ATPase, which is normally found at the basolateral plasma membrane of renal epithelial cells, is internalized and accumulates in intracellular compartments after renal ischemic injury. We previously reported that the subcellular distribution of Na(+),K(+)-ATPase is modulated by direct binding to Akt substrate of 160 kD (AS160), a Rab GTPase-activating protein that regulates the trafficking of glucose transporter 4 in response to insulin and muscle contraction. Here, we investigated the effect of AS160 on Na(+),K(+)-ATPase trafficking in response to energy depletion. We found that AS160 is required for the intracellular accumulation of Na(+),K(+)-ATPase that occurs in response to energy depletion in cultured epithelial cells. Energy depletion led to dephosphorylation of AS160 at S588, which was required for the energy depletion-induced accumulation of Na,K-ATPase in intracellular compartments. In AS160-knockout mice, the effects of renal ischemia on the distribution of Na(+),K(+)-ATPase were substantially reduced in the epithelial cells of distal segments of the renal tubules. These data demonstrate that AS160 has a direct role in linking the trafficking of Na(+),K(+)-ATPase to the energy state of renal epithelial cells. Copyright © 2015 by the American Society of Nephrology.

Laparoscopic bilateral nephroureterectomy and bladder cuff excision for native renal pelvic and ureteral transitional cell carcinoma after renal transplantation.

Directory of Open Access Journals (Sweden)

Chen C

2003-01-01

Full Text Available A 37-years-old female who was suffering from end-stage renal disease for about 6 years received allograft renal transplantation 4 years ago. She has been receiving 50mg of Cyclosporin A orally daily for immuno-suppression since then. Gross haematuria was noted and computerised tomography showed native left renal pelvic and ureteral multi-focal transitional cell carcinoma with severe hydronephrosis. Laparoscopic bilateral nephroureterectomy and bladder cuff excision were performed. In the past, history of previous operation was considered a relative contraindication for laparoscopic surgery. To our knowledge, we present the first case of laparoscopic treatment for native renal pelvic and ureteral transitional cell carcinoma after renal allograft transplantation without a hand-assisted device. This case shows the feasibility of laparoscopic bilateral nephroureterectomy in patients with transplanted kidneys.

Sistematização da Assistência de Enfermagem ao portador de Diabetes Mellitus e Insuficiência Renal Crônica

Directory of Open Access Journals (Sweden)

Nildo Batista Mascarenhas

Full Text Available Tratou-se de um estudo de caso clínico desenvolvido durante as atividades práticas da disciplina Enfermagem Clínico-Cirúrgica I, do curso de Graduação em Enfermagem de uma universidade pública do Estado da Bahia, que objetivou relatar a aplicação da Sistematização da Assistência de Enfermagem na assistência a um paciente portador de Diabetes Mellitus e Insuficiência Renal Crônica. Com o desenvolvimento do estudo, em especial após a melhora positiva da paciente face às condutas planejadas e implementadas e, considerando as reflexões que emergiram, foi possível constatar a necessidade da interface entre a Sistematização da Assistência de Enfermagem, equipe de enfermagem e paciente no processo do cuidar, frente à excelência e singularidade dos cuidados de enfermagem

Sistematização da Assistência de Enfermagem ao portador de Diabetes Mellitus e Insuficiência Renal Crônica

Directory of Open Access Journals (Sweden)

Nildo Batista Mascarenhas

2011-02-01

Full Text Available Tratou-se de um estudo de caso clínico desenvolvido durante as atividades práticas da disciplina Enfermagem Clínico-Cirúrgica I, do curso de Graduação em Enfermagem de uma universidade pública do Estado da Bahia, que objetivou relatar a aplicação da Sistematização da Assistência de Enfermagem na assistência a um paciente portador de Diabetes Mellitus e Insuficiência Renal Crônica. Com o desenvolvimento do estudo, em especial após a melhora positiva da paciente face às condutas planejadas e implementadas e, considerando as reflexões que emergiram, foi possível constatar a necessidade da interface entre a Sistematização da Assistência de Enfermagem, equipe de enfermagem e paciente no processo do cuidar, frente à excelência e singularidade dos cuidados de enfermagem

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.

Urinary Proteolytic Activation of Renal Epithelial Na+ Channels in Chronic Heart Failure.

Science.gov (United States)

Zheng, Hong; Liu, Xuefei; Sharma, Neeru M; Li, Yulong; Pliquett, Rainer U; Patel, Kaushik P

2016-01-01

One of the key mechanisms involved in renal Na(+) retention in chronic heart failure (CHF) is activation of epithelial Na(+) channels (ENaC) in collecting tubules. Proteolytic cleavage has an important role in activating ENaC. We hypothesized that enhanced levels of proteases in renal tubular fluid activate ENaC, resulting in renal Na(+) retention in rats with CHF. CHF was produced by left coronary artery ligation in rats. By immunoblotting, we found that several urinary serine proteases were significantly increased in CHF rats compared with sham rats (fold increases: furin 6.7, prostasin 23.6, plasminogen 2.06, and plasmin 3.57 versus sham). Similar increases were observed in urinary samples from patients with CHF. Whole-cell patch clamp was conducted in cultured renal collecting duct M-1 cells to record Na(+) currents. Protease-rich urine (from rats and patients with CHF) significantly increased the Na(+) inward current in M-1 cells. Two weeks of protease inhibitor treatment significantly abrogated the enhanced diuretic and natriuretic responses to ENaC inhibitor benzamil in rats with CHF. Increased podocyte lesions were observed in the kidneys of rats with CHF by transmission electron microscopy. Consistent with these results, podocyte damage markers desmin and podocin expressions were also increased in rats with CHF (increased ≈2-folds). These findings suggest that podocyte damage may lead to increased proteases in the tubular fluid, which in turn contributes to the enhanced renal ENaC activity, providing a novel mechanistic insight for Na(+) retention commonly observed in CHF. © 2015 American Heart Association, Inc.

Urinary proteolytic activation of renal epithelial Na+ channels in chronic heart failure

Science.gov (United States)

Zheng, Hong; Liu, Xuefei; Sharma, Neeru M.; Li, Yulong; Pliquett, Rainer U; Patel, Kaushik P.

2015-01-01

One of the key mechanisms involved in renal Na+ retention in chronic heart failure (CHF) is activation of epithelial Na+ channels (ENaC) in collecting tubules. Proteolytic cleavage has an important role in activating ENaC. We hypothesized that enhanced levels of proteases in renal tubular fluid activate ENaC resulting in renal Na+ retention in rats with CHF. CHF was produced by left coronary artery ligation in rats. By immunoblotting, we found that several urinary serine proteases were significantly increased in CHF rats compared to sham rats (fold increases: furin 6.7, prostasin 23.6, plasminogen 2.06 and plasmin 3.57 vs. sham). Similar increases were observed in urinary samples from patients with CHF. Whole-cell patch-clamp was conducted in cultured renal collecting duct M-1 cells to record Na+ currents. Protease-rich urine (from rats and patients with CHF) significantly increased the Na+ inward current in M-1 cells. Two weeks of protease inhibitor treatment significantly abrogated the enhanced diuretic and natriuretic responses to ENaC inhibitor benzamil in rats with CHF. Increased podocyte lesions were observed in the kidneys of rats with CHF by transmission electron microscopy. Consistent with these results, podocyte damage markers desmin and podocin expressions were also increased in rats with CHF (increased ~2 folds). These findings suggest that podocyte damage may lead to increased proteases in the tubular fluid which in turn contributes to the enhanced renal ENaC activity, providing a novel mechanistic insight for Na+ retention commonly observed in CHF. PMID:26628676

Reduction of {sup 68}Ga-PSMA renal uptake with mannitol infusion. Preliminary results

Energy Technology Data Exchange (ETDEWEB)

Matteucci, Federica; Caroli, Paola; Celli, Monica; Fantini, Lorenzo; Paganelli, Giovanni [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Nuclear Medicine Unit, Meldola (Italy); Mezzenga, Emilio; Sarnelli, Anna [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Medical Physics Unit, Meldola (Italy); Di Iorio, Valentina [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Oncology Pharmacy, Meldola (Italy); Moretti, Andrea; Galassi, Riccardo [AUSL Romagna, Nuclear Medicine Unit, Forli (Italy); De Giorgi, Ugo [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Department of Medical Oncology, Meldola (Italy)

2017-12-15

Urea-based prostate-specific membrane antigen (PSMA) ligands labelled with {sup 68}Ga or {sup 177}Lu are new tracers with great potential for theranostic approaches in prostate cancer. However, clinical studies have shown that the kidneys are one of the off-target organs along with the salivary and lacrimal glands. In the kidneys, PSMA is physiologically expressed in the apical epithelium of the proximal tubules, and mannitol acts as an osmotic diuretic in these tubules. We investigated the potential of mannitol to reduce renal uptake of {sup 68}Ga-PSMA. Kidney uptake (SUVmax) was calculated in nine patients undergoing {sup 68}Ga-PSMA PET/CT at baseline (b-PET/CT) and after intravenous infusion of 500 ml of 10% mannitol (m-PET/CT). Two different infusion schemes for mannitol were used: (1) 500 ml mannitol was infused over 40 min after {sup 68}Ga-PSMA administration (A-infusion) and (2) 250 ml mannitol was infused over 15 min before and again after {sup 68}Ga-PSMA administration (B-infusion). In patients receiving the A-infusion, mean SUV{sub max} increased by 11.9% and 7.4% in the right and left kidney, respectively. In patients receiving the B-infusion, mean SUV{sub max} decreased by 24.3% and 22.4% in the right and left kidney, respectively. Our preliminary findings indicate that mannitol may play a role in reducing off-target {sup 68}Ga-PSMA renal uptake. Administration of the osmotic diuretic should be rapid and start before {sup 68}Ga-PSMA injection. These results warrant dosimetric studies in patients treated with {sup 177}Lu-PSMA to find the best scheme for mannitol administration. (orig.)

Improved computer-assisted nuclear imaging in renovascular hypertension

International Nuclear Information System (INIS)

Gross, M.L.; Nally, J.V.; Potvini, W.J.; Clarke, H.S. Jr.; Higgins, J.T.; Windham, J.P.

1985-01-01

A computer-assisted program with digital background subtraction has been developed to analyze the initial 90 second Tc-99m DTPA renal flow scans in an attempt to quantitate the early isotope delivery to and uptake by the kidney. This study was designed to compare the computer-assisted 90 second DTPA scan with the conventional 30 minute I-131 Hippuran scan. Six patients with angiographically-proven unilateral renal artery stenosis were studied. The time activity curves for both studies were derived from regions of interest selected from the computer acquired dynamic images. The following parameters were used to assess renal blood flow: differential maximum activity, minimum/maximum activity ratio, and peak width. The computer-assisted DTPA study accurately predicted (6/6) the stenosed side documented angiographically, whereas the conventional Hippuran scan was clearly predictive in only 2/6. In selected cases successfully corrected surgically, the DTPA study proved superior in assessing the degree of patency of the graft. The best discriminatory factors when compared to a template synthesized from curves obtained from normal subjects were differential maximum activity and peak width. The authors conclude that: 1) the computer-assisted 90 second DTPA renal blood flow scan was superior to the conventional I-131 Hippuran scan in demonstrating unilateral reno-vascular disease; 2) the DTPA study was highly predictive of the angiographic findings; and 3) this non-invasive study should prove useful in the diagnosis and serial evaluation following surgery and/or angioplasty for renal artery stenosis

Mechanisms controlling renal hemodynamics and electrolyte excretion during amino acids

International Nuclear Information System (INIS)

Woods, L.L.; Mizelle, H.L.; Montani, J.P.; Hall, J.E.

1986-01-01

Our purpose was to investigate the mechanisms by which increased plasma amino acids elevate renal blood flow (RBF) and glomerular filtration rate (GFR). Since transport of amino acids and Na + is linked in the proximal tubule, the authors hypothesized that increased amino acids might stimulate proximal tubular Na + reabsorption (PR/sub Na/) and thus increase RBF and GFR by a macula densa feedback mechanism. A solution of four amino acids (Ala, Ser, Gly, Pro) was infused intravenously into anesthetized dogs with normal kidneys (NK) and with kidneys in which the tubuloglomerular feedback mechanism was blunted by lowering renal artery pressure (LPK) or blocked by making the kidneys nonfiltering (NFK). In NK, RBF and GFR increased by 35 +/- 4% and 30 +/- 7% after 90 min of amino acid infusion, while PR/sub Na/ (estimated from lithium clearance) and O 2 consumption increased by 31 +/- 5% and 29 +/- 5% and distal Na + delivery remained relatively constant. Autoregulation of RBF and GFR in response to step deceases in renal artery pressure was impaired during amino acids in NK. The hemodynamic responses to amino acids were abolished in LPK and NFK. Infusion of the nonmetabolized α-aminoisobutyric acid into NK produced changes in renal hemodynamics that were similar to the responses observed with the four metabolizable amino acids. These data are consistent with the hypothesis that elevation of plasma amino acids increases RBF and GFR by a mechanism that requires an intact macula densa feedback. Metabolism of the amino acids does not appear to be necessary for these changes to occur

Mechanisms controlling renal hemodynamics and electrolyte excretion during amino acids

Energy Technology Data Exchange (ETDEWEB)

Woods, L.L.; Mizelle, H.L.; Montani, J.P.; Hall, J.E.

1986-08-01

Our purpose was to investigate the mechanisms by which increased plasma amino acids elevate renal blood flow (RBF) and glomerular filtration rate (GFR). Since transport of amino acids and Na is linked in the proximal tubule, the authors hypothesized that increased amino acids might stimulate proximal tubular Na reabsorption (PR/sub Na/) and thus increase RBF and GFR by a macula densa feedback mechanism. A solution of four amino acids (Ala, Ser, Gly, Pro) was infused intravenously into anesthetized dogs with normal kidneys (NK) and with kidneys in which the tubuloglomerular feedback mechanism was blunted by lowering renal artery pressure (LPK) or blocked by making the kidneys nonfiltering (NFK). In NK, RBF and GFR increased by 35 +/- 4% and 30 +/- 7% after 90 min of amino acid infusion, while PR/sub Na/ (estimated from lithium clearance) and O2 consumption increased by 31 +/- 5% and 29 +/- 5% and distal Na delivery remained relatively constant. Autoregulation of RBF and GFR in response to step deceases in renal artery pressure was impaired during amino acids in NK. The hemodynamic responses to amino acids were abolished in LPK and NFK. Infusion of the nonmetabolized -aminoisobutyric acid into NK produced changes in renal hemodynamics that were similar to the responses observed with the four metabolizable amino acids. These data are consistent with the hypothesis that elevation of plasma amino acids increases RBF and GFR by a mechanism that requires an intact macula densa feedback. Metabolism of the amino acids does not appear to be necessary for these changes to occur.

Effect of metabolic acidosis on renal tubular sodium handling in rats as determined by lithium clearance

Directory of Open Access Journals (Sweden)

Menegon L.F.

1998-01-01

Full Text Available Systemic metabolic acidosis is known to cause a decrease in salt and water reabsorption by the kidney. We have used renal lithium clearance to investigate the effect of chronic, NH4Cl-induced metabolic acidosis on the renal handling of Na+ in male Wistar-Hannover rats (200-250 g. Chronic acidosis (pH 7.16 ± 0.13 caused a sustained increase in renal fractional Na+ excretion (267.9 ± 36.4%, accompanied by an increase in fractional proximal (113.3 ± 3.6% and post-proximal (179.7 ± 20.2% Na+ and urinary K+ (163.4 ± 5.6% excretion when compared to control and pair-fed rats. These differences occurred in spite of an unchanged creatinine clearance and Na+ filtered load. A lower final body weight was observed in the acidotic (232 ± 4.6 g and pair-fed (225 ± 3.6 g rats compared to the controls (258 ± 3.7 g. In contrast, there was a significant increase in the kidney weights of acidotic rats (1.73 ± 0.05 g compared to the other experimental groups (control, 1.46 ± 0.05 g; pair-fed, 1.4 ± 0.05 g. We suggest that altered renal Na+ and K+ handling in acidotic rats may result from a reciprocal relationship between the level of metabolism in renal tubules and ion transport.

Prolonged Pulmonary Exposure to Diesel Exhaust Particles Exacerbates Renal Oxidative Stress, Inflammation and DNA Damage in Mice with Adenine-Induced Chronic Renal Failure.

Science.gov (United States)

Nemmar, Abderrahim; Karaca, Turan; Beegam, Sumaya; Yuvaraju, Priya; Yasin, Javed; Hamadi, Naserddine Kamel; Ali, Badreldin H

2016-01-01

Epidemiological evidence indicates that patients with chronic kidney diseases have increased susceptibility to adverse outcomes related to long-term exposure to particulate air pollution. However, mechanisms underlying these effects are not fully understood. Presently, we assessed the effect of prolonged exposure to diesel exhaust particles (DEP) on chronic renal failure induced by adenine (0.25% w/w in feed for 4 weeks), which is known to involve inflammation and oxidative stress. DEP (0.5m/kg) was intratracheally (i.t.) instilled every 4th day for 4 weeks (7 i.t. instillation). Four days following the last exposure to either DEP or saline (control), various renal endpoints were measured. While body weight was decreased, kidney weight increased in DEP+adenine versus saline+adenine or DEP. Water intake, urine volume, relative kidney weight were significantly increased in adenine+DEP versus DEP and adenine+saline versus saline. Plasma creatinine and urea increased and creatinine clearance decreased in adenine+DEP versus DEP and adenine+saline versus saline. Tumor necrosis factor α, lipid peroxidation and reactive oxygen species were significantly increased in adenine+DEP compared with either DEP or adenine+saline. The antioxidant calase was significantly decreased in adenine+DEP compared with either adenine+saline or DEP. Notably, renal DNA damage was significantly potentiated in adenine+DEP compared with either adenine+saline or DEP. Similarly, systolic blood pressure was increased in adenine+DEP versus adenine+saline or DEP, and in DEP versus saline. Histological evaluation revealed more collagen deposition, higher number of necrotic cell counts and dilated tubules, cast formation and collapsing glomeruli in adenine+DEP versus adenine+saline or DEP. Prolonged pulmonary exposure to diesel exhaust particles worsen renal oxidative stress, inflammation and DNA damage in mice with adenine-induced chronic renal failure. Our data provide biological plausibility that air

Percutaneous and laparoscopic assisted cryoablation of small renal cell carcinomas

DEFF Research Database (Denmark)

Nielsen, Tommy Kjærgaard; Østraat, Øyvind; Borre, Michael

Aim: To evaluate the complication rate and short term oncological outcome of small renal cell carcinomas treated with cryoablation. Materials and methods: 91 biopsy verified renal cell carcinomas were cryoablated between 2006-11. Patients treated had primarily T1a tumors, but exceptions were made...... Medical® was used. Treatment was considered successful when tumors gradually shrunk and showed no sign of contrast enhancement, assessed by CT or MRI. Results: Mean patient age and tumor size was 65 yr [17 - 83] and 26 mm [10 - 62], respectively [min-max]. Treatment modalities consisted of percutaneous...

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

Initial Clinical Experience With Surgical Technique of Robot-assisted Transperitoneal Laparoscopic Partial Nephrectomy

Directory of Open Access Journals (Sweden)

Cheng-Kuang Yang

2009-12-01

Conclusion: Robot-assisted LPN is feasible and may be a viable alternative to open or LPN in selected patients with small exophytic renal tumors. Compared with standard LPN, the robotic assisted LPN approach with precise renal reconstruction under a safe warm ischemia time is feasible and can be easily adopted by those with experience in robot-assisted surgery.

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

Directory of Open Access Journals (Sweden)

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 dual-gate lumen model of renal monoamine transport

Directory of Open Access Journals (Sweden)

Marty Hinz

2010-07-01

Full Text Available Marty Hinz1, Alvin Stein2, Thomas Uncini31Clinical Research, NeuroResearch Clinics, Inc. Cape Coral, Florida, USA; 2Stein Orthopedic Associates, Plantation, Florida, USA; 3DBS Labs, Duluth, Minnesota, USAAbstract: The three-phase response of urinary serotonin and dopamine in subjects ­simultaneously taking amino acid precursors of serotonin and dopamine has been defined.1,2 No model exists regarding the renal etiology of the three-phase response. This writing outlines a model explaining the origin of the three-phase response of urinary serotonin and dopamine. A “dual-gate lumen transporter model” for the basolateral monoamine transporters of the kidneys is proposed as being the etiology of the three-phase urinary serotonin and dopamine responses.Purpose: The purpose of this writing is to document the internal renal function model that has evolved in research during large-scale assay with phase interpretation of urinary serotonin and dopamine.Patients and methods: In excess of 75,000 urinary monoamine assays from more than 7,500 patients were analyzed. The serotonin and the dopamine phase were determined for specimens submitted in the competitive inhibition state. The phase determination findings were then correlated with peer-reviewed literature.Results: The correlation between the three-phase response of urinary serotonin and dopamine with internal renal processes of the bilateral monoamine transporter and the apical monoamine transporter of the proximal convoluted renal tubule cells is defined.Conclusion: The phase of urinary serotonin and dopamine is dependent on the status of the serotonin gate, dopamine gate, and lumen of the basolateral monoamine transporter while in the competitive inhibition state.Keywords: serotonin, dopamine, basolateral, apical, kidney, proximal

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

Science.gov (United States)

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.

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...

Radiopharmaceuticals in evaluation of kidneys

International Nuclear Information System (INIS)

Winchell, H.S.

1979-01-01

The kidney may be thought of as a system which first filters low and medium molecular weight water-soluble materials from the blood and then either pumps or allows diffusion of such materials from the filtrate back into the blood after their passage through a chromatographic-like column contained within the renal tubules. Additionally, water-soluble materials in the blood may diffuse or be pumped in the opposite direction through the chromatographic column in the tubules to reach the filtrate. Materials whose renal handling is limited to filtration processes can be employed to measure glomerular filtration (e.g., radioinulin and possibly radiocations chelated by EDTA or DTPA). Materials whose renal handling is by a combination of filtration and quantitative pumping or diffusion from the blood to the filtrate, and for which retention in the chromatographic-like system of the tubules is negligible, can be employed for measuring renal plasma flow (e.g., radioiodohippurate). Materials which have prolonged retention times in the renal tubular chromatographic system can be used to evaluate renal anatomy and to infer aspects of renal physiology

Renal Effects and Underlying Molecular Mechanisms of Long-Term Salt Content Diets in Spontaneously Hypertensive Rats

Science.gov (United States)

Berger, Rebeca Caldeira Machado; Vassallo, Paula Frizera; Crajoinas, Renato de Oliveira; Oliveira, Marilene Luzia; Martins, Flávia Letícia; Nogueira, Breno Valentim; Motta-Santos, Daisy; Araújo, Isabella Binotti; Forechi, Ludimila; Girardi, Adriana Castello Costa; Santos, Robson Augusto Souza; Mill, José Geraldo

2015-01-01

Several evidences have shown that salt excess is an important determinant of cardiovascular and renal derangement in hypertension. The present study aimed to investigate the renal effects of chronic high or low salt intake in the context of hypertension and to elucidate the molecular mechanisms underlying such effects. To this end, newly weaned male SHR were fed with diets only differing in NaCl content: normal salt (NS: 0.3%), low salt (LS: 0.03%), and high salt diet (HS: 3%) until 7 months of age. Analysis of renal function, morphology, and evaluation of the expression of the main molecular components involved in the renal handling of albumin, including podocyte slit-diaphragm proteins and proximal tubule endocytic receptors were performed. The relationship between diets and the balance of the renal angiotensin-converting enzyme (ACE) and ACE2 enzymes was also examined. HS produced glomerular hypertrophy and decreased ACE2 and nephrin expressions, loss of morphological integrity of the podocyte processes, and increased proteinuria, characterized by loss of albumin and high molecular weight proteins. Conversely, severe hypertension was attenuated and renal dysfunction was prevented by LS since proteinuria was much lower than in the NS SHRs. This was associated with a decrease in kidney ACE/ACE2 protein and activity ratio and increased cubilin renal expression. Taken together, these results suggest that LS attenuates hypertension progression in SHRs and preserves renal function. The mechanisms partially explaining these findings include modulation of the intrarenal ACE/ACE2 balance and the increased cubilin expression. Importantly, HS worsens hypertensive kidney injury and decreases the expression nephrin, a key component of the slit diaphragm. PMID:26495970

Renal Effects and Underlying Molecular Mechanisms of Long-Term Salt Content Diets in Spontaneously Hypertensive Rats.

Directory of Open Access Journals (Sweden)

Rebeca Caldeira Machado Berger

Full Text Available Several evidences have shown that salt excess is an important determinant of cardiovascular and renal derangement in hypertension. The present study aimed to investigate the renal effects of chronic high or low salt intake in the context of hypertension and to elucidate the molecular mechanisms underlying such effects. To this end, newly weaned male SHR were fed with diets only differing in NaCl content: normal salt (NS: 0.3%, low salt (LS: 0.03%, and high salt diet (HS: 3% until 7 months of age. Analysis of renal function, morphology, and evaluation of the expression of the main molecular components involved in the renal handling of albumin, including podocyte slit-diaphragm proteins and proximal tubule endocytic receptors were performed. The relationship between diets and the balance of the renal angiotensin-converting enzyme (ACE and ACE2 enzymes was also examined. HS produced glomerular hypertrophy and decreased ACE2 and nephrin expressions, loss of morphological integrity of the podocyte processes, and increased proteinuria, characterized by loss of albumin and high molecular weight proteins. Conversely, severe hypertension was attenuated and renal dysfunction was prevented by LS since proteinuria was much lower than in the NS SHRs. This was associated with a decrease in kidney ACE/ACE2 protein and activity ratio and increased cubilin renal expression. Taken together, these results suggest that LS attenuates hypertension progression in SHRs and preserves renal function. The mechanisms partially explaining these findings include modulation of the intrarenal ACE/ACE2 balance and the increased cubilin expression. Importantly, HS worsens hypertensive kidney injury and decreases the expression nephrin, a key component of the slit diaphragm.

Protective Immunity and Reduced Renal Colonization Induced by Vaccines Containing Recombinant Leptospira interrogans Outer Membrane Proteins and Flagellin Adjuvant

Science.gov (United States)

Monaris, D.; Sbrogio-Almeida, M. E.; Dib, C. C.; Canhamero, T. A.; Souza, G. O.; Vasconcellos, S. A.; Ferreira, L. C. S.

2015-01-01

Leptospirosis is a global zoonotic disease caused by different Leptospira species, such as Leptospira interrogans, that colonize the renal tubules of wild and domestic animals. Thus far, attempts to develop effective leptospirosis vaccines, both for humans and animals, have failed to induce immune responses capable of conferring protection and simultaneously preventing renal colonization. In this study, we evaluated the protective immunity induced by subunit vaccines containing seven different recombinant Leptospira interrogans outer membrane proteins, including the carboxy-terminal portion of the immunoglobulinlike protein A (LigAC) and six novel antigens, combined with aluminum hydroxide (alum) or Salmonella flagellin (FliC) as adjuvants. Hamsters vaccinated with the different formulations elicited high antigen-specific antibody titers. Immunization with LigAC, either with alum or flagellin, conferred protective immunity but did not prevent renal colonization. Similarly, animals immunized with LigAC or LigAC coadministered with six leptospiral proteins with alum adjuvant conferred protection but did not reduce renal colonization. In contrast, immunizing animals with the pool of seven antigens in combination with flagellin conferred protection and significantly reduced renal colonization by the pathogen. The present study emphasizes the relevance of antigen composition and added adjuvant in the efficacy of antileptospirosis subunit vaccines and shows the complex relationship between immune responses and renal colonization by the pathogen. PMID:26108285

The renal effects of SGLT2 inhibitors and a mini-review of the literature.

Science.gov (United States)

Andrianesis, Vasileios; Glykofridi, Spyridoula; Doupis, John

2016-12-01

Sodium-glucose linked transporter 2 (SGLT2) inhibitors are a new and promising class of antidiabetic agents which target renal tubular glucose reabsorption. Their action is based on the blockage of SGLT2 sodium-glucose cotransporters that are located at the luminal membrane of tubular cells of the proximal convoluted tubule, inducing glucosuria. It has been proven that they significantly reduce glycated hemoglobin (HbA1c), along with fasting and postprandial plasma glucose in patients with type 2 diabetes mellitus (T2DM). The glucosuria-induced caloric loss as well as the osmotic diuresis significantly decrease body weight and blood pressure, respectively. Given that SGLT2 inhibitors do not interfere with insulin action and secretion, their efficacy is sustained despite the progressive β-cell failure in T2DM. They are well tolerated, with a low risk of hypoglycemia. Their most frequent adverse events are minor: genital and urinal tract infections. Recently, it was demonstrated that empagliflozin presents a significant cardioprotective effect. Although the SGLT2 inhibitors' efficacy is affected by renal function, new data have been presented that some SGLT2 inhibitors, even in mild and moderate renal impairment, induce significant HbA1c reduction. Moreover, recent data indicate that SGLT2 inhibition has a beneficial renoprotective effect. The role of this review paper is to explore the current evidence on the renal effects of SGLT2 inhibitors.

High-fat diet amplifies renal renin angiotensin system expression, blood pressure elevation, and renal dysfunction caused by Ceacam1 null deletion.

Science.gov (United States)

Li, Caixia; Culver, Silas A; Quadri, Syed; Ledford, Kelly L; Al-Share, Qusai Y; Ghadieh, Hilda E; Najjar, Sonia M; Siragy, Helmy M

2015-11-01

Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAMl), a substrate of the insulin receptor tyrosine kinase, regulates insulin action by promoting insulin clearance. Global null mutation of Ceacam1 gene (Cc1(-/-)) results in features of the metabolic syndrome, including insulin resistance, hyperinsulinemia, visceral adiposity, elevated blood pressure, and albuminuria. It also causes activation of the renal renin-angiotensin system (RAS). In the current study, we tested the hypothesis that high-fat diet enhances the expression of RAS components. Three-month-old wild-type (Cc1(+/+)) and Cc1(-/-) mice were fed either a regular or a high-fat diet for 8 wk. At baseline under regular feeding conditions, Cc1(-/-) mice exhibited higher blood pressure, urine albumin-to-creatinine ratio (UACR), and renal expression of angiotensinogen, renin/prorenin, angiotensin-converting enzyme, (pro)renin receptor, angiotensin subtype AT1 receptor, angiotensin II, and elevated PI3K phosphorylation, as detected by p85α (Tyr(508)) immunostaining, inflammatory response, and the expression of collagen I and collagen III. In Cc1(+/+) mice, high-fat diet increased blood pressure, UACR, the expression of angiotensin-converting enzyme and angiotensin II, PI3K phosphorylation, inflammatory response, and the expression of collagen I and collagen III. In Cc1(-/-) mice, high-fat intake further amplified these parameters. Immunohistochemical staining showed increased p-PI3K p85α (Tyr(508)) expression in renal glomeruli, proximal, distal, and collecting tubules of Cc1(-/-) mice fed a high-fat diet. Together, this demonstrates that high-fat diet amplifies the permissive effect of Ceacam1 deletion on renal expression of all RAS components, PI3K phosphorylation, inflammation, and fibrosis. Copyright © 2015 the American Physiological Society.

Wild boars (Sus scrofa scrofa seminiferous tubules morphometry

Directory of Open Access Journals (Sweden)

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.

Urinary C-type natriuretic peptide excretion: a potential novel biomarker for renal fibrosis during aging.

Science.gov (United States)

Sangaralingham, S Jeson; Heublein, Denise M; Grande, Joseph P; Cataliotti, Alessandro; Rule, Andrew D; McKie, Paul M; Martin, Fernando L; Burnett, John C

2011-11-01

Renal aging is characterized by structural changes in the kidney including fibrosis, which contributes to the increased risk of kidney and cardiac failure in the elderly. Studies involving healthy kidney donors demonstrated subclinical age-related nephropathy on renal biopsy that was not detected by standard diagnostic tests. Thus there is a high-priority need for novel noninvasive biomarkers to detect the presence of preclinical age-associated renal structural and functional changes. C-type natriuretic peptide (CNP) possesses renoprotective properties and is present in the kidney; however, its modulation during aging remains undefined. We assessed circulating and urinary CNP in a Fischer rat model of experimental aging and also determined renal structural and functional adaptations to the aging process. Histological and electron microscopic analysis demonstrated significant renal fibrosis, glomerular basement membrane thickening, and mesangial matrix expansion with aging. While plasma CNP levels progressively declined with aging, urinary CNP excretion increased, along with the ratio of urinary to plasma CNP, which preceded significant elevations in proteinuria and blood pressure. Also, CNP immunoreactivity was increased in the distal and proximal tubules in both the aging rat and aging human kidneys. Our findings provide evidence that urinary CNP and its ratio to plasma CNP may represent a novel biomarker for early age-mediated renal structural alterations, particularly fibrosis. Thus urinary CNP could potentially aid in identifying subjects with preclinical structural changes before the onset of symptoms and disease, allowing for the initiation of strategies designed to prevent the progression of chronic kidney disease particularly in the aging population.

Fluid transport and ion fluxes in mammalian kidney proximal tubule: a model analysis of isotonic transport

DEFF Research Database (Denmark)

Larsen, E.H.; Møbjerg, N.; Sørensen, Jens Nørkær

2006-01-01

transport similar to rat proximal tubule. Na+ recirculation is required for truly isotonic transport. The tonicity of the absorbate and the recirculation flux depend critically on ion permeabilities of interspace basement membrane. Conclusion: Our model based on solute-solvent coupling in lateral space......Aim: By mathematical modelling, we analyse conditions for near-isotonic and isotonic transport by mammalian kidney proximal tubule. Methods: The model comprises compliant lateral intercellular space (lis) and cells, and infinitely large luminal and peritubular compartments with diffusible species......: Na+, K+, Cl and an intracellular non-diffusible anion. Unknown model variables are solute concentrations, electrical potentials, volumes and hydrostatic pressures in cell and lis, and transepithelial potential. We used data mainly from rat proximal tubule to model epithelial cells and interspace...

Retrograde Renal Cooling to Minimize Ischemia

Directory of Open Access Journals (Sweden)

Janet L. Colli

2013-01-01

Full Text Available Objective: During partial nephrectomy, renal hypothermia has been shown to decrease ischemia induced renal damage which occurs from renal hilar clamping. In this study we investigate the infusion rate required to safely cool the entire renal unit in a porcine model using retrograde irrigation of iced saline via dual-lumen ureteral catheter. Materials and Methods: Renal cortical, renal medullary, bowel and rectal temperatures during retrograde cooling in a laparoscopic porcine model were monitored in six renal units. Iced normal saline was infused at 300 cc/hour, 600 cc/hour, 1000 cc/hour and gravity (800 cc/hour for 600 seconds with and without hilar clamping. Results: Retrograde cooling with hilar clamping provided rapid medullary renal cooling and significant hypothermia of the medulla and cortex at infusion rates ≥ 600 cc/hour. With hilar clamping, cortical temperatures decreased at -0.9° C/min. reaching a threshold temperature of 26.9° C, and medullary temperatures decreased at -0.90 C/min. reaching a temperature of 26.1° C over 600 seconds on average for combined data at infusion rates ≥ 600 cc/hour. The lowest renal temperatures were achieved with gravity infusion. Without renal hilum clamping, retrograde cooling was minimal at all infusion rates. Conclusions: Significant renal cooling by gravity infusion of iced cold saline via a duel lumen catheter with a clamped renal hilum was achieved in a porcine model. Continuous retrograde irrigation with iced saline via a two way ureteral catheter may be an effective method to induce renal hypothermia in patients undergoing robotic assisted and/or laparoscopic partial nephrectomy.

PARP Inhibition Attenuates Histopathological Lesion in Ischemia/Reperfusion Renal Mouse Model after Cold Prolonged Ischemia

Directory of Open Access Journals (Sweden)

Raimundo M. G. del Moral

2013-01-01

Full Text Available We test the hypothesis that PARP inhibition can decrease acute tubular necrosis (ATN and other renal lesions related to prolonged cold ischemia/reperfusion (IR in kidneys preserved at 4°C in University of Wisconsin (UW solution. Material and Methods. We used 30 male Parp1+/+ wild-type and 15 male Parp10/0 knockout C57BL/6 mice. Fifteen of these wild-type mice were pretreated with 3,4-dihydro-5-[4-(1-piperidinylbutoxyl]-1(2H-isoquinolinone (DPQ at a concentration of 15 mg/kg body weight, used as PARP inhibitor. Subgroups of mice were established (A: IR 45 min/6 h; B: IR + 48 h in UW solution; and C: IR + 48 h in UW solution plus DPQ. We processed samples for morphological, immunohistochemical, ultrastructural, and western-blotting studies. Results. Prolonged cold ischemia time in UW solution increased PARP-1 expression and kidney injury. Preconditioning with PARP inhibitor DPQ plus DPQ supplementation in UW solution decreased PARP-1 nuclear expression in renal tubules and renal damage. Parp10/0 knockout mice were more resistant to IR-induced renal lesion. In conclusion, PARP inhibition attenuates ATN and other IR-related renal lesions in mouse kidneys under prolonged cold storage in UW solution. If confirmed, these data suggest that pharmacological manipulation of PARP activity may have salutary effects in cold-stored organs at transplantation.

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

[Census of the renal and dialysis units by Italian Society of Nephrology: structure and organization for renal patient assistance in Italy (2014-2015)].

Science.gov (United States)

Quintaliani, Giuseppe; Di Luca, Marina; Di Napoli, Anteo; Viglino, Giusto; Postorino, Maurizio; Amore, Alessandro; Andrulli, Simeone; Bellasi, Antonio; Brunori, Giuliano; Buongiorno, Erasmo; Castellino, Santina; D'Amelio, Alessandro; De Nicola, Luca; Gesualdo, Loreto; Di Landro, Domenico; Feriozzi, Sandro; Strippoli, Giovanni; Teatini, Ugo; Santoro, Antonio

2016-01-01

Given the public health challenge and burden of chronic kidney disease, the Italian Society of Nephrology (SIN) promoted a census of the renal and dialysis units to analyse structural and human resources, organizational aspects, activities and workload referring to the year 2014. An online questionnaire, including 64 items exploring structural and human resources, organization aspects, activities and epidemiological data referred to 2014, was sent to chiefs of any renal or dialysis unit. 615 renal units were identified. From these 615 units, 332 were public renal centres (of which 318 centres answered to the census) and 283 were private dialysis centres (of which 113 centres answered to the census). The results show 6 public renal units pmp. Renal biopsies were 4624 (81 pmp). The nephrology beds are about 41 pmp. There are 7.304 nurses working in HD wards, 1.692 in the nephrology wards and only 613 for outpatients clinics. The benchmark data derived from this census show interesting comparisons between centres, regions and groups of regions. These data realised the clinical management of renal disease in Italy.

Robotic partial nephrectomy for complex renal tumors: surgical technique.

Science.gov (United States)

Rogers, Craig G; Singh, Amar; Blatt, Adam M; Linehan, W Marston; Pinto, Peter A

2008-03-01

Laparoscopic partial nephrectomy requires advanced training to accomplish tumor resection and renal reconstruction while minimizing warm ischemia times. Complex renal tumors add an additional challenge to a minimally invasive approach to nephron-sparing surgery. We describe our technique, illustrated with video, of robotic partial nephrectomy for complex renal tumors, including hilar, endophytic, and multiple tumors. Robotic assistance was used to resect 14 tumors in eight patients (mean age: 50.3 yr; range: 30-68 yr). Three patients had hereditary kidney cancer. All patients had complex tumor features, including hilar tumors (n=5), endophytic tumors (n=4), and/or multiple tumors (n=3). Robotic partial nephrectomy procedures were performed successfully without complications. Hilar clamping was used with a mean warm ischemia time of 31 min (range: 24-45 min). Mean blood loss was 230 ml (range: 100-450 ml). Histopathology confirmed clear-cell renal cell carcinoma (n=3), hybrid oncocytic tumor (n=2), chromophobe renal cell carcinoma (n=2), and oncocytoma (n=1). All patients had negative surgical margins. Mean index tumor size was 3.6 cm (range: 2.6-6.4 cm). Mean hospital stay was 2.6 d. At 3-mo follow-up, no patients experienced a statistically significant change in serum creatinine or estimated glomerular filtration rate and there was no evidence of tumor recurrence. Robotic partial nephrectomy is safe and feasible for select patients with complex renal tumors, including hilar, endophytic, and multiple tumors. Robotic assistance may facilitate a minimally invasive, nephron-sparing approach for select patients with complex renal tumors who might otherwise require open surgery or total nephrectomy.

Effects of Coptis chinensis decoction on the metabolic index and renal protection in rats with metabolism syndrome

Directory of Open Access Journals (Sweden)

Xiao-qing CHEN

2017-11-01

Full Text Available Objective To investigate the protective effects of Coptis chinensis decoction on the metabolic index and renal function of rats with fructose-induced metabolism syndrome (MS. Methods From 56 male Wistar rats, 6 were randomly selected as normal control group, the other rats were daily fed with 10% fructose water for 8 weeks to reproduce the MS model. Twenty-four rats were established successfully as MS model and randomly divided into 4 groups (6 each: model group, Coptis decoction group, tauroursodeoxycholic acid (TUDCA group and berberine hydrochloride (BH group. The body weight, visceral fat weight, fasting blood glucose (FBG, fasting insulin (FINS, insulin resistance index (HOMA-IR, cholesterol (TC, triglyceride (TG, systolic blood pressure (SBP, diastolic blood pressure (DBP, urinary N-acetyl-β-D-glucosidase (NAG, urine microalbumin (m-ALB, blood urea nitrogen (BUN and serum creatinine (Scr levels were compared between the groups, and the renal pathological changes were observed by light microscopy and electron microscopy. Results The levels of body weight, visceral fat weight, FINS, HOMA- IR, TC, TG, SBP, DBP and urinary NAG were obviously higher in the four MS model groups than in normal control group (P0.05. After the intervention, the levels of body weight, visceral fat weight, FINS, HOMA-IR, TC, TG, SBP and DBP decreased significantly in Coptis decoction group than in model group (P0.05. It was observed in model group by light microscopy and electron microscopy that the glomerular swelled obviously, the capillary basement membrane of glomerular and renal tubules thickened, mesangial region and interstitial substances hyperplasia, podocytes swelled markedly and most of fusion, the epithelial cells of renal tubules serious vacuolar degeneration, and a lot of secondary lysosomes formed, autophagy of organelles occurred, and most of endoplasmic reticulum and mitochondria disappeared. The kidney pathological damage reduced obviously after

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

A novel description of FDG excretion in the renal system: application to metformin-treated models

Science.gov (United States)

Garbarino, S.; Caviglia, G.; Sambuceti, G.; Benvenuto, F.; Piana, M.

2014-05-01

This paper introduces a novel compartmental model describing the excretion of 18F-fluoro-deoxyglucose (FDG) in the renal system and a numerical method based on the maximum likelihood for its reduction. This approach accounts for variations in FDG concentration due to water re-absorption in renal tubules and the increase of the bladder’s volume during the FDG excretion process. From the computational viewpoint, the reconstruction of the tracer kinetic parameters is obtained by solving the maximum likelihood problem iteratively, using a non-stationary, steepest descent approach that explicitly accounts for the Poisson nature of nuclear medicine data. The reliability of the method is validated against two sets of synthetic data realized according to realistic conditions. Finally we applied this model to describe FDG excretion in the case of animal models treated with metformin. In particular we show that our approach allows the quantitative estimation of the reduction of FDG de-phosphorylation induced by metformin.

Intermittent hypoxia alters dose dependent caffeine effects on renal prostanoids and receptors in neonatal rats.

Science.gov (United States)

Beharry, Kay D; Cai, Charles L; Soontarapornchai, Kultida; Ahmad, Taimur; Valencia, Gloria B; Aranda, Jacob V

2018-01-01

Caffeine, one of the most commonly prescribed drugs in preterm neonates, is given in standard or suprapharmacologic doses. Although known as a diuretic, its effects in the neonatal kidneys are not well studied. We tested the hypothesis that neonatal intermittent hypoxia (IH) and high caffeine doses (HCD) alter renal regulators of vasomotor tone and water balance. Newborn rats were randomized to room air, hyperoxia, or IH and treated with standard or high caffeine doses; or placebo saline. Renal prostanoids; histopathology; and cyclooxygenase (COX), prostanoid receptor, and aquaporin (AQP) immunoreactivity were determined. HCD in IH caused severe pathological changes in the glomeruli and proximal tubules, consistent with acute kidney injury. This was associated with reductions in anthropometric growth, PGI 2, and IP, DP, and AQP-4 immunoreactivity, well as a robust increase in COX-2, suggesting that the use of HCD should be avoided in preterm infants who experience frequent IH episodes. Published by Elsevier Inc.

A novel description of FDG excretion in the renal system: application to metformin-treated models

International Nuclear Information System (INIS)

Garbarino, S; Caviglia, G; Piana, M; Sambuceti, G; Benvenuto, F

2014-01-01

This paper introduces a novel compartmental model describing the excretion of 18F-fluoro-deoxyglucose (FDG) in the renal system and a numerical method based on the maximum likelihood for its reduction. This approach accounts for variations in FDG concentration due to water re-absorption in renal tubules and the increase of the bladder’s volume during the FDG excretion process. From the computational viewpoint, the reconstruction of the tracer kinetic parameters is obtained by solving the maximum likelihood problem iteratively, using a non-stationary, steepest descent approach that explicitly accounts for the Poisson nature of nuclear medicine data. The reliability of the method is validated against two sets of synthetic data realized according to realistic conditions. Finally we applied this model to describe FDG excretion in the case of animal models treated with metformin. In particular we show that our approach allows the quantitative estimation of the reduction of FDG de-phosphorylation induced by metformin. (paper)

Distal renal tubular acidosis and quadriparaesis in Sjögren′s syndrome: A cunning congregate

Directory of Open Access Journals (Sweden)

Arundhati G Diwan

2014-01-01

Full Text Available Sjögren′s syndrome (SS is a chronic autoimmune disease, chiefly affecting the exocrine glandular function of salivary glands and lacrimal glands. Rarely, it involves the kidneys, central and peripheral nervous system, muscloskeletal apparatus and lungs. We report a rare constellation of SS with distal renal tubular acidosis and quadriparaesis in a young female. History of quadriparaesis was acute, with rapid progression. Supplementary treatment for severe hypokalemia was instituted at the earliest, lest the patient develop respiratory muscle weakness. Concomitantly, metabolic acidosis with alkaline urine was suspected and subsequently investigated. Eventually, this was attributed to impaired renal acidification of urine in the distal tubules. History of dryness of eyes and mouth since 6 months justified salivary gland biopsy. The results yielded a lymphocytic infiltrative pathology strongly favoring SS. The patient benefited from prompt potassium replacement therapy and had complete resolution over the next week. Supportive treatment for predictable manifestations was continued along with potassium supplements.

Tacrolimus Modulates TGF-β Signaling to Induce Epithelial-Mesenchymal Transition in Human Renal Proximal Tubule Epithelial Cells

Directory of Open Access Journals (Sweden)

Jason Bennett

2016-04-01

Full Text Available Epithelial-mesenchymal transition (EMT, a process which describes the trans-differentiation of epithelial cells into motile mesenchymal cells, is pivotal in stem cell behavior, development and wound healing, as well as contributing to disease processes including fibrosis and cancer progression. Maintenance immunosuppression with calcineurin inhibitors (CNIs has become routine management for renal transplant patient, but unfortunately the nephrotoxicity of these drugs has been well documented. HK-2 cells were exposed to Tacrolimus (FK506 and EMT markers were assessed by RT PCR and western blot. FK506 effects on TGF-β mRNA were assessed by RT PCR and TGF-β secretion was measured by ELISA. The impact of increased TGF-β secretion on Smad signaling pathways was investigated. The impact of inhibition of TGF-β signaling on EMT processes was assessed by scratch-wound assay. The results presented in this study suggest that FK506 initiates EMT processes in the HK-2 cell line, with altered expression of epithelial and myofibroblast markers evident. Additionally, the study demonstrates that FK506 activation of the TGF-β/ SMAD pathways is an essential step in the EMT process. Overall the results demonstrate that EMT is heavily involved in renal fibrosis associated with CNI nephrotoxicity.

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.

Delayed Partial Nephrectomy for Hydronephrosis After Renal Trauma.

Science.gov (United States)

Setia, Shaan; Jackson, Jessica Nicole; Herndon, C D Anthony; Corbett, Sean T

2017-03-01

Delayed sequelae following conservative management of renal trauma in the pediatric population are uncommon. Reports of delayed operations to manage these sequelae are even less common. Here we present the case of a 16-year-old male patient who had delayed development of upper urinary tract obstruction with recurrent infections following high-grade renal trauma managed conservatively. Ultimately, he required a robotic-assisted partial nephrectomy 2 years after initial nonoperative management. This is unique as no prior studies to our knowledge have described delayed hydronephrosis and delayed partial nephrectomy over a year following renal trauma. Copyright © 2016 Elsevier Inc. All rights reserved.

TEM and SEM observation of uranium induced renal necrosis and the result of chelates treatment on rats

International Nuclear Information System (INIS)

Sun Shiquan; Li Baoxing; Lai Chixiang; You Zhanyun

1987-01-01

The TEM (transmission electron microscope) and SEM (scanning electron microscope) observation of uranium induced renal necrosis and the result of chelates treatment on rats are reported. Ultrastructural changes in kidney related with the impairment of intracellular fluid transportation can be found after acute uranium intoxication in rats, such as: condensation and swelling of mitochondria, matrix edema, dilatation of intercellular space, disappearance of basal folds, thickening of basal web, intensification of basal lamina of the proximal convoluted tubule epithelium cells, and foot processes swelling, diminishing of endothelium fenestrae of the renal glomerulus. Heavy metal chelates DTPA and H-73-10 treatment may result in intracellular fluid accumulation and condensed grannule formation in lysosome. Treatment with these chelates in the critical stage of uranium intoxication may accelerate the necrosis instead of diminishing. This may be related to the augment of the load of lysosome and intracellular system of fluid transportation

Mathematical rationalization for the renal tubular transport: revised concepts.

Science.gov (United States)

Mioni, Roberto; Marega, Alessandra; Romano, Giulio; Montanaro, Domenico

2017-09-01

The current emphasis on kinetics and in situ control of molecular exchanges, across the tubular membrane, has not been paralleled by corresponding improvements in our understanding of tubular behaviour at the macroscopic level of classical physiology. In this paper, we propose a mathematical rationalization of macroscopic tubular transport by means of a principal transport equation, originating from the law of mass action between substrate and carrier. The other equations, derived from the main one, demonstrate the possibility of distinguishing between transporters with low affinity and high capacity and transporters with high affinity and low capacity. Moreover, our model formalizes both tubular reabsorption and tubular secretion. Regarding the renal calcium handling, our model confirms the two-compartment system proposed by Mioni in 1971, with some important variants, which are in agreement with the fractional reabsorptions of this cation along the tubule, as verified by micro-puncture technique. To obtain the frequency distribution of saturated tubules, we have utilized the infinitesimal analysis method, starting from the equations proposed by Smith in 1943, concluding that all titration curves result from the combined effect of enzymatic approach and anatomical heterogeneity of the nephrons. The theoretical equations included in our manuscript reflect substantial and palpable physiological mechanisms able to suggest diagnosis and therapy of some electrolyte and hormonal disorders. At the end of this paper, we highlight advantages and disadvantages detectable by comparing our mathematical approach with Marshall's and Bijvoet's methods, proposed, respectively, in 1976 and 1984.

Activation of PI3K-Akt-GSK3β pathway mediates hepatocyte growth factor inhibition of RANTES expression in renal tubular epithelial cells

International Nuclear Information System (INIS)

Gong Rujun; Rifai, Abdalla; Dworkin, Lance D.

2005-01-01

Hepatocyte growth factor (HGF) was recently reported to ameliorate renal inflammation in a rat model of chronic renal failure. HGF exerted its action through suppression of RANTES expression in renal tubules. In the present study, we utilized an in vitro model of human kidney proximal tubule epithelial cells (HKC) to elucidate the mechanisms of RANTES suppression by HGF. HGF significantly suppressed basal and TNF-α-induced mRNA and protein expression of RANTES in a time and dose dependent fashion. HGF elicited PI3K-Akt activation and inhibited GSK3, a downstream transducer of PI3K-Akt, by inhibitory phosphorylation at Ser-9. When the PI3K-Akt pathway was blocked by wortmannin, HGF inhibition of RANTES was abrogated, demonstrating that the PI3K-Akt pathway is necessary for HGF action. In addition, specific inhibition of GSK3 activity by lithium ion suppressed basal and TNF-α-induced RANTES expression, reminiscent of the action of HGF. To further investigate the role of GSK3 in modulating RANTES expression, we examined the effect of forced expression of wild type GSK3β or an uninhibitable mutant GSK3β, in which the regulatory Ser-9 residue is changed to alanine (S9A-GSK3β) in HKC. Overexpression of wild type GSK3β did not alter the inhibitory action of HGF on RANTES. In contrast, expression of S9A-GSK3β abolished HGF inhibition of basal and TNF-α stimulated RANTES expression. These findings suggest that PI3K-Akt activation and subsequent inhibitory phosphorylation of GSK3β are required for HGF-induced suppression of RANTES in HKC

THE NEPHROTOXICITY RISK IN RATS SUBJECTED TO HEAVY MUSCLE ACTIVITY

Directory of Open Access Journals (Sweden)

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

Reproductive health in Irish female renal transplant recipients.

LENUS (Irish Health Repository)

Kennedy, C

2012-02-01

OBJECTIVE: To report the pregnancy outcomes in Irish female renal transplant recipients on modern maintenance immunosuppression. METHODS: The Republic of Ireland transplant database was accessed to identify the patient cohort in question. All female renal transplant recipients whose transplantation was in Ireland before or during their reproductive years were included. A questionnaire was sent to the identified women. A chart review was performed for those women who reported a pregnancy following renal transplantation. RESULTS: Two hundred and ten women met the inclusion criteria. There was a response rate of 70% (n = 148). Eighteen women reported 29 pregnancies. The live birth rate was 76%. The mean gestation of the live births was 36.2 weeks with a mean birth weight of 3.0 kg. There were six cases of pre-eclampsia. Twin pregnancies and those entering pregnancy with a creatinine greater than 135 micromol\\/l had particularly complicated clinical courses. Four women had not conceived post transplant despite actively trying for over 1 year. Two women utilised assisted fertility methods (in vitro fertilisation), one of whom became pregnant. CONCLUSIONS: A significant proportion of women who attempt to conceive following renal transplantation are successful, without the use of assisted fertility. Pregnancy in this setting warrants meticulous multidisciplinary care.

Arctigenin suppresses renal interstitial fibrosis in a rat model of obstructive nephropathy.

Science.gov (United States)

Li, Ao; Zhang, Xiaoxun; Shu, Mao; Wu, Mingjun; Wang, Jun; Zhang, Jingyao; Wang, Rui; Li, Peng; Wang, Yitao

2017-07-01

Renal tubulointerstitial fibrosis (TIF) is commonly the final result of a variety of progressive injuries and leads to end-stage renal disease. There are few therapeutic agents currently available for retarding the development of renal TIF. The aim of the present study is to evaluate the role of arctigenin (ATG), a lignan component derived from dried burdock (Arctium lappa L.) fruits, in protecting the kidney against injury by unilateral ureteral obstruction (UUO) in rats. Rats were subjected to UUO and then administered with vehicle, ATG (1 and 3mg/kg/d), or losartan (20mg/kg/d) for 11 consecutive days. The renoprotective effects of ATG were evaluated by histological examination and multiple biochemical assays. Our results suggest that ATG significantly protected the kidney from injury by reducing tubular dilatation, epithelial atrophy, collagen deposition, and tubulointerstitial compartment expansion. ATG administration dramatically decreased macrophage (CD68-positive cell) infiltration. Meanwhile, ATG down-regulated the mRNA levels of pro-inflammatory chemokine monocyte chemoattractant protein-1 (MCP-1) and cytokines, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interferon-γ (IFN-γ), in the obstructed kidneys. This was associated with decreased activation of nuclear factor κB (NF-κB). ATG attenuated UUO-induced oxidative stress by increasing the activity of renal manganese superoxide dismutase (SOD2), leading to reduced levels of lipid peroxidation. Furthermore, ATG inhibited the epithelial-mesenchymal transition (EMT) of renal tubules by reducing the abundance of transforming growth factor-β1 (TGF-β1) and its type I receptor, suppressing Smad2/3 phosphorylation and nuclear translocation, and up-regulating Smad7 expression. Notably, the efficacy of ATG in renal protection was comparable or even superior to losartan. ATG could protect the kidney from UUO-induced injury and fibrogenesis by suppressing inflammation, oxidative

Diglycolic acid inhibits succinate dehydrogenase activity in human proximal tubule cells leading to mitochondrial dysfunction and cell death.

Science.gov (United States)

Landry, Greg M; Dunning, Cody L; Conrad, Taylor; Hitt, Mallory J; McMartin, Kenneth E

2013-08-29

Diethylene glycol (DEG) is a solvent used in consumer products allowing the increased risk for consumer exposure. DEG metabolism produces two primary metabolites, 2-hydroxyethoxyacetic acid (2-HEAA) and diglycolic acid (DGA). DGA has been shown to be the toxic metabolite responsible for the proximal tubule cell necrosis seen in DEG poisoning. The mechanism of DGA toxicity in the proximal tubule cell is not yet known. The chemical structure of DGA is very similar to citric acid cycle intermediates. Studies were designed to assess whether its mechanism of toxicity involves disruption of cellular metabolic pathways resulting in mitochondrial dysfunction. First, DGA preferentially inhibited succinate dehydrogenase, including human kidney cell enzyme, but had no effect on other citric acid cycle enzyme activities. DGA produces a cellular ATP depletion that precedes cell death. Human proximal tubule (HPT) cells, pre-treated with increasing DGA concentrations, showed significantly decreased oxygen consumption. DGA did not increase lactate levels, indicating no effect on glycolytic activity. DGA increased reactive oxygen species (ROS) production in HPT cells in a concentration and time dependent manner. These results indicate that DGA produced proximal tubule cell dysfunction by specific inhibition of succinate dehydrogenase and oxygen consumption. Disruption of these processes results in decreased energy production and proximal tubule cell death. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

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.

NURSE STAFFING AND RENAL ANAEMIA OUTCOMES IN HAEMODIALYSIS CARE.

Science.gov (United States)

Erlingmark, Julia; Hedström, Mariann; Lindberg, Magnus

2016-09-01

Current trends in renal anaemia management place greater emphasis, and thus increased workload, on the role of the nurse in haemodialysis settings. However, there is little evidence that demonstrates the relationship between nurse staffing and patient outcomes. To describe nurse staffing in haemodialysis settings, its relationship with target levels of renal anaemia management and to describe target level achievement for different ways of organising anaemia management. Cross-sectional audit. Forty (out of 78) haemodialysis centres in Sweden reported quality assurance data. The numbers of bedside registered nurses, licensed nurse assistants and patients undergoing haemodialysis during a predefined morning shift; type of anaemia management and achieved target levels of anaemia management. The mean patient:registered nurse ratio was 2.4 and the mean patient:nurse assistant ratio was 12.8. There were no significant relationships between registered nurse staffing and target level achievement. On average, 45.6% of the patients had haemoglobin within the target levels at centres applying nurse-driven anaemia management, compared with 47.3% at physician-driven centres. These cross-sectional data suggest that renal anaemia outcomes are unrelated to the patient:registered nurse ratio. There is, however, room for improvement in renal anaemia management in the units included in this study, particularly the achievement of target levels of haemoglobin and transferrin saturation. © 2016 European Dialysis and Transplant Nurses Association/European Renal Care Association.

Exosome production and its regulation of EGFR during wound healing in renal tubular cells.

Science.gov (United States)

Zhou, Xiangjun; Zhang, Wei; Yao, Qisheng; Zhang, Hao; Dong, Guie; Zhang, Ming; Liu, Yutao; Chen, Jian-Kang; Dong, Zheng

2017-06-01

Kidney repair following injury involves the reconstitution of a structurally and functionally intact tubular epithelium. Growth factors and their receptors, such as EGFR, are important in the repair of renal tubules. Exosomes are cell-produced small (~100 nm in diameter) vesicles that contain and transfer proteins, lipids, RNAs, and DNAs between cells. In this study, we examined the relationship between exosome production and EGFR activation and the potential role of exosome in wound healing. EGFR activation occurred shortly after scratch wounding in renal tubular cells. Wound repair after scratching was significantly promoted by EGF and suppressed by EGFR inhibitor gefitinib. Interestingly, scratch wounding induced a significant increase of exosome production. The exosome production was decreased by EGF and increased by gefitinib, suggesting a suppressive role of EGFR signaling in exosome production. Conversely, inhibition of exosome release by GW4869 and manumycin A markedly increased EGFR activation and promoted wound healing. Moreover, exosomes derived from scratch-wounding cells could inhibit wound healing. Collectively, the results indicate that wound healing in renal tubular cells is associated with EGFR activation and exosome production. Although EGFR activation promotes wound healing, released exosomes may antagonize EGFR activation and wound healing. Copyright © 2017 the American Physiological Society.

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

Directory of Open Access Journals (Sweden)

Kohan Donald E

2002-08-01

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

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

Directory of Open Access Journals (Sweden)

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.

Direct Reprogramming of Human Bone Marrow Stromal Cells into Functional Renal Cells Using Cell-free Extracts

Directory of Open Access Journals (Sweden)

Evangelia Papadimou

2015-04-01

Full Text Available The application of cell-based therapies in regenerative medicine is gaining recognition. Here, we show that human bone marrow stromal cells (BMSCs, also known as bone-marrow-derived mesenchymal cells, can be reprogrammed into renal proximal tubular-like epithelial cells using cell-free extracts. Streptolysin-O-permeabilized BMSCs exposed to HK2-cell extracts underwent morphological changes—formation of “domes” and tubule-like structures—and acquired epithelial functional properties such as transepithelial-resistance, albumin-binding, and uptake and specific markers E-cadherin and aquaporin-1. Transmission electron microscopy revealed the presence of brush border microvilli and tight intercellular contacts. RNA sequencing showed tubular epithelial transcript abundance and revealed the upregulation of components of the EGFR pathway. Reprogrammed BMSCs integrated into self-forming kidney tissue and formed tubular structures. Reprogrammed BMSCs infused in immunodeficient mice with cisplatin-induced acute kidney injury engrafted into proximal tubuli, reduced renal injury and improved function. Thus, reprogrammed BMSCs are a promising cell resource for future cell therapy.

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

Renal PGC1α May Be Associated with Recovery after Delayed Graft Function.

Science.gov (United States)

Drury, Erika R; Zsengeller, Zsuzsanna K; Stillman, Isaac E; Khankin, Eliyahu V; Pavlakis, Martha; Parikh, Samir M

2018-01-01

Delayed renal graft function (DGF) contributes to the determination of length of hospitalization, risk of acute rejection, and graft loss. Existing tools aid the diagnosis of specific DGF etiologies such as antibody-mediated rejection, but markers of recovery have been elusive. The peroxisome proliferator gamma co-activator-1-alpha (PGC1α) is highly expressed in the renal tubule, regulates mitochondrial biogenesis, and promotes recovery from experimental acute kidney injury. We aimed to determine the association between renal allograft PGC1α expression and recovery from delayed graft function. We retrospectively analyzed patients undergoing renal transplantation at a single center from January 1, 2008 to June 30, 2014. PGC1α expression was assessed by immunostaining and ultrastructural characteristics by transmission electron microscopy. Of 34 patients who underwent renal biopsy for DGF within 30 days of transplant, 21 were included for analysis. Low PGC1α expression was associated with a significantly longer time on dialysis after transplant (median of 35.5 vs. 16 days, p < 0.05) and a significantly higher serum creatinine (sCr) at 4 weeks after transplantation among those who discontinued dialysis (5 vs. 1.65 mg/dL, p < 0.0001). Low PGC1α expression was not associated with higher sCr at 12 weeks after transplantation. Ultrastructural characteristics including apical membrane blebbing and necrotic luminal debris were not informative regarding clinical outcomes. These data suggest that higher PGC1α expression is associated with faster and more complete recovery from DGF. Mitochondrial biogenesis may be a therapeutic target for DGF. Larger studies are needed to validate these findings. © 2017 S. Karger AG, Basel.

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

Directory of Open Access Journals (Sweden)

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.

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

Directory of Open Access Journals (Sweden)

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.

Brown Norway chromosome 1 congenic reduces symptoms of renal disease in fatty Zucker rats.

Directory of Open Access Journals (Sweden)

Craig H Warden

Full Text Available We previously reported that a congenic rat with Brown Norway (BN alleles on chromosome 1 reduces renal disease of 15-week old fatty Zucker rats (ZUC. Development of renal disease in fatty BN congenic and fatty ZUC rats from 9 through 28 weeks is now examined. Analysis of urine metabolites by (1H nuclear magnetic resonance (NMR spectroscopy revealed a significantly increased urinary loss of glucose, myo-inositol, urea, creatine, and valine in ZUC. Food intake was lower in the BN congenic rats at weeks 9-24, but they weighed significantly more at 28 weeks compared with the ZUC group. Fasting glucose was significantly higher in ZUC than congenic and adiponectin levels were significantly lower in ZUC, but there was no significant genotype effect on Insulin levels. Glucose tolerance tests exhibited no significant differences between ZUC and congenic when values were normalized to basal glucose levels. Quantitative PCR on livers revealed evidence for higher gluconeogenesis in congenics than ZUC at 9 weeks. Plasma urea nitrogen and creatinine were more than 2-fold higher in 28-week ZUC. Twelve urine protein markers of glomerular, proximal and distal tubule disease were assayed at three ages. Several proteins that indicate glomerular and proximal tubular disease increased with age in both congenic and ZUC. Epidermal growth factor (EGF level, a marker whose levels decrease with distal tubule disease, was significantly higher in congenics. Quantitative histology of 28 week old animals revealed the most significant genotype effect was for tubular dilation and intratubular protein. The congenic donor region is protective of kidney disease, and effects on Type 2 diabetes are likely limited to fasting glucose and adiponectin. The loss of urea together with a small increase of food intake in ZUC support the hypothesis that nitrogen balance is altered in ZUC from an early age.

Mechanism of petroleum-induced sex-specific protein droplet nephropathy and renal cell proliferation in Fischer-344 rats: relevance to humans

International Nuclear Information System (INIS)

Charbonneau, M.; Short, B.G.; Lock, E.A.; Swenberg, J.A.

1987-01-01

Acute inhalation exposure of male rats to vaporized unleaded gasoline causes a protein droplet-nephropathy syndrome, whereas chronic exposure produces a significant increase renal tumor incidence. The renal lesions produced by chronic or acute exposure to UG have not been observed in kidneys of female rats, or either sex of mice. The assessment of the genotoxic properties of unleaded gasoline by a battery of tests has shown that unleaded gasoline is non-genotoxic. A 21-day histoautoradiographic study in male rats exposed to inhaled unleaded gasoline or gavaged with 2,2,4-trimethylpentane (TMP), a nephrotoxic component of unleaded gasoline selected as a model compound, has shown a dose-dependent increase in cell proliferation specifically in the proximal tubule, segments that have an increased protein droplet formation. A disposition study in male and female rats showed that after a single dose of [ 14 C]-TMP, TMP-derived radiolabel was retained in kidneys of male rats. An increase in the renal α2u-globulin concentration was concomitantly observed in male but not female rats

Renal Function and Outcomes With Use of Left Ventricular Assist Device Implantation and Inotropes in End-Stage Heart Failure: A Retrospective Single Center Study.

Science.gov (United States)

Verma, Sean; Bassily, Emmanuel; Leighton, Shane; Mhaskar, Rahul; Sunjic, Igor; Martin, Angel; Rihana, Nancy; Jarmi, Tambi; Bassil, Claude

2017-07-01

Left ventricular assist device (LVAD) and inotrope therapy serve as a bridge to transplant (BTT) or as destination therapy in patients who are not heart transplant candidates. End-stage heart failure patients often have impaired renal function, and renal outcomes after LVAD therapy versus inotrope therapy have not been evaluated. In this study, 169 patients with continuous flow LVAD therapy and 20 patients with continuous intravenous inotrope therapy were analyzed. The two groups were evaluated at baseline and at 3 and 6 months after LVAD or inotrope therapy was started. The incidence of acute kidney injury (AKI), need for renal replacement therapy (RRT), BTT rate, and mortality for 6 months following LVAD or inotrope therapy were studied. Results between the groups were compared using Mann-Whitney U test and Chi-square with continuity correction or Fischer's exact at the significance level of 0.05. Mean glomerular filtration rate (GFR) was not statistically different between the two groups, with P = 0.471, 0.429, and 0.847 at baseline, 3 and 6 months, respectively. The incidence of AKI, RRT, and BTT was not statistically different. Mortality was less in the inotrope group (P < 0.001). Intravenous inotrope therapy in end-stage heart failure patients is non-inferior for mortality, incidence of AKI, need for RRT, and renal function for 6-month follow-up when compared to LVAD therapy. Further studies are needed to compare the effectiveness of inotropes versus LVAD implantation on renal function and outcomes over a longer time period.

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.

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 ...

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

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

Science.gov (United States)

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.

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.

Expression of Nestin, Vimentin, and NCAM by Renal Interstitial Cells after Ischemic Tubular Injury

Directory of Open Access Journals (Sweden)

David Vansthertem

2010-01-01

Full Text Available This work explores the distribution of various markers expressed by interstitial cells in rat kidneys after ischemic injury (35 minutes during regeneration of S3 tubules of outer stripe of outer medulla (OSOM. Groups of experimental animals (n=4 were sacrificed every two hours during the first 24 hours post-ischemia as well as 2, 3, 7, 14 days post-ischemia. The occurrence of lineage markers was analyzed on kidney sections by immunohistochemistry and morphometry during the process of tubular regeneration. In postischemic kidneys, interstitial cell proliferation, assessed by 5-bromo-2′-deoxyuridine (BrdU and Proliferating Cell Nuclear Antigen (PCNA labeling, was prominent in outer medulla and reach a maximum between 24 and 72 hours after reperfusion. This population was characterized by the coexpression of vimentin and nestin. The density of -Neural Cell Adhesion Molecule (NCAM positive interstitial cells increased transiently (18–72 hours in the vicinity of altered tubules. We have also localized a small population of α-Smooth Muscle Actin (SMA-positive cells confined to chronically altered areas and characterized by a small proliferative index. In conclusion, we observed in the postischemic kidney a marked proliferation of interstitial cells that underwent transient phenotypical modifications. These interstitial cells could be implicated in processes leading to renal fibrosis.

Osteomalacia complicating renal tubular acidosis in association with Sjogren's syndrome.

Science.gov (United States)

El Ati, Zohra; Fatma, Lilia Ben; Boulahya, Ghada; Rais, Lamia; Krid, Madiha; Smaoui, Wided; Maiz, Hedi Ben; Beji, Soumaya; Zouaghi, Karim; Moussa, Fatma Ben

2014-09-01

Renal involvement in Sjogren's syndrome (SS) is not uncommon and may precede other complaints. Tubulointerstitial nephritis is the most common renal disease in SS and may lead to renal tubular acidosis (RTA), which in turn may cause osteomalacia. Nevertheless, osteomalacia rarely occurs as the first manifestation of a renal tubule disorder due to SS. We herewith describe a 43-year-old woman who was admitted to our hospital for weakness, lumbago and inability to walk. X-ray of the long bones showed extensive demineralization of the bones. Laboratory investigations revealed chronic kidney disease with serum creatinine of 2.3 mg/dL and creatinine clearance of 40 mL/min, hypokalemia (3.2 mmol/L), hypophosphatemia (0.4 mmol/L), hypocalcemia (2.14 mmol/L) and hyperchloremic metabolic acidosis (chlorine: 114 mmol/L; alkaline reserve: 14 mmol/L). The serum alkaline phosphatase levels were elevated. The serum levels of 25-hydroxyvitamin D and 1,25-dihydroxy vitamin D were low and borderline low, respectively, and the parathyroid hormone level was 70 pg/L. Urinalysis showed inappropriate alkaline urine (urinary PH: 7), glycosuria with normal blood glucose, phosphaturia and uricosuria. These values indicated the presence of both distal and proximal RTA. Our patient reported dryness of the mouth and eyes and Schirmer's test showed xerophthalmia. An accessory salivary gland biopsy showed changes corresponding to stage IV of Chisholm and Masson score. Kidney biopsy showed diffuse and severe tubulo-interstitial nephritis with dense lymphoplasmocyte infiltrates. Sicca syndrome and renal interstitial infiltrates indicated SS as the underlying cause of the RTA and osteomalacia. The patient received alkalinization, vitamin D (Sterogyl ®), calcium supplements and steroids in an initial dose of 1 mg/kg/day, tapered to 10 mg daily. The prognosis was favorable and the serum creatinine level was 1.7 mg/dL, calcium was 2.2 mmol/L and serum phosphate was 0.9 mmol/L.

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.

Illness/treatment perceptions and overprotection as determinants of labour participation in renal patients.

NARCIS (Netherlands)

Jansen, D.; Heijmans, M.; Rijken, M.

2006-01-01

Objectives (1): To gain insight into the role of illness/treatment perceptions and overprotection in the labour participation and autonomy of patients with renal insufficiency and (2) to develop a protocol to assist renal patients to start, stay or reintegrate on the labour market. Methods (1):

Renal response to L-arginine in diabetic rats. A possible link between nitric oxide system and aquaporin-2.

Directory of Open Access Journals (Sweden)

María C Ortiz

Full Text Available The aim of this study was to evaluate whether L-Arginine (L-Arg supplementation modifies nitric oxide (NO system and consequently aquaporin-2 (AQP2 expression in the renal outer medulla of streptozotocin-diabetic rats at an early time point after induction of diabetes. Male Wistar rats were divided in four groups: Control, Diabetic, Diabetic treated with L-Arginine and Control treated with L-Arginine. Nitric oxide synthase (NOS activity was estimated by [14C] L-citrulline production in homogenates of the renal outer medulla and by NADPH-diaphorase staining in renal outer medullary tubules. Western blot was used to detect the expression of AQP2 and NOS types I and III; real time PCR was used to quantify AQP2 mRNA. The expression of both NOS isoforms, NOS I and NOS III, was decreased in the renal outer medulla of diabetic rats and L-Arg failed to prevent these decreases. However, L-Arg improved NO production, NADPH-diaphorase activity in collecting ducts and other tubular structures, and NOS activity in renal homogenates from diabetic rats. AQP2 protein and mRNA were decreased in the renal outer medulla of diabetic rats and L-Arg administration prevented these decreases. These results suggest that the decreased NOS activity in collecting ducts of the renal outer medulla may cause, at least in part, the decreased expression of AQP2 in this model of diabetes and constitute additional evidence supporting a role for NO in contributing to renal water reabsorption through the modulation of AQP2 expression in this pathological condition. However, we cannot discard that another pathway different from NOS also exists that links L-Arg to AQP2 expression.

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 ...

A role for the organic anion transporter OAT3 in renal creatinine secretion in mice

Science.gov (United States)

Eraly, Satish A.; Rao, Satish Ramachandra; Gerasimova, Maria; Rose, Michael; Nagle, Megha; Anzai, Naohiko; Smith, Travis; Sharma, Kumar; Nigam, Sanjay K.; Rieg, Timo

2012-01-01

Tubular secretion of the organic cation, creatinine, limits its value as a marker of glomerular filtration rate (GFR) but the molecular determinants of this pathway are unclear. The organic anion transporters, OAT1 and OAT3, are expressed on the basolateral membrane of the proximal tubule and transport organic anions but also neutral compounds and cations. Here, we demonstrate specific uptake of creatinine into mouse mOat1- and mOat3-microinjected Xenopus laevis oocytes at a concentration of 10 μM (i.e., similar to physiological plasma levels), which was inhibited by both probenecid and cimetidine, prototypical competitive inhibitors of organic anion and cation transporters, respectively. Renal creatinine clearance was consistently greater than inulin clearance (as a measure of GFR) in wild-type (WT) mice but not in mice lacking OAT1 (Oat1−/−) and OAT3 (Oat3−/−). WT mice presented renal creatinine net secretion (0.23 ± 0.03 μg/min) which represented 45 ± 6% of total renal creatinine excretion. Mean values for renal creatinine net secretion and renal creatinine secretion fraction were not different from zero in Oat1−/− (−0.03 ± 0.10 μg/min; −3 ± 18%) and Oat3−/− (0.01 ± 0.06 μg/min; −6 ± 19%), with greater variability in Oat1−/−. Expression of OAT3 protein in the renal membranes of Oat1−/− mice was reduced to ∼6% of WT levels, and that of OAT1 in Oat3−/− mice to ∼60%, possibly as a consequence of the genes for Oat1 and Oat3 having adjacent chromosomal locations. Plasma creatinine concentrations of Oat3−/− were elevated in clearance studies under anesthesia but not following brief isoflurane anesthesia, indicating that the former condition enhanced the quantitative contribution of OAT3 for renal creatinine secretion. The results are consistent with a contribution of OAT3 and possibly OAT1 to renal creatinine secretion in mice. PMID:22338083

Study on the Renal Anemia: Experimental Study in Acute Renal Anemia

International Nuclear Information System (INIS)

Yoon, Zo Eun

1969-01-01

finding of renal biopsy of the cantharidin group shows a selective damage in glomerulus, while shows almost normal range or slight damage in tubules. And that of the pot. perchlomate group shows a selective damage in tubules with slight damage of glomerulus.

An experimental study on recovery of renal function using 99mTc DMSA scintigram after percutaneous nephrostomy in unilateral hydronephrosis

International Nuclear Information System (INIS)

Moon, Tae Yong; Nam, Sang Hwa; Park, Jong Yeon; Kim, Byung Soo

1992-01-01

Obstruction on the urinary tract eventually results in damage to the kidneys and lose of function. The questions that concern the clinician are the degree of nephron loss in that kidney and potential for recovery following the relief of obstruction. 99m Tc DMSA accumulates in tubule cells and has been proposed as a marker of the tubular mass. The authors estimated the renal uptake ratio of 99m Tc DMSA for the degree of nephron loss corresponding to duration of hydronephrosis following left ureteral ligation in 5 New Zealand white rabbits and the potential for recovery following percutaneous nephrostomy of hydronephrosis in 24 rabbits. While the renal uptake ratio of 99m Tc DMSA of the kidney with unilateral hydronephrosis following ureteral ligation reduced dramatically within 24 hour, that of the opposite healthy kidney increased, and the total renal uptake ratio was same as normal functioning kidneys before ureteral ligation. Upon ureteral release, there was no evidence of definite recovery or impairment in the experimental kidneys for 5 days. The authors conclude that a combination of ureteral release and administration of some drugs such as renal vasodilator or diuretics is an appropriate treatment for the recovery of function in unilateral hydronephrosis

FUROSEMIDE TEST: ITS PATTERN IN NOT SEVERE CHRONIC RENAL DISEASE

Directory of Open Access Journals (Sweden)

Carlos G. Musso

2008-01-01

Full Text Available Furosemide test is a simple and useful test of renal physiology used to evaluate the capability of the collecting tubules to secrete potassium under the effect of serum aldosterone. Its behaviour pattern has already been established in children and young adults but not described in chronic renal disease patients yet, which we explored in this study.Material & Method: Twenty-six young volunteers (between 20 and 40 years old, chronically on a low potassium diet (40 mmol of K day were studied: twenty of them were healthy young ( they were neither suffering form diseases nor on any medication, and the rest were young patients suffering from stage II / III chronic renal disease (damaged kidney with GFR between 83.1 ml-min to 39.2 ml-min secondary to glomerular diseases documented by kidney biopsy. None of the studied chronic renal disease patients were suffering from diabetes mellitus, urinary obstruction, nor treated with dyskalemia generating drugs, such as: diuretics, angiotensin converting enzyme inhibitors, angiotensin receptor antagonists, etc. Before, while the test was being carried out and after 180 minutes of a single dose of intravenous furosemide (1 mg/kg, urine and blood samples were obtained, for creatinine and potassium levels. From these data we calculated fractional excretion (FE of potassium. Statistical analysis was performed applying Student´s t-test.Results: There was no significant difference neither in pre-furosemide (basal and post-furosemide average FE of potassium between the healthy and chronic renal disease (CRD group: 16.4 ± 8.6% (CRD vs 11.5 ± 4.6% (healthy (p = NS ; 40.8 ± 3.2 % (CRD vs 35.4 ± 8.9% (healthy (p = NS respectively. Conversely, there was a significant difference in post-furosemide peak FE of potassium value, which was higher and delayed in the CRD group compared to the healthy one: 49.5 ± 8.2 % at 118 mins (CRD vs 31.6 ± 11% at 30 mins (healthy (p = 0.001.Conclusion: Furosemide test showed a

Hilar Renal Artery Aneurysm - Ex-vivo Reconstruction and Autotransplantation.

Science.gov (United States)

Pinto Sousa, Pedro; Veiga, Carlos; Matos, Arlindo; Sá Pinto, Pedro; Almeida, Rui

2017-01-01

Renal artery aneurysm (RAA) is a rare clinical entity with an estimated prevalence of 0.15% to 0.1%in the general population. The majority of patients present asymptomatically and the diagnosis is made incidentally during a hypertension study test, and more rarely, fortuitously after backache. Indications to treat have been subject of intense debate, nevertheless there seems to be some consensus that RAAs greater than 2 cm in diameter, expanding RAA, with thrombus or in pregnant women should be treated. Treatment options vary between surgical or endovascular approach. The complex (hilar) RAA constitute a subset of RAA that present a therapeutic dilemma because of their anatomic location and may require extracorporeal arterial reconstruction and auto-transplantation. We describe a 71-year-old woman with a personal history of hypertension for more than twenty years but normal renal function. Following the study for an abdominal discomfort a complex RAA was incidentally diagnosed. Computed tomographic angiography with three-dimensional reconstruction revealed a 13mm, saccular aneurysm located at the right renal hilum. We performed hand-assisted laparoscopic nephrectomy with ex vivo repair of the RAA. The aneurysm was resected and a polar renal artery was implanted over the resected area with a latero-terminal anastomosis. Complementarily, the renal vein was augmented with a spiral great saphenous vein graft and finally the kidney was implanted into the right iliac fossa. The intervention and postoperative course were uneventful and the patient submitted to ultrasound evaluation on the day after procedure. It revealed normal renal perfusion with normal flow indices. In the last follow-up realized, two months after surgery the patient was alive with a well-functioning auto-transplant. RAA may be nowadays more frequently diagnosed due to the increasing use of imaging techniques. While renal artery trunk aneurysms are most often treated using an endovascular procedure it

CD147/basigin reflects renal dysfunction in patients with acute kidney injury.

Science.gov (United States)

Nagaya, Hiroshi; Kosugi, Tomoki; Maeda-Hori, Mayuko; Maeda, Kayaho; Sato, Yuka; Kojima, Hiroshi; Hayashi, Hiroki; Kato, Noritoshi; Ishimoto, Takuji; Sato, Waichi; Yuzawa, Yukio; Matsuo, Seiichi; Kadomatsu, Kenji; Maruyama, Shoichi

2014-10-01

Acute tubular necrosis (ATN) describes a form of intrinsic acute kidney injury (AKI) that results from persistent hypoperfusion and subsequent activation of the immune system. A glycosylated transmembrane protein, CD147/basigin, is involved in the pathogenesis of renal ischemia and fibrosis. The present study investigated whether CD147 can reflect pathological features and renal dysfunction in patients with AKI. Plasma and spot urine samples were collected from 24 patients (12 controls and 12 with ATN) who underwent renal biopsy between 2008 and 2012. In another study, patients undergoing open surgery to treat abdominal aortic aneurysms (AAAs) were enrolled in 2004. We collected urine and plasma samples from seven patients with AKI and 33 patients without AKI, respectively. In these experiments, plasma and urinary CD147, and urinary L-fatty acid-binding protein (L-FABP) levels were measured, and the former expression in kidneys was examined by immunostaining. In biopsy tissues of ATN with severe histological features, CD147 induction was strikingly present in inflammatory cells such as macrophages and lymphocytes in the injured interstitium, but not in damaged tubules representing atrophy. Both plasma and urinary CD147 levels were strikingly increased in ATN patients; both values showed greater correlations with renal dysfunction compared to urinary L-FABP. In patients who had undergone open AAA surgery, urinary and plasma CD147 values in AKI patients were significantly higher than in non-AKI patients at post-operative day 1, similar to the profile of urinary L-FABP. CD147 was prominent in its ability to detect AKI and may allow the start of preemptive medication.

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)

Evidence of low dimensional chaos in renal blood flow control in genetic and experimental hypertension

Science.gov (United States)

Yip, K.-P.; Marsh, D. J.; Holstein-Rathlou, N.-H.

1995-01-01

We applied a surrogate data technique to test for nonlinear structure in spontaneous fluctuations of hydrostatic pressure in renal tubules of hypertensive rats. Tubular pressure oscillates at 0.03-0.05 Hz in animals with normal blood pressure, but the fluctuations become irregular with chronic hypertension. Using time series from rats with hypertension we produced surrogate data sets to test whether they represent linearly correlated noise or ‘static’ nonlinear transforms of a linear stochastic process. The correlation dimension and the forecasting error were used as discriminating statistics to compare surrogate with experimental data. The results show that the original experimental time series can be distinguished from both linearly and static nonlinearly correlated noise, indicating that the nonlinear behavior is due to the intrinsic dynamics of the system. Together with other evidence this strongly suggests that a low dimensional chaotic attractor governs renal hemodynamics in hypertension. This appears to be the first demonstration of a transition to chaotic dynamics in an integrated physiological control system occurring in association with a pathological condition.

Renal Protection by Genetic Deletion of the Atypical Chemokine Receptor ACKR2 in Diabetic OVE Mice

Directory of Open Access Journals (Sweden)

Shirong Zheng

2016-01-01

Full Text Available In diabetic nephropathy (DN proinflammatory chemokines and leukocyte infiltration correlate with tubulointerstitial injury and declining renal function. The atypical chemokine receptor ACKR2 is a chemokine scavenger receptor which binds and sequesters many inflammatory CC chemokines but does not transduce typical G-protein mediated signaling events. ACKR2 is known to regulate diverse inflammatory diseases but its role in DN has not been tested. In this study, we utilized ACKR2−/− mice to test whether ACKR2 elimination alters progression of diabetic kidney disease. Elimination of ACKR2 greatly reduced DN in OVE26 mice, an established DN model. Albuminuria was significantly lower at 2, 4, and 6 months of age. ACKR2 deletion did not affect diabetic blood glucose levels but significantly decreased parameters of renal inflammation including leukocyte infiltration and fibrosis. Activation of pathways that increase inflammatory gene expression was attenuated. Human biopsies stained with ACKR2 antibody revealed increased staining in diabetic kidney, especially in some tubule and interstitial cells. The results demonstrate a significant interaction between diabetes and ACKR2 protein in the kidney. Unexpectedly, ACKR2 deletion reduced renal inflammation in diabetes and the ultimate response was a high degree of protection from diabetic nephropathy.

Demonstration of the proliferation marker Ki-67 in renal biopsies: correlation to clinical findings.

Science.gov (United States)

Nabokov, A; Waldherr, R; Ritz, E

1997-07-01

Assessment of cell proliferation in renal biopsy samples is a potentially promising analytical tool to evaluate disease activity. So far no information is available on the correlation between proliferative activity in different anatomic compartments of the kidney and clinical symptoms. To elucidate this issue, we examined renal biopsy specimens from 20 patients with systemic vasculitis (15 Wegener's granulomatosis, five microscopic polyangiitis), 20 patients with immunoglobulin (Ig) A nephropathy (IgAN), 13 patients with minimal-change disease (MCD), 11 patients with tubulointerstitial nephritis, and five patients with diabetes mellitus. The streptavidin-biotin-peroxidase complex technique was applied to autoclave-pretreated, formalin-fixed, paraffin-embedded tissue sections to label different cell types with the antibody MIB1 directed against the Ki-67 antigen. Proliferation index (PI) was estimated as the number of positively stained nuclei per glomerular cross-section or per square millimeter section area. The interstitial cells were discriminated by additional staining of Ki-67-processed samples with specific immune markers. In patients with vasculitis, PI was considerably elevated in the extracapillary glomerular compartment (0.86), in proximal tubules (6.24), and in the interstitium (8.62). High proliferative activity was also noted in interstitium (3.98) and proximal tubules (1.35) of patients with IgAN. Of particular interest was the increased interstitial proliferative activity (15.0) in diabetic patients. Resident renal cells, but not infiltrating cells, seemed to constitute the majority of the proliferating cell population in the interstitium. In systemic vasculitis, clinical disease activity was significantly correlated to endocapillary (r(s) = 0.58), extracapillary (r(s) = 0.67), proximal tubular (r(s) = 0.67), and interstitial PI (r(s) = 0.61). By multiple linear regression analysis, proximal tubular PI was correlated to the presence of hematuria

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

Autophagy Limits Endotoxemic Acute Kidney Injury and Alters Renal Tubular Epithelial Cell Cytokine Expression.

Directory of Open Access Journals (Sweden)

Jeremy S Leventhal

Full Text Available Sepsis related acute kidney injury (AKI is a common in-hospital complication with a dismal prognosis. Our incomplete understanding of disease pathogenesis has prevented the identification of hypothesis-driven preventive or therapeutic interventions. Increasing evidence in ischemia-reperfusion and nephrotoxic mouse models of AKI support the theory that autophagy protects renal tubular epithelial cells (RTEC from injury. However, the role of RTEC autophagy in septic AKI remains unclear. We observed that lipopolysaccharide (LPS, a mediator of gram-negative bacterial sepsis, induces RTEC autophagy in vivo and in vitro through TLR4-initiated signaling. We modeled septic AKI through intraperitoneal LPS injection in mice in which autophagy-related protein 7 was specifically knocked out in the renal proximal tubules (ATG7KO. Compared to control littermates, ATG7KO mice developed more severe renal dysfunction (24hr BUN 100.1mg/dl +/- 14.8 vs 54.6mg/dl +/- 11.3 and parenchymal injury. After injection with LPS, analysis of kidney lysates identified higher IL-6 expression and increased STAT3 activation in kidney lysates from ATG7KO mice compared to controls. In vitro experiments confirmed an altered response to LPS in RTEC with genetic or pharmacological impairment of autophagy. In conclusion, RTEC autophagy protects against endotoxin induced injury and regulates downstream effects of RTEC TLR4 signaling.

Gender difference and sex hormone production in rodent renal ischemia reperfusion injury and repair

Directory of Open Access Journals (Sweden)

Ghazali Daniel

2011-06-01

Full Text Available Abstract Background Several lines of evidence suggest a protective effect of female sex hormones in several organs subjected to ischemia-reperfusion injury. The aim of the study was to investigate sex hormone production in male rats after a renal ischemia-reperfusion sequence and analyze the influence of gender differences on tissue remodelling during the recovery process. Method Age-matched sexually mature male and female rats were subjected to 60 min of renal unilateral ischemia by pedicle clamping with contralateral nephrectomy and followed for 1 or 5 days after reperfusion. Plasma creatinine, systemic testosterone, progesterone and estradiol levels were determined. Tubular injury, cell proliferation and inflammation, were evaluated as well as proliferating cell nuclear antigen, vimentin and translocator protein (TSPO expressions by immunohistochemistry. Results After 1 and 5 days of reperfusion, plasma creatinine was significantly higher in males than in females, supporting the high mortality in this group. After reperfusion, plasma testosterone levels decreased whereas estradiol significantly increased in male rats. Alterations of renal function, associated with tubular injury and inflammation persisted during the 5 days post-ischemia-reperfusion, and a significant improvement was observed in females at 5 days of reperfusion. Proliferating cell nuclear antigen and vimentin expression were upregulated in kidneys from males and attenuated in females, in parallel to injury development. TSPO expression was transiently increased in proximal tubules in male rats. Conclusions After ischemia, renal function recovery and tissue injury is gender-dependent. These differences are associated with a modulation of sex hormone production and a modification of tissue remodeling and proliferative cell processes.

An experimental study on recovery of renal function using {sup 99m}Tc DMSA scintigram after percutaneous nephrostomy in unilateral hydronephrosis

Energy Technology Data Exchange (ETDEWEB)

Moon, Tae Yong; Nam, Sang Hwa; Park, Jong Yeon; Kim, Byung Soo [College of Medicine, Pusan National University, Pusan (Korea, Republic of)

1992-07-15

Obstruction on the urinary tract eventually results in damage to the kidneys and lose of function. The questions that concern the clinician are the degree of nephron loss in that kidney and potential for recovery following the relief of obstruction. {sup 99m}Tc DMSA accumulates in tubule cells and has been proposed as a marker of the tubular mass. The authors estimated the renal uptake ratio of {sup 99m}Tc DMSA for the degree of nephron loss corresponding to duration of hydronephrosis following left ureteral ligation in 5 New Zealand white rabbits and the potential for recovery following percutaneous nephrostomy of hydronephrosis in 24 rabbits. While the renal uptake ratio of {sup 99m}Tc DMSA of the kidney with unilateral hydronephrosis following ureteral ligation reduced dramatically within 24 hour, that of the opposite healthy kidney increased, and the total renal uptake ratio was same as normal functioning kidneys before ureteral ligation. Upon ureteral release, there was no evidence of definite recovery or impairment in the experimental kidneys for 5 days. The authors conclude that a combination of ureteral release and administration of some drugs such as renal vasodilator or diuretics is an appropriate treatment for the recovery of function in unilateral hydronephrosis.

Brown spider dermonecrotic toxin directly induces nephrotoxicity

International Nuclear Information System (INIS)

Chaim, Olga Meiri; Sade, Youssef Bacila; Bertoni da Silveira, Rafael; Toma, Leny; Kalapothakis, Evanguedes; Chavez-Olortegui, Carlos; Mangili, Oldemir Carlos; Gremski, Waldemiro; Dietrich, Carl Peter von; Nader, Helena B.; Sanches Veiga, Silvio

2006-01-01

Brown spider (Loxosceles genus) venom can induce dermonecrotic lesions at the bite site and systemic manifestations including fever, vomiting, convulsions, disseminated intravascular coagulation, hemolytic anemia and acute renal failure. The venom is composed of a mixture of proteins with several molecules biochemically and biologically well characterized. The mechanism by which the venom induces renal damage is unknown. By using mice exposed to Loxosceles intermedia recombinant dermonecrotic toxin (LiRecDT), we showed direct induction of renal injuries. Microscopic analysis of renal biopsies from dermonecrotic toxin-treated mice showed histological alterations including glomerular edema and tubular necrosis. Hyalinization of tubules with deposition of proteinaceous material in the tubule lumen, tubule epithelial cell vacuoles, tubular edema and epithelial cell lysis was also observed. Leukocytic infiltration was neither observed in the glomerulus nor the tubules. Renal vessels showed no sign of inflammatory response. Additionally, biochemical analyses showed such toxin-induced changes in renal function as urine alkalinization, hematuria and azotemia with elevation of blood urea nitrogen levels. Immunofluorescence with dermonecrotic toxin antibodies and confocal microscopy analysis showed deposition and direct binding of this toxin to renal intrinsic structures. By immunoblotting with a hyperimmune dermonecrotic toxin antiserum on renal lysates from toxin-treated mice, we detected a positive signal at the region of 33-35 kDa, which strengthens the idea that renal failure is directly induced by dermonecrotic toxin. Immunofluorescence reaction with dermonecrotic toxin antibodies revealed deposition and binding of this toxin directly in MDCK epithelial cells in culture. Similarly, dermonecrotic toxin treatment caused morphological alterations of MDCK cells including cytoplasmic vacuoles, blebs, evoked impaired spreading and detached cells from each other and from

Osteomalacia complicating renal tubular acidosis in association with Sjogren′s syndrome

Directory of Open Access Journals (Sweden)

Zohra El Ati

2014-01-01

Full Text Available Renal involvement in Sjogren′s syndrome (SS is not uncommon and may precede other complaints. Tubulointerstitial nephritis is the most common renal disease in SS and may lead to renal tubular acidosis (RTA, which in turn may cause osteomalacia. Nevertheless, osteomalacia rarely occurs as the first manifestation of a renal tubule disorder due to SS. We herewith describe a 43-year-old woman who was admitted to our hospital for weakness, lumbago and inability to walk. X-ray of the long bones showed extensive demineralization of the bones. Laboratory investigations revealed chronic kidney disease with serum creatinine of 2.3 mg/dL and creatinine clearance of 40 mL/min, hypokalemia (3.2 mmol/L, hypophosphatemia (0.4 mmol/L, hypocalcemia (2.14 mmol/L and hyperchloremic metabolic acidosis (chlorine: 114 mmol/L; alkaline reserve: 14 mmol/L. The serum alkaline phosphatase levels were elevated. The serum levels of 25-hydroxyvitamin D and 1,25-dihydroxy vitamin D were low and borderline low, respectively, and the parathyroid hormone level was 70 pg/L. Urinalysis showed inappropriate alkaline urine (urinary PH: 7, glycosuria with normal blood glucose, phosphaturia and uricosuria. These values indicated the presence of both distal and proximal RTA. Our patient reported dryness of the mouth and eyes and Schirmer′s test showed xerophthalmia. An accessory salivary gland biopsy showed changes corresponding to stage IV of Chisholm and Masson score. Kidney biopsy showed diffuse and severe tubulo-interstitial nephritis with dense lymphoplasmocyte infiltrates. Sicca syndrome and renal interstitial infiltrates indicated SS as the underlying cause of the RTA and osteomalacia. The patient received alkalinization, vitamin D (Sterogyl ®, calcium supplements and steroids in an initial dose of 1 mg/kg/day, tapered to 10 mg daily. The prognosis was favorable and the serum creatinine level was 1.7 mg/dL, calcium was 2.2 mmol/L and serum phosphate was 0.9 mmol/L.

An experience of renal replacement therapy in children

International Nuclear Information System (INIS)

Jamal, A.; Ramzan, A.

2002-01-01

Objective: To determine the prevalence of renal failure in children requiring renal replacement therapy (RRT), the types of RRT being performed, problems encountered during the procedure and the outcome of the RRT in pediatric age group. Design: It was a retrospective study on pediatric patients with renal failure undergoing RRT. Place and Duration of Study: The study was carried out at National Institute of Child Health (N. I. C. H) covering a period of four years. Subjects and Methods: The study included all pediatric patients of acute renal failure, chronic renal failure and end stage renal disease who underwent RRT at N. I. C. H. Results: 17% of the patients with renal disease came in renal failure. A total of 65. 04 % patients received RT. Out of these, 84.7% underwent peritoneal dialysis (PD) while 15.3 % required hemodialysis and 2 were successfully transplanted. High cost of the RRT was the most commonly encountered problem during the procedure. Peritonitis was the commonest complication faced during the peritoneal dialysis while hypotension and complications related to vascular access were commonest during hemodialysis. About 50% of the patients undergoing peritoneal dialysis were left with persistent renal impairment while hemodialysis revealed a mortality of 37%. The two transplanted patients were doing well. Conclusion: The study showed that renal failure was a fairly common problem in pediatric age group and the prospects of successful RRT in Pakistan were quite high with a little effort on the part of medical professionals along with some financial assistance from the affluent of the country. (author)

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

Directory of Open Access Journals (Sweden)

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.

Aneurisma da Artéria Renal: caso clínico Renal Artery Aneurysm

Directory of Open Access Journals (Sweden)

Joana Moreira

2011-12-01

Full Text Available Apresenta-se o caso clínico de um doente com volumoso aneurisma da artéria renal esquerda. Do sexo masculino, de 22 anos de idade, com lombalgia à esquerda com algumas semanas de evolução. Recorreu ao médico assistente que solicitou estudo imagiológico por ecografia abdominal. Detectada imagem sugestiva de aneurisma da aorta abdominal. Este achado motivou a transferência para o nosso Hospital onde foi admitido consciente e orientado, hemodinamicamente estável, apresentando uma massa pulsátil epigástrica, com frémito e sopro sistólico à auscultação. Angio-TC revelou um aneurisma da artéria renal esquerda com 16 cm de diâmetro. Dada a estabilidade clínica e topografia lesional optou-se por tentar embolizar, sem sucesso, o tronco da artéria renal esquerda antes da abordagem cirúrgica. O doente foi então submetido a Nefrectomia total esquerda por via toraco-abdominal. Pós-operatório sem complicações, locais ou sistémicas. Alta ao 8ºdia, mantendo boa função renal e com níveis normais de hemoglobina. Diagnóstico de aneurisma da artéria renal confirmado por estudo anátomo-patológico da peça operatória.One case of a large left renal artery aneurysm in a young patient 22 years old is presented. He appealed to his assistant physician a few weeks after development of left back pain. Abdominal ultrasound imaging study has been requested. Suggestive abdominal aortic aneurysm was detected. This finding led to the transfer to our hospital where he was admitted conscious and hemodynamically stable. A pulsatile epigastric mass with a systolic murmur on auscultation and thrill were detected. Angio-CT scan revealed a left renal artery aneurysm, 16 cm in diameter. Given the clinical stability and lesional topography we decide a previous embolization of left renal artery, unsuccessfully. The patient underwent then left total nephrectomy, through thoraco-abdominal incision. No local or systemic complications in the postoperative

Cystine uptake by cultured cells originating from dog proximal tubule segments

International Nuclear Information System (INIS)

States, B.; Reynolds, R.; Lee, J.; Segal, S.

1990-01-01

Large numbers of kidney epithelial cells were cultured successfully from isolated dog proximal tubule segments. Cells in primary culture and in first passage retained the cystine-dibasic amino acid co-transporter system which is found in vivo and in freshly isolated proximal tubule segments. In contrast to other cultured cells, the cystine-glutamate anti-porter was absent in primary cultures. However, this anti-porter system seemed to be developing in cells in first passage. The intracellular ratio of cysteine:reduced glutathione (CSH:GSH) was maintained at 1:36 in both primary cultures and in low passage cells. Incubation of cells in primary culture for 5 min at 37 degrees C with 0.025 mM [ 35 S]L-cystine resulted in incorporation of approximately 36 and 8.5% of the label into intracellular CSH and GSH, respectively. These cultured cells, therefore, seem to be an excellent model system for the eventual elucidation of (a) the inticacies of cystine metabolism and (b) regulation of (1) the cystine-dibasic amino acid co-transporter system and (2) the development of the cysteine-glutamate anti-porter system

Inbred Rats as a Model to Study Persistent Renal Leptospirosis and Associated Cellular Immune Responsiveness

Directory of Open Access Journals (Sweden)

Jarlath E. Nally

2018-03-01

Full Text Available Pathogenic species of Leptospira cause leptospirosis, a bacterial zoonotic disease with a global distribution affecting over one million people annually. Rats are regarded as one of the most significant reservoir hosts of infection for human disease, and in the absence of clinical signs of infection, excrete large numbers of organisms in their urine. A unique biological equilibrium exists between pathogenic leptospires and reservoir hosts of infection, but surprisingly, little is known concerning the host's cellular immune response that facilitates persistent renal colonization. To address this deficiency, we established and applied an immunocompetent inbred rat model of persistent renal colonization; leptospires were detected in urine of experimentally infected rats by 3 weeks post-infection and remained positive until 8 weeks post-infection. However, there was little, if any, evidence of inflammation in colonized renal tubules. At 8 weeks post-infection, a robust antibody response was detected against lipopolysaccharide and protein outer membrane (OM components. Purified B and T cells derived from the spleen of infected and non-infected rats proliferated in response to stimulation with 0.5 μg of OM fractions of Leptospira, including CD4+ T cells, which comprised 40% of proliferating cells, compared to 25% in non-infected controls. However, analysis of gene expression did not determine which immunoregulatory pathways were activated. Lymphocytes purified from the lymph node draining the site of colonization, the renal lymph node, also showed an increase in percentage of proliferating B and T cells. However, in contrast to a phenotype of 40% CD4+ T cells in the spleen, the phenotype of proliferating T cells in the renal lymph node comprised 65% CD4+ T cells. These results confirm that the renal lymph node, the local lymphoid organ, is a dominant site containing Leptospira reactive CD4+ T cells and highlight the need to consider the local, vs

Robot-assisted partial nephrectomy in contemporary practice

Energy Technology Data Exchange (ETDEWEB)

Tanagho, Youssef S.; Bhayani, Sam B.; Figenshau, Robert S., E-mail: tanaghoy@wudosis.wustl.edu [Division of Urologic Surgery, Washington University School of Medicine, St. Louis, MO (United States)

2013-01-11

Laparoscopic renal surgery is associated with reduced blood loss, shorter hospital stay, enhanced cosmesis, and more rapid convalescence relative to open renal surgery. Laparoscopic partial nephrectomy (LPN) is a minimally invasive, nephron-sparing alternative to laparoscopic radical nephrectomy (RN) for the management of small renal masses. While offering similar oncological outcomes to laparoscopic RN, the technical challenges and prolonged learning curve associated with LPN limit its wider dissemination. Robot-assisted partial nephrectomy (RAPN), although still an evolving procedure with no long-term data, has emerged as a viable alternative to LPN, with favorable preliminary outcomes. This article provides an overview of the role of RAPN in the management of renal cell carcinoma. The clinical indications and principles of surgical technique for this procedure are discussed. The oncological, renal functional, and perioperative outcomes of RAPN are also evaluated, as are complication rates.

Robot-assisted partial nephrectomy in contemporary practice

International Nuclear Information System (INIS)

Tanagho, Youssef S.; Bhayani, Sam B.; Figenshau, Robert S.

2013-01-01

Laparoscopic renal surgery is associated with reduced blood loss, shorter hospital stay, enhanced cosmesis, and more rapid convalescence relative to open renal surgery. Laparoscopic partial nephrectomy (LPN) is a minimally invasive, nephron-sparing alternative to laparoscopic radical nephrectomy (RN) for the management of small renal masses. While offering similar oncological outcomes to laparoscopic RN, the technical challenges and prolonged learning curve associated with LPN limit its wider dissemination. Robot-assisted partial nephrectomy (RAPN), although still an evolving procedure with no long-term data, has emerged as a viable alternative to LPN, with favorable preliminary outcomes. This article provides an overview of the role of RAPN in the management of renal cell carcinoma. The clinical indications and principles of surgical technique for this procedure are discussed. The oncological, renal functional, and perioperative outcomes of RAPN are also evaluated, as are complication rates.

Gross, histological and ultrastructural morphology of the aglomerular kidney in the lined seahorse Hippocampus erectus.

Science.gov (United States)

Fogelson, S B; Yanong, R P E; Kane, A; Teal, C N; Berzins, I K; Smith, S A; Brown, C; Camus, A

2015-09-01

Histologic evaluation of the renal system in the lined seahorse Hippocampus erectus reveals a cranial kidney with low to moderate cellularity, composed of a central dorsal aorta, endothelial lined capillary sinusoids, haematopoietic tissue, fine fibrovascular stroma, ganglia and no nephrons. In comparison, the caudal kidney is moderately to highly cellular with numerous highly convoluted epithelial lined tubules separated by interlacing haematopoietic tissue, no glomeruli, fine fibrovascular stroma, numerous capillary sinusoids, corpuscles of Stannius and clusters of endocrine cells adjacent to large calibre vessels. Ultrastructural evaluation of the renal tubules reveals minimal variability of the tubule epithelium throughout the length of the nephron and the majority of tubules are characterized by epithelial cells with few apical microvilli, elaborate basal membrane infolding, rare electron dense granules and abundant supporting collagenous matrix. © 2015 The Fisheries Society of the British Isles.

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.

Diglycolic acid, the toxic metabolite of diethylene glycol, chelates calcium and produces renal mitochondrial dysfunction in vitro.

Science.gov (United States)

Conrad, Taylor; Landry, Greg M; Aw, Tak Yee; Nichols, Royce; McMartin, Kenneth E

2016-07-01

Diethylene glycol (DEG) has caused many cases of acute kidney injury and deaths worldwide. Diglycolic acid (DGA) is the metabolite responsible for the renal toxicity, but its toxic mechanism remains unclear. To characterize the mitochondrial dysfunction produced from DGA by examining several mitochondrial processes potentially contributing to renal cell toxicity. The effect of DGA on mitochondrial membrane potential was examined in normal human proximal tubule (HPT) cells. Isolated rat kidney mitochondria were used to assess the effects of DGA on mitochondrial function, including respiratory parameters (States 3 and 4), electron transport chain complex activities and calcium-induced opening of the mitochondrial permeability transition pore. DGA was compared with ethylene glycol tetraacetic acid (EGTA) to determine calcium chelating ability. DGA cytotoxicity was assessed using lactate dehydrogenase leakage from cultured proximal tubule cells. DGA decreased the mitochondrial membrane potential in HPT cells. In rat kidney mitochondria, DGA decreased State 3 respiration, but did not affect State 4 respiration or the ADP/O ratio. DGA reduced glutamate/malate respiration at lower DGA concentrations (0.5 mmol/L) than succinate respiration (100 mmol/L). DGA inhibited Complex II activity without altering Complex I, III or IV activities. DGA blocked calcium-induced mitochondrial swelling, indicating inhibition of the calcium-dependent mitochondrial permeability transition. DGA and EGTA reduced the free calcium concentration in solution in an equimolar manner. DGA toxicity and mitochondrial dysfunction occurred as similar concentrations. DGA inhibited mitochondrial respiration, but without uncoupling oxidative phosphorylation. The more potent effect of DGA on glutamate/malate respiration and the inhibition of mitochondrial swelling was likely due to its chelation of calcium. These results indicate that DGA produces mitochondrial dysfunction by chelating calcium to

Successful pregnancy following single blastocyst transfer in a renal transplant recipient.

Science.gov (United States)

Muthuvel, V Arun; Ravindran, Manipriya; Chander, Aravind; Veluswamy, Chandralekha

2016-01-01

Numerous spontaneous pregnancies have been reported in renal transplant recipients; however, only a few pregnancies after the use of assisted reproductive techniques. The authors report a case of renal transplant recipient with secondary infertility who delivered a healthy baby without any complications. The report highlights the importance of minimal stimulation protocol during ovarian stimulation, single embryo transfer, and the need for multispecialty care for these patients. To the best of the authors' knowledge, the present report is the first such case from India and also the second in the world to report a blastocyst transfer among renal transplant recipients.

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.

The clinical factors associated with benign renal tumors

International Nuclear Information System (INIS)

Yamashita, Ryo; Nakamura, Masafumi; Matsuzaki, Masato; Matsui, Takashi; Yamaguchi, Raizo; Niwakawa, Masashi; Tobisu, Kenichi; Asakura, Koiku; Ito, Ichiro

2009-01-01

In this study, we sought to define the incidence of benign renal tumors in our institute and to clarify the clinical factors associated with benign renal tumors, in order to assist in forming preoperative differential diagnoses. From October 2002 to July 2007, we performed 157 nephrectomies in patients preoperatively diagnosed with renal cell carcinoma. We chose 81 tumors, all of which were less than 5 cm, for further study. We reviewed double-phase helical CT imaging retrospectively, specifically focusing on attenuation patterns and homogeneity. We also compared clinical factors, including age, sex and tumor size, between the benign and malignant renal tumors. The patient's median age was 67 years (mean age, 63 years), and the median tumor diameter was 3.0 cm (mean, 3.2 cm). Benign renal tumors were found in 10 (12%) of the 81 tumors; these included seven cases of oncocytoma and three cases of angiomyolipoma with minimal fat. Several factors were significant clinical determinants of differentiation between benign and malignant renal tumors: homogeneity in CT, female gender, and small tumor size all predominated in cases of benign tumors. Attenuation pattern in CT, however, was not a significant factor (p=0.344). When a patient, especially a female, presents with a small and homogeneous renal tumor, careful consideration should be given to the possibility of a benign process, which needs further consideration before performing excessive surgery. (author)

Use systems pharmacology modeling to elucidate the operating characteristics of SGLT1 and SGLT2 in renal glucose reabsorption in humans

Directory of Open Access Journals (Sweden)

Yasong eLu

2014-12-01

Full Text Available In the kidney, glucose in glomerular filtrate is reabsorbed primarily by sodium-glucose cotransporters 1 (SGLT1 and 2 (SGLT2 along the proximal tubules. SGLT2 has been characterized as a high capacity, low affinity pathway responsible for reabsorption of the majority of filtered glucose in the early part of proximal tubules, and SGLT1 reabsorbs the residual glucose in the distal part. Inhibition of SGLT2 is a viable mechanism for removing glucose from the body and improving glycemic control in patients with diabetes. Despite demonstrating high levels (in excess of 80% of inhibition of glucose transport by SGLT2 in vitro, potent SGLT2 inhibitors, e.g., dapagliflozin and canagliflozin, inhibit renal glucose reabsorption by only 30-50% in clinical studies. Hypotheses for this apparent paradox are mostly focused on the compensatory effect of SGLT1. The paradox has been explained and the role of SGLT1 demonstrated in the mouse, but direct data in humans are lacking. To further explore the roles of SGLT1/2 in renal glucose reabsorption in humans, we developed a systems pharmacology model with emphasis on SGLT1/2 mediated glucose reabsorption and the effects of SGLT2 inhibition. The model was calibrated using robust clinical data in the absence or presence of dapagliflozin (DeFronzo et al. data (2013, and evaluated against clinical data from the literature (Mogensen, 1971;Wolf et al., 2009;Polidori et al., 2013. The model adequately described all four data sets. Simulations using the model clarified the operating characteristics of SGLT1/2 in humans in the healthy and diabetic state with or without SGLT2 inhibition. The modeling and simulations support our proposition that the apparent moderate, 30-50% inhibition of renal glucose reabsorption observed with potent SGLT2 inhibitors is a combined result of two physiological determinants: SGLT1 compensation and residual SGLT2 activity. This model will enable in silico inferences and predictions related to

Diffusion-weighted imaging versus contrast-enhanced MR imaging for the differentiation of renal oncocytomas and chromophobe renal cell carcinomas

Energy Technology Data Exchange (ETDEWEB)

Zhong, Yan; Wang, Haiyi; Shen, Yanguang; Ma, Lu; Pan, Jingjing; Ye, Huiyi [Chinese PLA General Hospital, Department of Radiology, Beijing (China); Guo, Aitao [Chinese PLA General Hospital, Department of Pathology, Beijing (China); Wang, Jia [Handan Central Hosptical, Department of Radiology, Hebei (China); Kang, Suhai [264 Hospital of PLA, X-ray Department, Taiyuan (China)

2017-12-15

To compare the performance of diffusion-weighted imaging (DWI) with that of contrast-enhanced MRI in differentiating renal oncocytomas from chromophobe renal cell carcinomas (RCCs). We recruited 48 patients with histopathologically confirmed renal oncocytomas (n=16) and chromophobe RCCs (n=32). All patients underwent preoperative DWI and contrast-enhanced MRI. Apparent diffusion coefficient (ADC) and signal intensity were measured in each patient. ADC ratio and percentage of signal intensity change were calculated. Mean ADC values for renal oncocytomas were significantly higher than those for chromophobe RCCs (1.59±0.21 vs. 1.09±0.29 x 10{sup -3} mm{sup 2}/s, p < 0.001). Area under the ROC curve, sensitivity and specificity were 0.931, 87.5% and 84.4%, respectively, for ADC measurement of DW imaging; 0.825, 87.5% and 75%, respectively, for enhancement ratio (p > 0.05). Adding ADC values to the enhancement ratios in the ROC, analysis to differentiate renal oncocytoma from chromophobe RCCs increased specificity from 75 to 87.5% at 87.5% sensitivity without significantly increasing the AUC (0.930). Both DWI and contrast-enhanced MRI may assist in differentiating renal oncocytomas from chromophobe RCCs, with DWI showing higher diagnostic value. The combination of the two parameters could potentially provide better performance in distinguishing these two tumours. (orig.)

A new human NHERF1 mutation decreases renal phosphate transporter NPT2a expression by a PTH-independent mechanism.

Directory of Open Access Journals (Sweden)

Marie Courbebaisse

Full Text Available BACKGROUND: The sodium-hydrogen exchanger regulatory factor 1 (NHERF1 binds to the main renal phosphate transporter NPT2a and to the parathyroid hormone (PTH receptor. We have recently identified mutations in NHERF1 that decrease renal phosphate reabsorption by increasing PTH-induced cAMP production in the renal proximal tubule. METHODS: We compared relevant parameters of phosphate homeostasis in a patient with a previously undescribed mutation in NHERF1 and in control subjects. We expressed the mutant NHERF1 protein in Xenopus Oocytes and in cultured cells to study its effects on phosphate transport and PTH-induced cAMP production. RESULTS: We identified in a patient with inappropriate renal phosphate reabsorption a previously unidentified mutation (E68A located in the PDZ1 domain of NHERF1.We report the consequences of this mutation on NHERF1 function. E68A mutation did not modify cAMP production in the patient. PTH-induced cAMP synthesis and PKC activity were not altered by E68A mutation in renal cells in culture. In contrast to wild-type NHERF1, expression of the E68A mutant in Xenopus oocytes and in human cells failed to increase phosphate transport. Pull down experiments showed that E68A mutant did not interact with NPT2a, which robustly interacted with wild type NHERF1 and previously identified mutants. Biotinylation studies revealed that E68A mutant was unable to increase cell surface expression of NPT2a. CONCLUSIONS: Our results indicate that the PDZ1 domain is critical for NHERF1-NPT2a interaction in humans and for the control of NPT2a expression at the plasma membrane. Thus we have identified a new mechanism of renal phosphate loss and shown that different mutations in NHERF1 can alter renal phosphate reabsorption via distinct mechanisms.

Different expression patterns of renal Na+/K+-ATPase α-isoform-like proteins between tilapia and milkfish following salinity challenges.

Science.gov (United States)

Yang, Wen-Kai; Chung, Chang-Hung; Cheng, Hui Chen; Tang, Cheng-Hao; Lee, Tsung-Han

2016-12-01

Euryhaline teleosts can survive in a broad range of salinity via alteration of the molecular mechanisms in certain osmoregulatory organs, including in the gill and kidney. Among these mechanisms, Na + /K + -ATPase (NKA) plays a crucial role in triggering ion-transporting systems. The switch of NKA isoforms in euryhaline fish gills substantially contributes to salinity adaptation. However, there is little information about switches in the kidneys of euryhaline teleosts. Therefore, the responses of the renal NKA α-isoform protein switch to salinity challenge in euryhaline tilapia (Oreochromis mossambicus) and milkfish (Chanos chanos) with different salinity preferences were examined and compared in this study. Immunohistochemical staining in tilapia kidneys revealed the localization of NKA in renal tubules rather than in the glomeruli, similar to our previous findings in milkfish kidneys. Protein abundance in the renal NKA pan α-subunit-like, α1-, and α3-isoform-like proteins in seawater-acclimated tilapia was significantly higher than in the freshwater group, whereas the α2-isoform-like protein exhibited the opposite pattern of expression. In the milkfish, higher protein abundance in the renal NKA pan α-subunit-like and α1-isoform-like proteins was found in freshwater-acclimated fish, whereas no difference was found in the protein abundance of α2- and α3-isoform-like proteins between groups. These findings suggested that switches for renal NKA α-isoforms, especially the α1-isoform, were involved in renal osmoregulatory mechanisms of euryhaline teleosts. Moreover, differences in regulatory responses of the renal NKA α-subunit to salinity acclimation between tilapia and milkfish revealed that divergent mechanisms for maintaining osmotic balance might be employed by euryhaline teleosts with different salinity preferences. Copyright © 2016 Elsevier Inc. All rights reserved.

Robot-Assisted Antegrade In-Situ Fenestrated Stent Grafting

International Nuclear Information System (INIS)

Riga, Celia V.; Bicknell, Colin D.; Wallace, Daniel; Hamady, Mohamad; Cheshire, Nicholas

2009-01-01

To determine the technical feasibility of a novel approach of in-situ fenestration of aortic stent grafts by using a remotely controlled robotic steerable catheter system in the porcine model. A 65-kg pig underwent robot-assisted bilateral antegrade in-situ renal fenestration of an abdominal aortic stent graft with subsequent successful deployment of a bare metal stent into the right renal artery. A 16-mm iliac extension covered stent served as the porcine aortic endograft. Under fluoroscopic guidance, the graft was punctured with a 20-G customized diathermy needle that was introduced and kept in place by the robotic arm. The needle was exchanged for a 4 x 20 mm cutting balloon before successful deployment of the renal stent. Robot-assisted antegrade in-situ fenestration is technically feasible in a large mammalian model. The robotic system enables precise manipulation, stable positioning, and minimum instrumentation of the aorta and its branches while minimizing radiation exposure.

Valutazione morfo-funzionale in pazienti ipertesi con stenosi dell'arteria renale

International Nuclear Information System (INIS)

Cuocolo, A.; Celentano, L.; Nappi, A.; Neumann, R.D.; Salvatore, M.

1991-01-01

Renovascula hypertension is the most important and common cause of secondary hypertension. We studied 10 patients with arterial hypertension and different degrees of renal artery stenosis to assess the usefulness of dynamic radionuclide renography in evaluating renal perfusion and funcion, and to compare funcional radionuclide results to the morphological findings of renal angiography. Computer-assisted dynamic renal with 00m Tc diethylenetriaminepentaacetic acid (DTPA) and 131 I orthoiodohippurate (OIH), and renal artheriography were also employed in all patients. In all patients, radionuclide results matched angiography findings in quality. In particular, 3 patients with hemodynamical insignificant renal artery stenosis exhibited normal perfusion and function at dynamic radionuclide renography. Seven patients had significant renal artery stenosis and associated functional changes at dynamic radionuclide renography. Quantitative comparison of all patients showed a significant correlation (r=0.866, p<0.001) between the degree of renal artery stenosis, quantified as the percentage of narrowing as compared to adjacent/contralateral normal vessel diameter, and the results of split renal function, as assessed during OIH studies and expressed per kidney as a percentage of the net total counts of both kidneys. In conclusion, our results demonstrated dynamic radionuclide renography to be a valuable secondary to renal artery stenosis in hypertensive patients, providing complementary results to arteriography

Ultrastructural study of electron dense deposits in renal tubular basement membrane: prevalence and relationship to epithelial atrophy.

Science.gov (United States)

Yong, Jim L C; Killingsworth, Murray C

2014-08-01

This study reports the prevalence of immune deposits associated with the proximal and distal tubules in a series of routine renal biopsies received in our department during a single calendar year. From 87 cases, 65 (74%) were found to have glomerular immune deposits by immunofluorescence. Tubular immune deposits were found in 12 cases (18%), 3 of which had no glomerular deposits. By transmission electron microscopy (EM), 58 cases (66%) were found to have deposits of granular or vesicular material associated with the tubular basement membranes (TBM). Finely granular electron dense deposits appeared to correspond to the immune deposits seen by immunofluorescence microscopy (IF) and may be a sensitive marker of immune deposition.

Analysis of renal cell transformation following exposure to trichloroethene in vivo and its metabolite S-(dichlorovinyl)-L-cysteine in vitro

International Nuclear Information System (INIS)

Mally, Angela; Walker, Cheryl L.; Everitt, Jeffrey I.; Dekant, Wolfgang; Vamvakas, Spiros

2006-01-01

Trichloroethene (TCE) is classified as a potential human carcinogen although there is a significant debate regarding the mechanism of TCE induced renal tumor formation. This controversy stems in part from the extremely high doses of TCE required to induce renal tumors and the potential contribution of the associated nephrotoxicity to tumorigenesis. We have used Eker rats, which are uniquely susceptible to renal carcinogens, to determine if exposures to TCE in vivo or exposure to its metabolite S-(dichlorovinyl)-L-cysteine (DCVC) in vitro can transform kidney epithelial cells in the absence of cytotoxicity. Treatment with TCE (0, 100, 250, 500, 1000 mg/kg bw by gavage, 5 days a week) for 13 weeks resulted in a significant increase in cell proliferation in kidney tubule cells, but did not enhance formation of preneoplastic lesions or tumor incidence in Eker rat kidneys as compared to controls. In vitro, concentrations of DCVC, which reduced cell survival to 50%, were able to transform rat kidney epithelial cells. However, no carcinogen-specific mutations were identified in the VHL or Tsc-2 tumor suppressor genes in the transformants. Taken together, the inability of TCE to enhance formation of preneoplastic changes or neoplasia and the absence of carcinogen-specific alteration of genes accepted to be critical for renal tumor development suggest that TCE mediated carcinogenicity may occur secondary to continuous toxic injury and sustained regenerative cell proliferation

Determination of spatial distribution of melamine-cyanuric acid crystals in rat kidney tissue by histology and imaging matrix-assisted laser desorption/ionization quadrupole time-of-flight mass spectrometry.

Science.gov (United States)

Kim, Chae-Wook; Yun, Jun-Won; Bae, Il-Hong; Lee, Joon-Seok; Kang, Hyun-Jin; Joo, Kyung-Mi; Jeong, Hye-Jin; Chung, Jin-Ho; Park, Young-Ho; Lim, Kyung-Min

2010-01-01

After the outbreak of acute renal failure associated with melamine-contaminated pet food, many attempts have been made to uncover the mechanism underlying the renal toxicity caused by melamine and melamine-related compounds. Using rat models, we investigated the renal crystal formation following the ingestion of a melamine-cyanuric acid mixture (M+CA, 1:1) to gain insight into the M+CA-induced renal toxicity. M+CA did not induce toxicity in precision-cut kidney slices, suggesting that M+CA does not have a direct nephrotoxicity. On the contrary, oral administration of M+CA for 3 days induced nephrotoxicity as determined by increased serum blood urea nitrogen and creatinine, reduced creatinine clearance, and enlarged kidneys in the animals treated with 50 mg/kg M+CA (melamine, 25 mg/kg, and cyanuric acid, 25 mg/kg; 2 of 10 animals) and 100 mg/kg M+CA (9 of 9 animals). While urine crystals were found in all animals treated with M+CA (25-100 mg/kg), histological examination revealed that renal crystals could be observed only in the kidneys of animals showing signs of nephrotoxicity. Remarkably, at 50 mg/kg M+CA, crystals were observed mainly in the medulla region of the kidney, while at 100 mg/kg, crystals were disseminated throughout the cortex and medulla regions. To further investigate the crystal formation by M+CA, matrix-assisted laser desorption/ionization quadrupole time-of-flight (MALDI-Q-TOF) imaging mass spectrometry detecting melamine distribution through monitoring the product ion (m/z 85, M + H) from melamine (m/z 127, M + H) was developed to directly obtain the image of melamine distribution in the kidney. The distribution image of melamine in kidney tissue confirmed that dense points of melamine were located only in the medulla region at 50 mg/kg M+CA, while at 100 mg/kg, they were disseminated widely from the cortex to medulla. These results demonstrated that M+CA ingestion could lead to crystal formation in kidney tubules along the osmotic gradient and

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.

Nephron segment specific microRNA biomarkers of pre-clinical drug-induced renal toxicity: Opportunities and challenges

Energy Technology Data Exchange (ETDEWEB)

Nassirpour, Rounak, E-mail: Rounak.nassirpour@pfizer.com [Drug Safety, Pfizer Worldwide Research and Development, 1 Burtt Rd, Andover, MA 01810 (United States); Ramaiah, Shashi K. [Drug Safety, Pfizer Worldwide Research and Development, 610 Main Street, Cambridge, MA 02139 (United States); Whiteley, Laurence O. [Drug Safety, Pfizer Worldwide Research and Development, 1 Burtt Rd, Andover, MA 01810 (United States)

2016-12-01

Drug-induced nephrotoxicity is a common drug development complication for pharmaceutical companies. Sensitive, specific, translatable and non-invasive biomarkers of renal toxicity are urgently needed to diagnose nephron segment specific injury. The currently available gold standard biomarkers for nephrotoxicity are not kidney-specific, lack sensitivity for early detection, and are not suitable for renal damage localization (glomerular vs tubulointerstitial injury). MicroRNAs (miRNAs) are increasingly gaining momentum as promising biomarkers of various organ toxicities, including drug induced renal injury. This is mostly due to their stability in easily accessible biofluids, ease of developing nucleic acids detection compared to protein detection assays, as well as their interspecies translatability. Increasing concordance of miRNA findings by standardizing methodology most suitable for their detection and quantitation, as well as characterization of their expression pattern in a cell type specific manner, will accelerate progress toward validation of these miRNAs as biomarkers in pre-clinical, and clinical settings. This review aims to highlight the current pre-clinical findings surrounding miRNAs as biomarkers in two important segments of the nephron, the glomerulus and tubules. - Highlights: • miRNAs are promising biomarkers of drug-induced kidney injury. • Summarized pre-clinical miRNA biomarkers of drug-induced nephrotoxicity. • Described the strengths and challenges associated with miRNAs as biomarkers.

Nociceptin/orphanin FQ peptide receptor agonist Ac-RYYRWKKKKKKK-NH2 (ZP120) induces antinatriuresis in rats by stimulation of amiloride-sensitive sodium reabsorption

DEFF Research Database (Denmark)

van Deurs, Ulla S K; Hadrup, Niels; Petersen, Jørgen Søberg

2008-01-01

receptors are expressed in the distal convoluted tubules, the connecting tubules, and the collecting ducts. Using clearance techniques, we evaluated renal excretory function during acute administration of ZP120 (1 nmol/kg/min) in chronically catheterized, conscious rats (n = 8/group). To examine...

Use of systems pharmacology modeling to elucidate the operating characteristics of SGLT1 and SGLT2 in renal glucose reabsorption in humans

Science.gov (United States)

Lu, Yasong; Griffen, Steven C.; Boulton, David W.; Leil, Tarek A.

2014-01-01

In the kidney, glucose in glomerular filtrate is reabsorbed primarily by sodium-glucose cotransporters 1 (SGLT1) and 2 (SGLT2) along the proximal tubules. SGLT2 has been characterized as a high capacity, low affinity pathway responsible for reabsorption of the majority of filtered glucose in the early part of proximal tubules, and SGLT1 reabsorbs the residual glucose in the distal part. Inhibition of SGLT2 is a viable mechanism for removing glucose from the body and improving glycemic control in patients with diabetes. Despite demonstrating high levels (in excess of 80%) of inhibition of glucose transport by SGLT2 in vitro, potent SGLT2 inhibitors, e.g., dapagliflozin and canagliflozin, inhibit renal glucose reabsorption by only 30–50% in clinical studies. Hypotheses for this apparent paradox are mostly focused on the compensatory effect of SGLT1. The paradox has been explained and the role of SGLT1 demonstrated in the mouse, but direct data in humans are lacking. To further explore the roles of SGLT1/2 in renal glucose reabsorption in humans, we developed a systems pharmacology model with emphasis on SGLT1/2 mediated glucose reabsorption and the effects of SGLT2 inhibition. The model was calibrated using robust clinical data in the absence or presence of dapagliflozin (DeFronzo et al., 2013), and evaluated against clinical data from the literature (Mogensen, 1971; Wolf et al., 2009; Polidori et al., 2013). The model adequately described all four data sets. Simulations using the model clarified the operating characteristics of SGLT1/2 in humans in the healthy and diabetic state with or without SGLT2 inhibition. The modeling and simulations support our proposition that the apparent moderate, 30–50% inhibition of renal glucose reabsorption observed with potent SGLT2 inhibitors is a combined result of two physiological determinants: SGLT1 compensation and residual SGLT2 activity. This model will enable in silico inferences and predictions related to SGLT1

Use of systems pharmacology modeling to elucidate the operating characteristics of SGLT1 and SGLT2 in renal glucose reabsorption in humans.

Science.gov (United States)

Lu, Yasong; Griffen, Steven C; Boulton, David W; Leil, Tarek A

2014-01-01

In the kidney, glucose in glomerular filtrate is reabsorbed primarily by sodium-glucose cotransporters 1 (SGLT1) and 2 (SGLT2) along the proximal tubules. SGLT2 has been characterized as a high capacity, low affinity pathway responsible for reabsorption of the majority of filtered glucose in the early part of proximal tubules, and SGLT1 reabsorbs the residual glucose in the distal part. Inhibition of SGLT2 is a viable mechanism for removing glucose from the body and improving glycemic control in patients with diabetes. Despite demonstrating high levels (in excess of 80%) of inhibition of glucose transport by SGLT2 in vitro, potent SGLT2 inhibitors, e.g., dapagliflozin and canagliflozin, inhibit renal glucose reabsorption by only 30-50% in clinical studies. Hypotheses for this apparent paradox are mostly focused on the compensatory effect of SGLT1. The paradox has been explained and the role of SGLT1 demonstrated in the mouse, but direct data in humans are lacking. To further explore the roles of SGLT1/2 in renal glucose reabsorption in humans, we developed a systems pharmacology model with emphasis on SGLT1/2 mediated glucose reabsorption and the effects of SGLT2 inhibition. The model was calibrated using robust clinical data in the absence or presence of dapagliflozin (DeFronzo et al., 2013), and evaluated against clinical data from the literature (Mogensen, 1971; Wolf et al., 2009; Polidori et al., 2013). The model adequately described all four data sets. Simulations using the model clarified the operating characteristics of SGLT1/2 in humans in the healthy and diabetic state with or without SGLT2 inhibition. The modeling and simulations support our proposition that the apparent moderate, 30-50% inhibition of renal glucose reabsorption observed with potent SGLT2 inhibitors is a combined result of two physiological determinants: SGLT1 compensation and residual SGLT2 activity. This model will enable in silico inferences and predictions related to SGLT1/2 modulation.

Can zero-hour cortical biopsy predict early graft outcomes after living donor renal transplantation?

Science.gov (United States)

Rathore, Ranjeet Singh; Mehta, Nisarg; Mehta, Sony Bhaskar; Babu, Manas; Bansal, Devesh; Pillai, Biju S; Sam, Mohan P; Krishnamoorthy, Hariharan

2017-11-01

The aim of this study was to identify relevance of subclinical pathological findings in the kidneys of living donors and correlate these with early graft renal function. This was a prospective study on 84 living donor kidney transplant recipients over a period of two years. In all the donors, cortical wedge biopsy was taken and sent for assessment of glomerular, mesangial, and tubule status. The graft function of patients with normal histology was compared with those of abnormal histological findings at one, three, and six months, and one year post-surgery. Most abnormal histological findings were of mild degree. Glomerulosclerosis (GS, 25%), interstitial fibrosis (IF, 13%), acute tubular necrosis (ATN 5%), and focal tubal atrophy (FTA, 5%) were the commonly observed pathological findings in zero-hour biopsies. Only those donors who had histological changes of IF and ATN showed progressive deterioration of renal function at one month, three months, six months, and one year post-transplantation. In donors with other histological changes, no significant effect on graft function was observed. Zero-hour cortical biopsy gave us an idea of the general status of the donor kidney and presence or absence of subclinical pathological lesions. A mild degree of subclinical and pathological findings on zero-hour biopsy did not affect early graft renal function in living donor kidney transplantation. Zero-hour cortical biopsy could also help in discriminating donor-derived lesions from de novo alterations in the kidney that could happen subsequently.

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.

CT appearance of acute inflammatory disease of the renal interstitium

International Nuclear Information System (INIS)

Gold, R.P.; McClennan, B.L.; Rottenberg, R.R.

1983-01-01

Today, infection remains the most common disease of the urinary tract and constitutes almost 75% of patient problems requiring urologic evaluation. There have been several major factors responsible for our better understanding of the nature and pathophysiology of urinary tract infection. One has been quantitated urine bacteriology and another, the discovery that a significant part of the apparently healthy adult female population has asymptomatic bacteriuria. Abnormal conditions such as neurogenic bladder, bladder malignancy, prolonged catheter drainage and reflux, altered host resistance, diabetes mellitus, and urinary tract obstruction, as well as pregnancy, may either predispose to or be implicated in the pathogenesis of urinary tract infection. There is a wide range of conditions that result in acute renal inflammation and those under discussion affect primarily the interstitium. This term refers to the connective tissue elements separating the tubules in the cortex and medulla. Hence, the interstitial nephritides are to be distinguished from the glomerulonephritides and fall into two general etiologic categories: infectious and noninfectious

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

Science.gov (United States)

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)

Experimental studies of renal blood flow by digitized functional angiography

International Nuclear Information System (INIS)

Buersch, J.H.; Ochs, C.; Hahne, H.J.; Heintzen, P.H.

1985-01-01

New techniques of digital image processing have been experimentally tested for the assessment of renal blood flow. The underlying principle in functional angiography is the extraction of flow parameters. Basically, density-time variations of the contrast medium are analayzed from to each picture element of a 256x256 matrix. The real-time acquisition rate of images was 25/sec. For the calculation of angiographic flow a PDP 11/40 computer was used to interactively perform a time dependent segmentation of the renal arteries and the aorta. Subsequently, volume flow was calculated in relative units for the specific vascular segments under study. 15 control angiograms were made in 5 animals with cardiac output ranging between 0.8 to 2.2l/min. Unilateral renal blood flow was calculated as 24+-3.4% of pre-renal aortic flow without systematic side differences. Reproducibility from repeated flow measurements showed an SD of +-1.8% of the individual pre-renal aortic flow. Renal flow was also measured in 3 animals with an experimentally created 50% flow reduction of the left kidney. Angiographic flow in the left renal artery dropped to 12+-2% of pre-renal flow. The present experimental data suggest that digital angiography has sufficient diagnostic capabilities for the detection of abnormal renal blood flow. The technique may serve as a useful diagnostic adjunct to conventional angiography and has the potential of assisting in the evaluation of renal vascular hypertension. (orig.) [de

Anatomically-specific intratubular and interstitial biominerals in the human renal medullo-papillary complex.

Directory of Open Access Journals (Sweden)

Ling Chen

Full Text Available Limited information exists on the anatomically-specific early stage events leading to clinically detectable mineral aggregates in the renal papilla. In this study, quantitative multiscale correlative maps of structural, elemental and biochemical properties of whole medullo-papillary complexes from human kidneys were developed. Correlative maps of properties specific to the uriniferous and vascular tubules using high-resolution X-ray computed tomography, scanning and transmission electron microscopy, energy dispersive X-ray spectroscopy, and immunolocalization of noncollagenous proteins (NCPs along with their association with anatomy specific biominerals were obtained. Results illustrated that intratubular spherical aggregates primarily form at the proximal regions distant from the papillary tip while interstitial spherical and fibrillar aggregates are distally located near the papillary tip. Biominerals at the papillary tip were closely localized with 10 to 50 μm diameter vasa recta immunolocalized for CD31 inside the medullo-papillary complex. Abundant NCPs known to regulate bone mineralization were localized within nanoparticles, forming early pathologic mineralized regions of the complex. Based on the physical association between vascular and urothelial tubules, results from light and electron microscopy techniques suggested that these NCPs could be delivered from vasculature to prompt calcification of the interstitial regions or they might be synthesized from local vascular smooth muscle cells after transdifferentiation into osteoblast-like phenotypes. In addition, results provided insights into the plausible temporal events that link the anatomically specific intratubular mineral aggregates with the interstitial biomineralization processes within the functional unit of the kidney.

Sympathetic nerve-derived ATP regulates renal medullary blood flow via vasa recta pericytes

Directory of Open Access Journals (Sweden)

Scott S Wildman

2013-10-01

Full Text Available Pericyte cells are now known to be a novel locus of blood flow control, being able to regulate capillary diameter via their unique morphology and expression of contractile proteins. We have previously shown that exogenous ATP causes constriction of vasa recta via renal pericytes, acting at a variety of membrane bound P2 receptors on descending vasa recta, and therefore may be able to regulate medullary blood flow (MBF. Regulation of MBF is essential for appropriate urine concentration and providing essential oxygen and nutrients to this region of high, and variable, metabolic demand. Various sources of endogenous ATP have been proposed, including from epithelial, endothelial and red blood cells in response to stimuli such as mechanical stimulation, local acidosis, hypoxia, and exposure to various hormones. Extensive sympathetic innervation of the nephron has previously been shown, however the innervation reported has focused around the proximal and distal tubules, and ascending loop of Henle. We hypothesise that sympathetic nerves are an additional source of ATP acting at renal pericytes and therefore regulate MBF. Using a rat live kidney slice model in combination with video imaging and confocal microscopy techniques we firstly show sympathetic nerves in close proximity to vasa recta pericytes in both the outer and inner medulla. Secondly, we demonstrate pharmacological stimulation of sympathetic nerves in situ (by tyramine evokes pericyte-mediated vasoconstriction of vasa recta capillaries; inhibited by the application of the P2 receptor antagonist suramin. Lastly, tyramine-evoked vasoconstriction of vasa recta by pericytes is significantly less than ATP-evoked vasoconstriction. Sympathetic innervation may provide an additional level of functional regulation in the renal medulla that is highly localized. It now needs to be determined under which physiological/pathophysiological circumstances that sympathetic innervation of renal pericytes is

Effects of Sodium Selenite on Formaldehyde Induced Renal Toxicity in Mice

Directory of Open Access Journals (Sweden)

Shabnam Mohammadi 1,2 * , Maryam Moghimian 3, Hanieh Torabzadeh 4, Mahla Langari 4, Roghayeh Nazeri 4, Zahra Karimi 4, Elham Sangari 4, Najmeh Jagarmi 5, Alireza Mohammad Zadeh 3, Mehdi Karimi 7, Kamyar Tavakkoli 8, Ali Delshad 9, Fatemeh Mohammadzadeh 3, Majid Ghayour-Mobarhan 10

2016-12-01

Full Text Available Background: Formaldehyde is widely used for industrial applications. Renal injury is an adverse effect associated with formaldehyde. Few studies have explored the potential benefits of protective factors on formaldehyde induced renal toxicity. This study evaluated the dose dependent effects of sodium selenite on the biochemical and histopathological effects of formaldehyde on murine kidney. Methods: Forty eight adult Balb/c male mice were randomized into six groups: a control group, a formaldehyde group and experimental III-VI groups. Formaldehyde group was injected with 10 mg/kg formaldehyde and groups III-VI received intraperitoneally doses of 0.1, 0.2, 0.4, 0.8 mg/kg selenium. After two weeks, a stereological study was done in accordance with the principle of Cavalieri and serum concentrations of urea and creatinine were measured. Data were analyzed using ANOVA and SPSS software. Results: Glomerosclerosis, necrosis and vacuolization were observed in the convoluted tubules of animals treated with formaldehyde. The biochemical markers, volume and count of glomeruli in the group treated with formaldehyde was significantly difference compared to the control group (P<0.05. The volume of the glomeruli in the group treated with 0.2 and 0.4 mg selenium and urea level in the group treated with 0.4 and 0.1 mg/kg selenium was significantly difference compared to the control group (P <0.05. The count of glomeruli and creatinine level in the selenium group was significantly difference compared to the control group (P ≤ 0.0001. Conclusions: A dose of 0.2 mg/kg of sodium selenite caused partial protective effect on the renal tissue and function in exposed to formaldehyde.

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.

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

Update on the renal toxicity of iodinated contrast drugs used in clinical medicine

Directory of Open Access Journals (Sweden)

Andreucci M

2017-05-01

Full Text Available Michele Andreucci,1 Teresa Faga,1 Raffaele Serra,2 Giovambattista De Sarro,3 Ashour Michael1 1Renal Unit, Department of Health Sciences, 2Interuniversity Center of Phlebolymphology (CIFL, International Research and Educational Program in Clinical and Experimental Biotechnology, Department of Medical and Surgical Sciences, 3Pharmacology Unit, Department of Health Sciences, Magna Graecia University, Catanzaro, Italy Abstract: An important side effect of diagnostic contrast drugs is contrast-induced acute kidney injury (CI-AKI; a sudden decrease in renal function occurring 48–72 hours after injection of a contrast drug that cannot be attributed to other causes. Its existence has recently been challenged, because of some retrospective studies in which the incidence of AKI was not different between subjects who received a contrast drug and those who did not, even using propensity score matching to prevent selection bias. For some authors, only patients with estimated glomerular filtration rate <30 mL/min/1.73 m2 are at significant risk of CI-AKI. Most agree that when renal function is normal, there is no CI-AKI risk. Many experimental studies, however, are in favor of the existence of CI-AKI. Contrast drugs have been shown to cause the following changes: renal vasoconstriction, resulting in a rise in intrarenal resistance (decrease in renal blood flow and glomerular filtration rate and medullary hypoxia; epithelial vacuolization and dilatation and necrosis of proximal tubules; potentiation of angiotensin II effects, reducing nitric oxide (NO and causing direct constriction of descending vasa recta, leading to formation of reactive oxygen species in isolated descending vasa recta of rats microperfused with a solution of iodixanol; increasing active sodium reabsorption in the thick ascending limbs of Henle’s loop (increasing O2 demand and consequently medullary hypoxia; direct cytotoxic effects on endothelial and tubular epithelial cells (decrease

Spontaneous Retroperitoneal Hemorrhage (Wunderlich Syndrome due to Large Upper Pole Renal Angiomyolipoma: Does Robotic-Assisted Laparoscopic Partial Nephrectomy Have a Role in Primary Treatment?

Directory of Open Access Journals (Sweden)

Achilles Ploumidis

2013-01-01

Full Text Available Spontaneous rapture with consequent retroperitoneal hemorrhage (Wunderlich’s syndrome is the complication mostly feared from large renal angiomyolipomas (RAMLs. In hemodynamic stable patients, minimal invasive therapies have superseded open surgery as the mainstay of treatment, with contemporary cases mostly treated by selective arterial embolization. Robotic-assisted laparoscopic partial nephrectomy (RALPN is an established minimal access treatment that has been used in the past for benign and malignant lesions of the kidney in the elective setting, but rarely in urgent situations as primary treatment. We present a case of a ruptured RAML in a young female treated effectively by RALPN.

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.

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

Directory of Open Access Journals (Sweden)

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.

Stimulation of renal afferent fibers leads to activation of catecholaminergic and non-catecholaminergic neurons in the medulla oblongata.

Science.gov (United States)

Nishi, Erika E; Martins, Beatriz S; Milanez, Maycon I O; Lopes, Nathalia R; de Melo, Jose F; Pontes, Roberto B; Girardi, Adriana C; Campos, Ruy R; Bergamaschi, Cássia T

2017-05-01

Presympathetic neurons in the rostral ventrolateral medulla (RVLM) including the adrenergic cell groups play a major role in the modulation of several reflexes required for the control of sympathetic vasomotor tone and blood pressure (BP). Moreover, sympathetic vasomotor drive to the kidneys influence natriuresis and diuresis by inhibiting the cAMP/PKA pathway and redistributing the Na + /H + exchanger isoform 3 (NHE3) to the body of the microvilli in the proximal tubules. In this study we aimed to evaluate the effects of renal afferents stimulation on (1) the neurochemical phenotype of Fos expressing neurons in the medulla oblongata and (2) the level of abundance and phosphorylation of NHE3 in the renal cortex. We found that electrical stimulation of renal afferents increased heart rate and BP transiently and caused activation of tyrosine hydroxylase (TH)-containing neurons in the RVLM and non-TH neurons in the NTS. Additionally, activation of the inhibitory renorenal reflex over a 30-min period resulted in increased natriuresis and diuresis associated with increased phosphorylation of NHE3 at serine 552, a surrogate for reduced activity of this exchanger, in the contralateral kidney. This effect was not dependent of BP changes considering that no effects on natriuresis or diuresis were found in the ipsilateral-stimulated kidney. Therefore, our data show that renal afferents leads to activation of catecholaminergic and non-catecholaminergic neurons in the medulla oblongata. When renorenal reflex is induced, NHE3 exchanger activity appears to be decreased, resulting in decreased sodium and water reabsorption in the contralateral kidney. Copyright © 2017 Elsevier B.V. All rights reserved.

Urinary exosomes: a novel means to non-invasively assess changes in renal gene and protein expression.

Directory of Open Access Journals (Sweden)

Silvia Spanu

Full Text Available BACKGROUND: In clinical practice, there is a lack of markers for the non-invasive diagnosis and follow-up of kidney disease. Exosomes are membrane vesicles, which are secreted from their cells of origin into surrounding body fluids and contain proteins and mRNA which are protected from digestive enzymes by a cell membrane. METHODS: Toxic podocyte damage was induced by puromycin aminonucleoside in rats (PAN. Urinary exosomes were isolated by ultracentrifugation at different time points during the disease. Exosomal mRNA was isolated, amplified, and the mRNA species were globally assessed by gene array analysis. Tissue-specific gene and protein expression was assessed by RT-qPCR analysis and immunohistochemistry. RESULTS: Gene array analysis of mRNA isolated from urinary exosomes revealed cystatin C mRNA as one of the most highly regulated genes. Its gene expression increased 7.5-fold by day 5 and remained high with a 1.9-fold increase until day 10. This was paralleled by a 2-fold increase in cystatin C mRNA expression in the renal cortex. Protein expression in the kidneys also dramatically increased with de novo expression of cystatin C in glomerular podocytes in parts of the proximal tubule and the renal medulla. Urinary excretion of cystatin C increased approximately 2-fold. CONCLUSION: In this proof-of-concept study, we could demonstrate that changes in urinary exosomal cystatin C mRNA expression are representative of changes in renal mRNA and protein expression. Because cells lining the urinary tract produce urinary exosomal cystatin C mRNA, it might be a more specific marker of renal damage than glomerular-filtered free cystatin C.

Efeitos da ciclosporina a sobre a função renal de cães da raça Golden Retriever normais ou afetados pela distrofia muscular

Directory of Open Access Journals (Sweden)

Adriana Caroprezo Morini

2008-10-01

Full Text Available The muscular dystrophy of Golden Retriever is a degenerative miopaty caused by the absence of dystrophy and it is genetically homologue of the Duchenne muscular dystrophy in humans, so, these dogs are considerably experimental models for studies on cellular therapy. Their successful depends of the adequate immunosuppression. Cyclosporin A is indicated for that and the monitoring of blood concentration and adverse effects are essential to viabilise the therapy. It was studied GRMD dogs, and normal dogs from the same breed, submitted for therapy with CsA, associated, on GRMD, of cell transplantation. It was evaluated the possible effects of the drug on renal functions. It has been considerate the clinic manifestations, urinalisis, testis of glomerular function and blood concentrations of urea, cretinine, sodium and potassium. In our results we found a discrete increase of blood urea on booth groups; increased levels of urine's cylinders and protein and also increase of urinary density on GRMD group. CsA therapy could make acute lesions on renal tubules, especially on GRMD. These dogs also have different reactions than normal dogs on relation of ions homeostasis and renal function. However, earlier diagnosis and adequate treatment could prevent the development of renal diseases.

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

Viscosity of iodinated contrast agents during renal excretion

International Nuclear Information System (INIS)

Jost, Gregor; Lengsfeld, Philipp; Lenhard, Diana C.; Pietsch, Hubertus; Huetter, Joachim; Sieber, Martin A.

2011-01-01

Objective: Modern iodinated non-ionic contrast agents (CAs) can be classified based on their molecular structure into monomeric and dimeric CAs and have at comparable iodine concentrations a different viscosity and osmolality. During their renal excretion, CAs are concentrated in the renal tubuli which might enhance the viscosity difference between monomeric and dimeric CAs. The viscosity of a CA might have an underestimated importance for renal safety, as suggested by recent publications. In this study, we investigated the viscosities of CAs at the concentrations expected to be present in renal tubules. This concentration process was simulated in vitro using dialysis. Furthermore, we investigated urine viscosity and urine flow in rodents after administration of several non-ionic monomeric and dimeric CAs. Materials and methods: To estimate the viscosity of the CAs in vivo, we performed an in vitro dialysis of monomeric and dimeric CAs at various physiological osmolalities of the renal tubulus (290, 400, 500, 700 and 1000 mOsm/kg H 2 O). Following the dialysis, the iodine concentrations and the viscosities of the CAs were determined. Furthermore, to investigate the concentration process in vivo, we measured the urine viscosity and the urine flow in Han Wister rats after the administration of Iopromide, Iohexol, Ioversol, Iomeprol, Iodixanol, and Iosimenol at comparable iodine concentrations. As a control, saline was injected at the same volume. Results: In vitro dialysis of the dimeric CA increased the iodine concentration and strongly increased the viscosity at all tested osmolalities. In contrast, for the monomeric agents an increase in concentration and viscosity was observed only at 700 as well 1000 mOsm/kg H 2 O but to a lesser extent. In summary, dialysis strongly enhanced the viscosity differences between the non-ionic monomeric and dimeric CAs. The administration of dimeric CAs leads to a strong increase in urine viscosity; this was not observed for the

Viscosity of iodinated contrast agents during renal excretion

Energy Technology Data Exchange (ETDEWEB)

Jost, Gregor, E-mail: Gregor.Jost@bayer.com [TRG Diagnostic Imaging, Bayer Schering Pharma AG, Berlin (Germany); Lengsfeld, Philipp, E-mail: Philipp.Lengsfeld@bayer.com [Global Medical Affairs Diagnostic Imaging, Bayer Schering Pharma AG, Berlin (Germany); Lenhard, Diana C., E-mail: Diana.Lenhard@bayer.com [TRG Diagnostic Imaging, Bayer Schering Pharma AG, Berlin (Germany); Pietsch, Hubertus, E-mail: Hubertus.Pietsch@bayer.com [TRG Diagnostic Imaging, Bayer Schering Pharma AG, Berlin (Germany); Huetter, Joachim, E-mail: Joachim.Huetter@bayer.com [TRG Diagnostic Imaging, Bayer Schering Pharma AG, Berlin (Germany); Sieber, Martin A., E-mail: Martin.Sieber@bayer.com [TRG Diagnostic Imaging, Bayer Schering Pharma AG, Berlin (Germany)

2011-11-15

Objective: Modern iodinated non-ionic contrast agents (CAs) can be classified based on their molecular structure into monomeric and dimeric CAs and have at comparable iodine concentrations a different viscosity and osmolality. During their renal excretion, CAs are concentrated in the renal tubuli which might enhance the viscosity difference between monomeric and dimeric CAs. The viscosity of a CA might have an underestimated importance for renal safety, as suggested by recent publications. In this study, we investigated the viscosities of CAs at the concentrations expected to be present in renal tubules. This concentration process was simulated in vitro using dialysis. Furthermore, we investigated urine viscosity and urine flow in rodents after administration of several non-ionic monomeric and dimeric CAs. Materials and methods: To estimate the viscosity of the CAs in vivo, we performed an in vitro dialysis of monomeric and dimeric CAs at various physiological osmolalities of the renal tubulus (290, 400, 500, 700 and 1000 mOsm/kg H{sub 2}O). Following the dialysis, the iodine concentrations and the viscosities of the CAs were determined. Furthermore, to investigate the concentration process in vivo, we measured the urine viscosity and the urine flow in Han Wister rats after the administration of Iopromide, Iohexol, Ioversol, Iomeprol, Iodixanol, and Iosimenol at comparable iodine concentrations. As a control, saline was injected at the same volume. Results: In vitro dialysis of the dimeric CA increased the iodine concentration and strongly increased the viscosity at all tested osmolalities. In contrast, for the monomeric agents an increase in concentration and viscosity was observed only at 700 as well 1000 mOsm/kg H{sub 2}O but to a lesser extent. In summary, dialysis strongly enhanced the viscosity differences between the non-ionic monomeric and dimeric CAs. The administration of dimeric CAs leads to a strong increase in urine viscosity; this was not observed for

sup(99m)Tc-DMSA renal scintigraphy in renal failure due to various renal diseases

Energy Technology Data Exchange (ETDEWEB)

Hosokawa, S; Daijo, K; Okabe, T; Kawamura, J; Hara, A [Kyoto Univ. (Japan). Hospital

1979-08-01

Renal contours in renal failure were studied by means of sup(99m)Tc-dimercaptosuccinic acid (DMSA) renoscintigraphy. Renal cortical images were obtained even in renal failure cases. Causes of renal failure were chronic glomerulonephritis in 7, bilateral renal tuberculosis in 2, chronic pyelonephritis in 3, bilateral renal calculi in 3, diabetic nephropathy in 2, polycystic kidney disease in 2 and stomach cancer in 1.

sup(99m)Tc-DMSA renal scintigraphy in renal failure due to various renal diseases

International Nuclear Information System (INIS)

Hosokawa, Shin-ichi; Daijo, Kazuyuki; Okabe, Tatsushiro; Kawamura, Juichi; Hara, Akira

1979-01-01

Renal contours in renal failure were studied by means of sup(99m)Tc-dimercaptosuccinic acid (DMSA) renoscintigraphy. Renal cortical images were obtained even in renal failure cases. Causes of renal failure were chronic glomerulonephritis in 7, bilateral renal tuberculosis in 2, chronic pyelonephritis in 3, bilateral renal calculi in 3, diabetic nephropathy in 2, polycystic kidney disease in 2 and stomach cancer in 1. (author)

Virtual and Augmented Reality Systems for Renal Interventions: A Systematic Review.

Science.gov (United States)

Detmer, Felicitas J; Hettig, Julian; Schindele, Daniel; Schostak, Martin; Hansen, Christian

2017-01-01

Many virtual and augmented reality systems have been proposed to support renal interventions. This paper reviews such systems employed in the treatment of renal cell carcinoma and renal stones. A systematic literature search was performed. Inclusion criteria were virtual and augmented reality systems for radical or partial nephrectomy and renal stone treatment, excluding systems solely developed or evaluated for training purposes. In total, 52 research papers were identified and analyzed. Most of the identified literature (87%) deals with systems for renal cell carcinoma treatment. About 44% of the systems have already been employed in clinical practice, but only 20% in studies with ten or more patients. Main challenges remaining for future research include the consideration of organ movement and deformation, human factor issues, and the conduction of large clinical studies. Augmented and virtual reality systems have the potential to improve safety and outcomes of renal interventions. In the last ten years, many technical advances have led to more sophisticated systems, which are already applied in clinical practice. Further research is required to cope with current limitations of virtual and augmented reality assistance in clinical environments.

[Effects of the of renal warm ischemia time on the recovery of filtration function in the experiment].

Science.gov (United States)

Guseinov, R G; Popov, S V; Gorshkov, A N; Sivak, K V; Martov, A G

2017-12-01

To investigate experimentally ultrastructural and biochemical signs of acute injury to the renal parenchyma after warm renal ischemia of various duration and subsequent reperfusion. The experiments were performed on 44 healthy conventional female rabbits of the "Chinchilla" breed weighted 2.6-2.7 kg, which were divided into four groups. In the first, control, group included pseudo-operated animals. In the remaining three groups, an experimental model of warm ischemia of renal tissue was created, followed by a 60-minute reperfusion. The renal warm ischemia time was 30, 60 and 90 minutes in the 2nd, 3rd and 4th groups, respectively. Electron microscopy was used to study ultrastructural disturbances of the renal parenchyma. Biochemical signs of acute kidney damage were detected by measuring the following blood serum and/or urine analytes: NGAL, cystatin C, KIM-1, L-FABP, interleukin-18. The glomerular filtration was evaluated by creatinine clearance, which was determined on days 1, 5, 7, 14, 21 and 35 of follow-up. A 30-minute renal warm ischemia followed by a 60-minute reperfusion induced swelling and edema of the brush membrane, vacuolation of the cytoplasm of the endothelial cells of the proximal tubules, and microvilli restructuring. The observed disorders were reversible, and the epithelial cells retained their viability. After 60 minutes of ischemia and 60 minutes of reperfusion, the observed changes in the ultrastructure of the epithelial cells were much more pronounced, some of the epithelial cells were in a state of apoptosis. 90 min of ischemia and 60 min of reperfusion resulted in electron-microscopic signs of the mass cellular death of the tubular epithelium. Concentration in serum and/or biochemical urine markers of acute renal damage increased sharply after ischemic-reperfusion injury. Restoration of indicators was observed only in cases when the renal warm ischemia time did not exceed 60 minutes. The decrease in creatinine clearance occurred in the

General Information about Wilms Tumor and Other Childhood Kidney Tumors

Science.gov (United States)

... through the urethra and leaves the body. Enlarge Anatomy of the female urinary system showing the kidneys, adrenal glands, ureters, bladder, and urethra. Urine is made in the renal tubules and collects in the renal pelvis of ...

Stages of Wilms Tumor

Science.gov (United States)

... through the urethra and leaves the body. Enlarge Anatomy of the female urinary system showing the kidneys, adrenal glands, ureters, bladder, and urethra. Urine is made in the renal tubules and collects in the renal pelvis of ...

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

ERK1/2 pathway is involved in renal gluconeogenesis inhibition under conditions of lowered NADPH oxidase activity.

Science.gov (United States)

Winiarska, Katarzyna; Jarzyna, Robert; Dzik, Jolanta M; Jagielski, Adam K; Grabowski, Michal; Nowosielska, Agata; Focht, Dorota; Sierakowski, Bartosz

2015-04-01

The aim of this study was to elucidate the mechanisms involved in the inhibition of renal gluconeogenesis occurring under conditions of lowered activity of NADPH oxidase (Nox), the enzyme considered to be one of the main sources of reactive oxygen species in kidneys. The in vitro experiments were performed on primary cultures of rat renal proximal tubules, with the use of apocynin, a selective Nox inhibitor, and TEMPOL (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl), a potent superoxide radical scavenger. In the in vivo experiments, Zucker diabetic fatty (ZDF) rats, a well established model of diabetes type 2, were treated with apocynin solution in drinking water. The main in vitro findings are the following: (1) both apocynin and TEMPOL attenuate the rate of gluconeogenesis, inhibiting the step catalyzed by phosphoenolpyruvate carboxykinase (PEPCK), a key enzyme of the process; (2) in the presence of the above-noted compounds the expression of PEPCK and the phosphorylation of transcription factor CREB and ERK1/2 kinases are lowered; (3) both U0126 (MEK inhibitor) and 3-(2-aminoethyl)-5-((4-ethoxyphenyl)methylene)-2,4-thiazolidinedione (ERK inhibitor) diminish the rate of glucose synthesis via mechanisms similar to those of apocynin and TEMPOL. The observed apocynin in vivo effects include: (1) slight attenuation of hyperglycemia; (2) inhibition of renal gluconeogenesis; (3) a decrease in renal PEPCK activity and content. In view of the results summarized above, it can be concluded that: (1) the lowered activity of the ERK1/2 pathway is of importance for the inhibition of renal gluconeogenesis found under conditions of lowered superoxide radical production by Nox; (2) the mechanism of this phenomenon includes decreased PEPCK expression, resulting from diminished activity of transcription factor CREB; (3) apocynin-evoked inhibition of renal gluconeogenesis contributes to the hypoglycemic action of this compound observed in diabetic animals. Thus, the study has

Association between As and Cu renal cortex accumulation and physiological and histological alterations after chronic arsenic intake

Energy Technology Data Exchange (ETDEWEB)

Rubatto Birri, Paolo N. [Instituto de Biologia Celular, Facultad de Ciencias Medicas (FCM), Universidad Nacional de Cordoba (UNC), Ciudad Universitaria, Cordoba (Argentina); Perez, Roberto D. [Facultad de Matematica, Astronomia y Fisica (FAMAF-UNC), Ciudad Universitaria, Cordoba (Argentina); Consejo Nacional de Investigaciones Cientificas y Tecnologicas (CONICET), Buenos Aires (Argentina); Cremonezzi, David [Catedra Anatomia Patologica, Hospital Nacional de Clinicas (FCM-UNC), Cordoba (Argentina); Perez, Carlos A. [Laboratorio Nacional de Luz Sincrotron (LNLS), Linha D09B-XRF, Campinas SP (Brazil); Rubio, Marcelo [Facultad de Matematica, Astronomia y Fisica (FAMAF-UNC), Ciudad Universitaria, Cordoba (Argentina); Consejo Nacional de Investigaciones Cientificas y Tecnologicas (CONICET), Buenos Aires (Argentina); Bongiovanni, Guillermina A., E-mail: gbongiovanni@conicet.gov.ar [Consejo Nacional de Investigaciones Cientificas y Tecnologicas (CONICET), Buenos Aires (Argentina); Laboratorio de Investigaciones Bioquimicas, Quimicas y de Medio Ambiente (LIBIQUIMA), Consejo Nacional de Investigaciones Cientificas y Tecnologicas (CONICET), Universidad Nacional del Comahue, Buenos Aires 1400, CP 8300 Neuquen (Argentina)

2010-07-15

Arsenic (As) is one of the most abundant hazards in the environment and it is a human carcinogen. Related to excretory functions, the kidneys in humans, animal models or naturally exposed fauna, are target organs for As accumulation and deleterious effects. Previous studies carried out using X-ray fluorescence spectrometry by synchrotron radiation (SR-{mu}XRF) showed a high concentration of As in the renal cortex of chronically exposed rats, suggesting that this is a suitable model for studies on renal As accumulation. This accumulation was accompanied by a significant increase in copper (Cu) concentration. The present study focused on the localization of these elements in the renal cortex and their correlation with physiological and histological As-related renal effects. Experiments were performed on nine male Wistar rats, divided into three experimental groups. Two groups received 100 {mu}g/ml sodium arsenite in drinking water for 60 and 120 consecutive days, respectively. The control group received water without sodium arsenite (<50 ppb As). For histological analysis, 5-{mu}m-thick sections of kidneys were stained with hematoxylin and eosin. Biochemical analyses were used to determine concentrations of plasma urea and creatinine. The As and Cu mapping were carried out by SR-{mu}XRF using a collimated white synchrotron spectrum (300 {mu}mx300 {mu}m) on kidney slices (2 mm thick) showing As and Cu co-distribution in the renal cortex. Then, renal cortical slices (100 {mu}m thick) were scanned with a focused white synchrotron spectrum (30 {mu}mx30 {mu}m). Peri-glomerular accumulation of As and Cu at 60 and 120 days was found. The effects of 60 days of arsenic consumption were seen in a decreased Bowman's space as well as a decreased plasma blood urea nitrogen (BUN)/creatinine ratio. Major deleterious effects; however, were seen on tubules at 120 days of exposition. This study supports the hypothesis that tubular accumulation of As-Cu may have some bearing on

Association between As and Cu renal cortex accumulation and physiological and histological alterations after chronic arsenic intake

International Nuclear Information System (INIS)

Rubatto Birri, Paolo N.; Perez, Roberto D.; Cremonezzi, David; Perez, Carlos A.; Rubio, Marcelo; Bongiovanni, Guillermina A.

2010-01-01

Arsenic (As) is one of the most abundant hazards in the environment and it is a human carcinogen. Related to excretory functions, the kidneys in humans, animal models or naturally exposed fauna, are target organs for As accumulation and deleterious effects. Previous studies carried out using X-ray fluorescence spectrometry by synchrotron radiation (SR-μXRF) showed a high concentration of As in the renal cortex of chronically exposed rats, suggesting that this is a suitable model for studies on renal As accumulation. This accumulation was accompanied by a significant increase in copper (Cu) concentration. The present study focused on the localization of these elements in the renal cortex and their correlation with physiological and histological As-related renal effects. Experiments were performed on nine male Wistar rats, divided into three experimental groups. Two groups received 100 μg/ml sodium arsenite in drinking water for 60 and 120 consecutive days, respectively. The control group received water without sodium arsenite (<50 ppb As). For histological analysis, 5-μm-thick sections of kidneys were stained with hematoxylin and eosin. Biochemical analyses were used to determine concentrations of plasma urea and creatinine. The As and Cu mapping were carried out by SR-μXRF using a collimated white synchrotron spectrum (300 μmx300 μm) on kidney slices (2 mm thick) showing As and Cu co-distribution in the renal cortex. Then, renal cortical slices (100 μm thick) were scanned with a focused white synchrotron spectrum (30 μmx30 μm). Peri-glomerular accumulation of As and Cu at 60 and 120 days was found. The effects of 60 days of arsenic consumption were seen in a decreased Bowman's space as well as a decreased plasma blood urea nitrogen (BUN)/creatinine ratio. Major deleterious effects; however, were seen on tubules at 120 days of exposition. This study supports the hypothesis that tubular accumulation of As-Cu may have some bearing on the arsenic

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

Renal computed angiography. Part I: Renal CT phlebography. Renal veins variants

International Nuclear Information System (INIS)

Al-Amin, M.; Krupev, M.; Hadjidekov, V.; Plachkov, I.

2012-01-01

The changing trend in renal surgery, transplantation and minimal invasive urology implies preprocedure evaluation of renal veins. Development of imaging methods offers new possibilities for venographic visualization. The goal of this study is to present authors experience in visualization of renal veins using 64 MDCT and to evaluate the utility in assessments of their variants. 128 patients (68 females and 60 males, mean age 53,3) with urological complaints underwent 64MDCT examination including CT angiography. Contrast enhancement includes 3-4ml/sec injection flow of 90 ml contrast medium followed by 20 ml saline at the same rate. In 23 out of 128 examined patients some of the common variants of the renal vein is found. 64 MDCT angiography visualize very well renal veins and becomes method of choice in preoperative assessment of renal vein anatomy. (authors)

Kefir administration reduced progression of renal injury in STZ-diabetic rats by lowering oxidative stress.

Science.gov (United States)

Punaro, Giovana R; Maciel, Fabiane R; Rodrigues, Adelson M; Rogero, Marcelo M; Bogsan, Cristina S B; Oliveira, Marice N; Ihara, Silvia S M; Araujo, Sergio R R; Sanches, Talita R C; Andrade, Lucia C; Higa, Elisa M S

2014-02-15

This study aimed at assessing the effects of Kefir, a probiotic fermented milk, on oxidative stress in diabetic animals. The induction of diabetes was achieved in adult male Wistar rats using streptozotocin (STZ). The animals were distributed into four groups as follows: control (CTL); control Kefir (CTLK); diabetic (DM) and diabetic Kefir (DMK). Starting on the 5th day of diabetes, Kefir was administered by daily gavage at a dose of 1.8 mL/day for 8 weeks. Before and after Kefir treatment, the rats were placed in individual metabolic cages to obtain blood and urine samples to evaluate urea, creatinine, proteinuria, nitric oxide (NO), thiobarbituric acid reactive substances (TBARS) and C-reactive protein (CRP). After sacrificing the animals, the renal cortex was removed for histology, oxidative stress and NOS evaluation. When compared to CTL rats, DM rats showed increased levels of glycemia, plasmatic urea, proteinuria, renal NO, superoxide anion, TBARS, and plasmatic CRP; also demonstrated a reduction in urinary urea, creatinine, and NO. However, DMK rats showed a significant improvement in most of these parameters. Despite the lack of differences observed in the expression of endothelial NO synthase (eNOS), the expression of inducible NO synthase (iNOS) was significantly lower in the DMK group when compared to DM rats, as assessed by Western blot analysis. Moreover, the DMK group presented a significant reduction of glycogen accumulation within the renal tubules when compared to the DM group. These results indicate that Kefir treatment may contribute to better control of glycemia and oxidative stress, which is associated with the amelioration of renal function, suggesting its use as a non-pharmacological adjuvant to delay the progression of diabetic complications. Copyright © 2014 Elsevier Inc. All rights reserved.

The development and piloting of the REnal specific Advanced Communication Training (REACT) programme to improve Advance Care Planning for renal patients.

Science.gov (United States)

Bristowe, Katherine; Shepherd, Kate; Bryan, Liz; Brown, Heather; Carey, Irene; Matthews, Beverley; O'Donoghue, Donal; Vinen, Katie; Murtagh, Fliss E M

2014-04-01

In recent years, the End-Stage Kidney Disease population has increased and is ever more frail, elderly and co-morbid. A care-focused approach needs to be incorporated alongside the disease focus, to identify those who are deteriorating and improve communication about preferences and future care. Yet many renal professionals feel unprepared for such discussions. To develop and pilot a REnal specific Advanced Communication Training (REACT) programme to address the needs of End-Stage Kidney Disease patients and renal professionals. Two-part study: (1) development of the REnal specific Advanced Communication Training programme informed by multi-professional focus group and patient survey and (2) piloting of the programme. The REnal specific Advanced Communication Training programme was piloted with 16 participants (9 renal nurses/health-care assistants and 7 renal consultants) in two UK teaching hospitals. The focus group identified the need for better information about end-of-life phase, improved awareness of patient perspectives, skills to manage challenging discussions, 'hands on' practice in a safe environment and follow-up to discuss experiences. The patient survey demonstrated a need to improve communication about concerns, treatment plans and decisions. The developed REnal specific Advanced Communication Training programme was acceptable and feasible and was associated with a non-significant increase in confidence in communicating about end-of-life issues (pre-training: 6.6/10, 95% confidence interval: 5.7-7.4; post-training: 6.9/10, 95% confidence interval: 6.1-7.7, unpaired t-test - p = 0.56), maintained at 3 months. There is a need to improve end-of-life care for End-Stage Kidney Disease patients, to enable them to make informed decisions about future care. Challenges include prioritising communication training among service providers.

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

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...

Computer-assisted imaging algorithms facilitate histomorphometric quantification of kidney damage in rodent renal failure models

Directory of Open Access Journals (Sweden)

Marcin Klapczynski

2012-01-01

Full Text Available Introduction: Surgical 5/6 nephrectomy and adenine-induced kidney failure in rats are frequently used models of progressive renal failure. In both models, rats develop significant morphological changes in the kidneys and quantification of these changes can be used to measure the efficacy of prophylactic or therapeutic approaches. In this study, the Aperio Genie Pattern Recognition technology, along with the Positive Pixel Count, Nuclear and Rare Event algorithms were used to quantify histological changes in both rat renal failure models. Methods: Analysis was performed on digitized slides of whole kidney sagittal sections stained with either hematoxylin and eosin or immunohistochemistry with an anti-nestin antibody to identify glomeruli, regenerating tubular epithelium, and tubulointerstitial myofibroblasts. An anti-polymorphonuclear neutrophil (PMN antibody was also used to investigate neutrophil tissue infiltration. Results: Image analysis allowed for rapid and accurate quantification of relevant histopathologic changes such as increased cellularity and expansion of glomeruli, renal tubular dilatation, and degeneration, tissue inflammation, and mineral aggregation. The algorithms provided reliable and consistent results in both control and experimental groups and presented a quantifiable degree of damage associated with each model. Conclusion: These algorithms represent useful tools for the uniform and reproducible characterization of common histomorphologic features of renal injury in rats.

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

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.

Valutazione morfo-funzionale in pazienti ipertesi con stenosi dell'arteria renale; Correlazioni tra angiografia e scintigrafia dinamica. Morpho-functional evaluation in hypertensive patients with renal artery stenosis; Correlations between angiography and radionuclide renography

Energy Technology Data Exchange (ETDEWEB)

Cuocolo, A; Celentano, L; Nappi, A [Naples Univ. (Italy). Ist. di Scienze Radiologiche; Neumann, R D; Salvatore, M [Naples Univ. (Italy). Cattedra di Medicina Nucleare

1991-01-01

Renovascula hypertension is the most important and common cause of secondary hypertension. We studied 10 patients with arterial hypertension and different degrees of renal artery stenosis to assess the usefulness of dynamic radionuclide renography in evaluating renal perfusion and funcion, and to compare funcional radionuclide results to the morphological findings of renal angiography. Computer-assisted dynamic renal with {sup 00m}Tc diethylenetriaminepentaacetic acid (DTPA) and {sup 131}I orthoiodohippurate (OIH), and renal artheriography were also employed in all patients. In all patients, radionuclide results matched angiography findings in quality. In particular, 3 patients with hemodynamical insignificant renal artery stenosis exhibited normal perfusion and function at dynamic radionuclide renography. Seven patients had significant renal artery stenosis and associated functional changes at dynamic radionuclide renography. Quantitative comparison of all patients showed a significant correlation (r=0.866, p<0.001) between the degree of renal artery stenosis, quantified as the percentage of narrowing as compared to adjacent/contralateral normal vessel diameter, and the results of split renal function, as assessed during OIH studies and expressed per kidney as a percentage of the net total counts of both kidneys. In conclusion, our results demonstrated dynamic radionuclide renography to be a valuable secondary to renal artery stenosis in hypertensive patients, providing complementary results to arteriography.

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.

Gluteal Black Market Silicone-induced Renal Failure: A Case Report and Literature Review.

Science.gov (United States)

Matson, Andrea; Faibisoff, Burt

2017-11-01

Very few cases of successful surgical treatment for renal failure due to gluteal silicone injections have been reported in the literature. The silicone toxicity and subsequent renal failure seem to follow repetitive silicone injections and silicone injections in large quantities. This is a case of a 31-year-old woman who developed renal failure after 6 years of gluteal silicone injections who underwent radical resection of bilateral gluteal regions in an attempt to mitigate her impending complete renal failure. A systematic review of the literature was conducted using PubMed database and with assistance from medical library staff to conduct keyword searches for "Silicone," "Renal failure," "Silicone emboli syndrome," "Silicone granuloma," and "Silicone end organ toxicity." The search results were reviewed by the authors and selected based on the relevance to the case report presented. Extensive literature relating to silicone granulomas and their systemic effects supports the use of steroids for immediate treatment and eventual surgical resection for cure of the various silicone-related end-organ toxicities including renal failure.

Reversible uranyl fluoride nephrotoxicity in the Long Evans rat

International Nuclear Information System (INIS)

Diamond, G.L.; Morrow, P.E.; Panner, B.J.; Gelein, R.M.; Baggs, R.B.

1989-01-01

Severity and duration of renal injury produced by low levels of uranyl fluoride (UO2F2) were examined in the rat. Rats received multiple ip injections of UO2F2 (cumulative dose: 0.66 or 1.32 mg U/kg body wt). Renal injury was characterized histologically by cellular and tubular necrosis of pars recta of proximal tubule (S2 and S3), with less severe cellular injury to thick ascending limb of loop of Henle and collecting tubule. Injury was evident when renal uranium levels were between 0.7 and 1.4 micrograms U/g wet kidney and was most severe when renal uranium burden was between 3.4 and 5.6 micrograms U/g. Repair of injury was rapid, with complete restoration within 35 days after exposure. Associated with injury were abnormalities in renal function, including impaired tubular reabsorption, proteinuria, and enzymuria, which appeared temporally related, to variable degrees, to progression of renal injury. Thus, reversible renal injury occurs in the rat at levels of uranium in kidney below the present Nuclear Regulatory Commission standard of 3 micrograms U/g kidney for renal injury in humans

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.

Nursing procedures during continuous renal replacement therapies: a national survey.

Science.gov (United States)

Ricci, Zaccaria; Benelli, Sonia; Barbarigo, Fabio; Cocozza, Giulia; Pettinelli, Noemi; Di Luca, Emanuela; Mettifogo, Mariangela; Toniolo, Andrea; Ronco, Claudio

2015-01-01

The current role of nurses in the management of critically ill patients needing continuous renal replacement therapies is clearly fundamental. The care of these complex patients is typically shared by critical care and dialysis nurses: their precise duties may vary from country to country. To clarify this issue we conducted a national-level survey at a recent Italian course on nursing practices during continuous renal replacement therapies. A total of 119 questionnaires were analysed. The participants, who were equally divided between critical care and dialysis nurses, came from 44 different hospitals and 35 Italian cities. Overall, 23% of participants answered that "the dialysis staff" were responsible for continuous renal replacement therapies in the Intensive Care Unit, while 39% answered "the critical care nurse", and 38% "a shared organization". Interestingly, less than the half of participants claimed specific continuous renal replacement therapies training was provided to employees before handling an acute dialysis machine. Finally, about 60% of participants had experience of extra-corporeal membrane oxygenation machines used in conjunction with continuous renal replacement therapies. Workload coordination and management of critically ill patients undergoing continuous renal replacement therapies in Italy is not standardized. At present, the duties of critical care and dialysis nurses vary significantly across the country. They frequently overlap or leave gaps in the assistance received by patients. The role of nurses involved in the care of continuous renal replacement therapies patients in Italy currently requires better organization, possibly starting with intensive standardized training and educational programs.

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.)

Anatomic renal artery branch microdissection to facilitate zero-ischemia partial nephrectomy.

Science.gov (United States)

Ng, Casey K; Gill, Inderbir S; Patil, Mukul B; Hung, Andrew J; Berger, Andre K; de Castro Abreu, Andre Luis; Nakamoto, Masahiko; Eisenberg, Manuel S; Ukimura, Osamu; Thangathurai, Duraiyah; Aron, Monish; Desai, Mihir M

2012-01-01