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Sample records for renal tubule hyperplasia

  1. Neonatal multiorgan failure due to ACAD9 mutation and complex I deficiency with mitochondrial hyperplasia in liver, cardiac myocytes, skeletal muscle, and renal tubules.

    Science.gov (United States)

    Leslie, Nancy; Wang, Xinjian; Peng, Yanyan; Valencia, C Alexander; Khuchua, Zaza; Hata, Jessica; Witte, David; Huang, Taosheng; Bove, Kevin E

    2016-03-01

    Complex I deficiency causes Leigh syndrome, fatal infant lactic acidosis, and neonatal cardiomyopathy. Mutations in more than 100 nuclear DNA and mitochondrial DNA genes miscode for complex I subunits or assembly factors. ACAD9 is an acyl-CoA dehydrogenase with a novel function in assembly of complex I; biallelic mutations cause progressive encephalomyopathy, recurrent Reye syndrome, and fatal cardiomyopathy. We describe the first autopsy in fatal neonatal lethal lactic acidosis due to mutations in ACAD9 that reduced complex I activity. We identified mitochondrial hyperplasia in cardiac myocytes, diaphragm muscle, and liver and renal tubules in formalin-fixed, paraffin-embedded tissue using immunohistochemistry for mitochondrial antigens. Whole-exome sequencing revealed compound heterozygous variants in the ACAD9 gene: c.187G>T (p.E63*) and c.941T>C (p.L314P). The nonsense mutation causes late infantile lethality; the missense variant is novel. Autopsy-derived fibroblasts had reduced complex I activity (53% of control) with normal activity in complexes II to IV, similar to reported cases of ACAD9 deficiency.

  2. Renal tubule cell repair following acute renal injury.

    Science.gov (United States)

    Humes, H D; Lake, E W; Liu, S

    1995-01-01

    Experimental data suggests the recovery of renal function after ischemic or nephrotoxic acute renal failure is due to a replicative repair process dependent upon predominantly paracrine release of growth factors. These growth factors promote renal proximal tubule cell proliferation and a differentiation phase dependent on the interaction between tubule cells and basement membrane. These insights identify the molecular basis of renal repair and ischemic and nephrotoxic acute renal failure, and may lead to potential therapeutic modalities that accelerate renal repair and lessen the morbidity and mortality associated with these renal disease processes. In this regard, there is a prominent vasoconstrictor response of the renal vasculature during the postischemic period of developing acute renal failure. The intravenous administration of pharmacologic doses of atrial natriuretic factor (ANF) in the postischemic period have proven efficacious by altering renal vascular resistance, so that renal blood flow and glomerular filtration rate improve. ANF also appears to protect renal tubular epithelial integrity and holds significant promise as a therapeutic agent in acute renal failure. Of equal or greater promise are the therapeutic interventions targeting the proliferative reparative zone during the postischemic period. The exogenous administration of epidermal growth factor or insulin-like growth factor-1 in the postischemic period have effectively decreased the degree of renal insufficiency as measured by the peak serum creatinine and has hastened renal recovery as measured by the duration of time required to return the baseline serum creatinine values. A similarly efficacious role for hepatocyte growth factor has also been recently demonstrated.

  3. Innervation of the renal proximal convoluted tubule of the rat

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    Barajas, L.; Powers, K. (Harbor-UCLA Medical Center, Torrance (USA))

    1989-12-01

    Experimental data suggest the proximal tubule as a major site of neurogenic influence on tubular function. The functional and anatomical axial heterogeneity of the proximal tubule prompted this study of the distribution of innervation sites along the early, mid, and late proximal convoluted tubule (PCT) of the rat. Serial section autoradiograms, with tritiated norepinephrine serving as a marker for monoaminergic nerves, were used in this study. Freehand clay models and graphic reconstructions of proximal tubules permitted a rough estimation of the location of the innervation sites along the PCT. In the subcapsular nephrons, the early PCT (first third) was devoid of innervation sites with most of the innervation occurring in the mid (middle third) and in the late (last third) PCT. Innervation sites were found in the early PCT in nephrons located deeper in the cortex. In juxtamedullary nephrons, innervation sites could be observed on the PCT as it left the glomerulus. This gradient of PCT innervation can be explained by the different tubulovascular relationships of nephrons at different levels of the cortex. The absence of innervation sites in the early PCT of subcapsular nephrons suggests that any influence of the renal nerves on the early PCT might be due to an effect of neurotransmitter released from renal nerves reaching the early PCT via the interstitium and/or capillaries.

  4. CFTR mediated chloride secretion in the avian renal proximal tubule.

    Science.gov (United States)

    Laverty, Gary; Anttila, Ashley; Carty, Jenava; Reddy, Varudhini; Yum, Jamie; Arnason, Sighvatur S

    2012-01-01

    In primary cell cultures of the avian (Gallus gallus) renal proximal tubule parathyroid hormone and cAMP activation generate a Cl(-)-dependent short circuit current (I(SC)) response, consistent with net transepithelial Cl(-) secretion. In this study we investigated the expression and physiological function of the Na-K-2Cl (NKCC) transporter and CFTR chloride channel, both associated with Cl(-) secretion in a variety of tissues, in these proximal tubule cells. Using both RT-PCR and immunoblotting approaches, we showed that NKCC and CFTR are expressed, both in proximal tubule primary cultures and in a proximal tubule fraction of non-cultured (native tissue) fragments. We also used electrophysiological methods to assess the functional contribution of NKCC and CFTR to forskolin-activated I(SC) responses in filter grown cultured monolayers. Bumetanide (10 μM), a specific blocker of NKCC, inhibited forskolin activated I(SC) by about 40%, suggesting that basolateral uptake of Cl(-) is partially mediated by NKCC transport. In monolayers permeabilized on the basolateral side with nystatin, forskolin activated an apical Cl(-) conductance, manifested as bidirectional diffusion currents in the presence of oppositely directed Cl(-) gradients. Under these conditions the apical conductance appeared to show some bias towards apical-to-basolateral Cl(-) current. Two selective CFTR blockers, CFTR Inhibitor 172 and GlyH-101 (both at 20 μM) inhibited the forskolin activated diffusion currents by 38-68%, with GlyH-101 having a greater effect. These data support the conclusion that avian renal proximal tubules utilize an apical CFTR Cl(-) channel to mediate cAMP-activated Cl(-) secretion.

  5. Cellular localization of uranium in the renal proximal tubules during acute renal uranium toxicity.

    Science.gov (United States)

    Homma-Takeda, Shino; Kitahara, Keisuke; Suzuki, Kyoko; Blyth, Benjamin J; Suya, Noriyoshi; Konishi, Teruaki; Terada, Yasuko; Shimada, Yoshiya

    2015-12-01

    Renal toxicity is a hallmark of uranium exposure, with uranium accumulating specifically in the S3 segment of the proximal tubules causing tubular damage. As the distribution, concentration and dynamics of accumulated uranium at the cellular level is not well understood, here, we report on high-resolution quantitative in situ measurements by high-energy synchrotron radiation X-ray fluorescence analysis in renal sections from a rat model of uranium-induced acute renal toxicity. One day after subcutaneous administration of uranium acetate to male Wistar rats at a dose of 0.5 mg uranium kg(-1) body weight, uranium concentration in the S3 segment of the proximal tubules was 64.9 ± 18.2 µg g(-1) , sevenfold higher than the mean renal uranium concentration (9.7 ± 2.4 µg g(-1) ). Uranium distributed into the epithelium of the S3 segment of the proximal tubules and highly concentrated uranium (50-fold above mean renal concentration) in micro-regions was found near the nuclei. These uranium levels were maintained up to 8 days post-administration, despite more rapid reductions in mean renal concentration. Two weeks after uranium administration, damaged areas were filled with regenerating tubules and morphological signs of tissue recovery, but areas of high uranium concentration (100-fold above mean renal concentration) were still found in the epithelium of regenerating tubules. These data indicate that site-specific accumulation of uranium in micro-regions of the S3 segment of the proximal tubules and retention of uranium in concentrated areas during recovery are characteristics of uranium behavior in the kidney.

  6. Towards a Guided Regeneration of Renal Tubules at a Polyester Interstitium

    Directory of Open Access Journals (Sweden)

    Will W. Minuth

    2010-03-01

    Full Text Available Stem/progenitor cells are promising candidates for a therapy of renal failure. However, sound knowledge about implantation and regeneration is lacking. Therefore, mechanisms leading from stem/progenitor cells into tubules are under research. Renal stem/progenitor cells were isolated from neonatal rabbit kidney and mounted between layers of polyester fleece. It creates an artificial interstitium and replaces coating by extracellular matrix proteins. Tubulogenic development is induced by aldosterone. Electron microscopy illuminates growth of tubules in close vicinity to polyester fibers. Tubules contain a differentiated epithelium. The spatial extension of tubules opens a new strategy for testing morphogenic drugs and biocompatible fleece materials.

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

    Directory of Open Access Journals (Sweden)

    Anna Giovanna Sciancalepore

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

  8. Megalin and cubilin: synergistic endocytic receptors in renal proximal tubule.

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    Christensen, E I; Birn, H

    2001-04-01

    The multiligand, endocytic receptors megalin and cubilin are colocalized in the renal proximal tubule. They are heavily expressed in the apical endocytic apparatus. Megalin is a 600-kDa transmembrane protein belonging to the low-density lipoprotein-receptor family. The cytoplasmic tail contains three NPXY motifs that mediate the clustering in coated pits and are possibly involved in signaling functions. Cubilin, also known as the intestinal intrinsic factor-cobalamin receptor, is a 460-kDa receptor with no transmembrane domain and no known signal for endocytosis. Because the two receptors bind each other with high affinity and colocalize in several tissues, it is highly conceivable that megalin mediates internalization of cubilin and its ligands. Both receptors are important for normal tubular reabsorption of proteins, including albumin. Among the proteins normally filtered in the glomeruli, cubilin has been shown to bind albumin, immunoglobulin light chains, and apolipoprotein A-I. The variety of filtered ligands identified for megalin include vitamin-binding proteins, hormones, enzymes, apolipoprotein H, albumin, and beta(2)- and alpha(1)-microglobulin. Loss of these proteins and vitamins in the urine of megalin-deficient mice illustrates the physiological importance of this receptor.

  9. Ultrastructural changes in renal proximal tubules after tetraethyllead intoxication

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    Chang, L.W. (Univ. of Arkansas for Medical Sciences, Little Rock); Wade, P.R.; Reuhl, K.R.; Olson, M.J.

    1980-10-01

    Tetraethyllead (TEL) has been shown to be both an occupational and an environmental hazard to human health. The present study investigates pathological changes in the kidney as a result of TEL poisoning. Rabbits were injected (ip) with 100 to 200 mg TEL, and controls were injected with an equal volume of normal saline solution. Animals were sacrificed upon onset of toxic symptoms (hyperirritation, tremor, and convulsion). Animals were perfused with 2.5% glutaraldehyde. Tissue samples from the renal cortex were obtained for electron microscopy. Pathological changes were not remarkable at the light microscopic level; however, electron microscopic examination revealed marked cytological changes in the epithelial cells of the proximal tubules (PT) of animals treated with TEL. Enlargement of apical vacuoles and accumulation of lysosomes and microbodies were prominent findings in many PT epithelial cells. Many lysosomes appeared to be atypical in nature, displaying a high degree of pleomorphism in size, shape, and density. Giant lysosomes measuring 8 to 10 ..mu..m in diameter and crystalloid bodies within lysosomes were also observed. Configurational changes (increased convolution, branching, vesiculation, and degranulation) of the rough endoplasmic reticulum leading to the formation of honeycomb-like bodies were also found in many PT epithelial cells. The formation of the honeycomb-like bodies may represent a hyperplastic, hypoactive form of the rough endoplasmic reticulum and denotes a disruption of protein synthesis in these cells by TEL.

  10. [N-acetyl-beta-hexosaminidase--marker of damage to renal proximal tubules].

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    Kepka, Alina; Szajda, Sławomir D; Jankowska, Anna; Waszkiewicz, Napoleon; Chojnowska, Sylwia; Zwierz, Krzysztof

    2008-09-01

    Cells of the renal epithelium synthesize and excrete to urine many enzymes. Among more than 50 enzymes produced by epithelial cells of proximal tubules, only few have a diagnostic value. Determination of the enzymatic activities in urine is sensitive and not invasive method for evaluation the function of renal tubules. Urinary N-acetyl-beta-hexosaminidase (HEX) activity is approved and practically utilized marker of the renal function. HEX is a lysosomal exoglycosidase taking part in catabolism of the sugar chains of glycoconjugates (glycoproteins, glycolipids and proteoglycans). HEX catalyses release of N-acetylglucosamine and N-acetylgalactosamine from a non reducing ends of glycoconjugates. In urine of healthy persons activity of HEX is negligible, but significantly increases after damage to the proximal tubules. The cells of renal proximal tubules are very sensitive to hypoxia. Therefore all renal processes with hypoxia lead to dysfunction of proximal renal tubules and release HEX to urine. Increased activity of HEX in urine was found after intoxication by heavy metals, nephrotoxic drugs, contrast media, fewer, bacterial as well as immunological nephritis and hypertension, diabetes, neoplasms and during renal graft rejection. In the paper we presented review of literature concerning HEX, and its presence in renal tissue and urine, as well as application in diagnostics.

  11. Induction of Heme Oxygenase-1 Can Halt and Even Reverse Renal Tubule-Interstitial Fibrosis

    NARCIS (Netherlands)

    Correa-Costa, Matheus; Semedo, Patricia; Monteiro, Ana Paula F. S.; Silva, Reinaldo C.; Pereira, Rafael L.; Goncalves, Giselle M.; Marcusso Marques, Georgia Daniela; Cenedeze, Marcos A.; Faleiros, Ana C. G.; Keller, Alexandre C.; Shimizu, Maria H. M.; Seguro, Antonio C.; Reis, Marlene A.; Pacheco-Silva, Alvaro; Camara, Niels O. S.

    2010-01-01

    Background: The tubule-interstitial fibrosis is the hallmark of progressive renal disease and is strongly associated with inflammation of this compartment. Heme-oxygenase-1 (HO-1) is a cytoprotective molecule that has been shown to be beneficial in various models of renal injury. However, the role o

  12. Altered renal distal tubule structure and renal Na(+) and Ca(2+) handling in a mouse model for Gitelman's syndrome.

    NARCIS (Netherlands)

    Loffing, J.; Vallon, V.; Loffing-Cueni, D.; Aregger, F.; Richter, K.H.; Pietri, L.; Bloch-Faure, M.; Hoenderop, J.G.J.; Shull, G.E.; Meneton, P.; Kaissling, B.

    2004-01-01

    Gitelman's syndrome, an autosomal recessive renal tubulopathy caused by loss-of-function mutations in the thiazide-sensitive NaCl co-transporter (NCC) of the distal convoluted tubule (DCT), is characterized by mild renal Na(+) wasting, hypocalciuria, hypomagnesemia, and hypokalemic alkalosis. For ga

  13. PKB and megalin determine the survival or death of renal proximal tubule cells

    OpenAIRE

    Caruso-Neves, Celso; Pinheiro, Ana Acacia S.; Cai, Hui; Souza-Menezes, Jackson; Guggino, William B.

    2006-01-01

    Renal proximal tubule cells have a remarkable ability to reabsorb large quantities of albumin through megalin-mediated endocytosis. This is an essential process for overall body homeostasis. Overstressing this endocytic system with a prolonged excess of albumin is injurious to proximal tubule cells. How these cells function and protect themselves from injury is unknown. Here, we show that megalin is the sensor that determines whether cells will be protected or injured by albumin. Megalin, thr...

  14. Cubilin Is Essential for Albumin Reabsorption in the Renal Proximal Tubule

    OpenAIRE

    Amsellem, S.; Gburek, J.; Hamard, G.; Nielsen, R.; Willnow, T.E.; Devuyst, O.; Nexo, E.; Verroust, P. J.; Christensen, E I; Kozyraki, R.

    2010-01-01

    Receptor-mediated endocytosis is responsible for protein reabsorption in the proximal tubule. This process involves two interacting receptors, megalin and cubilin, which form a complex with amnionless. Whether these proteins function in parallel or as part of an integrated system is not well understood. Here, we report the renal effects of genetic ablation of cubilin, with or without concomitant ablation of megalin, using a conditional Cre-loxP system. We observed that proximal tubule cells d...

  15. Increased expression of intranuclear matrix metalloproteinase 9 in atrophic renal tubules is associated with renal fibrosis.

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    Jen-Pi Tsai

    Full Text Available BACKGROUND: Reduced turnover of extracellular matrix has a role in renal fibrosis. Matrix metalloproteinases (MMPs is associated with many glomerular diseases, but the histological association of MMPs and human renal fibrosis is unclear. METHODS: This is a retrospective study. Institutional Review Board approval was obtained for the review of patients' medical records, data analysis and pathological specimens staining with waiver of informed consents. Specimens of forty-six patients were examined by immunohistochemical stain of MMP-9 in nephrectomized kidneys, and the association of renal expression of MMP-9 and renal fibrosis was determined. MMP-9 expression in individual renal components and fibrosis was graded as high or low based on MMP-9 staining and fibrotic scores. RESULTS: Patients with high interstitial fibrosis scores (IFS and glomerular fibrosis scores (GFS had significantly higher serum creatinine, lower estimated glomerular filtration rate (eGFR, and were more likely to have chronic kidney disease (CKD and urothelial cell carcinoma. Univariate analysis showed that IFS and GFS were negatively associated with normal and atrophic tubular cytoplasmic MMP-9 expression and IFS was positively correlated with atrophic tubular nuclear MMP-9 expression. Multivariate stepwise regression indicated that MMP-9 expression in atrophic tubular nuclei (r = 0.4, p = 0.002 was an independent predictor of IFS, and that MMP-9 expression in normal tubular cytoplasm (r = -0.465, p<0.001 was an independent predictor of GFS. CONCLUSIONS: Interstitial fibrosis correlated with MMP-9 expression in the atrophic tubular nuclei. Our results indicate that renal fibrosis is associated with a decline of MMP-9 expression in the cytoplasm of normal tubular cells and increased expression of MMP-9 in the nuclei of tubular atrophic renal tubules.

  16. Kidney-on-a-chip technology for renal proximal tubule tissue reconstruction.

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    Nieskens, Tom T G; Wilmer, Martijn J

    2016-11-05

    The renal proximal tubule epithelium is responsible for active secretion of endogenous and exogenous waste products from the body and simultaneous reabsorption of vital compounds from the glomerular filtrate. The complexity of this transport machinery makes investigation of processes such as tubular drug secretion a continuous challenge for researchers. Currently available renal cell culture models often lack sufficient physiological relevance and reliability. Introducing complex biological culture systems in a 3D microfluidic design improves the physiological relevance of in vitro renal proximal tubule epithelium models. Organ-on-a-chip technology provides a promising alternative, as it allows the reconstruction of a renal tubule structure. These microfluidic systems mimic the in vivo microenvironment including multi-compartmentalization and exposure to fluid shear stress. Increasing data supports that fluid shear stress impacts the phenotype and functionality of proximal tubule cultures, for which we provide an extensive background. In this review, we discuss recent developments of kidney-on-a-chip platforms with current and future applications. The improved proximal tubule functionality using 3D microfluidic systems is placed in perspective of investigating cellular signalling that can elucidate mechanistic aberrations involved in drug-induced kidney toxicity. Copyright © 2016. Published by Elsevier B.V.

  17. Aldosterone and angiotensin II induced protein aggregation in renal proximal tubules

    DEFF Research Database (Denmark)

    Cheema, Muhammad Umar; Poulsen, Ebbe Toftgaard; Enghild, Jan J

    2013-01-01

    contained various rat keratins known to be expressed in renal tubules as assessed by protein mass spectrometry. Aldosterone administration increased the abundance of the proximal tubular aggresomal protein keratin 5, the ribosomal protein RPL27, ataxin-3, and the chaperone heat shock protein 70...

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

    DEFF Research Database (Denmark)

    de Seigneux, Sophie; Malte, Hans; Dimke, Henrik;

    2007-01-01

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

  19. Kidney-on-a-chip technology for renal proximal tubule tissue reconstruction

    NARCIS (Netherlands)

    Nieskens, T.T.G.; Wilmer, M.J.G.

    2016-01-01

    The renal proximal tubule epithelium is responsible for active secretion of endogenous and exogenous waste products from the body and simultaneous reabsorption of vital compounds from the glomerular filtrate. The complexity of this transport machinery makes investigation of processes such as tubular

  20. Role of the distal convoluted tubule in renal Mg(2+) handling: molecular lessons from inherited hypomagnesemia

    NARCIS (Netherlands)

    Ferre, S.; Hoenderop, J.G.J.; Bindels, R.J.M.

    2011-01-01

    In healthy individuals, Mg(2+) homeostasis is tightly regulated by the concerted action of intestinal absorption, exchange with bone, and renal excretion. The kidney, more precisely the distal convoluted tubule (DCT), is the final determinant of plasma Mg(2+) concentrations. Positional cloning strat

  1. Effect of radiologic contrast media on cell volume regulation in rabbit proximal renal tubules.

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    Galtung, H K; Løken, M; Sakariassen, K S

    2001-05-01

    Most radiographic contrast media are hyperosmotic and able to shrink cells with which they are in contact. The authors studied cell volume control in rabbit proximal renal tubules after incubation with three contrast media: iohexol, ioxaglate, and iodixanol. Proximal renal tubules were isolated from rabbit kidneys. The tubules were exposed to Ringer solutions containing 5% vol/vol iohexol (final osmolality, 330 mOsm), ioxaglate (323 mOsm), iodixanol (305 mOsm), or mannitol (control solutions with identical osmolalities), and tubule volumes were monitored. After 2 hours of incubation, the tubules were stimulated with a hyposmotic Ringer solution (165 mOsm). Three groups of 10 experiments were performed. All solutions induced cell shrinkage (8.3%+/-3.8 [standard error] to 15.4%+/-0.5), which was completely or partly reversible in most experiments (volume increase, 44.8%+/-14.7 to 149.9%+/-107.3) but not those with iohexol and iodixanol. With exposure to the hyposmotic solution, the cells swelled by 11.0%+/-1.8 to 39.7%+/-4.8. In general, the tubules that had been exposed to the most hyperosmotic solution swelled the most. Those exposed to contrast media showed less swelling than the mannitol-exposed controls. In all control experiments, the cells exhibited a gradual shrinkage (43.6%+/-28.5 to 87.0%+/-13). This regulatory response was partly inhibited in tubules exposed to iohexol (39.9%+/-15.8 shrinkage) or iodixanol (8.9%+/-15.8) and completely inhibited in those exposed to ioxaglate. Iohexol and ioxaglate exposure also led to a decrease in water permeability. Exposure to hyperosmotic contrast medium tends to induce prolonged cell shrinkage, decrease the water permeability of the cellular plasma membranes, and compromise the ability to regulate cellular volume. These changes seem to reflect both the hyperosmolality of the solutions and their inherent chemical properties.

  2. Bioprinting of 3D Convoluted Renal Proximal Tubules on Perfusable Chips

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    Homan, Kimberly A.; Kolesky, David B.; Skylar-Scott, Mark A.; Herrmann, Jessica; Obuobi, Humphrey; Moisan, Annie; Lewis, Jennifer A.

    2016-10-01

    Three-dimensional models of kidney tissue that recapitulate human responses are needed for drug screening, disease modeling, and, ultimately, kidney organ engineering. Here, we report a bioprinting method for creating 3D human renal proximal tubules in vitro that are fully embedded within an extracellular matrix and housed in perfusable tissue chips, allowing them to be maintained for greater than two months. Their convoluted tubular architecture is circumscribed by proximal tubule epithelial cells and actively perfused through the open lumen. These engineered 3D proximal tubules on chip exhibit significantly enhanced epithelial morphology and functional properties relative to the same cells grown on 2D controls with or without perfusion. Upon introducing the nephrotoxin, Cyclosporine A, the epithelial barrier is disrupted in a dose-dependent manner. Our bioprinting method provides a new route for programmably fabricating advanced human kidney tissue models on demand.

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

    DEFF Research Database (Denmark)

    Brasen, Jens Christian; Burford, James L.; McDonough, Alicia A.

    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 o...

  4. Hyperplasia

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    Hyperplasia is increased cell production in a normal tissue or organ. Hyperplasia may be a sign of abnormal or precancerous changes. This is called pathologic hyperplasia. It can also be due to the growth ...

  5. Cubilin is essential for albumin reabsorption in the renal proximal tubule.

    Science.gov (United States)

    Amsellem, Sabine; Gburek, Jakub; Hamard, Ghislaine; Nielsen, Rikke; Willnow, Thomas E; Devuyst, Olivier; Nexo, Ebba; Verroust, Pierre J; Christensen, Erik I; Kozyraki, Renata

    2010-11-01

    Receptor-mediated endocytosis is responsible for protein reabsorption in the proximal tubule. This process involves two interacting receptors, megalin and cubilin, which form a complex with amnionless. Whether these proteins function in parallel or as part of an integrated system is not well understood. Here, we report the renal effects of genetic ablation of cubilin, with or without concomitant ablation of megalin, using a conditional Cre-loxP system. We observed that proximal tubule cells did not localize amnionless to the plasma membrane in the absence of cubilin, indicating a mutual dependency of cubilin and amnionless to form a functional membrane receptor complex. The cubilin-amnionless complex mediated internalization of intrinsic factor-vitamin B12 complexes, but megalin considerably increased the uptake. Furthermore, cubilin-deficient mice exhibited markedly decreased uptake of albumin by proximal tubule cells and resultant albuminuria. Inactivation of both megalin and cubilin did not increase albuminuria, indicating that the main role of megalin in albumin reabsorption is to drive the internalization of cubilin-albumin complexes. In contrast, cubulin deficiency did not affect urinary tubular uptake or excretion of vitamin D-binding protein (DBP), which binds cubilin and megalin. In addition, we observed cubilin-independent reabsorption of the "specific" cubilin ligands transferrin, CC16, and apoA-I, suggesting a role for megalin and perhaps other receptors in their reabsorption. In summary, with regard to albumin, cubilin is essential for its reabsorption by proximal tubule cells, and megalin drives internalization of cubilin-albumin complexes. These genetic models will allow further analysis of protein trafficking in the progression of proteinuric renal diseases.

  6. Dopamine and angiotensin type 2 receptors cooperatively inhibit sodium transport in human renal proximal tubule cells.

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    Gildea, John J; Wang, Xiaoli; Shah, Neema; Tran, Hanh; Spinosa, Michael; Van Sciver, Robert; Sasaki, Midori; Yatabe, Junichi; Carey, Robert M; Jose, Pedro A; Felder, Robin A

    2012-08-01

    Little is known regarding how the kidney shifts from a sodium and water reclaiming state (antinatriuresis) to a state where sodium and water are eliminated (natriuresis). In human renal proximal tubule cells, sodium reabsorption is decreased by the dopamine D(1)-like receptors (D(1)R/D(5)R) and the angiotensin type 2 receptor (AT(2)R), whereas the angiotensin type 1 receptor increases sodium reabsorption. Aberrant control of these opposing systems is thought to lead to sodium retention and, subsequently, hypertension. We show that D(1)R/D(5)R stimulation increased plasma membrane AT(2)R 4-fold via a D(1)R-mediated, cAMP-coupled, and protein phosphatase 2A-dependent specific signaling pathway. D(1)R/D(5)R stimulation also reduced the ability of angiotensin II to stimulate phospho-extracellular signal-regulated kinase, an effect that was partially reversed by an AT(2)R antagonist. Fenoldopam did not increase AT(2)R recruitment in renal proximal tubule cells with D(1)Rs uncoupled from adenylyl cyclase, suggesting a role of cAMP in mediating these events. D(1)Rs and AT(2)Rs heterodimerized and cooperatively increased cAMP and cGMP production, protein phosphatase 2A activation, sodium-potassium-ATPase internalization, and sodium transport inhibition. These studies shed new light on the regulation of renal sodium transport by the dopaminergic and angiotensin systems and potential new therapeutic targets for selectively treating hypertension.

  7. Far infrared radiation promotes rabbit renal proximal tubule cell proliferation and functional characteristics, and protects against cisplatin-induced nephrotoxicity.

    Science.gov (United States)

    Chiang, I-Ni; Pu, Yeong-Shiau; Huang, Chao-Yuan; Young, Tai-Horng

    2017-01-01

    Far infrared radiation, a subdivision of the electromagnetic spectrum, is beneficial for long-term tissue healing, anti-inflammatory effects, growth promotion, sleep modulation, acceleration of microcirculation, and pain relief. We investigated if far infrared radiation is beneficial for renal proximal tubule cell cultivation and renal tissue engineering. We observed the effects of far infrared radiation on renal proximal tubules cells, including its effects on cell proliferation, gene and protein expression, and viability. We also examined the protective effects of far infrared radiation against cisplatin, a nephrotoxic agent, using the human proximal tubule cell line HK-2. We found that daily exposure to far infrared radiation for 30 min significantly increased rabbit renal proximal tubule cell proliferation in vitro, as assessed by MTT assay. Far infrared radiation was not only beneficial to renal proximal tubule cell proliferation, it also increased the expression of ATPase Na+/K+ subunit alpha 1 and glucose transporter 1, as determined by western blotting. Using quantitative polymerase chain reaction, we found that far infrared radiation enhanced CDK5R1, GNAS, NPPB, and TEK expression. In the proximal tubule cell line HK-2, far infrared radiation protected against cisplatin-mediated nephrotoxicity by reducing apoptosis. Renal proximal tubule cell cultivation with far infrared radiation exposure resulted in better cell proliferation, significantly higher ATPase Na+/K+ subunit alpha 1 and glucose transporter 1 expression, and significantly enhanced expression of CDK5R1, GNAS, NPPB, and TEK. These results suggest that far infrared radiation improves cell proliferation and differentiation. In HK-2 cells, far infrared radiation mediated protective effects against cisplatin-induced nephrotoxicity by reducing apoptosis, as indicated by flow cytometry and caspase-3 assay.

  8. Double knockout of Bax and Bak from kidney proximal tubules reduces unilateral urethral obstruction associated apoptosis and renal interstitial fibrosis

    Science.gov (United States)

    Mei, Shuqin; Li, Lin; Wei, Qingqing; Hao, Jielu; Su, Yunchao; Mei, Changlin; Dong, Zheng

    2017-01-01

    Interstitial fibrosis, a common pathological feature of chronic kidney diseases, is often associated with apoptosis in renal tissues. To determine the associated apoptotic pathway and its role in renal interstitial fibrosis, we established a mouse model in which Bax and Bak, two critical genes in the intrinsic pathway of apoptosis, were deleted specifically from kidney proximal tubules and used this model to examine renal apoptosis and interstitial fibrosis following unilateral urethral obstruction (UUO). It was shown that double knockout of Bax and Bak from proximal tubules attenuated renal tubular cell apoptosis and suppressed renal interstitial fibrosis in UUO. The results indicate that the intrinsic pathway of apoptosis contributes significantly to the tubular apoptosis and renal interstitial fibrosis in kidney diseases. PMID:28317867

  9. Urinary β2-Microglobulin Is a Good Indicator of Proximal Tubule Injury: A Correlative Study with Renal Biopsies

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    Xu Zeng

    2014-01-01

    Full Text Available Objective. After filtration through glomeruli, β2-microglobulin is reabsorbed in proximal tubules. Increased urinary β2-microglobulin indicates proximal tubule injury and measurement of β2-microglobulin in urine is useful to determine the source of renal injury. Kidney injury molecule-1 (KIM-1 has been characterized as a selective proximal tubule injury marker. This study was designed to evaluate the correlation of urinary β2-microglobulin concentration and KIM-1 expression as evidence of proximal tubule injury. Methods. Between 2009 and 2012, 46 patients with urine β2-microglobulin (RenalVysion had follow-up kidney biopsy. Diagnoses included glomerular and tubule-interstitial disease. Immunohistochemical staining for KIM-1 was performed and the intensity was graded from 0 to 3+. Linear regression analysis was applied to correlate the values of urinary β2-microglobulin and KIM-1 staining scores. P < 0.05 was considered statistically significant. Results. Thirty patients had elevated urinary β2-microglobulin. KIM-1 staining was positive in 35 kidney biopsies. There was a significant correlation between urinary β2-microglobulin and KIM-1 staining (P < 0.05. Sensitivity was 86.6%, specificity was 43.7%, positive predictive value was 74.2%, and negative predictive value was 63.6%. Conclusion. Increased urinary β2-microglobulin is significantly correlated with KIM-1 staining in injured proximal tubules. Measurement of urine β2-microglobulin is a sensitive assay for proximal tubule injury.

  10. 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

  11. Roles of renal proximal tubule transport in the pathogenesis of hypertension.

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    Horita, Shoko; Seki, George; Yamada, Hideomi; Suzuki, Masashi; Koike, Kazuhiko; Fujita, Toshiro

    2013-05-01

    Hypertension is a key factor of cardiovascular disease. Many organs and systems including heart, blood vessel, kidney, sympathetic nerve, and endocrine systems are involved in the regulation of blood pressure. In particular, the kidney plays an essential role in the regulation of blood pressure, but is also quite vulnerable to hypertensive tissue damage. For example, most chronic kidney disease (CKD) patients have hypertension and are revealed to have higher mortality than normal population. Furthermore, hypertensive renal sclerosis is emerging as the third main cause of dialysis patients. This mini review is to summarize the effects of angiotensin II and dopamine on renal proximal tubule transport, which may have important roles in the regulation of blood pressure.

  12. Stokes flow through a slit with periodic reabsorption: An application to renal tubule

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    T. Haroon

    2016-06-01

    Full Text Available This paper is concerned with the Stokes flow of an incompressible viscous fluid through a slit with periodic reabsorption at the walls. The momentum equation for the two dimensional flow is exactly solved in terms of stream function for two different cases of boundary conditions. Dimensional forms of stream function, velocity components, axial flow rate, pressure distribution, mean pressure drop, wall shear stress, fractional reabsorption and leakage flux are obtained. The points of maximum velocity components are also identified for fixed axial distance. Using physiological data of rat kidney, the theoretical values of periodic reabsorption and pressure drop for various values of fractional reabsorption are tabulated. The graphs of flow properties for both the cases are compared with the case of uniform reabsorption. It is shown that the periodic reabsorption parameter for both the cases plays a vital role in altering the flow properties, which are useful in analyzing flow behavior during the reabsorption of glomerular filtrate through a renal tubule in normal and diseased conditions. It is found that 50% reabsorption of fluid from a single nephron can be achieved by setting α=3.197500134cm for one of the cases which indicates that there is a need of artificial kidney for survival. In case 2, a minor treatment is needed as the value of α for 80% reabsorption is not possible. Streamlines are also drawn to analyze the flow behavior through an abnormal renal tubule.

  13. [Fructose-1,6-bisphosphatase--marker of damage to proximal renal tubules].

    Science.gov (United States)

    Kepka, Alina; Szajda, Sławomir D; Zwierz, Krzysztof

    2008-02-01

    Pathological processes disturbing function of renal proximal tubules, increase activity of fructose-1,6-bisphosphatase (FBP-1) in urine. FBP-1 is cytosolic enzyme which occured mainly in cells of proximal renal tubules, and to small extent in cells of pars recta. After damage to the cell membrane FBP-1 is more rapidly excreted to the urine, than enzymes residing in other cell organelles. Fructose-1,6-bisphosphatase was isolated from rabbit muscle in 1943 by Gomori, and from spinach in 1958 by Racker i Schröder. Highest activity of FBP-1 was found in liver and kidneys, lesser in ileum, leucocytes, muscles and brain. Fructose-1,6-bisphosphatase is one of four key enzymes of gluconeogenesis performing synthesis of glucose from non sugar substrates. FBP-1 catalyses hydrolysis of fructose-1,6-bisphosphate in cytoplasm of the cell. There are many reports on properties and significance of FBP-1 in plant and animal tissues, but only few reports on activity of this enzyme in urine. Reason for little interest in determination of FBP-1 activity in urine, is relative instability of this enzyme in urine.

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

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    E.V. Seliverstova

    2015-04-01

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

  15. P-glycoprotein- and mrp2-mediated octreotide transport in renal proximal tubule

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    Gutmann, Heike; Miller, David S; Droulle, Agathe; Drewe, Jürgen; Fahr, Alfred; Fricker, Gert

    2000-01-01

    Transepithelial transport of a fluorescent derivative of octreotide (NBD-octreotide) was studied in freshly isolated, functionally intact renal proximal tubules from killifish (Fundulus heteroclitus). Drug accumulation in the tubular lumen was visualized by means of confocal microscopy and was measured by image analysis. Secretion of NBD-octreotide into the tubular lumen was demonstrated and exhibited the all characteristics of specific and energy-dependent transport. Steady state luminal fluorescence averaged about five times cellular fluorescence and was reduced to cellular levels when metabolism was inhibited by NaCN. NBD-octreotide secretion was inhibited in a concentration-dependent manner by unlabelled octreotide, verapamil and leukotriene C4 (LTC4). Conversely, unlabelled octreotide reduced in a concentration dependent manner the p-glycoprotein (Pgp)-mediated secretion of a fluorescent cyclosporin A derivative (NBDL-CS) and the mrp2-mediated secretion of fluorescein methotrexate (FL-MTX). This inhibition was not due to impaired metabolism or toxicity since octreotide had no influence on the active transport of fluorescein (FL), a substrate for the classical renal organic anion transport system. The data are consistent with octreotide being transported across the brush border membrane of proximal kidney tubules by both Pgp and mrp2. PMID:10694230

  16. Myelin-like structures seen intracellularly in renal tubule cells subjected to ischemia.

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    Yamada,Teruo

    1980-02-01

    Full Text Available Renal cortex was studied during experimentally induced ischemia. A transient increase in anerobic glycolysis occurred with concomitant swelling of both the Golgi apparatus and mitochondria. These intracytoplasmic organelles underwent marked changes in their intracellular positions. Infolding of cytoplasmic membrane at the basal side of proximal tubule cells increased in complexity and proceeded to enclose various intracytoplasmic microorganelles such as mitochondria and the Golgi apparatus. Piling up in layers was particularly marked around mitochondria. This piling up appeared as myelin-like structures on the free surface of, and within, proximal tubule cells, and followed disruption of the brush border at the free surface. Histological examination of thin sections showed that the fused portions of this brush border were actually brush border cytoplasmic membrane piled up in layers giving the appearance of myelin-like structures. After two hours of ischemia, parts of the membrane of these myelin-like structures were disrupted. Large vacuoles developed and these were thought to be related to the large vacuoles seen during cell degeneration.

  17. In vitro safety assessment of food ingredients in canine renal proximal tubule cells.

    Science.gov (United States)

    Koči, J; Jeffery, B; Riviere, J E; Monteiro-Riviere, N A

    2015-03-01

    In vitro models are useful tools to initially assess the toxicological safety hazards of food ingredients. Toxicities of cinnamaldehyde (CINA), cinnamon bark oil, lemongrass oil (LGO), thymol, thyme oil (TO), clove leaf oil, eugenol, ginger root extract (GRE), citric acid, guanosine monophosphate, inosine monophosphate and sorbose (SORB) were assessed in canine renal proximal tubule cells (CPTC) using viability assay and renal injury markers. At LC50, CINA was the most toxic (0.012mg/ml), while SORB the least toxic (>100mg/ml). Toxicities (LC50) of positive controls were as follows: 4-aminophenol (0.15mg/ml in CPTC and 0.083mg/ml in human PTC), neomycin (28.6mg/ml in CPTC and 27.1mg/ml in human PTC). XYL displayed lowest cytotoxic potency (LC50=82.7mg/ml in CPTC). In vivo renal injury markers in CPTC were not significantly different from controls. The LGO toxicity mechanism was analyzed using qPCR and electron microscopy. Out of 370 genes, 57 genes (15.4%) were significantly up (34, 9.1%) or down (23, 6.2%) regulated, with the most upregulated gene gsta3 (∼200-fold) and the most affected pathway being oxidative stress. LGO induced damage of mitochondria, phospholipid accumulation and lack of a brush border. Viability assays along with mechanistic studies in the CPTC model may serve as a valuable in vitro toxicity screening tool.

  18. Elucidation of the distal convoluted tubule transcriptome identifies new candidate genes involved in renal Mg2+ handling.

    NARCIS (Netherlands)

    Baaij, J.H.F. de; Groot Koerkamp, M.J.; Lavrijsen, M.; Zeeland, F. van; Meijer, H.; Holstege, F.C.; Bindels, R.J.M.; Hoenderop, J.G.J.

    2013-01-01

    The kidney plays a key role in the maintenance of Mg(2+) homeostasis. Specifically, the distal convoluted tubule (DCT) is instrumental in the fine-tuning of renal Mg(2+) handling. In recent years, hereditary Mg(2+) transport disorders have helped to identify important players in DCT Mg(2+) homeostas

  19. Thyroid hormone modulates ClC-2 chloride channel gene expression in rat renal proximal tubules.

    Science.gov (United States)

    Santos Ornellas, D; Grozovsky, R; Goldenberg, R C; Carvalho, D P; Fong, P; Guggino, W B; Morales, M

    2003-09-01

    Thyroid hormones has its main role in controlling metabolism, but it can also modulate extracellular fluid Volume (ECFV) through its action on the expression and activity of Na(+) transporters. Otherwise, chloride is the main anion in the ECFV and the influence of thyroid hormones in the regulation of chloride transporters is not yet understood. In this work, we studied the effect of thyroid hormones in the expression of ClC-2, a cell Volume-, pH- and voltage-sensitive Cl(-) channel, in rat kidney. To analyze the modulation of ClC-2 gene expression by thyroid hormones, we used hypothyroid (Hypo) rats with or without thyroxine (T(4)) replacement and hyperthyroid (Hyper) rats as our experimental models. Total RNA was isolated and the expression of ClC-2 mRNA was evaluated by a ribonuclease protection assay, and/or semi-quantitative RT-PCR. Renal ClC-2 expression decreased in Hypo rats and increased in Hyper rats. In addition, semi-quantitative RT-PCR of different nephron segments showed that these changes were due exclusively to the modulation of ClC-2 mRNA expression by thyroid hormone in convoluted and straight proximal tubules. To investigate whether thyroid hormones action was direct or indirect, renal proximal tubule primary culture cells were prepared and subjected to different T(4) concentrations. ClC-2 mRNA expression was increased by T(4) in a dose-dependent fashion, as analyzed by RT-PCR. Western blotting demonstrated that ClC-2 protein expression followed the same profile of mRNA expression.

  20. Induction of heme oxygenase-1 can halt and even reverse renal tubule-interstitial fibrosis.

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    Matheus Correa-Costa

    Full Text Available BACKGROUND: The tubule-interstitial fibrosis is the hallmark of progressive renal disease and is strongly associated with inflammation of this compartment. Heme-oxygenase-1 (HO-1 is a cytoprotective molecule that has been shown to be beneficial in various models of renal injury. However, the role of HO-1 in reversing an established renal scar has not yet been addressed. AIM: We explored the ability of HO-1 to halt and reverse the establishment of fibrosis in an experimental model of chronic renal disease. METHODS: Sprague-Dawley male rats were subjected to unilateral ureteral obstruction (UUO and divided into two groups: non-treated and Hemin-treated. To study the prevention of fibrosis, animals were pre-treated with Hemin at days -2 and -1 prior to UUO. To investigate whether HO-1 could reverse established fibrosis, Hemin therapy was given at days 6 and 7 post-surgery. After 7 and/or 14 days, animals were sacrificed and blood, urine and kidney tissue samples were collected for analyses. Renal function was determined by assessing the serum creatinine, inulin clearance, proteinuria/creatininuria ratio and extent of albuminuria. Arterial blood pressure was measured and fibrosis was quantified by Picrosirius staining. Gene and protein expression of pro-inflammatory and pro-fibrotic molecules, as well as HO-1 were performed. RESULTS: Pre-treatment with Hemin upregulated HO-1 expression and significantly reduced proteinuria, albuminuria, inflammation and pro-fibrotic protein and gene expressions in animals subjected to UUO. Interestingly, the delayed treatment with Hemin was also able to reduce renal dysfunction and to decrease the expression of pro-inflammatory molecules, all in association with significantly reduced levels of fibrosis-related molecules and collagen deposition. Finally, TGF-β protein production was significantly lower in Hemin-treated animals. CONCLUSION: Treatment with Hemin was able both to prevent the progression of fibrosis and

  1. Mesenchymal stem cell-conditioned medium accelerates regeneration of human renal proximal tubule epithelial cells after gentamicin toxicity.

    Science.gov (United States)

    Moghadasali, Reza; Mutsaers, Henricus A M; Azarnia, Mahnaz; Aghdami, Nasser; Baharvand, Hossein; Torensma, Ruurd; Wilmer, Martijn J G; Masereeuw, Rosalinde

    2013-07-01

    Bone marrow-derived mesenchymal stem cells (MSCs) have the capacity to regenerate renal tubule epithelia and repair renal function without fusing with resident tubular cells. The goal of the present project was to investigate the role of MSCs secreted cytokines on tubule cell viability and regeneration after a toxic insult, using a conditionally immortalized human proximal tubule epithelial cell (ciPTEC) line. Gentamicin was used to induce nephrotoxicity, and cell viability and migration were studied in absence and presence of human MSC-conditioned medium (hMSC-CM) i.e. medium containing soluble factors produced and secreted by MSCs. Exposure of ciPTEC to 0-3000 μg/ml gentamicin for 24 h caused a significant dose-dependent increase in cell death. We further demonstrated that the nephrotoxic effect of 2000 μg/ml gentamicin was recovered partially by exposing cells to hMSC-CM. Moreover, exposure of ciPTEC to gentamicin (1500-3000 μg/ml) for 7 days completely attenuated the migratory capacity of the cells. In addition, following scrape-wounding, cell migration of both untreated and gentamicin-exposed cells was increased in the presence of hMSC-CM, as compared to exposures to normal medium, indicating improved cell recovery. Our data suggest that cytokines secreted by MSCs stimulate renal tubule cell regeneration after nephrotoxicity. Copyright © 2012 Elsevier GmbH. All rights reserved.

  2. Relationship between gingival hyperplasia and class II histocompatibility antigens in renal transplant recipients.

    Science.gov (United States)

    Türkmen, A; Ak, G; Furuncuoglu, Y; Akar, U; Seyhun, Y; Türk, S; Carin, M; Sever, M S

    2000-01-01

    Gingival hyperplasia, a well-known side effect of ciclosporin A (CS-A), is much more prominent when CS-A is used in combination with calcium channel blockers, especially dihydropyridines. On the other hand, it is interesting to note that this complication is not observed in all patients using this drug combination. This study was conducted in order to investigate the relationship (if any) between major histocompatibility complex antigens and gingival hyperplasia. Seventy-six renal transplantation patients were evaluated by an experienced dentist for gingival hyperplasia. The patients were then divided into two groups according to the presence (group 1, n = 18) or absence (group 2, n = 58) of gingival hyperplasia. There was no significant difference between the two groups regarding age, sex, transplant age, donor type, antihypertensive and immunosuppressive therapy protocols, and CS-A levels. HLA-DR2 antigen was present in 63% of the patients with gingival hyperplasia and in 34% of the patients without gingival hyperplasia. However, the HLA-DR1 antigen frequencies were found to be 11 and 22% in group 1 and group 2, respectively. In patients receiving nifedipine as an antihypertensive therapy, gingival hyperplasia developed more often than in patients receiving verapamil or diltiazem. As a result, in renal allograft recipients with HLA-DR1 antigen, gingival hyperplasia was seen less frequently than in HLA-DR2-positive patients. It is believed that the presence of these antigens regulates the response of the patients to either CS-A and/or calcium channel blockers.

  3. Malformations of the epididymis, incomplete regression of the mesonephric tubules and hyperplasia of Leydig cells in canine persistence of Müllerian duct syndrome.

    Science.gov (United States)

    Whyte, Ana; Monteagudo, Luis V; Díaz-Otero, Angel; Lebrero, M Eugenia; Tejedor, M Teresa; Falceto, M Victoria; Whyte, Jaime; Gallego, Margarita

    2009-10-01

    Persistence of the Müllerian duct syndrome (PMDS) is a rare form of pseudohermaphroditism characterized by the presence of uterus and oviducts in otherwise normally differentiated SRY-positive 78 XY canine males. Undescended testicles are also common. We report a case of a male PMDS dog with a uterus and bilateral cryptorchidism. The dog had an incomplete regression of the mesonephric tubules. As a consequence of this an abnormally enlarged head of the epididymis was observed. In addition, an extreme reduction in size of both the body and the tail was found. Microscopic examination of both testicles revealed bilateral hyperplasia of Leydig cells. The progesterone blood level was measured by ELISA and was found to be abnormally high (3.18 ng/ml) compared to that of normal male dogs (lower than 1 ng/ml). Three months after surgical removal of the internal genitalia, the serum progesterone, testosterone and oestradiol levels were normal for a castrated male dog.

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

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Senyan [Kidney Institute and Division of Nephrology, Changzheng Hospital, Shanghai 200003 (China); Wadsworth Center, New York State Department of Health, and School of Public Health, State University of New York, Albany, NY 12201 (United States); Yao, Yunyi; Lu, Shijun; Aldous, Kenneth; Ding, Xinxin [Wadsworth Center, New York State Department of Health, and School of Public Health, State University of New York, Albany, NY 12201 (United States); Mei, Changlin, E-mail: chlmei1954@126.com [Kidney Institute and Division of Nephrology, Changzheng Hospital, Shanghai 200003 (China); Gu, Jun, E-mail: jungu@wadsworth.org [Wadsworth Center, New York State Department of Health, and School of Public Health, State University of New York, Albany, NY 12201 (United States)

    2013-10-01

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

  5. Proteomic profiling and pathway analysis of the response of rat renal proximal convoluted tubules to metabolic acidosis.

    Science.gov (United States)

    Schauer, Kevin L; Freund, Dana M; Prenni, Jessica E; Curthoys, Norman P

    2013-09-01

    Metabolic acidosis is a relatively common pathological condition that is defined as a decrease in blood pH and bicarbonate concentration. The renal proximal convoluted tubule responds to this condition by increasing the extraction of plasma glutamine and activating ammoniagenesis and gluconeogenesis. The combined processes increase the excretion of acid and produce bicarbonate ions that are added to the blood to partially restore acid-base homeostasis. Only a few cytosolic proteins, such as phosphoenolpyruvate carboxykinase, have been determined to play a role in the renal response to metabolic acidosis. Therefore, further analysis was performed to better characterize the response of the cytosolic proteome. Proximal convoluted tubule cells were isolated from rat kidney cortex at various times after onset of acidosis and fractionated to separate the soluble cytosolic proteins from the remainder of the cellular components. The cytosolic proteins were analyzed using two-dimensional liquid chromatography and tandem mass spectrometry (MS/MS). Spectral counting along with average MS/MS total ion current were used to quantify temporal changes in relative protein abundance. In all, 461 proteins were confidently identified, of which 24 exhibited statistically significant changes in abundance. To validate these techniques, several of the observed abundance changes were confirmed by Western blotting. Data from the cytosolic fractions were then combined with previous proteomic data, and pathway analyses were performed to identify the primary pathways that are activated or inhibited in the proximal convoluted tubule during the onset of metabolic acidosis.

  6. Proteomic profiling and pathway analysis of the response of rat renal proximal convoluted tubules to metabolic acidosis

    Science.gov (United States)

    Schauer, Kevin L.; Freund, Dana M.; Prenni, Jessica E.

    2013-01-01

    Metabolic acidosis is a relatively common pathological condition that is defined as a decrease in blood pH and bicarbonate concentration. The renal proximal convoluted tubule responds to this condition by increasing the extraction of plasma glutamine and activating ammoniagenesis and gluconeogenesis. The combined processes increase the excretion of acid and produce bicarbonate ions that are added to the blood to partially restore acid-base homeostasis. Only a few cytosolic proteins, such as phosphoenolpyruvate carboxykinase, have been determined to play a role in the renal response to metabolic acidosis. Therefore, further analysis was performed to better characterize the response of the cytosolic proteome. Proximal convoluted tubule cells were isolated from rat kidney cortex at various times after onset of acidosis and fractionated to separate the soluble cytosolic proteins from the remainder of the cellular components. The cytosolic proteins were analyzed using two-dimensional liquid chromatography and tandem mass spectrometry (MS/MS). Spectral counting along with average MS/MS total ion current were used to quantify temporal changes in relative protein abundance. In all, 461 proteins were confidently identified, of which 24 exhibited statistically significant changes in abundance. To validate these techniques, several of the observed abundance changes were confirmed by Western blotting. Data from the cytosolic fractions were then combined with previous proteomic data, and pathway analyses were performed to identify the primary pathways that are activated or inhibited in the proximal convoluted tubule during the onset of metabolic acidosis. PMID:23804448

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

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    Peiying Yu

    2014-01-01

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

  8. The caspase 3 sensor Phiphilux G2D2 is activated non-specifically in S1 renal proximal tubules

    Science.gov (United States)

    Hato, Takashi; Sandoval, Ruben; Dagher, Pierre C

    2016-01-01

    Tubular cell apoptosis is a major phenotype of cell death in various forms of acute kidney injury. Quantifying apoptosis in fixed tissues is problematic because apoptosis evolves over time and dead cells are rapidly cleared by the phagocytic system. Phiphilux is a fluorescent probe that is activated specifically by caspase 3 and does not inhibit the subsequent activity of this effector caspase. It has been used successfully to quantify apoptosis in cell culture. Here we examined the feasibility of using Phiphilux to measure renal tubular apoptosis progression over time in live animals using intravital 2-photon microscopy. Our results show that Phiphilux can detect apoptosis in S2 tubules but is activated non-specifically in S1 tubules.

  9. Adeno-Associated Virus-Mediated Gene Transfer to Renal Tubule Cells via a Retrograde Ureteral Approach

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    Daniel C. Chung

    2011-11-01

    Full Text Available Background/Aims: Gene therapy involves delivery of exogenous DNA to provide a therapeutic protein. Ideally, a gene therapy vector should be non-toxic, non-immunogenic, easy to produce, and efficient in protecting and delivering DNA into target cells. Methods: Adeno-associated virus (AAV offers these advantages and few, if any, disadvantages, and over 100 isolates exist. We previously showed that AAV-mediated gene therapy can be used to restore vision to patients with Leber’s congenital amaurosis, a disease of childhood blindness. Results: Here we show that novel recombinant AAV2/8 and AAV2/9 transduce kidney tubule cells with high efficiency both in vitroin cell culture and in vivoin mice. In addition, we adapted and modified a retrograde approach to allow for optimal transgene delivery to renal tubular cells that further minimizes the risk of an immunogenic reaction. Conclusions: We believe that recombinant AAV2, especially AAV2/8, gene delivery to renal tubule cells via a retrograde approach represents a viable method for gene therapy for a multitude of renal disorders ranging from autosomal dominant polycystic kidney disease to acute kidney injury.

  10. Insulin production and signaling in renal tubules of Drosophila is under control of tachykinin-related peptide and regulates stress resistance.

    Directory of Open Access Journals (Sweden)

    Jeannette A E Söderberg

    Full Text Available The insulin-signaling pathway is evolutionarily conserved in animals and regulates growth, reproduction, metabolic homeostasis, stress resistance and life span. In Drosophila seven insulin-like peptides (DILP1-7 are known, some of which are produced in the brain, others in fat body or intestine. Here we show that DILP5 is expressed in principal cells of the renal tubules of Drosophila and affects survival at stress. Renal (Malpighian tubules regulate water and ion homeostasis, but also play roles in immune responses and oxidative stress. We investigated the control of DILP5 signaling in the renal tubules by Drosophila tachykinin peptide (DTK and its receptor DTKR during desiccative, nutritional and oxidative stress. The DILP5 levels in principal cells of the tubules are affected by stress and manipulations of DTKR expression in the same cells. Targeted knockdown of DTKR, DILP5 and the insulin receptor dInR in principal cells or mutation of Dilp5 resulted in increased survival at either stress, whereas over-expression of these components produced the opposite phenotype. Thus, stress seems to induce hormonal release of DTK that acts on the renal tubules to regulate DILP5 signaling. Manipulations of S6 kinase and superoxide dismutase (SOD2 in principal cells also affect survival at stress, suggesting that DILP5 acts locally on tubules, possibly in oxidative stress regulation. Our findings are the first to demonstrate DILP signaling originating in the renal tubules and that this signaling is under control of stress-induced release of peptide hormone.

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

    Science.gov (United States)

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

    2014-12-01

    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.

  12. The paradox of dopamine and angiotensin II-mediated Na(+), K(+)-ATPase regulation in renal proximal tubules.

    Science.gov (United States)

    Zhang, Linan; Guo, Fang; Guo, Huicai; Wang, Haiyan; Zhang, Zhe; Liu, Xu; Shi, Xiaolu; Gou, Xiangbo; Su, Qian; Yin, Jian; Wang, Yongli

    2010-01-01

    Accumulated studies reported that the natruretic dopamine (DA) and the anti-natruretic angiotensin II (Ang II) represent an important mechanism to regulate renal Na(+) and water excretion through intracellular secondary messengers to inhibit or activate renal proximal tubule (PT) Na(+), K(+)-ATPase (NKA). The antagonistic actions were mediated by the phosphorylation of different position of NKA α₁-subunit and different Pals-associated tight junction protein (PATJ) PDZ domains, the different protein kinase C (PKC) isoforms (PKC-β, PKC-ζ), the common adenylyl cyclase (AC) pathway, and the crosstalk and balance between DA and Ang II to NKA regulation. Besides, Ang II-mediated NKA modulation has bi-phasic effects.

  13. 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

  14. Effect of radiologic contrast material on cell volume regulation in proximal renal tubules from trout (Salmo trutta).

    Science.gov (United States)

    Galtung, H K; Løken, M; Sakariassen, K S

    2000-11-01

    Most radiographic contrast media (CM) are hyperosmotic and pose an osmotic threat to cells they are in contact with. To study these effects at the cellular level, cell volume regulatory mechanisms were observed in proximal renal tubules following exposure to the CM iohexol, ioxaglate, and iodixanol. Isolated renal tubules from trout (Salmo trutta) were exposed to 5% vol/vol iohexol (326 mOsm), ioxaglate (314 mOsm), or iodixanol (300 mOsm) or mannitol (to achieve the same osmolalities), and cell volume changes were observed videometrically. Iohexol and ioxaglate solutions induced a rapid shrinkage (12%-13%) not followed by cell volume regulation. Without CM (same osmolality), the cells shrank 11% but then showed a 77%-88% volume recovery. This reswelling was inhibited by 55% with the Na+, K+, Cl- symporter inhibitor bumetanide (50 micromol/L). Iodixanol did not significantly affect cell volume. Tubules preincubated with CM or mannitol were then stimulated with a hypoosmotic Ringer solution (160 mOsm) resulting in a 26%-36% cellular volume increase. Compared with results of experiments without mannitol and CM, preexposure to iohexol or ioxaglate almost completely inhibited the expected regulatory shrinkage phase, while previous exposure to hyperosmotic solutions with mannitol reduced the shrinkage response by 40%-53%. In this system, the hyperosmotic iohexol and ioxaglate cause cell shrinkage followed by an impaired cell volume regulatory response. Exposure to these two CM also inhibits cell volume regulation on hypoosmotic stimulation. The isosmotic iodixanol has no such effects. These changes appear to some extent to be a result of the CM's degree of hyperosmolality, but this property alone does not explain these findings.

  15. Activation of D4 dopamine receptor decreases angiotensin II type 1 receptor expression in rat renal proximal tubule cells.

    Science.gov (United States)

    Chen, Ken; Deng, Kun; Wang, Xiaoyan; Wang, Zhen; Zheng, Shuo; Ren, Hongmei; He, Duofen; Han, Yu; Asico, Laureano D; Jose, Pedro A; Zeng, Chunyu

    2015-01-01

    The dopaminergic and renin-angiotensin systems interact to regulate blood pressure. Disruption of the D4 dopamine receptor gene in mice produces hypertension that is associated with increased renal angiotensin type 1 (AT1) receptor expression. We hypothesize that the D4 receptor can inhibit AT1 receptor expression and function in renal proximal tubule cells from Wistar-Kyoto (WKY) rats, but the D4 receptor regulation of AT1 receptor is aberrant in renal proximal tubule cells from spontaneously hypertensive rats (SHRs). The D4 receptor agonist, PD168077, decreased AT1 receptor protein expression in a time- and concentration-dependent manner in WKY cells. By contrast, in SHR cells, PD168077 increased AT1 receptor protein expression. The inhibitory effect of D4 receptor on AT1 receptor expression in WKY cells was blocked by a calcium channel blocker, nicardipine, or calcium-free medium, indicating that calcium is involved in the D4 receptor-mediated signaling pathway. Angiotensin II increased Na(+)-K(+) ATPase activity in WKY cells. Pretreatment with PD168077 decreased the stimulatory effect of angiotensin II on Na(+)-K(+) ATPase activity in WKY cells. In SHR cells, the inhibitory effect of D4 receptor on angiotensin II-mediated stimulation of Na(+)-K(+) ATPase activity was aberrant; pretreatment with PD168077 augmented the stimulatory effect of AT1 receptor on Na(+)-K(+) ATPase activity in SHR cells. This was confirmed in vivo; pretreatment with PD128077 for 1 week augmented the antihypertensive and natriuretic effect of losartan in SHRs but not in WKY rats. We suggest that an aberrant interaction between D4 and AT1 receptors may play a role in the abnormal regulation of sodium excretion in hypertension.

  16. A modified system for in vitro perfusion of isolated renal tubules.

    Science.gov (United States)

    Greger, R; Hampel, W

    1981-01-01

    A modified system for the in vitro perfusion of isolated tubule segments is presented. The system consists of four holders each of which carries an acrylic cylinder. The acrylic cylinders are used to fix the glass pipettes in a concentric position. The four holders are mounted onto a support consisting of two holding pieces and three steel rods. Three of the holders contain ball-races so that they can slide on the rods with high accuracy and little friction. The holders to which the sylgard pipette and the perfusion pipette are attached are moved by electric motors. Compared with the classical V-track system this modification has the advantage of higher precision. Once the different pipettes are centered, concentricity is maintained even when the pipettes are moved forward or backward. Thus, this equipment facilitates the cannulation of tubules and increases the number of successful experiments.

  17. Dapagliflozin Binds Specifically to Sodium-Glucose Cotransporter 2 in the Proximal Renal Tubule.

    Science.gov (United States)

    Ghezzi, Chiara; Yu, Amy S; Hirayama, Bruce A; Kepe, Vladimir; Liu, Jie; Scafoglio, Claudio; Powell, David R; Huang, Sung-Cheng; Satyamurthy, Nagichettiar; Barrio, Jorge R; Wright, Ernest M

    2017-03-01

    Kidneys contribute to glucose homeostasis by reabsorbing filtered glucose in the proximal tubules via sodium-glucose cotransporters (SGLTs). Reabsorption is primarily handled by SGLT2, and SGLT2-specific inhibitors, including dapagliflozin, canagliflozin, and empagliflozin, increase glucose excretion and lower blood glucose levels. To resolve unanswered questions about these inhibitors, we developed a novel approach to map the distribution of functional SGLT2 proteins in rodents using positron emission tomography with 4-[(18)F]fluoro-dapagliflozin (F-Dapa). We detected prominent binding of intravenously injected F-Dapa in the kidney cortexes of rats and wild-type and Sglt1-knockout mice but not Sglt2-knockout mice, and injection of SGLT2 inhibitors prevented this binding. Furthermore, imaging revealed only low levels of F-Dapa in the urinary bladder, even after displacement of kidney binding with dapagliflozin. Microscopic ex vitro autoradiography of kidney showed F-Dapa binding to the apical surface of early proximal tubules. Notably, in vivo imaging did not show measureable specific binding of F-Dapa in heart, muscle, salivary glands, liver, or brain. We propose that F-Dapa is freely filtered by the kidney, binds to SGLT2 in the apical membranes of the early proximal tubule, and is subsequently reabsorbed into blood. The high density of functional SGLT2 transporters detected in the apical membrane of the proximal tubule but not detected in other organs likely accounts for the high kidney specificity of SGLT2 inhibitors. Overall, these data are consistent with data from clinical studies on SGLT2 inhibitors and provide a rationale for the mode of action of these drugs. Copyright © 2017 by the American Society of Nephrology.

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

    Energy Technology Data Exchange (ETDEWEB)

    Chatton, J.Y.; Roch-Ramel, F. (Institut de Pharmacologie, Lausanne (Switzerland))

    1991-03-01

    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 ({sup 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.

  19. Mode of Action: Oxalate Crystal-Induced Renal Tubule Degeneration and Glycolic Acid-Induced Dysmorphogenesis—Renal and Developmental Effects of Ethylene Glycol

    Energy Technology Data Exchange (ETDEWEB)

    Corley, Rick A.; Meek, M E.; Carney, E W.

    2005-10-01

    Ethylene glycol can cause both renal and developmental toxicity, with metabolism playing a key role in the mode of action (MOA) for each form of toxicity. Renal toxicity is ascribed to the terminal metabolite oxalic acid, which precipitates in the kidney in the form of calcium oxalate crystals and is believed to cause physical damage to the renal tubules. The human relevance of the renal toxicity of ethylene glycol is indicated by the similarity between animals and humans of metabolic pathways, the observation of renal oxalate crystals in toxicity studies in experimental animals and human poisonings, and cases of human kidney and bladder stones related to dietary oxalates and oxalate precursors. High-dose gavage exposures to ethylene glycol also cause axial skeletal defects in rodents (but not rabbits), with the intermediary metabolite, glycolic acid, identified as the causative agent. However, the mechanism by which glycolic acid perturbs development has not been investigated sufficiently to develop a plausible hypothesis of mode of action, nor have any cases of ethylene glycol-induced developmental effects been reported in humans. Given this, and the variations in sensitivity between animal species in response, the relevance to humans of ethylene glycol-induced developmental toxicity in animals is unknown at this time.

  20. Silencing megalin and cubilin genes inhibits myeloma light chain endocytosis and ameliorates toxicity in human renal proximal tubule epithelial cells.

    Science.gov (United States)

    Li, Min; Balamuthusamy, Saravanan; Simon, Eric E; Batuman, Vecihi

    2008-07-01

    Using target-specific short interfering (si) RNAs, we silenced the tandem endocytic receptors megalin and cubilin genes in cultured human renal proximal tubule epithelial cells. Transfection by siRNA resulted in up to 90% suppression of both megalin and cubilin protein and mRNA expression. In HK-2 cells exposed to kappa-light chain for up to 24 h, light chain endocytosis was reduced in either megalin- or cubilin-silenced cells markedly but incompletely. Simultaneous silencing of both the cubilin and megalin genes, however, resulted in near-complete inhibition of light chain endocytosis, as determined by measuring kappa-light chain protein concentration in cell cytoplasm and by flow cytometry using FITC-labeled kappa-light chain. In these cells, light chain-induced cytokine responses (interleukin-6 and monocyte chemoattractant protein-1) and epithelial-to-mesenchymal transition as well as the associated cellular and morphological alterations were also markedly suppressed. The results demonstrate that light chain endocytosis is predominantly mediated by the megalin-cubilin tandem endocytic receptor and identify endocytosis as a key step in light chain cytotoxicity. Blocking light chain endocytosis prevents its nephrotoxic effects on human kidney proximal tubule cells.

  1. Megalin is essential for renal proximal tubule reabsorption and accumulation of transcobalamin-B(12)

    DEFF Research Database (Denmark)

    Birn, Henrik; Willnow, Thomas E; Nielsen, Rikke;

    2002-01-01

    Megalin has previously been shown to bind and mediate endocytosis of transcobalamin (TC)-B(12). However, the physiological significance of this has not been established, and other TC-B(12) binding proteins have been suggested to mediate renal uptake of this vitamin complex. The present study...... demonstrates by the use of megalin-deficient mice that megalin is, in fact, essential for the normal renal reabsorption of TC-vitamin B(12) and for renal accumulation of this highly conserved vitamin. Megalin-deficient mice excrete increased amounts of TC and B(12) in the urine, revealing a defective renal...... tubular uptake of TC-B(12). The urinary B(12) excretion is increased approximately 4-fold, resulting in an approximately 28-fold higher renal B(12) clearance. This is associated with an approximately 4-fold decrease in B(12) content in megalin-deficient kidney cortex. Thus megalin is important to prevent...

  2. Exocyst Sec10 protects renal tubule cells from injury by EGFR/MAPK activation and effects on endocytosis.

    Science.gov (United States)

    Fogelgren, Ben; Zuo, Xiaofeng; Buonato, Janine M; Vasilyev, Aleksandr; Baek, Jeong-In; Choi, Soo Young; Chacon-Heszele, Maria F; Palmyre, Aurélien; Polgar, Noemi; Drummond, Iain; Park, Kwon Moo; Lazzara, Matthew J; Lipschutz, Joshua H

    2014-12-15

    Acute kidney injury is common and has a high mortality rate, and no effective treatment exists other than supportive care. Using cell culture models, we previously demonstrated that exocyst Sec10 overexpression reduced damage to renal tubule cells and speeded recovery and that the protective effect was mediated by higher basal levels of mitogen-activated protein kinase (MAPK) signaling. The exocyst, a highly-conserved eight-protein complex, is known for regulating protein trafficking. Here we show that the exocyst biochemically interacts with the epidermal growth factor receptor (EGFR), which is upstream of MAPK, and Sec10-overexpressing cells express greater levels of phosphorylated (active) ERK, the final step in the MAPK pathway, in response to EGF stimulation. EGFR endocytosis, which has been linked to activation of the MAPK pathway, increases in Sec10-overexpressing cells, and gefitinib, a specific EGFR inhibitor, and Dynasore, a dynamin inhibitor, both reduce EGFR endocytosis. In turn, inhibition of the MAPK pathway reduces ligand-mediated EGFR endocytosis, suggesting a potential feedback of elevated ERK activity on EGFR endocytosis. Gefitinib also decreases MAPK signaling in Sec10-overexpressing cells to levels seen in control cells and, demonstrating a causal role for EGFR, reverses the protective effect of Sec10 overexpression following cell injury in vitro. Finally, using an in vivo zebrafish model of acute kidney injury, morpholino-induced knockdown of sec10 increases renal tubule cell susceptibility to injury. Taken together, these results suggest that the exocyst, acting through EGFR, endocytosis, and the MAPK pathway is a candidate therapeutic target for acute kidney injury.

  3. 5-Lypoxygenase products are involved in renal tubulointerstitial injury induced by albumin overload in proximal tubules in mice.

    Directory of Open Access Journals (Sweden)

    Sharon Schilling Landgraf

    Full Text Available The role of albumin overload in proximal tubules (PT in the development of tubulointerstitial injury and, consequently, in the progression of renal disease has become more relevant in recent years. Despite the importance of leukotrienes (LTs in renal disease, little is known about their role in tubulointerstitial injury. The aim of the present work was to investigate the possible role of LTs on tubulointerstitial injury induced by albumin overload. An animal model of tubulointerstitial injury challenged by bovine serum albumin was developed in SV129 mice (wild-type and 5-lipoxygenase-deficient mice (5-LO(-/-. The changes in glomerular morphology and nestin expression observed in wild-type mice subjected to kidney insult were also observed in 5-LO(-/- mice. The levels of urinary protein observed in the 5-LO(-/- mice subjected or not to kidney insult were lower than those observed in respective wild-type mice. Furthermore, the increase in lactate dehydrogenase activity, a marker of tubule damage, observed in wild-type mice subjected to kidney insult did not occur in 5-LO(-/- mice. LTB4 and LTD4, 5-LO products, decreased the uptake of albumin in LLC-PK1 cells, a well-characterized porcine PT cell line. This effect correlated with activation of protein kinase C and inhibition of protein kinase B. The level of proinflammatory cytokines, tumor necrosis factor-α and interleukin (IL-6, increased in mice subjected to kidney insult but this effect was not modified in 5-LO(-/- mice. However, 5-LO(-/- mice subjected to kidney insult presented lower macrophage infiltration and higher levels of IL-10 than wild-type mice. Our results reveal that LTs have an important role in tubulointerstitial disease induced by albumin overload.

  4. 5-Lypoxygenase products are involved in renal tubulointerstitial injury induced by albumin overload in proximal tubules in mice.

    Science.gov (United States)

    Landgraf, Sharon Schilling; Silva, Leandro Souza; Peruchetti, Diogo Barros; Sirtoli, Gabriela Modenesi; Moraes-Santos, Felipe; Portella, Viviane Gomes; Silva-Filho, João Luiz; Pinheiro, Carla Silva; Abreu, Thiago Pereira; Takiya, Christina Maeda; Benjamin, Claudia Farias; Pinheiro, Ana Acacia Sá; Canetti, Claudio; Caruso-Neves, Celso

    2014-01-01

    The role of albumin overload in proximal tubules (PT) in the development of tubulointerstitial injury and, consequently, in the progression of renal disease has become more relevant in recent years. Despite the importance of leukotrienes (LTs) in renal disease, little is known about their role in tubulointerstitial injury. The aim of the present work was to investigate the possible role of LTs on tubulointerstitial injury induced by albumin overload. An animal model of tubulointerstitial injury challenged by bovine serum albumin was developed in SV129 mice (wild-type) and 5-lipoxygenase-deficient mice (5-LO(-/-)). The changes in glomerular morphology and nestin expression observed in wild-type mice subjected to kidney insult were also observed in 5-LO(-/-) mice. The levels of urinary protein observed in the 5-LO(-/-) mice subjected or not to kidney insult were lower than those observed in respective wild-type mice. Furthermore, the increase in lactate dehydrogenase activity, a marker of tubule damage, observed in wild-type mice subjected to kidney insult did not occur in 5-LO(-/-) mice. LTB4 and LTD4, 5-LO products, decreased the uptake of albumin in LLC-PK1 cells, a well-characterized porcine PT cell line. This effect correlated with activation of protein kinase C and inhibition of protein kinase B. The level of proinflammatory cytokines, tumor necrosis factor-α and interleukin (IL)-6, increased in mice subjected to kidney insult but this effect was not modified in 5-LO(-/-) mice. However, 5-LO(-/-) mice subjected to kidney insult presented lower macrophage infiltration and higher levels of IL-10 than wild-type mice. Our results reveal that LTs have an important role in tubulointerstitial disease induced by albumin overload.

  5. Hepatitis B virus X protein promotes renal epithelial-mesenchymal transition in human renal proximal tubule epithelial cells through the activation of NF-κB.

    Science.gov (United States)

    Li, Mei; Hu, Liping; Zhu, Fengxin; Zhou, Zhangmei; Tian, Jianwei; Ai, Jun

    2016-08-01

    Hepatitis B virus (HBV)-associated glomerulo-nephritis is the most common extra-hepatic disorder occurring with hepatitis B virus infection. In the present study, we hypothesized that HBV X protein (HBx) may play a critical role in renal interstitial fibrosis, as HBx has been shown to induce epithelial-mesenchymal transition (EMT) in renal cells. For this purpose, we successfully transfected HBx plasmid into human renal proximal tubule epithelial cells (HK-2 cells). We found that transfection with HBx plasmid significantly downregulated E-cadherin expression and upregulated α-smooth muscle actin, collagen I and fibronectin expression in a time- and concentration-dependent manner (at the lower concentrations and earlier time points). HBx also increased nuclear factor-κB (NF-κB) phosphorylation in a time- and concentration-dependent manner (again at the lower concentrations and earlier time points); however, it did not alter the phosphorylation of Smad2, Smad3, p38, phosphoinositide 3-kinase (PI3K) or extracellular signal-regulated kinase (ERK). Thus, the findings of this study demonstrate that HBx promotes EMT in renal HK-2 cells, and the potential underlying mechanisms may involve the activation of the NF-κB signaling pathway.

  6. Renal proximal tubule Na,K-ATPase is controlled by CREB-regulated transcriptional coactivators as well as salt-inducible kinase 1.

    Science.gov (United States)

    Taub, Mary; Garimella, Sudha; Kim, Dongwook; Rajkhowa, Trivikram; Cutuli, Facundo

    2015-12-01

    Sodium reabsorption by the kidney is regulated by locally produced natriuretic and anti-natriuretic factors, including dopamine and norepinephrine, respectively. Previous studies indicated that signaling events initiated by these natriuretic and anti-natriuretic factors achieve their effects by altering the phosphorylation of Na,K-ATPase in the renal proximal tubule, and that protein kinase A (PKA) and calcium-mediated signaling pathways are involved. The same signaling pathways also control the transcription of the Na,K-ATPase β subunit gene atp1b1 in renal proximal tubule cells. In this report, evidence is presented that (1) both the recently discovered cAMP-regulated transcriptional coactivators (CRTCs) and salt-inducible kinase 1 (SIK1) contribute to the transcriptional regulation of atp1b1 in renal proximal tubule (RPT) cells and (2) renal effectors, including norepinephrine, dopamine, prostaglandins, and sodium, play a role. Exogenously expressed CRTCs stimulate atp1b1 transcription. Evidence for a role of endogenous CRTCs includes the loss of transcriptional regulation of atp1b1 by a dominant-negative CRTC, as well as by a CREB mutant, with an altered CRTC binding site. In a number of experimental systems, SIK phosphorylates CRTCs, which are then sequestered in the cytoplasm, preventing their nuclear effects. Consistent with such a role of SIK in primary RPT cells, atp1b1 transcription increased in the presence of a dominant-negative SIK1, and in addition, regulation by dopamine, norepinephrine, and monensin was disrupted by a dominant-negative SIK1. These latter observations can be explained if SIK1 is phosphorylated and inactivated in the presence of these renal effectors. Our results support the hypothesis that Na,K-ATPase in the renal proximal tubule is regulated at the transcriptional level via SIK1 and CRTCs by renal effectors, in addition to the previously reported control of the phosphorylation of Na,K-ATPase.

  7. Astragalus membranaceus reduces free radical-mediated injury to renal tubules in rabbits receiving high-energy shock waves

    Institute of Scientific and Technical Information of China (English)

    SHENG Bin-wu; CHEN Xing-fa; ZHAO Jun; HE Da-lin; NAN Xun-yi

    2005-01-01

    Background Recent studies have revealed the important role of free radicals in renal damage induced by high-energy shock waves (HESW). This study aimed at investigating the effects of Astragalus membranaceus, a traditional Chinese medicinal herb, on free radical-mediated HESW-induced damage to renal tubules in a live rabbit model.Methods Forty-five healthy male New Zealand white rabbits were randomly divided into three groups: control group (n=15), sham group (n=15), and herb-treated group (n=15). Three days prior to HESW application, the controls received verapamil (0.4 mg/kg), the shams received physiological saline (20 ml), and the herb-treated animals received Astragalus membranaceus (2.4 g/kg) intravenously. HESW (1500 shocks, 18kV) was applied to the right kidneys of all anesthetized rabbits. We measured superoxide dismutase (SOD) and malondialdehyde (MDA) levels before and after shock treatment in blood and kidney homogenates. Histopathological changes were also observed.Results MDA levels increased and SOD activity decreased significantly in the sham group (P0.05). SOD values were significantly higher in the controls than in the shams (P<0.05). By contrast, SOD levels recovered rapidly in the rabbits receiving Astragalus membranaceus, reaching a nadir within 24 hours, and returning to baseline more quickly than in control and sham rabbits (P<0.05). Histopathological examinations showed that renal tubular damage in the controls was less severe than in the shams, while damage in the Astragalus membranaceus group was even more mild, with rapid recovery in comparison with the controls.Conclusion This study provides preliminary evidence indicating that Astragalus membranaceus has strong protective effects on free radical-mediated renal tubular damage induced by HESW and that these effects are superior to the effects of verapamil.

  8. Renal tubule-specific expression and urinary secretion of human growth hormone: a kidney-based transgenic bioreactor growth.

    Science.gov (United States)

    Zhu, Xinhua; Cheng, Jin; Huang, Liwei; Gao, Jin; Zhang, Zhong-Ting; Pak, Joanne; Wu, Xue-Ru

    2003-04-01

    Tissue-specific expression of human genes and secretion of human proteins into the body fluids in transgenic animals provides an important means of manufacturing large-quantity and high-quality pharmaceuticals. The present study demonstrates using transgenic mice that a 3.0 kb promoter of the mouse Tamm-Horsfall protein (THP, or uromodulin) gene directs the specific expression of human growth hormone (hGH) gene in the kidney followed by the secretion of hGH protein into the urine. hGH expression was detected in renal tubules that actively produce the THP, that is, the ascending limb of Henle's loop and distal convoluted tubules. Up to 500 ng/ml of hGH was detected in the urine, and this level remained constant throughout the 10-month observation period. hGH was also detectable in the stomach epithelium and serum in two of the transgenic lines, suggesting position-dependent effects of the transgene and leakage of hGH from the site of synthesis into the bloodstream, respectively. These results indicate that the 3.0 kb mouse THP promoter is primarily kidney-specific and can be used to convert kidney into a bioreactor in transgenic animals to produce recombinant proteins. Given the capacity of urine production independent of age, sex and lactation, the ease of urinary protein purification, and the potentially distinct machinery for post-translational modifications in the kidney epithelial cells, the kidney-based transgenic bioreactor may offer unique opportunities for producing certain complex pharmaceuticals.

  9. 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

  10. Single-nucleotide polymorphisms of the dopamine D2 receptor increase inflammation and fibrosis in human renal proximal tubule cells.

    Science.gov (United States)

    Jiang, Xiaoliang; Konkalmatt, Prasad; Yang, Yu; Gildea, John; Jones, John E; Cuevas, Santiago; Felder, Robin A; Jose, Pedro A; Armando, Ines

    2014-03-01

    The dopamine D2 receptor (D2R) negatively regulates inflammation in mouse renal proximal tubule cells (RPTCs), and lack or downregulation of the receptor in mice increases the vulnerability to renal inflammation independent of blood pressure. Some common single-nucleotide polymorphisms (SNPs; rs6276, rs6277, and rs1800497) in the human DRD2 gene are associated with decreased D2R expression and function, as well as high blood pressure. We tested the hypothesis that human RPTCs (hRPTCs) expressing these SNPs have increased expression of inflammatory and injury markers. We studied immortalized hRPTCs carrying D2R SNPs and compared them with cells carrying no D2R SNPs. RPTCs with D2R SNPs had decreased D2R expression and function. The expressions of the proinflammatory tumor necrosis factor-α and the profibrotic transforming growth factor-β1 and its signaling targets Smad3 and Snail1 were increased in hRPTC with D2R SNPs. These cells also showed induction of epithelial mesenchymal transition and production of extracellular matrix proteins, assessed by increased vimentin, fibronectin 1, and collagen I a1. To test the specificity of these D2R SNP effects, hRPTC with D2R SNPs were transfected with a plasmid encoding wild-type DRD2. The expression of D2R was increased and that of transforming growth factor-β1, Smad3, Snail1, vimentin, fibronectin 1, and collagen I a1 was decreased in hRPTC with D2R SNPs transfected with wild-type DRD2 compared with hRPTC-D2R SNP transfected with empty vector. These data support the hypothesis that D2R function has protective effects in hRPTCs and suggest that carriers of these SNPs may be prone to chronic renal disease and high blood pressure.

  11. Acute leptin exposure reduces megalin expression and upregulates TGFβ1 in cultured renal proximal tubule cells.

    Science.gov (United States)

    Briffa, Jessica F; Grinfeld, Esther; Mathai, Michael L; Poronnik, Phillip; McAinch, Andrew J; Hryciw, Deanne H

    2015-02-05

    Increased leptin concentrations observed in obesity can lead to proteinuria, suggesting that leptin may play a role in obesity-related kidney disease. Obesity reduces activation of AMP-activated protein kinase (AMPK) and increases transforming growth factor-β1 (TGF-β1) expression in the kidney, leading to albuminuria. Thus we investigated if elevated leptin altered AMPK and TGF-β1 signaling in proximal tubule cells (PTCs). In opossum kidney (OK) PTCs Western blot analysis demonstrated that leptin upregulates TGF-β1 secretion (0.50 µg/ml) and phosphorylated AMPKα (at 0.25, and 0.50 µg/ml), and downregulates megalin expression at all concentrations (0.05-0.50 µg/ml). Using the AMPK inhibitor, Compound C, leptin exposure regulated TGF-β1 expression and secretion in PTCs via an AMPK mediated pathway. In addition, elevated leptin exposure (0.50 µg/ml) reduced albumin handling in OK cells independently of megalin expression. This study demonstrates that leptin upregulates TGF-β1, reduces megalin, and reduces albumin handling in PTCs by an AMPK mediated pathway.

  12. Characterization of FGF23-Dependent Egr-1 Cistrome in the Mouse Renal Proximal Tubule.

    Directory of Open Access Journals (Sweden)

    Anthony A Portale

    Full Text Available Fibroblast growth factor 23 (FGF23 is a potent regulator of phosphate (Pi and vitamin D homeostasis. The transcription factor, early growth response 1 (egr-1, is a biomarker for FGF23-induced activation of the ERK1/2 signaling pathway. We have shown that ERK1/2 signaling blockade suppresses renal egr-1 gene expression and prevents FGF23-induced hypophosphatemia and 1,25-dihydroxyvitamin D (1,25(OH2D suppression in mice. To test whether egr-1 itself mediates these renal actions of FGF23, we administered FGF23 to egr-1-/- and wild-type (WT mice. In WT mice, FGF23 induced hypophosphatemia and suppressed expression of the renal Na/Pi cotransporters, Npt2a and Npt2c. In FGF23-treated egr-1-/- mice, hypophosphatemic response was greatly blunted and Na/Pi cotransporter expression was not suppressed. In contrast, FGF23 induced equivalent suppression of serum 1,25(OH2D concentrations by suppressing renal cyp27b1 and stimulating cyp24a1 mRNA expression in both groups of mice. Thus, downstream of receptor binding and ERK1/2 signaling, we can distinguish the effector pathway that mediates FGF23-dependent inhibition of Pi transport from the pathway that mediates inhibition of 1,25(OH2D synthesis in the kidney. Furthermore, we demonstrate that the hypophosphatemic effect of FGF23 is significantly blunted in Hyp/egr-1-/- mice; specifically, serum Pi concentrations and renal Npt2a and Npt2c mRNA expression are significantly higher in Hyp/egr-1-/- mice than in Hyp mice. We then characterized the egr-1 cistrome in the kidney using ChIP-sequencing and demonstrate recruitment of egr-1 to regulatory DNA elements in proximity to several genes involved in Pi transport. Thus, our data demonstrate that the effect of FGF23 on Pi homeostasis is mediated, at least in part, by activation of egr-1.

  13. Podocyturia parallels proximal tubule dysfunction in type 2 diabetes mellitus patients independently of albuminuria and renal function decline: A cross-sectional study.

    Science.gov (United States)

    Petrica, Ligia; Vlad, Mihaela; Vlad, Adrian; Gluhovschi, Gheorghe; Gadalean, Florica; Dumitrascu, Victor; Popescu, Roxana; Gluhovschi, Cristina; Matusz, Petru; Velciov, Silvia; Bob, Flaviu; Ursoniu, Sorin; Vlad, Daliborca

    2017-09-01

    Detection of podocytes in the urine of patients with type 2 diabetes may indicate severe injury to the podocytes. In the course of type 2 diabetes the proximal tubule is involved in urinary albumin processing. We studied the significance of podocyturia in relation with proximal tubule dysfunction in type 2 diabetes. A total of 86 patients with type 2 diabetes (34-normoalbuminuria; 30-microalbuminuria; 22-macroalbuminuria) and 28 healthy subjects were enrolled in the study and assessed concerning urinary podocytes, podocyte-associated molecules, and biomarkers of proximal tubule dysfunction. Urinary podocytes were examined in cell cultures by utilizing monoclonal antibodies against podocalyxin and synaptopodin. Podocytes were detected in the urine of 10% of the healthy controls, 24% of the normoalbuminuric, 40% of the microalbuminuric, and 82% of the macroalbuminuric patients. In multivariate logistic regression analysis, urinary podocytes correlated with urinary albumin:creatinine ratio (p=0.006), urinary nephrin/creat (p=0.001), urinary vascular endothelial growth factor/creat (p=0.001), urinary kidney injury molecule-1/creat (p=0.003), cystatin C (p=0.001), urinary advanced glycation end-products (p=0.002), eGFR (p=0.001). In patients with type 2 diabetes podocyturia parallels proximal tubule dysfunction independently of albuminuria and renal function decline. Advanced glycation end-products may impact the podocytes and the proximal tubule. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. 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

  15. A computationally identified compound antagonizes excess FGF-23 signaling in renal tubules and a mouse model of hypophosphatemia.

    Science.gov (United States)

    Xiao, Zhousheng; Riccardi, Demian; Velazquez, Hector A; Chin, Ai L; Yates, Charles R; Carrick, Jesse D; Smith, Jeremy C; Baudry, Jerome; Quarles, L Darryl

    2016-11-22

    Fibroblast growth factor-23 (FGF-23) interacts with a binary receptor complex composed of α-Klotho (α-KL) and FGF receptors (FGFRs) to regulate phosphate and vitamin D metabolism in the kidney. Excess FGF-23 production, which causes hypophosphatemia, is genetically inherited or occurs with chronic kidney disease. Among other symptoms, hypophosphatemia causes vitamin D deficiency and the bone-softening disorder rickets. Current therapeutics that target the receptor complex have limited utility clinically. Using a computationally driven, structure-based, ensemble docking and virtual high-throughput screening approach, we identified four novel compounds predicted to selectively inhibit FGF-23-induced activation of the FGFR/α-KL complex. Additional modeling and functional analysis found that Zinc13407541 bound to FGF-23 and disrupted its interaction with the FGFR1/α-KL complex; experiments in a heterologous cell expression system showed that Zinc13407541 selectivity inhibited α-KL-dependent FGF-23 signaling. Zinc13407541 also inhibited FGF-23 signaling in isolated renal tubules ex vivo and partially reversed the hypophosphatemic effects of excess FGF-23 in a mouse model. These chemical probes provide a platform to develop lead compounds to treat disorders caused by excess FGF-23.

  16. 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.

  17. Long-term aldosterone administration increases renal Na+-Cl- cotransporter abundance in late distal convoluted tubule

    DEFF Research Database (Denmark)

    Poulsen, Søren Brandt; Christensen, Birgitte M

    2016-01-01

    Renal Na+-Cl- cotransporter (NCC) is expressed in early distal convoluted tubule (DCT) 1 and late DCT (DCT2). NCC activity can be stimulated by aldosterone, and the mechanism is assumed to depend on the enzyme, 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), which inactivates glucocorticoids...... that would otherwise occupy aldosterone receptors. Because 11β-HSD2 in rat may only be abundantly expressed in DCT2 cells and not in DCT1 cells, it has been speculated that aldosterone specifically stimulates NCC activity in DCT2 cells. In mice, however, it is debated if 11β-HSD2 is expressed in DCT2 cells....... The present study examined whether aldosterone-administration in mice stimulates NCC abundance and phosphorylation in DCT2 cells but not in DCT1 cells. B6/C57 male mice were administered 100 µg aldosterone (kg body weight)-1 (24 h)-1 for 6 days and euthanized during isoflurane inhalation. Western blotting...

  18. Proximal tubule epithelial cell specific ablation of the spermidine/spermine N1-acetyltransferase gene reduces the severity of renal ischemia/reperfusion injury.

    Directory of Open Access Journals (Sweden)

    Kamyar Zahedi

    Full Text Available BACKGROUND: Expression and activity of spermidine/spermine N1-acetyltransferase (SSAT increases in kidneys subjected to ischemia/reperfusion (I/R injury, while its ablation reduces the severity of such injuries. These results suggest that increased SSAT levels contribute to organ injury; however, the role of SSAT specifically expressed in proximal tubule epithelial cells, which are the primary targets of I/R injury, in the mediation of renal damage remains unresolved. METHODS: Severity of I/R injury in wt and renal proximal tubule specific SSAT-ko mice (PT-SSAT-Cko subjected to bilateral renal I/R injury was assessed using cellular and molecular biological approaches. RESULTS: Severity of the loss of kidney function and tubular damage are reduced in PT-SSAT-Cko- compared to wt-mice after I/R injury. In addition, animals treated with MDL72527, an inhibitor of polyamine oxidases, had less severe renal damage than their vehicle treated counter-parts. The renal expression of HMGB 1 and Toll like receptors (TLR 2 and 4 were also reduced in PT-SSAT-Cko- compared to wt mice after I/R injury. Furthermore, infiltration of neutrophils, as well as expression of tumor necrosis factor-α (TNF-α, monocyte chemoattractant protein-1 (MCP-1 and interleukin-6 (IL-6 transcripts were lower in the kidneys of PT-SSAT-Cko compared to wt mice after I/R injury. Finally, the activation of caspase3 was more pronounced in the wt compared to PT-SSAT-Cko animals. CONCLUSIONS: Enhanced SSAT expression by proximal tubule epithelial cells leads to tubular damage, and its deficiency reduces the severity of renal I/R injury through reduction of cellular damage and modulation of the innate immune response.

  19. 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.

  20. Physiologically based pharmacokinetic-pharmacodynamic modeling to predict concentrations and actions of sodium-dependent glucose transporter 2 inhibitor canagliflozin in human intestines and renal tubules.

    Science.gov (United States)

    Mori, Kazumi; Saito, Ryuta; Nakamaru, Yoshinobu; Shimizu, Makiko; Yamazaki, Hiroshi

    2016-11-01

    Canagliflozin is a recently developed sodium-glucose cotransporter (SGLT) 2 inhibitor that promotes renal glucose excretion and is considered to inhibit renal SGLT2 from the luminal side of proximal tubules. Canagliflozin reportedly inhibits SGLT1 weakly and suppresses postprandial plasma glucose, suggesting that it also inhibits intestinal SGLT1. However, it is difficult to measure the drug concentrations of these assumed sites of action directly. The pharmacokinetic-pharmacodynamic (PK/PD) relationships of canagliflozin remain poorly characterized. Therefore, a physiologically based pharmacokinetic (PBPK) model of canagliflozin was developed based on clinical data from healthy volunteers and it was used to simulate luminal concentrations in intestines and renal tubules. In small intestine simulations, the inhibition ratios for SGLT1 were predicted to be 40%-60% after the oral administration of clinical doses (100-300 mg/day). In contrast, inhibition ratios of canagliflozin for renal SGLT2 and SGLT1 were predicted to be approximately 100% and 0.2%-0.4%, respectively. These analyses suggest that canagliflozin only inhibits SGLT2 in the kidney. Using the simulated proximal tubule luminal concentrations of canagliflozin, the urinary glucose excretion rates in canagliflozin-treated diabetic patients were accurately predicted using the renal glucose reabsorption model as a PD model. Because the simulation of canagliflozin pharmacokinetics was successful, this PBPK methodology was further validated by successfully simulating the pharmacokinetics of dapagliflozin, another SGLT2 inhibitor. The present results suggest the utility of this PBPK/PD model for predicting canagliflozin concentrations at target sites and help to elucidate the pharmacological effects of SGLT1/2 inhibition in humans. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  1. Benign prostatic hyperplasia presenting with renal failure--what is the role for transurethral resection of the prostate (TURP)?

    LENUS (Irish Health Repository)

    Thomas, A Z

    2009-02-01

    The aim of the study was to determine the role of transurethralresection of prostate (TURP) in normalising renal function in men presenting with obstructive renal failure secondary to benign prostatic hyperplasia. We reviewed the cases of 14 men who presented in the last 5 years with renal impairment associated with symptoms of bladder outflow obstruction and radiological evidence of obstructive uropathy. The mean serum creatinine at presentation was 632 ng\\/mL (range 1299 - 225). The mean age at presentation was 68.2 years (range 50 - 83 years). Duration of symptoms prior to presentation ranged between 1 - 118 months (mean 21.5 months). Following catheter insertion, all patients underwent TURP. Six of the 14 patients required dialysis prior to surgery. Histology of the resected prostate confirmed benign prostatic hypertrophy and\\/or hyperplasia in all cases. Patients with carcinoma of the prostate were excluded from the study. Following TURP, 2 of the 14 men (14%) failed to void spontaneously following removal of catheter - one patient performs clean self intermittent catheterization (CSIC), the other man has an in-dwelling catheter in situ. One patient died 7 months following TURP due to a myocardial infarction. However, 8 patients, (57%) remained dialysis dependent following TURP. Two of these patients have since undergone successful renal transplantation. Of the remaining 6 patients, only 3 have normal renal function with the other 3 experiencing moderately elevated serum creatinine (range 236 - 344 ng\\/mL). In patients presenting with renal failure due to bladder outflow obstruction, TURP restores normal voiding pattern in many cases. However renal failure due to bladder outflow obstruction tends to be more refractory and only 3 of 14 patients experienced return to normal renal function post treatment.

  2. Benign prostatic hyperplasia presenting with renal failure--what is the role for transurethral resection of the prostate (TURP)?

    Science.gov (United States)

    Thomas, A Z; Thomas, A A; Conlon, P; Hickey, D; Little, D M

    2009-02-01

    The aim of the study was to determine the role of transurethralresection of prostate (TURP) in normalising renal function in men presenting with obstructive renal failure secondary to benign prostatic hyperplasia. We reviewed the cases of 14 men who presented in the last 5 years with renal impairment associated with symptoms of bladder outflow obstruction and radiological evidence of obstructive uropathy. The mean serum creatinine at presentation was 632 ng/mL (range 1299 - 225). The mean age at presentation was 68.2 years (range 50 - 83 years). Duration of symptoms prior to presentation ranged between 1 - 118 months (mean 21.5 months). Following catheter insertion, all patients underwent TURP. Six of the 14 patients required dialysis prior to surgery. Histology of the resected prostate confirmed benign prostatic hypertrophy and/or hyperplasia in all cases. Patients with carcinoma of the prostate were excluded from the study. Following TURP, 2 of the 14 men (14%) failed to void spontaneously following removal of catheter - one patient performs clean self intermittent catheterization (CSIC), the other man has an in-dwelling catheter in situ. One patient died 7 months following TURP due to a myocardial infarction. However, 8 patients, (57%) remained dialysis dependent following TURP. Two of these patients have since undergone successful renal transplantation. Of the remaining 6 patients, only 3 have normal renal function with the other 3 experiencing moderately elevated serum creatinine (range 236 - 344 ng/mL). In patients presenting with renal failure due to bladder outflow obstruction, TURP restores normal voiding pattern in many cases. However renal failure due to bladder outflow obstruction tends to be more refractory and only 3 of 14 patients experienced return to normal renal function post treatment.

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

    Science.gov (United States)

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

    2017-08-01

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

  4. Evidence for increased renal tubule and parathyroid gland sensitivity to serum calcium in human idiopathic hypercalciuria.

    Science.gov (United States)

    Worcester, Elaine M; Bergsland, Kristin J; Gillen, Daniel L; Coe, Fredric L

    2013-09-15

    Patients with idiopathic hypercalciuria (IH) have decreased renal calcium reabsorption, most marked in the postprandial state, but the mechanisms are unknown. We compared 29 subjects with IH and 17 normal subjects (N) each fed meals providing identical amounts of calcium. Urine and blood samples were collected fasting and after meals. Levels of three candidate signalers, serum calcium (SCa), insulin (I), and plasma parathyroid hormone (PTH), did not differ between IH and N either fasting or fed, but all changed with feeding, and the change in SCa was greater in IH than in N. Regression analysis of fractional excretion of calcium (FECa) was significant for PTH and SCa in IH but not N. With the use of multivariable analysis, Sca entered the model while PTH and I did not. To avoid internal correlation we decomposed FECa into its independent terms: adjusted urine calcium (UCa) and UFCa molarity. Analyses using adjusted Uca and unadjusted Uca parallel those using FECa, showing a dominant effect of SCa with no effect of PTH or I. The effect of SCa may be mediated via vitamin D receptor-stimulated increased abundance of basolateral Ca receptor, which is supported by the fact PTH levels also seem more responsive to serum Ca in IH than in N. Although our data support an effect of SCa on FECa and UCa, which is more marked in IH than in N, it can account for only a modest fraction of the meal effect, perhaps 10-20%, suggesting additional mediators are also responsible for the exaggerated postprandial hypercalciuria seen in IH.

  5. Haptoglobin attenuates hemoglobin-induced heme oxygenase-1 in renal proximal tubule cells and kidneys of a mouse model of sickle cell disease.

    Science.gov (United States)

    Chintagari, Narendranath Reddy; Nguyen, Julia; Belcher, John D; Vercellotti, Gregory M; Alayash, Abdu I

    2015-03-01

    Sickle cell disease (SCD), a hereditary hemolytic disorder is characterized by chronic hemolysis, oxidative stress, vaso-occlusion and end-organ damage. Hemolysis releases toxic cell-free hemoglobin (Hb) into circulation. Under physiologic conditions, plasma Hb binds to haptoglobin (Hp) and forms Hb-Hp dimers. The dimers bind to CD163 receptors on macrophages for further internalization and degradation. However, in SCD patients plasma Hp is depleted and free Hb is cleared primarily by proximal tubules of kidneys. Excess free Hb in plasma predisposes patients to renal damage. We hypothesized that administration of exogenous Hp reduces Hb-mediated renal damage. To test this hypothesis, human renal proximal tubular cells (HK-2) were exposed to HbA (50μM heme) for 24h. HbA increased the expression of heme oxygenase-1 (HO-1), an enzyme which degrades heme, reduces heme-mediated oxidative toxicity, and confers cytoprotection. Similarly, infusion of HbA (32μM heme/kg) induced HO-1 expression in kidneys of SCD mice. Immunohistochemistry confirmed the increased HO-1 expression in the proximal tubules of the kidney. Exogenous Hp attenuated the HbA-induced HO-1 expression in vitro and in SCD mice. Our results suggest that Hb-mediated oxidative toxicity may contribute to renal damage in SCD and that Hp treatment reduces heme/iron toxicity in the kidneys following hemolysis.

  6. Signaling cascade of insulin-induced stimulation of L-dopa uptake in renal proximal tubule cells.

    Science.gov (United States)

    Carranza, Andrea; Musolino, Patricia L; Villar, Marcelo; Nowicki, Susana

    2008-12-01

    The inward l-dihydroxyphenylalanine (L-dopa) transport supplies renal proximal tubule cells (PTCs) with the precursor for dopamine synthesis. We have previously described insulin-induced stimulation of L-dopa uptake into PTCs. In the present paper we examined insulin-related signaling pathways involved in the increase of l-dopa transport into isolated rat PTCs. Insulin (50-500 microU/ml) increased L-dopa uptake by PTCs, reaching the maximal increment (60% over the control) at 200 microU/ml. At this concentration, insulin also increased insulin receptor tyrosine phosphorylation. Both effects were abrogated by the tyrosine kinase inhibitor genistein (5 microM). In line, inhibition of the protein tyrosine phosphatase by pervanadate (0.2-100 microM) caused a concentration-dependent increase in both the uptake of L-dopa (up to 400%) and protein tyrosine phosphorylation. A synergistic effect between pervanadate and insulin on L-dopa uptake was observed only when threshold (0.2 microM), but not maximal (5 microM), concentrations of pervanadate were assayed. Insulin-induced stimulation of L-dopa uptake was also abolished by inhibition of phosphatidylinositol 3-kinase (PI3K; 100 nM wortmannin, and 25 microM LY-294002) and protein kinase C (PKC; 1 microM RO-318220). Insulin-induced activation of PKC-zeta was confirmed in vitro by its translocation from the cytosol to the membrane fraction, and in vivo by immunohistochemistry studies. Insulin caused a wortmannin-sensitive increase in Akt/protein kinase B (Akt/PKB) phosphorylation and a dose-dependent translocation of Akt/PKB to the membrane fraction. Our findings suggest that insulin activates PKC-zeta, and Akt/PKB downstream of PI3K, and that these pathways contribute to the insulin-induced increase of L-dopa uptake into PTCs.

  7. Parathyroid hyperplasia

    Science.gov (United States)

    Enlarged parathyroid glands; Osteoporosis - parathyroid hyperplasia; Bone thinning - parathyroid hyperplasia; Osteopenia - parathyroid hyperplasia; High calcium level - parathyroid hyperplasia; Chronic ...

  8. 13-year-old tuberous sclerosis patient with renal cell carcinoma associated with multiple renal angiomyolipomas developing multifocal micronodular pneumocyte hyperplasia

    Directory of Open Access Journals (Sweden)

    Behnes Carl Ludwig

    2013-02-01

    Full Text Available Abstract Background The autosomal dominant tumor syndrome tuberous sclerosis complex is caused by the mutated TSC1 gene, hamartin, and the TSC2 gene, tuberin. Patients with this complex develop typical cutaneus symptoms such as peau chagrin or angiofibromas of the skin as well as other lesions such as astrocytomas in the brain and lymphangioleiomyomatosis in the lung. Only a few tuberous sclerosis patients have been described who showed a multifocal micronodular pneumocyte hyperplasia of the lung. Another benign tumor which often occurs together with tuberous sclerosis is the angiomyolipoma of the kidney. Furthermore, an increased incidence of renal cell carcinoma in connection with tuberous sclerosis has also been proven. Case presentation We report a 13-year-old white girl with epilepsy and hypopigmented skin lesions. Radiological studies demonstrated the typical cortical tubers leading to the diagnosis of tuberous sclerosis. In the following examinations a large number of angiomyolipomas were found in both kidneys. One lesion showed an increasing size and tumor like aspects in magnetic resonance imaging. The pathological examination of the following tumorectomy demonstrated an unclassified renal cell carcinoma. Four months postoperatively, a follow-up computer tomography revealed multiple bilateral pulmonary nodules. To exclude lung metastases of the renal cell carcinoma, multiple open-lung biopsies were performed. Conclusion Here we report a diagnostically challenging case of a 13-year-old patient with tuberous sclerosis and angiomyolipomas of the kidney who developed an unclassified renal cell carcinoma as well as multifocal micronodular pneumocyte hyperplasia.

  9. Quantification of Aquaporin-CHIP water channel protein in microdissected renal tubules by fluorescence-based ELISA.

    OpenAIRE

    Maeda, Y; Smith, B L; Agre, P; Knepper, M A

    1995-01-01

    Several transporters have been localized along the nephron by physiological methods or immunocytochemistry. However, the actual abundance of these molecules has not been established. To accomplish this goal, we have developed a fluorescence-based ELISA method and have used it to quantitate Aquaporin-CHIP (AQP-CHIP) water channel protein in rat kidney tubules. Microdissected tubules (2 mm/sample, permeabilized with 0.5% Triton X-100) or purified AQP-CHIP standards (0-200 fmol) were utilized in...

  10. Gingival hyperplasia in renal allograft recipients receiving cyclosporin-A and calcium antagonists.

    Science.gov (United States)

    King, G N; Fullinfaw, R; Higgins, T J; Walker, R G; Francis, D M; Wiesenfeld, D

    1993-04-01

    Although it is established that the immunosuppressant cyclosporin-A (CsA) and calcium antagonists [Nifedipine (Nif) and Diltiazem (Dz)] can independently induce gingival enlargement, little has been documented on the significance of the salivary CsA levels and the combined effect of CsA and a calcium antagonist upon gingival tissues. In the present cross-sectional investigation, clinical periodontal parameters and the pharmacologic profiles of CsA, Nif, and Dz were determined for 66 renal transplant recipients. Subjects were divided into the following groups: Group (Gp) 1: CsA [n = 18]; Gp 2: CsA + Nif [n = 15]; Gp 3: CsA + Dz [n = 12] and a negative Control Gp 4: azathioprine [n = 21]. A gingival enlargement score was assessed for each patient from study models using a hyperplastic index (HI). Pharmacologic profiles included CsA whole blood and whole saliva levels as measured by fluorescence polarization immunoassay. The HI scores between Gp 1, 2 and 3 were not significantly different. However, when compared with controls (Gp 4), there was a significant difference in HI and all individual groups (Gp 1, 2, 3) (p < 0.05). Gingival hyperplasia was only weakly related to plaque and calculus but was unrelated to CsA dose (mg/kg/day), duration of CsA therapy (months), CsA blood or saliva levels (ng/ml), or the concurrent administration of a Nif or Dz. Gingival enlargement was found to occur in 49% of subjects who were either on CsA or CsA and a calcium antagonist. It is concluded that CsA alone or in combination with a calcium antagonist caused a significant increase in gingival enlargement compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS)

  11. Angiotensin metabolism in renal proximal tubules, urine, and serum of sheep: evidence for ACE2-dependent processing of angiotensin II.

    Science.gov (United States)

    Shaltout, Hossam A; Westwood, Brian M; Averill, David B; Ferrario, Carlos M; Figueroa, Jorge P; Diz, Debra I; Rose, James C; Chappell, Mark C

    2007-01-01

    Despite the evidence that angiotensin-converting enzyme (ACE)2 is a component of the renin-angiotensin system (RAS), the influence of ACE2 on angiotensin metabolism within the kidney is not well known, particularly in experimental models other than rats or mice. Therefore, we investigated the metabolism of the angiotensins in isolated proximal tubules, urine, and serum from sheep. Radiolabeled [(125)I]ANG I was hydrolyzed primarily to ANG II and ANG-(1-7) by ACE and neprilysin, respectively, in sheep proximal tubules. The ACE2 product ANG-(1-9) from ANG I was not detected in the absence or presence of ACE and neprilysin inhibition. In contrast, the proximal tubules contained robust ACE2 activity that converted ANG II to ANG-(1-7). Immunoblots utilizing an NH(2) terminal-directed ACE2 antibody revealed a single 120-kDa band in proximal tubule membranes. ANG-(1-7) was not a stable product in the tubule preparation and was rapidly hydrolyzed to ANG-(1-5) and ANG-(1-4) by ACE and neprilysin, respectively. Comparison of activities in the proximal tubules with nonsaturating concentrations of substrate revealed equivalent activities for ACE (ANG I to ANG II: 248 +/- 17 fmol x mg(-1) x min(-1)) and ACE2 [ANG II to ANG-(1-7): 253 +/- 11 fmol x mg(-1) x min(-1)], but lower neprilysin activity [ANG II to ANG-(1-4): 119 +/- 24 fmol x mg(-1) x min(-1); P < 0.05 vs. ACE or ACE2]. Urinary metabolism of ANG I and ANG II was similar to the proximal tubules; soluble ACE2 activity was also detectable in sheep serum. In conclusion, sheep tissues contain abundant ACE2 activity that converts ANG II to ANG-(1-7) but does not participate in the processing of ANG I into ANG-(1-9).

  12. 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.

  13. The pro-oxidant gene p66shc increases nicotine exposure-induced lipotoxic oxidative stress in renal proximal tubule cells.

    Science.gov (United States)

    Arany, Istvan; Hall, Samuel; Reed, Dustin K; Dixit, Mehul

    2016-09-01

    Nicotine (NIC) exposure augments free fatty acid (FFA) deposition and oxidative stress, with a concomitant increase in the expression of the pro-oxidant p66shc. In addition, a decrease in the antioxidant manganese superoxide dismutase (MnSOD) has been observed in the kidneys of mice fed a high‑fat diet. The present study aimed to determine whether the pro‑oxidant p66shc mediates NIC‑dependent increases in renal oxidative stress by augmenting the production of reactive oxygen species (ROS) and suppressing the FFA‑induced antioxidant response in cultured NRK52E renal proximal tubule cells. Briefly, NRK52E renal proximal tubule cells were treated with 200 µM NIC, 100 µM oleic acid (OA), or a combination of NIC and OA. The expression levels of p66shc and MnSOD were modulated according to genetic methods. ROS production and cell injury, in the form of lactate dehydrogenase release, were subsequently detected. Promoter activity of p66shc and MnSOD, as well as forkhead box (FOXO)‑dependent transcription, was investigated using reporter luciferase assays. The results demonstrated that NIC exacerbated OA‑mediated intracellular ROS production and cell injury through the transcriptional activation of p66shc. NIC also suppressed OA‑mediated induction of the antioxidant MnSOD promoter activity through p66shc‑dependent inactivation of FOXO activity. Overexpression of p66shc and knockdown of MnSOD had the same effect as treatment with NIC on OA‑mediated lipotoxicity. These data may be used to generate a therapeutic means to ameliorate renal lipotoxicity in obese smokers.

  14. Expression of renal distal tubule transporters TRPM6 and NCC in a rat model of cyclosporine nephrotoxicity and effect of EGF treatment.

    Science.gov (United States)

    Ledeganck, Kristien J; Boulet, Gaëlle A; Horvath, Caroline A; Vinckx, Marleen; Bogers, Johannes J; Van Den Bossche, Rita; Verpooten, Gert A; De Winter, Benedicte Y

    2011-09-01

    Renal magnesium (Mg(2+)) and sodium (Na(+)) loss are well-known side effects of cyclosporine (CsA) treatment in humans, but the underlying mechanisms still remain unclear. Recently, it was shown that epidermal growth factor (EGF) stimulates Mg(2+) reabsorption in the distal convoluted tubule (DCT) via TRPM6 (Thébault S, Alexander RT, Tiel Groenestege WM, Hoenderop JG, Bindels RJ. J Am Soc Nephrol 20: 78-85, 2009). In the DCT, the final adjustment of renal sodium excretion is regulated by the thiazide-sensitive Na(+)-Cl(-) cotransporter (NCC), which is activated by the renin-angiotensin-aldosterone system (RAAS). The aim of this study was to gain more insight into the molecular mechanisms of CsA-induced hypomagnesemia and hyponatremia. Therefore, the renal expression of TRPM6, TRPM7, EGF, EGF receptor, claudin-16, claudin-19, and the NCC, and the effect of the RAAS on NCC expression, were analyzed in vivo in a rat model of CsA nephrotoxicity. Also, the effect of EGF administration on these parameters was studied. CsA significantly decreased the renal expression of TRPM6, TRPM7, NCC, and EGF, but not that of claudin-16 and claudin-19. Serum aldosterone was significantly lower in CsA-treated rats. In control rats treated with EGF, an increased renal expression of TRPM6 together with a decreased fractional excretion of Mg(2+) (FE Mg(2+)) was demonstrated. EGF did not show this beneficial effect on TRPM6 and FE Mg(2+) in CsA-treated rats. These data suggest that CsA treatment affects Mg(2+) homeostasis via the downregulation of TRPM6 in the DCT. Furthermore, CsA downregulates the NCC in the DCT, associated with an inactivation of the RAAS, resulting in renal sodium loss.

  15. Activation of the ALK-5 Pathway is not per se Sufficient for the Antiproliferative Effect of TGF-β1 on Renal Tubule Epithelial Cells

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    Omar García-Sánchez

    2015-10-01

    Full Text Available Background/Aims: Defective tissue repair underlies renal tissue degeneration during chronic kidney disease (CKD progression. Unbalanced presence of TGF-β opposes effective cell proliferation and differentiation processes, necessary to replace damaged epithelia. TGF-β also retains arrested cells in a fibrotic phenotype responsible for irreversible scarring. In order to identify prospective molecular targets to prevent the effect of TGF-β during CKD, we studied the signaling pathways responsible for the antiproliferative effect of this cytokine. Methods: Tubule epithelial HK2 and MDCK cells were treated with TGF-β (or not as control to study cell proliferation (by MTT, cell signaling (by Western blot, cell cycle (by flow cytometry and apoptosis (DNA fragmentation. Results: TGF-β fully activates the ALK-5 receptor pathway, whereas it has no effect on the ALK-1 and MAPK pathways in both HK2 and MDCK cells. Interestingly, TGF-β exerts an antiproliferative effect only on MDCK cells, through a cytostatic effect in G0/G1. Inhibition of the ALK-5 pathway with SB431542 prevents the cytostatic effect of TGF-β on MDCK cells. Conclusion: Activation of the ALK-5 pathway is not sufficient for the antiproliferative effect of TGF-β. The presence of undetermined permissive conditions or absence of undetermined inhibitory conditions seems to be necessary for this effect. The ALK-5 pathway appears to provide targets to modulate fibrosis, but further research is necessary to identify critical circumstances allowing or inhibiting its role at modulating tubule epithelial cell proliferation and tubule regeneration in the context of CKD progression.

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

    Science.gov (United States)

    Li, Yiyi; Piermarini, Peter M; Esquivel, Carlos J; Drumm, Hannah E; Schilkey, Faye D; Hansen, Immo A

    2017-01-01

    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 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.

  17. Sorting nexin 1 loss results in D5 dopamine receptor dysfunction in human renal proximal tubule cells and hypertension in mice.

    Science.gov (United States)

    Villar, Van Anthony M; Jones, John Edward; Armando, Ines; Asico, Laureano D; Escano, Crisanto S; Lee, Hewang; Wang, Xiaoyan; Yang, Yu; Pascua-Crusan, Annabelle M; Palmes-Saloma, Cynthia P; Felder, Robin A; Jose, Pedro A

    2013-01-04

    The peripheral dopaminergic system plays a crucial role in blood pressure regulation through its actions on renal hemodynamics and epithelial ion transport. The dopamine D5 receptor (D(5)R) interacts with sorting nexin 1 (SNX1), a protein involved in receptor retrieval from the trans-Golgi network. In this report, we elucidated the spatial, temporal, and functional significance of this interaction in human renal proximal tubule cells and HEK293 cells stably expressing human D(5)R and in mice. Silencing of SNX1 expression via RNAi resulted in the failure of D(5)R to internalize and bind GTP, blunting of the agonist-induced increase in cAMP production and decrease in sodium transport, and up-regulation of angiotensin II receptor expression, of which expression was previously shown to be negatively regulated by D(5)R. Moreover, siRNA-mediated depletion of renal SNX1 in C57BL/6J and BALB/cJ mice resulted in increased blood pressure and blunted natriuretic response to agonist in salt-loaded BALB/cJ mice. These data demonstrate a crucial role for SNX1 in D(5)R trafficking and that SNX1 depletion results in D(5)R dysfunction and thus may represent a novel mechanism for the pathogenesis of essential hypertension.

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

    NARCIS (Netherlands)

    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, 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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1988-09-01

    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 /sup 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.

  20. 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

  1. Urosepsis in infants with vesicoureteral reflux masquerading as the salt-losing type of congenital adrenal hyperplasia

    Energy Technology Data Exchange (ETDEWEB)

    Vaid, Y.N.; Lebowitz, R.L.

    1989-08-01

    Three male infants with vomiting, dehydration, hyponatremia, hyperkalemia and metabolic acidosis were found to have vesicoureteral reflux (VUR) and urinary tract infection. Two were initially thought to have the salt-losing form of congenital adrenal hyperplasia. Although prompt diagnosis of this potentially fatal condition is critical, its mimicry by urosepsis in infants with VUR is actually more common. Infection probably causes unresponsiveness of the distal renal tubules to aldoterone. (orig.).

  2. Glucosamine-induced Sp1 O-GlcNAcylation ameliorates hypoxia-induced SGLT dysfunction in primary cultured renal proximal tubule cells.

    Science.gov (United States)

    Suh, Han Na; Lee, Yu Jin; Kim, Mi Ok; Ryu, Jung Min; Han, Ho Jae

    2014-10-01

    The aim of this study is to determine whether GlcN could recover the endoplasmic reticulum (ER) stress-induced dysfunction of Na(+) /glucose cotransporter (SGLT) in renal proximal tubule cells (PTCs) under hypoxia. With the rabbit model, the renal ischemia induced tubulointerstitial abnormalities and decreased SGLTs expression in tubular brush-border, which were recovered by GlcN. Thus, the protective mechanism of GlcN against renal ischemia was being examined by using PTCs. Hypoxia decreased the level of protein O-GlcNAc and the expression of O-GlcNAc transferase (OGT) while increased O-GlcNAcase (OGA) and these were reversed by GlcN. Hypoxia also decreased the expression of SGLTs (SGLT1 and 2) and [(14) C]-α-methyl-D-glucopyranoside (α-MG) uptake which were recovered by GlcN and PUGNAc (OGA inhibitor). Hypoxia enhanced reactive oxygen species (ROS) and then ER stress proteins, glucose-regulated protein 78 (GRP78), and C/EBP-homologous protein (CHOP). However, the expression of GRP78 increased till 6 h and then decreased whereas CHOP increased gradually. Moreover, decreased GRP78 and increased CHOP were reversed by NAC (antioxidant) and GlcN. GlcN ameliorated hypoxia-induced decrease of O-GlcNAc modification of Sp1 but OGT or Sp1 siRNAs blocked the recovery effect of GlcN on SGLT expression and α-MG uptake. In addition, hypoxia-decreased GRP78 and HIF-1α expression was reversed by GlcN but OGT siRNA or Sp1 siRNA ameliorated the effect of GlcN. When PTCs were transfected with GRP78 siRNA or HIF-1α siRNA, SGLT expression and α-MG uptake was decreased. Taken together, these data suggest that GlcN-induced O-GlcNAc modified Sp1 with stimulating GRP78 and HIF-1α activity ameliorate hypoxia-induced SGLT dysfunction in renal PTCs. J. Cell. Physiol. 229: 1557-1568, 2014. © 2014 Wiley Periodicals, Inc.

  3. 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.

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

    Science.gov (United States)

    Ness, Daniel; Ren, Zhao; Gardai, Shyra; Sharpnack, Douglas; Johnson, Victor J; Brennan, Richard J; Brigham, Elizabeth F; Olaharski, Andrew J

    2013-01-01

    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.

  5. 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.

  6. Potentiation by nitric oxide of cyclosporin A and FK506-induced apoptosis in renal proximal tubule cells.

    Science.gov (United States)

    Hortelano, S; Castilla, M; Torres, A M; Tejedor, A; Boscá, L

    2000-12-01

    Proximal tubular epithelial cells (PTEC) exhibit a high sensitivity to undergo apoptosis in response to proinflammatory stimuli and immunosuppressors and participate in the onset of several renal diseases. This study examined the expression of inducible nitric oxide (NO) synthase after challenge of PTEC with bacterial cell wall molecules and inflammatory cytokines and analyzed the pathways that lead to apoptosis in these cells by measuring changes in the mitochondrial transmembrane potential and caspase activation. The data show that the apoptotic effects of proinflammatory stimuli mainly were due to the expression of inducible NO synthase. Cyclosporin A and FK506 inhibited partially NO synthesis. However, both NO and immunosuppressors induced apoptosis, probably through a common mechanism that involved the irreversible opening of the mitochondrial permeability transition pore. Activation of caspases 3 and 7 was observed in cells treated with high doses of NO and with moderate concentrations of immunosuppressors. The conclusion is that the cooperation between NO and immunosuppressors that induce apoptosis in PTEC might contribute to the renal toxicity observed in the course of immunosuppressive therapy.

  7. 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.

  8. Oral Reference Dose for ethylene glycol based on oxalate crystal-induced renal tubule degeneration as the critical effect

    Energy Technology Data Exchange (ETDEWEB)

    Snellings, William M.; Corley, Richard A.; McMartin, K. E.; Kirman, Christopher R.; Bobst, Sol M.

    2013-03-31

    Several risk assessments have been conducted for ethylene glycol (EG). These assessments identified the kidney as the primary target organ for chronic effects. None of these assessments have incorporated the robust database of species-specific toxicokinetic and toxicodynamic studies with EG and its metabolites in defining uncertainty factors used in reference value derivation. Pertinent in vitro and in vivo studies related to one of these metabolites, calcium oxalate, and its role in crystal-induced nephropathy are summarized, and the weight of evidence to establish the mode of action for renal toxicity is reviewed. Previous risk assessments were based on chronic rat studies using a strain of rat that was later determined to be less sensitive to the toxic effects of EG. A recently published 12-month rat study using the more sensitive strain (Wistar) was selected to determine the point of departure for a new risk assessment. This approach incorporated toxicokinetic and toxicodynamic data and used Benchmark Dose methods to calculate a Human Equivalent Dose. Uncertainty factors were chosen, depending on the quality of the studies available, the extent of the database, and scientific judgment. The Reference Dose for long-term repeat oral exposure to EG was determined to be 15 mg/kg bw/d.

  9. SGLT2 inhibitor lowers serum uric acid through alteration of uric acid transport activity in renal tubule by increased glycosuria

    Science.gov (United States)

    Chino, Yukihiro; Samukawa, Yoshishige; Sakai, Soichi; Nakai, Yasuhiro; Yamaguchi, Jun-ichi; Nakanishi, Takeo; Tamai, Ikumi

    2014-01-01

    Sodium glucose cotransporter 2 (SGLT2) inhibitors have been reported to lower the serum uric acid (SUA) level. To elucidate the mechanism responsible for this reduction, SUA and the urinary excretion rate of uric acid (UEUA) were analysed after the oral administration of luseogliflozin, a SGLT2 inhibitor, to healthy subjects. After dosing, SUA decreased, and a negative correlation was observed between the SUA level and the UEUA, suggesting that SUA decreased as a result of the increase in the UEUA. The increase in UEUA was correlated with an increase in urinary d-glucose excretion, but not with the plasma luseogliflozin concentration. Additionally, in vitro transport experiments showed that luseogliflozin had no direct effect on the transporters involved in renal UA reabsorption. To explain that the increase in UEUA is likely due to glycosuria, the study focused on the facilitative glucose transporter 9 isoform 2 (GLUT9ΔN, SLC2A9b), which is expressed at the apical membrane of the kidney tubular cells and transports both UA and d-glucose. It was observed that the efflux of [14C]UA in Xenopus oocytes expressing the GLUT9 isoform 2 was trans-stimulated by 10 mm d-glucose, a high concentration of glucose that existed under SGLT2 inhibition. On the other hand, the uptake of [14C]UA by oocytes was cis-inhibited by 100 mm d-glucose, a concentration assumed to exist in collecting ducts. In conclusion, it was demonstrated that the UEUA could potentially be increased by luseogliflozin-induced glycosuria, with alterations of UA transport activity because of urinary glucose. PMID:25044127

  10. 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.

  11. Regulation of SGLT expression and localization through Epac/PKA-dependent caveolin-1 and F-actin activation in renal proximal tubule cells.

    Science.gov (United States)

    Lee, Yu Jin; Kim, Mi Ok; Ryu, Jung Min; Han, Ho Jae

    2012-04-01

    This study demonstrated that exchange proteins directly activated by cAMP (Epac) and protein kinase A (PKA) by 8-bromo (8-Br)-adenosine 3',5'-cyclic monophosphate (cAMP) stimulated [(14)C]-α-methyl-D-glucopyranoside (α-MG) uptake through increased sodium-glucose cotransporters (SGLTs) expression and translocation to lipid rafts in renal proximal tubule cells (PTCs). In PTCs, SGLTs were colocalized with lipid raft caveolin-1 (cav-1), disrupted by methyl-β-cyclodextrin (MβCD). Selective activators of Epac or PKA, 8-Br-cAMP, and forskolin stimulated expressions of SGLTs and α-MG uptake in PTCs. In addition, 8-Br-cAMP-induced PKA and Epac activation increased phosphorylation of extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (MAPK), and nuclear factor kappa B (NF-κB), which were involved in expressions of SGLTs. Furthermore, 8-Br-cAMP stimulated SGLTs translocation to lipid rafts via filamentous actin (F-actin) organization, which was blocked by cytochalasin D. In addition, cav-1 and SGLTs stimulated by 8-Br-cAMP were detected in lipid rafts, which were blocked by cytochalasin D. Furthermore, 8-Br-cAMP-induced SGLTs translocation and α-MG uptake were attenuated by inhibition of cav-1 activation with cav-1 small interfering RNA (siRNA) and inhibition of F-actin organization with TRIO and F-actin binding protein (TRIOBP). In conclusion, 8-Br-cAMP stimulated α-MG uptake via Epac and PKA-dependent SGLTs expression and trafficking through cav-1 and F-actin in PTCs.

  12. Effect of BSA-induced ER stress on SGLT protein expression levels and alpha-MG uptake in renal proximal tubule cells.

    Science.gov (United States)

    Lee, Yu Jin; Suh, Han Na; Han, Ho Jae

    2009-06-01

    Recent studies demonstrated that endoplasmic reticulum (ER) stress regulates glucose homeostasis and that ER stress preconditioning which induces an adaptive, protective unfolded protein response (UPR) offers cytoprotection against nephrotoxins. Thus the aim of the present study was to use renal proximal tubule cells (PTCs) to further elucidate the link between the BSA-induced ER stress and alpha-methyl-d-glucopyranoside (alpha-MG) uptake and to identify related signaling pathways. Among ER stress inducers such as high glucose, BSA, H2O2, or tumicamycin, BSA pretreatment ameliorated the reduction of Na(+)-glucose cotransporter (SGLT) expression and alpha-MG uptake by gentamicin or cyclosporine A. Immunofluorescence studies revealed that BSA (10 mg/ml) stimulated the expression of glucose-regulated protein 78 (GRP78), an ER stress biomarker. In addition, BSA increased levels of GRP78 protein expression and eukaryotic initiation factor 2alpha (eIF2alpha) phosphorylation in a time-dependent manner. Furthermore, transfection with a GRP78-specific small interfering RNA (siRNA) inhibited BSA-stimulated SGLT expression and alpha-MG uptake. In experiments designed to unravel the mechanisms underlying BSA-induced ER stress, BSA stimulated the production of cellular reactive oxygen species (ROS), and antioxidants such as ascorbic acid or N-acetylcysteine (NAC) blocked BSA-induced increases in GRP78 activation, eIF2alpha phosphorylation, SGLT expression, and alpha-MG uptake. Moreover, the cells upregulated peroxisome proliferator-activated receptor-gamma (PPARgamma) mRNA levels in response to BSA or troglitazone (a PPARgamma agonist), but BSA was ineffective in the presence of GW9662 (a PPARgamma antagonist). In addition, both BSA and troglitazone stimulated GRP78 and eIF2alpha activation, SGLT expression, and alpha-MG uptake, whereas GW9662 inhibited the effects of BSA. BSA also stimulated phosphorylation of JNK and NF-kappaB, and GW9662 or GRP78 siRNA attenuated this

  13. 肾移植术后牙眼增生的临床分析%The Clinical Analysis of Gingival Hyperplasia in Patients after Renal Transplantation

    Institute of Scientific and Technical Information of China (English)

    马小平; 刘洋; 李阳波; 许亚宏; 林涛

    2011-01-01

    目的 探讨肾移植术后药物(环孢素A和钙离子拮抗剂)、口腔卫生与牙龈增生的关系.方法 随访2003年1月-2010年3月间321例肾移植患者,记录患者术后药物使用和口腔卫生情况,观察牙龈增生程度.结果 口腔卫生水平与牙龈增生程度之间存在统计学相关性(rs=0.344,P=0.000),口腔卫生水平越差,牙龈增生越严重.服用环孢素A和钙离子拮抗剂患者(A组)牙龈增生发生率为62.15%,高于单纯服用环孢素A患者(B组)23.40%,二者比较,差异有统计学意义(χ2=39.220,P=O.000).结论 肾移植术后环抱素A和钙离子拮抗剂联合应用明显增加了牙龈增生的发病率.口腔卫生水平与牙龈增生程度之间存在重要关联,口腔卫生差是牙龈增生的危险因素.%Objective To investigate the correlation between drugs (cyclosporine A and calcium channel blocker),oral hygiene and gingival hyperplasia in patients after renal transplantation.Methods We continuously followed up 321patients undergoing renal transplantation from January 2003 to July 2009 in our hospital.The levels of oral hygiene,medication and gingival hyperplasia were recorded.Results There was a close relationship between the level of oral hygiene and the degree of gingival hyperplasia (rs =0.344, P=0.000).Higher grades of gingival hyperplasia (grades Ⅱand Ⅲ ) were found exclusively in patients who did not have good oral hygiene.There was a higher tendency of developing gingival hyperplasia among patients who received cyclosporine A and calcium channel blocker than those who only received cyclosporine A (62.15% vs.23.40%;X2 =39.220, P=0.000).Conclusion The prevalence of gingival hyperplasia is higher in renal transplant recipients taking cyclosporine A and calcium channel blockers.There is a significant relationship between the level of oral hygiene and the development of gingival hyperplasia.Poor oral hygiene is a risk factor of gingival hyperplasia.

  14. Lymphofollicular hyperplasia

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/001377.htm Lymphofollicular hyperplasia To use the sharing features on this page, please enable JavaScript. Lymphofollicular hyperplasia is an increase in the size of the ...

  15. A Human Renal Proximal Tubule Cell Line with Stable Organic Anion Transporter 1 and 3 Expression Predictive for Antiviral-Induced Toxicity

    NARCIS (Netherlands)

    Nieskens, Tom T G; Peters, Janny G P; Schreurs, Marieke J; Smits, Niels; Woestenenk, Rob; Jansen, Katja; van der Made, Thom K; Röring, Melanie; Hilgendorf, Constanze; Wilmer, Martijn J; Masereeuw, Roos

    2016-01-01

    Drug-induced nephrotoxicity still hampers drug development, because current translation from in vitro or animal studies to human lacks high predictivity. Often, renal adverse effects are recognized only during clinical stages of drug development. The current study aimed to establish a robust and a m

  16. Metabolic alkalosis transition in renal proximal tubule cells facilitates an increase in CYP27B1, while blunting responsiveness to PTH

    Science.gov (United States)

    Parathyroid hormone (PTH) is the central activator of renal proximal 1-alpha-hydroxylase (CYP27B1), the enzyme responsible for synthesis of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). Past studies have documented a disruption of CYP27B1 activity in chronic metabolic acidosis in vivo, while simulated ac...

  17. Loss of NHERF-1 expression prevents dopamine-mediated Na-K-ATPase regulation in renal proximal tubule cells from rat models of hypertension: aged F344 rats and spontaneously hypertensive rats.

    Science.gov (United States)

    Barati, Michelle T; Ketchem, Corey J; Merchant, Michael L; Kusiak, Walter B; Jose, Pedro A; Weinman, Edward J; LeBlanc, Amanda J; Lederer, Eleanor D; Khundmiri, Syed J

    2017-08-01

    Dopamine decreases Na-K-ATPase (NKA) activity by PKC-dependent phosphorylation and endocytosis of the NKA α1. Dopamine-mediated regulation of NKA is impaired in aging and some forms of hypertension. Using opossum (OK) proximal tubule cells (PTCs), we demonstrated that sodium-hydrogen exchanger regulatory factor-1 (NHERF-1) associates with NKA α1 and dopamine-1 receptor (D1R). This association is required for the dopamine-mediated regulation of NKA. In OK cells, dopamine decreases NHERF-1 association with NKA α1 but increases its association with D1R. However, it is not known whether NHERF-1 plays a role in dopamine-mediated NKA regulation in animal models of hypertension. We hypothesized that defective dopamine-mediated regulation of NKA results from the decrease in NHERF-1 expression in rat renal PTCs isolated from animal models of hypertension [spontaneously hypertensive rats (SHRs) and aged F344 rats]. To test this hypothesis, we isolated and cultured renal PTCs from 22-mo-old F344 rats and their controls, normotensive 4-mo-old F344 rats, and SHRs and their controls, normotensive Wistar-Kyoto (WKY) rats. The results demonstrate that in both hypertensive models (SHR and aged F344), NHERF-1 expression, dopamine-mediated phosphorylation of NKA, and ouabain-inhibitable K(+) transport are reduced. Transfection of NHERF-1 into PTCs from aged F344 and SHRs restored dopamine-mediated inhibition of NKA. These results suggest that decreased renal NHERF-1 expression contributes to the impaired dopamine-mediated inhibition of NKA in PTCs from animal models of hypertension.

  18. Malpighian Tubules as Novel Targets for Mosquito Control.

    Science.gov (United States)

    Piermarini, Peter M; Esquivel, Carlos J; Denton, Jerod S

    2017-01-24

    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.

  19. Endometrial Hyperplasia

    Science.gov (United States)

    ... of certain conditions, such as diabetes mellitus , polycystic ovary syndrome, gallbladder disease, or thyroid disease Obesity Cigarette smoking Family history of ovarian, colon, or uterine cancer What are the types of endometrial hyperplasia? Endometrial ...

  20. ANGIOLYMPHOID HYPERPLASIA

    National Research Council Canada - National Science Library

    RAMESH ARAVAMUTHAN; Mani Suriyakumar; SARANKUMAR SUDHAKAR

    2015-01-01

    Angiolymphoid hyperplasia with eosinophilia (ALHE) is an uncommon benign idiopathic condition that manifests in adults, characterized by isolated or grouped papules, plaques, or nodules in the skin of the head and neck...

  1. SIRT1 overexpression decreases cisplatin-induced acetylation of NF-{kappa}B p65 subunit and cytotoxicity in renal proximal tubule cells

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Yu Jin; Lee, Jung Eun; Lee, Ae Sin [Department of Internal Medicine, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Kang, Kyung Pyo; Lee, Sik; Park, Sung Kwang [Department of Internal Medicine, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Institute for Medical Sciences, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Lee, Sang Yong [Department of Diagnostic Radiology, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Institute for Medical Sciences, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Han, Myung Kwan [Department of Microbiology, Institute for Medical Sciences, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Kim, Duk Hoon [Division of Forensic Medicine, National Forensic Service, Seoul (Korea, Republic of); Kim, Won, E-mail: kwon@jbnu.ac.kr [Department of Internal Medicine, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Institute for Medical Sciences, Chonbuk National University Medical School, Jeonju (Korea, Republic of)

    2012-03-09

    Highlights: Black-Right-Pointing-Pointer Cisplatin increases acetylation of NF-{kappa}B p65 subunit in HK2 cells. Black-Right-Pointing-Pointer SIRT1 overexpression decreases cisplatin-induced p65 acetylation and -cytotoxicity. Black-Right-Pointing-Pointer Resveratrol decreased cisplatin-induced cell viability through deacetylation of p65. -- Abstract: As the increased acetylation of p65 is linked to nuclear factor-{kappa}B (NF-{kappa}B) activation, the regulation of p65 acetylation can be a potential target for the treatment of inflammatory injury. Cisplatin-induced nephrotoxicity is an important issue in chemotherapy of cancer patients. SIRT1, nicotinamide adenine dinucleotide (NAD{sup +})-dependent protein deacetylase, has been implicated in a variety of cellular processes such as inflammatory injury and the control of multidrug resistance in cancer. However, there is no report on the effect of SIRT1 overexpression on cisplatin-induced acetylation of p65 subunit of NF-{kappa}B and cell injury. To investigate the effect of SIRT1 in on cisplatin-induced acetylation of p65 subunit of NF-{kappa}B and cell injury, HK2 cells were exposed with SIRT1 overexpression, LacZ adenovirus or dominant negative adenovirus after treatment with cisplatin. While protein expression of SIRT1 was decreased by cisplatin treatment compared with control buffer treatment, acetylation of NF-{kappa}B p65 subunit was significantly increased after treatment with cisplatin. Overexpression of SIRT1 ameliorated the increased acetylation of p65 of NF-{kappa}B during cisplatin treatment and cisplatin-induced cytotoxicity. Further, treatment of cisplatin-treated HK2 cells with resveratrol, a SIRT1 activator, also decreased acetylation of NF-{kappa}B p65 subunit and cisplatin-induced increase of the cell viability in HK2 cells. Our findings suggests that the regulation of acetylation of p65 of NF-{kappa}B through SIRT1 can be a possible target to attenuate cisplatin-induced renal cell damage.

  2. [The assessment of the regularity of the nephron anlage tubule formation on the basis of provisionality principle].

    Science.gov (United States)

    Panteleev, S M; Vikhareva, L V; Mal'tseva, N G; Ushakov, A L; Khamoshina, I Ia; Iaroslavtseva, O F; Chivshina, R V; Pal'chenkova, N O; Margarian, A V; Belkhoroeva, M M

    2011-01-01

    The study of the definitive kidneys of 94 human embryos and fetuses at 4.5 to 12 weeks of gestation, has demonstrated that the formation of the proximal nephron tubules resulted from the cellular proliferation in the area of transition of the capsule of the renal corpuscle into the tubular part of the nephron that occurs only after the completion of the segregation of the renal corpuscle and the distal tubule within the nephron anlage. The formation of the renal tubules in the nephron anlage seems to be determined phylogenetically, while the initial differentiation of the distal tubule is a provisional feature.

  3. Renal histopathology in toxicity and carcinogenicity studies with tert-butyl alcohol administered in drinking water to F344 rats: a pathology working group review and re-evaluation.

    Science.gov (United States)

    Hard, Gordon C; Bruner, Richard H; Cohen, Samuel M; Pletcher, John M; Regan, Karen S

    2011-04-01

    An independent Pathology Working Group (PWG) re-evaluated the kidney changes in National Toxicology Program (NTP) toxicology/carcinogenicity studies of tert-butyl alcohol (TBA) in F344/N rats to determine possible mode(s) of action underlying renal tubule tumors in male rats at 2-years. In the 13-week study, the PWG confirmed that the normal pattern of round hyaline droplets in proximal convoluted tubules was replaced by angular droplet accumulation, and identified precursors of granular casts in the outer medulla, changes typical of alpha(2u)-globulin (α(2u)-g) nephropathy. In the 2-year study, the PWG confirmed the NTP observation of increased renal tubule tumors in treated male groups. Linear papillary mineralization, another hallmark of the α(2u)-g pathway was present only in treated male rats. Chronic progressive nephropathy (CPN) was exacerbated in high-dose males and females, with a relationship between advanced grades of CPN and renal tumor occurrence. Hyperplasia of the papilla lining was a component of CPN in both sexes, but there was no pelvic urothelial hyperplasia. High-dose females showed no TBA-related nephrotoxicity. The PWG concluded that both α(2u)-g nephropathy and exacerbated CPN modes of action were operative in TBA renal tumorigenicity in male rats, neither of which has relevance for human cancer risk.

  4. Insulin uptake across the luminal membrane of the rat proximal tubule in vivo and in vitro

    OpenAIRE

    Kolman, Pavel; Pica, Angelo; Carvou, Nicolas; Boyde, Alan; Cockcroft, Shamshad; Loesch, Andrew; Pizzey, Arnold; Simeoni, Mariadelina; Capasso, Giovambattista; Unwin, Robert J.

    2009-01-01

    We visualized insulin uptake in vivo across the apical membrane of the rat proximal tubule (PT) by confocal microscopy; we compared it with in vitro findings in a rat PT cell line (WKPT) using fluorescence microscopy and flow cytometry. Surface tubules were observed in vivo with a 633-nm single laser-illuminated real-time video-rate confocal scanning microscope in upright configuration for optical sectioning below the renal capsule. Fields were selected containing proximal and distal tubules;...

  5. A New Look at Electrolyte Transport in the Distal Tubule

    OpenAIRE

    Eladari, Dominique; Chambrey, Régine; Peti-Peterdi, Janos

    2011-01-01

    The distal nephron plays a critical role in the renal control of homeostasis. Until very recently most studies focused on the control of Na+, K+, and water balance by principal cells of the collecting duct and the regulation of solute and water by hormones from the renin-angiotensin-aldosterone system and by antidiuretic hormone. However, recent studies have revealed the unexpected importance of renal intercalated cells, a subtype of cells present in the connecting tubule and collecting ducts...

  6. Albumin-stimulated DNA synthesis is mediated by Ca2+/PKC as well as EGF receptor-dependent p44/42 MAPK and NF-kappaB signal pathways in renal proximal tubule cells.

    Science.gov (United States)

    Lee, Yu Jin; Han, Ho Jae

    2008-03-01

    It is now recognized that significant tubular reabsorption of albumin occurs under physiological conditions that may play an important role in maintaining proximal tubular integrity and function. Therefore, this study examined the effect of bovine serum albumin (BSA) on DNA synthesis and its related signal molecules in primary cultured rabbit renal proximal tubule cells (PTCs). BSA increased the level of [(3)H]thymidine incorporation in a dose (> or =3 mg/ml)- and time (> or =3 h)-dependent manner, intracellular Ca(2+) concentration, and the level of protein kinase C (PKC) phosphorylation and stimulated the phosphorylation of the epidermal growth factor receptor (EGFR), which was inhibited by EGTA (extracellular Ca(2+) chelator), 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid acetoxymethyl ester (BAPTA-AM, intracellular Ca(2+) chelator), or PKC inhibitors (staurosporine or bisindolylmaleimide I). In addition, the PKC inhibitors or an EGFR inhibitor (AG-1478) blocked the BSA-induced phosphorylation of p44/42 mitogen-activated protein kinases (MAPKs). BSA also increased the level of nuclear factor-kappaB (NF-kappaB) and inhibitor of NF-kappaB (IkappaB) phosphorylation, which was blocked by staurosporine, AG-1478, or PD-98059 (p44/42 MAPK inhibitor). Inhibition of Ca(2+), PKC, EGFR, p44/42 MAPK, or NF-kappaB signal pathways blocked the BSA-induced incorporation of [(3)H]thymidine. Consequently, the inhibition of Ca(2+), PKC, EGFR, p44/42 MAPKs, or NF-kappaB blocked the BSA-induced increases in cyclin D1, cyclin-dependent kinase (CDK)4, cyclin E, or CDK2 and restored the BSA-induced inhibition of p21(WAF/Cip1) and p27(Kip1) expression. In conclusion, BSA stimulates DNA synthesis that is mediated by Ca(2+)/PKC as well as the EGFR-dependent p44/42 MAPK and NF-kappaB signal pathways in PTCs.

  7. Verrucous Hyperplasia

    Science.gov (United States)

    Grover, Sonal; Jha, Mihir; Sharma, Bhushan; Kapoor, Shekhar; Mittal, Kumud; Parakkat, Nithin K.; Shivappa, Anil B.; Kaur, Ravleen

    2017-01-01

    Verrucous hyperplasia (VH) is a rare exophytic oral mucosal lesion which can transform into verrucous carcinoma (VC), its malignant but clinically similar counterpart. These entities can be distinguished by the lack of invasive growth in VH cases; as such, it is essential to include a margin with adequate depth when performing a biopsy of the epithelium of the lesion. We report an 80-year-old male patient who presented to the Bapuji Dental College & Hospital, Davangere, Karanataka, India, in 2011 with a warty whitish-pink growth on the inside of his cheek. The patient was treated with wide surgical excision of the lesion and a diagnosis of VH was made based on histopathological features. There was no evidence of recurrence at a five-year follow-up. This report highlights the histological variations, pathogenesis and differential diagnosis of VH. PMID:28417036

  8. Value of Ultrasound in the Diagnosis of Chronic Renal Failure With Parathyroid Hyperplasia%超声对慢性肾功能衰竭继发甲状旁腺增生的诊断价值

    Institute of Scientific and Technical Information of China (English)

    王建敏

    2016-01-01

    目的:探析超声对慢性肾功能衰竭继发甲状旁腺增生的诊断价值。方法选择我院2015年3月~2016年2月收治的80例慢性肾功能衰竭患者为研究对象,采用超声对甲状旁腺进行检查,并观察患者形态;内部回声等情况。结果超声检查结果发现甲状旁腺增生共有105枚,病理检查显示甲状旁腺增生病灶有96枚,淋巴结反应性增生22枚;超声诊断符合率为91.43%(P<0.05)。结论超声可有效查出甲状旁腺增生,是一种具有高价值的影像筛查法。%Objective To explore the value of ultrasonography in the diagnosis of parathyroid hyperplasia secondary to chronic renal failure. Methods 80 cases of chronic renal failure in our hospital from March 2015 to February 2016 were selected as the study subjects,the parathyroid glands were examined by ultrasound,and the morphology of the patients were observed and the internal echo was observed in cases. Results The results of ultrasound examination revealed that there were 105 parathyroid glands. The pathological examination showed that there were 96 lesions in the parathyroid gland and 22 lymph node reactive hyperplasia. The diagnostic accuracy rate was 91.43%(P < 0.05). Conclusion Ultrasound can be effective in the treatment of parathyroid hyperplasia,and it is a kind of imaging method with high value. It is worth of clinical application and promotion.

  9. 多巴胺受体和脂筏对高血压患者细胞NADPH氧化酶的作用%Dopamine receptor and raft lipids regulate NADPH oxidase activity in hypertensive renal proximal tubule cells

    Institute of Scientific and Technical Information of China (English)

    鹿敏; 刘晓颖; 韩卫星

    2013-01-01

    目的 探讨还原型烟酰胺腺嘌呤二核苷酸磷酸氧化酶(NADPH氧化酶即Nox)亚单位在高血压患者肾脏近曲小管细胞中的表达及其活性变化,以及多巴胺受体和脂筏在其中的调节作用.方法 细胞分为正常组和高血压组,未经任何药物刺激的两组细胞分别作为正常对照组和高血压对照组,采用葡萄糖浓度梯度超速离心法提取细胞膜的脂筏和非脂筏区蛋白,经Western blot检测Nox亚单位蛋白的表达,光泽精化学发光法动态测定细胞膜Nox的活性.结果 多巴胺受体激动剂fenoldopam明显减少gp91phox在正常对照组[(17±3.3)%]和高血压对照组[(20±3.4)%,P<0.05]细胞膜脂筏区域的表达,降低正常对照组p22phox[(15±2.0)%,P<0.05]、p67phox、rac1在脂筏区的表达,但不能减少高血压对照组p22phox、p67phox、rac1蛋白的表达;胆固醇耗竭剂β-CD减少正常对照组gp91phox、p22phox在脂筏区的表达,不能减少高血压对照组Nox亚单位的表达;高血压对照组Nox的基础活性是正常对照组的5倍.结论 高血压患者肾脏近曲小管细胞具有较高的Nox亚单位的活性,多巴胺受体和脂筏对Nox亚单位的抑制作用减弱.%Objective To investigate the expression and activity of NADPH oxidase ( Nox ) subunit in hypertensive renal proximal tubule cells ( HT ) and the regulatory role of dopamine receptors and lipid boat. Methods Cells were seperated into normotensive group( NT ) and hypertensive group ( HT ), and their respective control group was established by learing the cells intact. Glucose concentration gradient was used to extract cell membrane lipid rafts and non-lipid rafts region. The expression levels of Nox subunits were detected by Western blot, and NADPH oxidase activity were measured by Lucigenin Chemiluminescence. Results Compared with control group, dopamine receptor agonist of fenoldopam significantly reduced gp91 expression in membrane lipid raft regions both in NT[ (17 ±3

  10. Targeting Strategies for Renal Cell Carcinoma: From Renal Cancer Cells to Renal Cancer Stem Cells

    OpenAIRE

    Zhi-xiang Yuan; Jingxin Mo; Guixian Zhao; Gang Shu; Hua-lin Fu; Wei Zhao

    2016-01-01

    Renal cell carcinoma (RCC) is a common form of urologic tumor that originates from the highly heterogeneous epithelium of renal tubules. Over the last decade, targeting therapies to renal cancer cells have transformed clinical care for RCC. Recently, it was proposed that renal cancer stem cells (CSCs) isolated from renal carcinomas were responsible for driving tumor growth and resistance to conventional chemotherapy and radiotherapy, according to the theory of CSCs; this has provided the rati...

  11. Stages of Renal Cell Cancer

    Science.gov (United States)

    ... cell cancer is a disease in which malignant (cancer) cells form in tubules of the kidney. Renal cell ... diagnosed, tests are done to find out if cancer cells have spread within the kidney or to other ...

  12. 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. In Drosophila, the Malpighian tubules are thought to be very stable and no stem cells have been identified.

  13. Re-evaluation of the kidney tumors and renal histopathology occurring in a 2-year rat carcinogenicity bioassay of quercetin.

    Science.gov (United States)

    Hard, Gordon C; Seely, John Curtis; Betz, Laura J; Hayashi, Shim-Mo

    2007-04-01

    Renal histopathology in the most recent 2-year carcinogenicity bioassay of quercetin, in Fischer 344 rats, was re-evaluated in an attempt to determine a mode of action underlying a small increase in renal tubule tumors reported in the males (). The re-evaluation confirmed the reported increase in renal tumors in mid- and high-dose males, including a single carcinoma in a high-dose male, as well as an exacerbation of spontaneous, chronic progressive nephropathy (CPN) in male rats only. The re-evaluation also showed that there were no cellular alterations in the kidney indicative of chemical toxicity at 6 months, 15 months, or 2 years. The evidence linked the occurrence of the predominant basophilic adenomas and foci of atypical tubule hyperplasia (ATH) with the exacerbation of CPN to advanced grades of severity, supporting a mode of action involving quercetin interaction with CPN. This mode of action represents a secondary mechanism for renal tumor development, with no relevance for extrapolation to humans. In addition, the single carcinoma present in the high-dose males, along with 4 other lesions ranging from ATH to adenoma in male and female groups, were considered to have a unique phenotype associated previously with neoplasms of spontaneous and familial origin.

  14. Renal failure

    Institute of Scientific and Technical Information of China (English)

    1993-01-01

    930150 Epidermal growth factor and its recep-tor in the renal tissue of patients with acute re-nal failure and normal persons.LIU Zhihong(刘志红),et al.Jinling Hosp,Nanjing,210002.Natl Med J China 1992;72(10):593-595.Epidermal growth factor(EGF)and its receptor(EGF-R)were identified by immunohis-tochemical method(4 layer PAP)in the renaltissue specimens obtained from 11 normal kid-neys and 17 cases of acute renal failure(ARF).The quantitative EGF and EGF-R in the tissuewere expressed as positive tubules per mm~2.The amount of EGF and EGF-R in renal tissue

  15. A new look at electrolyte transport in the distal tubule.

    Science.gov (United States)

    Eladari, Dominique; Chambrey, Régine; Peti-Peterdi, Janos

    2012-01-01

    The distal nephron plays a critical role in the renal control of homeostasis. Until very recently most studies focused on the control of Na(+), K(+), and water balance by principal cells of the collecting duct and the regulation of solute and water by hormones from the renin-angiotensin-aldosterone system and by antidiuretic hormone. However, recent studies have revealed the unexpected importance of renal intercalated cells, a subtype of cells present in the connecting tubule and collecting ducts. Such cells were thought initially to be involved exclusively in acid-base regulation. However, it is clear now that intercalated cells absorb NaCl and K(+) and hence may participate in the regulation of blood pressure and potassium balance. The second paradigm-challenging concept we highlight is the emerging importance of local paracrine factors that play a critical role in the renal control of water and electrolyte balance.

  16. Benign prostate hyperplasia (BPH) - resources

    Science.gov (United States)

    Resources - benign prostatic hyperplasia (BPH); Prostate enlargement resources; BPH resources ... The following organizations provide information on benign prostatic hyperplasia ( prostate enlargement ... Urology Care Foundation -- www. ...

  17. Transport of a fluorescent cAMP analog in teleost proximal tubules

    NARCIS (Netherlands)

    Reichel, V.; Masereeuw, R.; Heuvel, J.J.M.W. van den; Miller, D.S.; Fricker, G.

    2007-01-01

    Previous studies have shown that killifish (Fundulus heteroclitus) renal proximal tubules express a luminal membrane transporter that is functionally and immunologically analogous to the mammalian multidrug resistance-associated protein isoform 2 (Mrp2, ABCC2). Here we used confocal microscopy to in

  18. Glycogen accumulation in the pars recta of the proximal tubule in Fanconi syndrome.

    Science.gov (United States)

    Bendon, R W; Hug, G

    1986-01-01

    We reviewed the renal pathology in 10 cases of renal Fanconi syndrome. Five cases showed the Armanni-Ebstein lesion, i.e., clear glycogen-filled cells limited to the pars recta of the proximal tubules. The 5 cases included 2 siblings with a unique syndrome characterized by death in infancy, severe Fanconi syndrome, severe rickets, carnitine deficiency, and atrophy of the exocrine pancreas. Two other siblings had glycogen storage disease type XI. One of 4 cases of putative tyrosinemia had the lesion. The ultrastructure was studied in 2 cases. The Armanni-Ebstein lesion in these cases was morphologically indistinguishable from that seen in diabetic patients dying after prolonged hyperglycemia. Glycosuria is the only common factor in both diabetic hyperglycemia and the varied proximal tubular diseases studied. The mechanism of the glycogen accumulation in this short parts recta segment of the proximal renal tubule was further investigated by reviewing the renal histology in cases of glycogen storage disease types I, II, III, and VIII. None showed the Armanni-Ebstein lesion, but type I showed glycogen deposition throughout the proximal tubule. Thus, the Armanni-Ebstein lesion is not the result of an enzymatic deficiency for glycogen synthesis in the convoluted tubules.

  19. New molecular players facilitating Mg(2+) reabsorption in the distal convoluted tubule.

    NARCIS (Netherlands)

    Glaudemans, B.; Knoers, N.V.A.M.; Hoenderop, J.G.J.; Bindels, R.J.M.

    2010-01-01

    The renal distal convoluted tubule (DCT) has an essential role in maintaining systemic magnesium (Mg(2+)) concentration. The DCT is the final determinant of plasma Mg(2+) levels, as the more distal nephron segments are largely impermeable to Mg(2+). In the past decade, positional candidate strategie

  20. New molecular players facilitating Mg(2+) reabsorption in the distal convoluted tubule.

    NARCIS (Netherlands)

    Glaudemans, B.; Knoers, N.V.A.M.; Hoenderop, J.G.J.; Bindels, R.J.M.

    2010-01-01

    The renal distal convoluted tubule (DCT) has an essential role in maintaining systemic magnesium (Mg(2+)) concentration. The DCT is the final determinant of plasma Mg(2+) levels, as the more distal nephron segments are largely impermeable to Mg(2+). In the past decade, positional candidate strategie

  1. Isolation of surface tubules of fowlpox virus.

    Science.gov (United States)

    Carter, J K; Cheville, N F

    1981-01-01

    Surface tubules of fowlpox virus were isolated using chemical and physical methods. Suspensions of lipid cytoplasmic inclusion bodies were obtained by treating infected chorioallantoic membranes with 1% trypsin. Inclusions were treated with ultrasonic sound, detergents, and enzymes and were examined by electron microscopy. Although lipase treatment altered the morphology of lipid inclusions, no viral surface tubules were recovered. Treatment with the detergent Nonidet-P40 followed by 2-mercaptoethanol disrupted virions without allowing surface tubules to be recovered. Disruption of lipid inclusions by ultrasonic sound or manual grinding of chorioallantoic membranes produced free virions but only small numbers of tubules. These results indicate that surface tubules can be recovered, but that the lipid nature of cytoplasmic inclusions interferes with procedures commonly used in tubule purification.

  2. Angiolymphoid Hyperplasia With Eosinophilia

    Directory of Open Access Journals (Sweden)

    Rath Namita

    2002-01-01

    Full Text Available Angiolymphoid hyperplasia with eosinophilia is a disease of the occident. It is mainly seen in middle aged women. It presents as multiple small pink or purple popular or nodular eruptions, in the head and neck area. Lesions of angiolymphoid hyperplasia with eosinophilia are often confused with lesions of Kimura’s disease, which is more common in young males. We report a case of angiolymphoid hyperplasia with eosinophilia in a 34 year old female. The patient is responding to monthly intralesional triamcinolone acetate along with cryotherapy with liquid nitrogen. This case is being reported due to its rarity in Indian patients.

  3. Treatment Options for Renal Cell Cancer

    Science.gov (United States)

    ... cell cancer is a disease in which malignant (cancer) cells form in tubules of the kidney. Renal cell ... diagnosed, tests are done to find out if cancer cells have spread within the kidney or to other ...

  4. General Information about Renal Cell Cancer

    Science.gov (United States)

    ... cell cancer is a disease in which malignant (cancer) cells form in tubules of the kidney. Renal cell ... diagnosed, tests are done to find out if cancer cells have spread within the kidney or to other ...

  5. Treatment Option Overview (Renal Cell Cancer)

    Science.gov (United States)

    ... cell cancer is a disease in which malignant (cancer) cells form in tubules of the kidney. Renal cell ... diagnosed, tests are done to find out if cancer cells have spread within the kidney or to other ...

  6. Reactive oxygen species and IRF1 stimulate IFNα production by proximal tubules during ischemic AKI

    Science.gov (United States)

    Winterberg, Pamela D.; Wang, Yanxia; Lin, Keng-Mean; Hartono, John R.; Nagami, Glenn T.; Zhou, Xin J.; Shelton, John M.; Richardson, James A.

    2013-01-01

    We previously reported that expression of the transcription factor interferon regulatory factor 1 (IRF1) is an early, critical maladaptive signal expressed by renal tubules during murine ischemic acute kidney injury (AKI). We now show that IRF1 mediates signals from reactive oxygen species (ROS) generated during ischemic AKI and that these signals ultimately result in production of α-subtypes of type I interferons (IFNαs). We found that genetic knockout of the common type I IFN receptor (IFNARI−/−) improved kidney function and histology during AKI. There are major differences in the spatial-temporal production of the two major IFN subtypes, IFNβ and IFNαs: IFNβ expression peaks at 4 h, earlier than IFNαs, and continues at the same level at 24 h; expression of IFNαs also increases at 4 h but continues to increase through 24 h. The magnitude of the increase in IFNαs relative to baseline is much greater than that of IFNβ. We show by immunohistology and study of isolated cells that IFNβ is produced by renal leukocytes and IFNαs are produced by renal tubules. IRF1, IFNαs, and IFNARI were found on the same renal tubules during ischemic AKI. Furthermore, we found that ROS induced IFNα expression by renal tubules in vitro. This expression was inhibited by small interfering RNA knockdown of IRF1. Overexpression of IRF1 resulted in the production of IFNαs. Furthermore, we found that IFNα stimulated production of maladaptive proinflammatory CXCL2 by renal tubular cells. Altogether our data support the following autocrine pathway in renal tubular cells: ROS > IRF1 > IFNα > IFNARI > CXCL2. PMID:23657854

  7. Angiolymphoid hyperplasia with eosinophilia

    National Research Council Canada - National Science Library

    Farhadian, Joshua A; Shvartsbeyn, Marianna; Meehan, Shane A; Urbanek, Richard W

    2015-01-01

    Angiolymphoid hyperplasia with eosinophilia is a rare, benign, vascular proliferation that presents as dome-shaped, light-pink-to-red-brown papules or subcutaneous masses that lack distinguishing surface changes...

  8. Congenital Adrenal Hyperplasia

    National Research Council Canada - National Science Library

    Speiser, Phyllis W

    2015-01-01

    Congenital adrenal hyperplasia associated with deficiency of steroid 21-hydroxylase is the most common inborn error in adrenal function and the most common cause of adrenal insufficiency in the pediatric age group...

  9. Congenital adrenal hyperplasia

    Science.gov (United States)

    ... to treat congenital adrenal hyperplasia do not usually cause side effects such as obesity or weak bones, because the doses replace the hormones that the child's body cannot make. It is important for parents ...

  10. Membrane tubulation by elongated and patchy nanoparticles

    CERN Document Server

    Raatz, Michael

    2016-01-01

    Advances in nanotechnology lead to an increasing interest in how nanoparticles interact with biomembranes. Nanoparticles are wrapped spontaneously by biomembranes if the adhesive interactions between the particles and membranes compensate for the cost of membrane bending. In the last years, the cooperative wrapping of spherical nanoparticles in membrane tubules has been observed in experiments and simulations. For spherical nanoparticles, the stability of the particle-filled membrane tubules strongly depends on the range of the adhesive particle-membrane interactions. In this article, we show via modeling and energy minimization that elongated and patchy particles are wrapped cooperatively in membrane tubules that are highly stable for all ranges of the particle-membrane interactions, compared to individual wrapping of the particles. The cooperative wrapping of linear chains of elongated or patchy particles in membrane tubules may thus provide an efficient route to induce membrane tubulation, or to store such...

  11. Hyperplasia and endometrial precancer

    Directory of Open Access Journals (Sweden)

    O. A. Gornikh

    2011-01-01

    Full Text Available Hyperplastic process is nothing but excessive proliferation determining by histological or cytological method. Extending of theprecancer" conception including not only atypical endometrial hyperplasia but also other pathological changes of the endometriu m (glandu- lar-cystic hyperplasia, polyposis, with the marked endocrine and metabolic disorders background is of some scientific interest and encour- ages a search for a wide range of hypothetical pathogenetic mechanisms and w ays to prevent precancer and endometrial cancer . However, such an extension of the view on the endometrial precancer is not an equivalent of the nosological diagnosis which involves anexact morpho- logic substrate of the pathological process and a specific treatment policy.

  12. [Focal epithelial hyperplasia].

    Science.gov (United States)

    Vera-Iglesias, E; García-Arpa, M; Sánchez-Caminero, P; Romero-Aguilera, G; Cortina de la Calle, P

    2007-11-01

    Focal epithelial hyperplasia is a rare disease of the oral mucosa caused by the human papilloma virus (HPV). It appears as a benign epithelial growth, usually in the mucosa of the lower lip. It is mainly associated with HPV serotypes 13 and 32 and there is a clear racial predilection for the disease in Native Americans and Eskimos. We describe the case of a 17-year-old girl from Ecuador with multiple papular lesions in both lips that were clinically and histologically consistent with focal epithelial hyperplasia. Analysis by polymerase chain reaction detected HPV serotype 13.

  13. Mitochondrial DNA deletion of proximal tubules is the result of itai-itai disease.

    Science.gov (United States)

    Takebayashi, Shigeo; Jimi, Shiro; Segawa, Masaru; Takaki, Aya

    2003-03-01

    The pathogenesis of itai-itai disease continues to be controversial, although cadmium (Cd) poisoning which arises via polluted water and rice in Japan is likely involved. Until recently, however, a well-defined animal model for Cd intoxication was not available. An animal model for itai-itai disease was produced in rats by low-dose Cd treatment, intraperitoneally for a period of 70-80 weeks. Osteomalacia followed the renal damage. A gene deletion in the mitochondrial DNA was found in the mitochondria of the proximal tubule cells of rats with chronic Cd intoxication, as was shown by the increased smaller PCR product seen by gel electrophoresis in one DNA region, where ATPase and cytochrome oxidase genes are located. However, the PCR product was different from that seen with a gene deletion associated with aging: del4834bp. Renal damage from Cd intoxication initially caused mitochondrial dysfunction indicated by the disturbance in reabsorption in the proximal tubules and decreased amounts of ATP, ATPase, and cytochrome oxidase with gradually progressing tubular proteinuria, and, finally, chronic renal failure with tubulointerstitial damage throughout the renal cortex. These gave rise to osteomalacia, subsequently. We concluded that in Cd poisoning, a mitochondrial gene deletion in the mitochondria of the proximal tubule cells was the primary event for the pathogenesis of osteomalacia in itai-itai disease.

  14. Benign Prostatic Hyperplasia

    Science.gov (United States)

    ... prostate gets bigger, it may press on the urethra and cause the flow of urine to be slower and less forceful. "Benign" means the enlargement isn't caused by cancer or infection. "Hyperplasia" means enlargement. SymptomsWhat are the ...

  15. Subareolar Sclerosing Ductal Hyperplasia.

    Science.gov (United States)

    Cheng, Esther; D'Alfonso, Timothy M; Arafah, Maria; Marrero Rolon, Rebecca; Ginter, Paula S; Hoda, Syed A

    2017-02-01

    Subareolar sclerosing duct hyperplasia (SSDH) remains to be fully characterized nearly 20 years after initial description. Thirty-five SSDH cases diagnosed over a 16-year period (January 2000 to December 2015) were reviewed. All patients were female (mean age = 59 years, range = 18-80) who had presented with a unilateral solitary lesion (left 22, right 13) with a mean size of 1.3 cm (range = 0.4-3.0 cm), and showed florid and papillary epithelial hyperplasia with dense sclerosis without involvement of nipple or areolar epidermis. Significant lesions concurrent within SSDH included low-grade adenosquamous carcinoma (n = 1), ductal carcinoma in situ (DCIS; n = 1), lobular carcinoma in situ (LCIS; n = 1), and atypical ductal hyperplasia (ADH; n = 13). No case of SSDH recurred in a mean follow-up of 44 months (range = 6-189). Subsequent significant lesions occurred in 6 patients: DCIS (n = 3; ipsilateral 2, contralateral 1), ipsilateral ADH (n = 2), and ipsilateral atypical lobular hyperplasia (n = 1). Long-term follow-up for patients with SSDH is indicated as DCIS can occur subsequently in either breast.

  16. Development of Pulsating Tubules with Chiral Inversion

    Science.gov (United States)

    2013-09-21

    assemblies, such as tubules, toroids , porous capsules, and helical fibers, by adjusting the relative volume fraction between hydrophobic and hydrophilic...1 could change their shape into helical tubules at higher and discrete macrocycles at lower concentrations. Metal- containing macrocycles were found to...this direction of research in mind, we synthesized self-assembling molecules 1 and 2 consisting of a long bent-shaped aromatic segment containing m

  17. Calcium Oxalate Accumulation in Malpighian Tubules of Silkworm (Bombyx mori)

    Science.gov (United States)

    Wyman, Aaron J.; Webb, Mary Alice

    2007-04-01

    Silkworm provides an ideal model system for study of calcium oxalate crystallization in kidney-like organs, called Malpighian tubules. During their growth and development, silkworm larvae accumulate massive amounts of calcium oxalate crystals in their Malpighian tubules with no apparent harm to the organism. This manuscript reports studies of crystal structure in the tubules along with analyses identifying molecular constituents of tubule exudate.

  18. Growth factors and cytokines in acute renal failure.

    Science.gov (United States)

    Harris, R C

    1997-04-01

    The mammalian kidney is susceptible to injury by ischemia/reperfusion and toxins, and regeneration after injury is characterized by hyperplasia and recovery of the damaged epithelial cells that line the tubules. Locally produced growth factors may serve as mediators of nephrogenesis and differentiation during renal development and of renal regeneration after acute injury. In cultured cells, administration of one or a mixture of growth factors to quiescent cells will initiate progression through the cell cycle and cell division. In the adult kidney, cell division normally is very low, but will increase up to 10-fold after acute injury. In addition to proliferation after lethal injury, there also is cellular repair in cells that have undergone sublethal injury. Recent studies indicate that growth factors inhibit programmed cell death in response to acute injury. Growth factors also may initiate or promote protein and lipid biosynthesis and provide an intracellular milieu that promotes cellular repair. In addition to cellular repair, growth factors also may be involved in the re-establishment of cell-extracellular matrix and cell-cell integrity. Finally, growth factors may limit injury by decreasing the factors that induce damage. Increased local renal expression of growth factors in response to acute injury include heparin binding epidermal growth factor (HB-EGF), hepatocyte growth factor (HGF), insulin-like growth factor-I (IGF-I), transforming growth factor-beta, parathyroid hormone-related peptide, and acidic fibroblast growth factor. In a number of experimental models of acute renal injury, administration of exogenous growth factors has been shown to accelerate both structural and functional recovery. Specifically, EGF, IGF-1, and HGF all have been shown to be effective in this regard. These studies are reviewed and potential therapeutic uses of growth factors and cytokines will be discussed.

  19. 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.

  20. 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.

  1. 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...

  2. The syndrome of renal tubular acidosis with nerve deafness.

    Science.gov (United States)

    Donckerwolcke, R A; Van Biervliet, J P; Koorevaar, G; Kuijten, R H; Van Stekelenburg, G J

    1976-01-01

    Two brothers with renal tubular acidosis and nerve deafness are described. Studies of the physiopathological characteristics of the renal acidification defect show that the defect is limited to the distal tubule. Renal tubular acidosis with nerve deafness is a distinct nosologic entity that is determined by an autosomal recessive trait.

  3. Benign Prostatic Hyperplasia

    OpenAIRE

    Gil Ortega, Joan

    2015-01-01

    Benign prostatic hyperplasia (BPH) is a prevalent disease but its molecular mechanism remains unknown. Using human tissue samples from 16 patients diagnosed with BPH, we performed an ultrastructural study to clarify the mechanism and the role of glandular cells in this pathology. We have made a description of all the changes that suffers the prostatic epithelium. We have shown that the glandular architecture presents many non-physiological forms such as papillae and papillary fronds. Basal c...

  4. Oral focal epithelial hyperplasia.

    Science.gov (United States)

    López-Jornet, Pía; Camacho-Alonso, Fabio; Berdugo, Lucero

    2010-01-01

    Focal epithelial hyperplasia (FEH) is a benign, asymptomatic disease. It appears as papules, principally on the lower lip, although it can also be found on the retro-commissural mucosa and tongue and, less frequently, on the upper lip, gingiva and palate. FEH is caused by human papillomavirus subtype 13 or 32. The condition occurs in many populations and ethnic groups. We present the clinical case of a 31-year-old male with lesions that clinically and histologically corresponded to FEH.

  5. Value of Prophylactic Cervical Thymectomy in Parathyroid Hyperplasia.

    Science.gov (United States)

    Boltz, Melissa M; Zhang, Ning; Zhao, Carrie; Thiruvengadam, Sujan; Siperstein, Allan E; Jin, Judy

    2015-12-01

    In parathyroid hyperplasia (HPT), parathyroid glands within the cervical thymus are a cause for recurrence. As a result of differences in pathophysiology, variable practice patterns exist regarding performing bilateral cervical thymectomy (BCT) in primary hyperplasia versus hyperplasia from renal failure or familial disease. The objective of this study was to capture patients where thymic tissue was found with subtotal parathyroidectomy (PTX) and intended BCT, identify number of thymic supernumerary glands (SNGs), and determine overall cure rate. Retrospective review of patients with four-gland exploration and intended BCT for HPT from 2000 to 2013 was performed. Identification of thymic tissue and SNGs were determined by operative/pathology reports. Univariate analysis identified differences in cure rate for patients undergoing subtotal PTX with or without BCT. Thymic tissue was found in 52 % of 328 primary HPT (19 % unilateral, 33 % bilateral), 77 % of 128 renal HPT (28 % unilateral, 49 % bilateral), and 100 % of familial HPT (24 % unilateral, 76 % bilateral) patients. Nine percent of primary, 18 % of renal, and 10 % of familial HPT patients had SNGs within thymectomy specimens. Cure rates of primary HPT patients with BCT were 99 % compared to 94 % in subtotal PTX alone. Renal HPT cure rates were 94 % with BCT compared to 89 % without BCT. Renal HPT patients benefited most in cure when thymectomy was performed. Although the rate of SNGs found in primary HPT was lower than renal HPT, the cure rate mimicked the pattern in renal disease. Furthermore, the incidences of SNGs in primary and familial HPT were similar. On the basis of these data, we advocate that BCT be considered in primary HPT when thymic tissue is readily identified.

  6. Occluding effect of dentifrices on dentinal tubules.

    Science.gov (United States)

    Arrais, César Augusto Galvão; Micheloni, Carolina Diniz; Giannini, Marcelo; Chan, Daniel C N

    2003-11-01

    The objective of this study was to evaluate the tubule occluding ability of three commercial available dentifrices (Sensodyne, Emoform and Sorriso) by Scanning Electron Microscopy. Fifty cervical areas from buccal and lingual surfaces of sound third human molars were used. Cervical enamel was wet abraded to expose flat dentin surfaces and further polished with diamond pastes. Specimens were randomly divided into five groups (n=10): G1-no brushing; G2-brushing without dentifrice; G3-brushing with Sensodyne; G4-brushing with Emoform; G5-brushing with Sorriso. Brushed specimens were treated for 4 min per day, for 7 days in a toothbrushing machine. Specimens were prepared and observed under SEM for calculation of the percentage of occluded tubules. In addition, slurries of toothpastes were analyzed by X-ray microanalysis. Data were statistically analyzed by ANOVA and Tukey test (p<0.05). Means of occluded tubules in descending order were: G5-98.83+/-3.31% (a), G4-96.02+/-5.24% (a), G3-80.12+/-24.65% (a), G1-37.31+/-24.22% (b); G2-22.92+/-15.19% (b). The three tested dentifrices produced increased dentinal occlusion as compared to controls (p<0.05) but equivalent occlusion among each other. Calcium from calcium-carbonate abrasive was identified in all dentifrices. Results indicated that the use of all dentifrices occluded tubules more than no brushing and brushing without dentifrices groups. Thus, the tested dentifrices seem effective for desensitization by tubule occlusion.

  7. Renal involvement in antiphospholipid syndrome.

    Science.gov (United States)

    Pons-Estel, Guillermo J; Cervera, Ricard

    2014-02-01

    Renal involvement can be a serious problem for patients with antiphospholipid syndrome (APS). However, this complication has been poorly recognized and studied. It can be present in patients who have either primary or systemic lupus erythematosus-associated APS. Clinical and laboratory features of renal involvement in APS include hypertension, hematuria, acute renal failure, and progressive chronic renal insufficiency with mild levels of proteinuria that can progress to nephrotic-range proteinuria. The main lesions are renal artery stenosis, venous renal thrombosis, and glomerular lesions (APS nephropathy) that may be acute (thrombotic microangiopathy) and/or chronic (arteriosclerosis, arterial fibrous intimal hyperplasia, tubular thyroidization, arteriolar occlusions, and focal cortical atrophy). APS can also cause end-stage renal disease and allograft vascular thrombosis. This article reviews the range of renal abnormalities associated with APS, and their diagnosis and treatment options.

  8. Potential molecular therapy for acute renal failure.

    Science.gov (United States)

    Humes, H D

    1993-01-01

    Ischemic and toxic acute renal failure is reversible, due to the ability of renal tubule cells to regenerate and differentiate into a fully functional lining epithelium. Recent data support the thesis that recruitment or activation of macrophages to the area of injury results in local release of growth factors to promote regenerative repair. Because of intrinsic delay in the recruitment of inflammatory cells, the exogenous administration of growth promoters early in the repair phase of acute renal failure enhances renal tubule cell regeneration and accelerates renal functional recovery in animal models of acute renal failure. Molecular therapy for the acceleration of tissue repair in this disease process may be developed in the near future.

  9. Pathologic pancreatic endocrine cell hyperplasia

    Institute of Scientific and Technical Information of China (English)

    Debra Ouyang; Deepti Dhall; Run Yu

    2011-01-01

    Pathologic hyperplasia of various pancreatic endocrine cells is rare but has been long known. β cell hyperplasia contributes to persistent hyperinsulinemic hypoglycemia of infancy, which is commonly caused by mutations in the islet ATP-sensitive potassium channel, and to noninsulinoma pancreatogenous hypoglycemia in adults,which may or may not be associated with bariatric surgery.α cell hyperplasia may cause glucagonoma syndrome or induce pancreatic neuroendocrine tumors. An inactivating mutation of the glucagon receptor causes α cell hyperplasia and asymptomatic hyperglucagonemia.Pancreatic polypeptide cell hyperplasia has been described without a clearly-characterized clinical syndrome and hyperplasia of other endocrine cells inside the pancreas has not been reported to our knowledge.Based on morphological evidence, the main pathogenetic mechanism for pancreatic endocrine cell hyperplasia is increased endocrine cell neogenesis from exocrine ductal epithelium. Pancreatic endocrine cell hyperplasia should be considered in the diagnosis and management of hypoglycemia, elevated islet hormone levels,and pancreatic neuroendocrine tumors. Further studies of pathologic pancreatic endocrine cell hyperplasia will likely yield insights into the pathogenesis and treatment of diabetes and pancreatic neuroendocrine tumors.

  10. Pathologic pancreatic endocrine cell hyperplasia

    Science.gov (United States)

    Ouyang, Debra; Dhall, Deepti; Yu, Run

    2011-01-01

    Pathologic hyperplasia of various pancreatic endocrine cells is rare but has been long known. β cell hyperplasia contributes to persistent hyperinsulinemic hypoglycemia of infancy, which is commonly caused by mutations in the islet ATP-sensitive potassium channel, and to non-insulinoma pancreatogenous hypoglycemia in adults, which may or may not be associated with bariatric surgery. α cell hyperplasia may cause glucagonoma syndrome or induce pancreatic neuroendocrine tumors. An inactivating mutation of the glucagon receptor causes α cell hyperplasia and asymptomatic hyperglucagonemia. Pancreatic polypeptide cell hyperplasia has been described without a clearly-characterized clinical syndrome and hyperplasia of other endocrine cells inside the pancreas has not been reported to our knowledge. Based on morphological evidence, the main pathogenetic mechanism for pancreatic endocrine cell hyperplasia is increased endocrine cell neogenesis from exocrine ductal epithelium. Pancreatic endocrine cell hyperplasia should be considered in the diagnosis and management of hypoglycemia, elevated islet hormone levels, and pancreatic neuroendocrine tumors. Further studies of pathologic pancreatic endocrine cell hyperplasia will likely yield insights into the pathogenesis and treatment of diabetes and pancreatic neuroendocrine tumors. PMID:21245985

  11. Invasion of dentinal tubules by oral bacteria.

    Science.gov (United States)

    Love, R M; Jenkinson, H F

    2002-01-01

    Bacterial invasion of dentinal tubules commonly occurs when dentin is exposed following a breach in the integrity of the overlying enamel or cementum. Bacterial products diffuse through the dentinal tubule toward the pulp and evoke inflammatory changes in the pulpo-dentin complex. These may eliminate the bacterial insult and block the route of infection. Unchecked, invasion results in pulpitis and pulp necrosis, infection of the root canal system, and periapical disease. While several hundred bacterial species are known to inhabit the oral cavity, a relatively small and select group of bacteria is involved in the invasion of dentinal tubules and subsequent infection of the root canal space. Gram-positive organisms dominate the tubule microflora in both carious and non-carious dentin. The relatively high numbers of obligate anaerobes present-such as Eubacterium spp., Propionibacterium spp., Bifidobacterium spp., Peptostreptococcus micros, and Veillonella spp.-suggest that the environment favors growth of these bacteria. Gram-negative obligate anaerobic rods, e.g., Porphyromonas spp., are less frequently recovered. Streptococci are among the most commonly identified bacteria that invade dentin. Recent evidence suggests that streptococci may recognize components present within dentinal tubules, such as collagen type I, which stimulate bacterial adhesion and intra-tubular growth. Specific interactions of other oral bacteria with invading streptococci may then facilitate the invasion of dentin by select bacterial groupings. An understanding the mechanisms involved in dentinal tubule invasion by bacteria should allow for the development of new control strategies, such as inhibitory compounds incorporated into oral health care products or dental materials, which would assist in the practice of endodontics.

  12. Proximal Tubule Glutamine Synthetase Expression is Necessary for the Normal Response to Dietary Protein Restriction.

    Science.gov (United States)

    Lee, Hyun-Wook; Osis, Gunars; Handlogten, Mary E; Verlander, Jill W; Weiner, I David

    2017-03-22

    Dietary protein restriction has multiple benefits in kidney disease. Because protein intake is a major determinant of endogenous acid production, it is important that net acid excretion change in parallel during changes in dietary protein intake. Dietary protein restriction decreases endogenous acid production and ¬decreases urinary ammonia excretion, a major component of net acid excretion. Glutamine synthetase (GS) catalyzes the reaction of NH4+ and glutamate, which regenerates the essential amino acid glutamine and decreases net ammonia generation. Because renal proximal tubule GS expression increases during dietary protein restriction, this could contribute to the decreased ammonia excretion. The current study's purpose was to determine proximal tubule GS's role in the renal response to protein restriction. We generated mice with proximal tubule-specific GS deletion (PT-GS-KO) using Cre-loxP techniques. Cre-negative (Control) and PT-GS-KO mice in metabolic cages were provided 20% protein diet for 2 days and were then changed to low protein (6%) diet for the next 7 days. Additional PT-GS-KO mice were maintained on 20% protein diet. Dietary protein restriction caused a rapid decrease in urinary ammonia excretion in both genotypes, but PT-GS-KO blunted this adaptive response significantly. This occurred despite no significant genotype-dependent differences in urinary pH or in serum electrolytes. There were no significant differences between Control and PT-GS-KO mice in expression of multiple other proteins involved in renal ammonia handling. We conclude that proximal tubule glutamine synthetase expression is necessary for the appropriate decrease in ammonia excretion during dietary protein restriction.

  13. FGF23 regulates renal sodium handling and blood pressure

    OpenAIRE

    Andrukhova, Olena; Slavic, Svetlana; Smorodchenko, Alina; Zeitz, Ute; Shalhoub, Victoria; Lanske, Beate; Pohl, Elena E.; Erben, Reinhold G.

    2014-01-01

    Fibroblast growth factor-23 (FGF23) is a bone-derived hormone regulating renal phosphate reabsorption and vitamin D synthesis in renal proximal tubules. Here, we show that FGF23 directly regulates the membrane abundance of the Na+:Cl− co-transporter NCC in distal renal tubules by a signaling mechanism involving the FGF receptor/αKlotho complex, extracellular signal-regulated kinase 1/2 (ERK1/2), serum/glucocorticoid-regulated kinase 1 (SGK1), and with-no lysine kinase-4 (WNK4). Renal sodium (...

  14. Nonclassic Congenital Adrenal Hyperplasia

    Directory of Open Access Journals (Sweden)

    Selma Feldman Witchel

    2010-01-01

    Full Text Available Nonclassic congenital adrenal hyperplasia (NCAH due to P450c21 (21-hydroxylase deficiency is a common autosomal recessive disorder. This disorder is due to mutations in the CYP21A2 gene which is located at chromosome 6p21. The clinical features predominantly reflect androgen excess rather than adrenal insufficiency leading to an ascertainment bias favoring diagnosis in females. Treatment goals include normal linear growth velocity and “on-time” puberty in affected children. For adolescent and adult women, treatment goals include regularization of menses, prevention of progression of hirsutism, and fertility. This paper will review key aspects regarding pathophysiology, diagnosis, and treatment of NCAH.

  15. Dentin tubule occluding ability of dentin desensitizers.

    Science.gov (United States)

    Han, Linlin; Okiji, Takashi

    2015-04-01

    To compare the dentin tubule-occluding ability of fluoroaluminocalciumsilicate-based (Nanoseal), calcium phosphate-based (Teethmate Desensitizer), resin-containing oxalate (MS Coat ONE) and diamine silver fluoride (Saforide) dentin desensitizers using artificially demineralized bovine dentin. Simulated hypersensitive dentin was created using cervical dentin sections derived from bovine incisors using phosphoric acid etching followed by polishing with a paste containing hydroxyapatite. The test desensitizers were applied in one, two, or three cycles, where each cycle involved desensitizer application, brushing, and immersion in artificial saliva (n= 5 each). The dentin surfaces were examined with scanning electron microscopy, and the dentin tubule occlusion rate was calculated. The elemental composition of the deposits was analyzed with electron probe microanalysis. Data were analyzed by one-way ANOVA and the Tukey honestly significant different test. Marked deposit formation was observed on the specimens treated with Nanoseal or Teethmate Desensitizer, and tags were detected in the specimens' dentin tubules. These findings became more prominent as the number of application cycles increased. The major elemental components of the tags were Ca, F, and Al (Nanoseal) and Ca and P (Teethmate Desensitizer). The tubule occlusion rates of MS Coat ONE and Saforide were significantly lower than those of Nanoseal and Teethmate Desensitizer (P< 0.05).

  16. Oncocytic hyperplasia of the larynx.

    Science.gov (United States)

    Thawley, S E; Berlin, B P; Berkowitz, W P

    1977-07-01

    Oncocytic hyperplasia of the larynx is rare. The lesion most commonly arises from the false vocal chord. A distinction arises between oncocytomas of the salivary glands which are considered to be neoplasms and extrasalivary oncocytic lesions which are secondary to hyperplasia. Oncocytic lesions of the larynx are benign and treatment is excision. They may be multiple, but recurrences are rare.

  17. Renal histology and immunopathology in distal renal tubular acidosis.

    Science.gov (United States)

    Feest, T G; Lockwood, C M; Morley, A R; Uff, J S

    1978-11-01

    Renal biospy studies are reported from 10 patients with distal renal tubular acidosis (DRTA). On the biopsies from 6 patients who had associated immunological abnormalities immunofluorescent studies for immunoglobulins, complement, and fibrin were performed. Interstitial cellular infiltration and fibrosis were common findings in patients with and without immunological abnormalities, and were usually associated with nephrocalcinosis and/or recurrent urinary infection. No immune deposits were demonstrated in association with the renal tubules. This study shows that DRTA in immunologically abnormal patients is not caused by tubular deposition of antibody or immune complexes. The possibility of cell mediated immune damage is discussed.

  18. Megalin and cubilin in proximal tubule protein reabsorption: from experimental models to human disease.

    Science.gov (United States)

    Nielsen, Rikke; Christensen, Erik Ilsø; Birn, Henrik

    2016-01-01

    Proximal tubule protein uptake is mediated by 2 receptors, megalin and cubilin. These receptors rescue a variety of filtered ligands, including biomarkers, essential vitamins, and hormones. Receptor gene knockout animal models have identified important functions of the receptors and have established their essential role in modulating urinary protein excretion. Rare genetic syndromes associated with dysfunction of these receptors have been identified and characterized, providing additional information on the importance of these receptors in humans. Using various disease models in combination with receptor gene knockout, the implications of receptor dysfunction in acute and chronic kidney injury have been explored and have pointed to potential new roles of these receptors. Based on data from animal models, this paper will review current knowledge on proximal tubule endocytic receptor function and regulation, and their role in renal development, protein reabsorption, albumin uptake, and normal renal physiology. These findings have implications for the pathophysiology and diagnosis of proteinuric renal diseases. We will examine the limitations of the different models and compare the findings to phenotypic observations in inherited human disorders associated with receptor dysfunction. Furthermore, evidence from receptor knockout mouse models as well as human observations suggesting a role of protein receptors for renal disease will be discussed in light of conditions such as chronic kidney disease, diabetes, and hypertension.

  19. Cadmium transport by the gut and Malpighian tubules of Chironomus riparius

    Energy Technology Data Exchange (ETDEWEB)

    Leonard, Erin M., E-mail: leonarem@mcmaster.ca [Department of Biology, McMaster University, Hamilton, ON, L8S 4K1 (Canada); Pierce, Laura M. [Department of Biology, McMaster University, Hamilton, ON, L8S 4K1 (Canada); Gillis, Patricia L. [Aquatic Ecosystem Protection Research Division, Environment Canada, Burlington, ON, L7R 4A6 (Canada); Wood, Chris M.; O' Donnell, Michael J. [Department of Biology, McMaster University, Hamilton, ON, L8S 4K1 (Canada)

    2009-05-05

    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{sup 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 {mu}mol l{sup -1} Cd, the tubules can secrete the entire hemolymph burden of Cd in {approx}15 h.

  20. Renal rickets-practical approach

    Directory of Open Access Journals (Sweden)

    Manisha Sahay

    2013-01-01

    Full Text Available 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.

  1. Congenital hemifacial hyperplasia

    Directory of Open Access Journals (Sweden)

    S A Deshingkar

    2011-01-01

    Full Text Available Congenital hemifacial hyperplasia (CHH is a rare congenital malformation characterized by marked unilateral overdevelopment of hard and soft tissues of the face. Asymmetry in CHH is usually evident at birth and accentuated with age, especially at puberty. The affected side grows at a rate proportional to the nonaffected side so that the disproportion is maintained thr oughout the life. Multisystem involvement has resulted in etiological heterogeneity including heredity, chromosomal abnormalities, atypical forms of twinning, altered intrauterine environment, and endocrine dysfunctions; however, no single theory explains the etiology adequately. Deformities of all tissues of face, including teeth and their related tissues in the jaw, are key findings for correct diagnosis of CHH. Here an attempt has been made to present a case of CHH with its archetypal features and to supplement existing clinical knowledge.

  2. Extensive focal epithelial hyperplasia.

    Science.gov (United States)

    Hashemipour, Maryam Alsadat; Shoryabi, Ali; Adhami, Shahrzad; Mehrabizadeh Honarmand, Hoda

    2010-01-01

    Heck's disease or focal epithelial hyperplasia is a benign contagious disease caused by human papillomavirus types 13 or 32. It occurs with low frequency in the Iranian population. This condition is characterized by the occurrence of multiple, small papules or nodules in the oral cavity, especially on the labial and buccal mucosa and tongue. In some populations, up to 39% of children are affected. Conservative surgical excision of lesions may be performed for diagnostic or aesthetic purposes. The risk of recurrence after this therapy is minimal, and there seems to be no malignant transformation potential. In the present work, we presented the clinical case of a 12-year-old Iranian girl with oral lesions that clinically and histologically correspond to Heck's disease.

  3. 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

    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 (blood pressure to 51 +/- 3 mmHg, decreased urine output, and shifted NHE3 and NaPi2 out of the low......-density membranes enriched in apical markers. PTH at much lower doses (blood pressure and was diuretic. In conclusion, acute hypotension per se increases proximal tubule Na(+) reabsorption without changing NHE3 or NaPi2 subcellular distribution, indicating that trafficking...... in renal cortical membranes fractionated on sorbitol density gradients. Aortic clamp-induced acute hypotension (from 100 +/- 3 to 78 +/- 2 mmHg) provoked a 62% decrease in urine output and a significant decrease in volume flow from the proximal tubule detected as a 66% decrease in endogenous lithium...

  4. 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.

  5. Transport of a fluorescent cAMP analog in teleost proximal tubules.

    Science.gov (United States)

    Reichel, Valeska; Masereeuw, Rosalinde; van den Heuvel, Jeroen J M W; Miller, David S; Fricker, Gert

    2007-12-01

    Previous studies have shown that killifish (Fundulus heteroclitus) renal proximal tubules express a luminal membrane transporter that is functionally and immunologically analogous to the mammalian multidrug resistance-associated protein isoform 2 (Mrp2, ABCC2). Here we used confocal microscopy to investigate in killifish tubules the transport of a fluorescent cAMP analog (fluo-cAMP), a putative substrate for Mrp2 and Mrp4 (ABCC4). Steady-state luminal accumulation of fluo-cAMP was concentrative, specific, and metabolism-dependent, but not reduced by high K+ medium or ouabain. Transport was not affected by p-aminohippurate (organic anion transporter inhibitor) or p-glycoprotein inhibitor (PSC833), but cell-to-lumen transport was reduced in a concentration-dependent manner by Mrp inhibitor MK571, leukotriene C4 (LTC4), azidothymidine (AZT), cAMP, and adefovir; the latter two compounds are Mrp4 substrates. Although MK571 and LTC4 reduced transport of the Mrp2 substrate fluorescein-methotrexate (FL-MTX), neither cAMP, adefovir, nor AZT affected FL-MTX transport. Fluo-cAMP transport was not reduced when tubules were exposed to endothelin-1, Na nitroprusside (an nitric oxide generator) or phorbol ester (PKC activator), all of which signal substantial reductions in cell-to-lumen FL-MTX transport. Fluo-cAMP transport was reduced by forskolin, and this reduction was blocked by the PKA inhibitor H-89. Finally, in membrane vesicles from Spodoptera frugiperda (Sf9) cells containing human MRP4, ATP-dependent and specific uptake of fluo-cAMP could be demonstrated. Thus, based on inhibitor specificity and regulatory signaling, cell-to-lumen transport of fluo-cAMP in killifish renal tubules is mediated by a transporter distinct from Mrp2, presumably a teleost form of Mrp4.

  6. Spontaneous renal tumors in two rats from a thirteen week rodent feeding study with grain from molecular stacked trait lepidopteran and coleopteran resistant (DP-ØØ4114-3) maize.

    Science.gov (United States)

    Hardisty, Jerry F; Banas, Deborah A; Gopinath, Chirukandath; Hall, William C; Hard, Gordon C; Takahashi, Michihito

    2013-03-01

    A thirteen week feeding study was conducted by feeding young adult male and female Sprague Dawley [Crl:CD®(SD)] rats diets containing grain from genetically modified (GM) DP-ØØ4114-3 maize that was either untreated (4114) or treated in the field with glufosinate ammonium (4114GLU). Control rats were fed diets containing the same concentration of near isogenic, non-GM maize grain (091) or one of three types of commercially available non-GM maize grain. At the end of the in-life phase, renal tubule tumors were reported in two male rats consuming diets containing 4114 maize grain. An expert panel of pathologists was convened as a Pathology Working Group (PWG) to review coded kidney histology sections from control (091) and treated (4114 and 4114GLU) male rats. The objectives were for the panel to characterize the histopathologic findings and to interpret their relationship to consumption of the indicated diet. The PWG concluded unanimously that the kidney tumors were characteristic of amphophilic-vacuolar (AV) tumors and AV atypical tubular hyperplasia which represent a distinctive phenotype that has been reported to occur sporadically in young Sprague Dawley Rats. The PWG determined that the neoplasms and atypical tubular hyperplasias were multicentric and bilateral which typifies tumors of familial origin. Degenerative/regenerative or cytotoxic changes consistent with nephrotoxicity leading to tumor induction were not observed in these rats and thus supports the conclusion that tumors were unrelated to consumption of the test diet. It was the unanimous opinion of the PWG that the proliferative renal tubule cell lesions were spontaneous and not related to consumption of diets containing 4114 maize grain.

  7. Renal cell therapy is associated with dynamic and individualized responses in patients with acute renal failure.

    Science.gov (United States)

    Humes, H David; Weitzel, William F; Bartlett, Robert H; Swaniker, Fresca C; Paganini, Emil P

    2003-01-01

    Renal cell therapy in conjunction with continuous hemofiltration techniques may provide important cellular metabolic activities to patients with acute renal failure (ARF) and may thereby change the natural history of this disorder. The development of a tissue-engineered bioartificial kidney consisting of a conventional hemofiltration cartridge in series with a renal tubule assist device (RAD) containing 10(9) human renal proximal tubule cells provides an opportunity to evaluate this form of therapy in patients with ARF in the intensive care unit. Nine patients with ARF and multi-organ systems failure (MOSF) have been treated so far with a tissue-engineered kidney in an FDA-approved Phase I/II clinical study currently underway. Acute physiologic parameters and serum cytokine levels were assessed before, during and after treatment with a bioartificial kidney. Use of the RAD in this clinical setting demonstrates maintenance of cell viability and functionality. Cardiovascular stability appears to be maintained during RAD treatment. Human tubule cells in the RAD demonstrated differentiated metabolic and endocrinologic activity. Acute physiologic and plasma cytokine data demonstrate that renal cell therapy is associated with rapid and variable responses in patients with ARF and MOSF. The initial clinical experience with the bioartificial kidney and the RAD suggests that renal tubule cell therapy may provide a dynamic and individualized treatment program as assessed by acute physiologic and biochemical indices. Copyright 2003 S. Karger AG, Basel

  8. Thymic hyperplasia in Graves’ disease

    OpenAIRE

    Narendra Kotwal; Yashpal Singh; Anil Menon; Vineet Behera

    2013-01-01

    Graves′ disease is an autoimmune thyroid condition characterized by the production of autoantibodies against the thyrotropin receptor. It is known to be associated with autoimmune conditions such as myasthenia gravis, Addison′s disease, type 1 diabetes mellitus, and vitiligo. We present a case of rare autoimmune association of Graves′ disease with thymic hyperplasia which regressed after treatment with antithyroid drugs. Exact pathophysiology of thymic hyperplasia in Graves′ is not well under...

  9. [Congenital Adrenal Hyperplasia in Adults].

    Science.gov (United States)

    Vrbíková, Jana

    2016-01-01

    Congenital adrenal hyperplasia is a life-long disease requiring an integrated therapy. It may negatively influence the quality of life. In childhood, the main problems of the care of these patients involve sex determination and ensuring optimum growth and puberty. The therapeutic goals for adults are the prevention of Addisonian crisis and ensuring the best possible quality of life, including fertility.Key words: androgens - cardiovascular risk - congenital adrenal hyperplasia - bone density - testicular rest tumors.

  10. Severe venous neointimal hyperplasia prior to dialysis access surgery

    Science.gov (United States)

    Lee, Timmy; Chauhan, Vibha; Krishnamoorthy, Mahesh; Wang, Yang; Arend, Lois; Mistry, Meenakshi J.; El-Khatib, Mahmoud; Banerjee, Rupak; Munda, Rino; Roy-Chaudhury, Prabir

    2011-01-01

    Background. Venous neointimal hyperplasia is the most common cause of arteriovenous (AV) fistula and graft dysfunction following dialysis access surgery. However, the pathogenetic impact of pre-existing venous neointimal hyperplasia at the time of AV access creation on final clinical success is currently unknown in the setting of advanced chronic kidney disease (CKD) and end-stage renal disease (ESRD) patients. The aim of this study was to perform a detailed histological, morphometric, and immunohistochemical analysis of vein specimens in advanced CKD and ESRD patients collected at the time of new vascular access placement. Methods. Vein samples from 12 patients were collected at the time of AV access creation near the site of AV anastomosis. Histological, immunohistochemistry and morphometric studies were performed on these vein samples. Results. Examination of the tissue specimens obtained at the time of surgery showed neointimal hyperplasia in 10 of 12 specimens, ranging from minimal to very severe. The majority of cells within the neointima were myofibroblasts with a minority of contractile smooth muscle cells present. Conclusion. Our work represents a detailed description of the morphometric and cellular phenotypic lesions present in the veins of CKD and ESRD patients, prior to dialysis access placement. These studies (i) suggest the future possibility of a new predictive marker (pre-existing venous neointimal hyperplasia) for AV dialysis access dysfunction and (ii) open the door for the future development of novel local therapies for optimization of the venous substrate on which the dialysis access is created. PMID:21220751

  11. Canine renal failure syndrome in three dogs.

    Science.gov (United States)

    Jeong, Won Il; Do, Sun Hee; Jeong, Da Hee; Chung, Jae Yong; Yang, Hai Jie; Yuan, Dong Wei; Hong, Il Hwa; Park, Jin Kyu; Goo, Moon Jung; Jeong, Kyu Shik

    2006-09-01

    Three dead dogs were brought to the College of Veterinary Medicine, Kyungpook National University for study. Clinically, all the dogs showed emaciation, anorexia, depression, hemorrhagic vomiting and diarrhea for 7-10 days before death. All the clinical signs were first noted for about one month after feeding the dogs with commercial diets. At necropsy, all 3 dogs had severe renal damage with the same green-yellowish colored nephroliths in the renal pelvis. They also showed systemic hemorrhage and calcification of several organs, which might have been induced by uremia. Microscopically, necrosis, calcification and calculi were detected in the renal tubules, and especially in the proximal convoluted tubules and collecting ducts of the kidney. These findings were supportive of a mycotoxic effect, and especially on their kidneys. However, the precise cause of the toxic effect in these cases of canine renal failure could not be determined.

  12. Renal varices. Diagnosis with CT scan and treatment with embolization; Varices renales. Deagnostic tomodensitometrique et traitement par embolisation

    Energy Technology Data Exchange (ETDEWEB)

    Lenoir, S.; Strauss, Ch.; Fontanelle, L.; Bouzar, N.; Veillon, B.; Vallancien, G.; Palou, R. [Institut Mutualiste Montsouris, 75 - Paris (France)

    1997-09-01

    Two cases of recurrent macroscopic Hematuria in which the diagnosis of left renal vein varices was suggested on CT are described. Bloody efflux was seen from the left ureteric orifice. On CT scans, tubulated contrast-enhanced densities in left perirenal fat were seen. Selective renal angiography was normal. Selective left renal phlebography demonstrated intra and perirenal varices. In the two cases, embolization with metallic coil was successfully performed during left renal phlebography, to stop renal varices flux. Diagnostic and therapeutic modalities of renal varices are discussed with predominant place for CT and phlebography. (authors). 13 refs.

  13. 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.

  14. Excretion of alkaloids by malpighian tubules of insects.

    Science.gov (United States)

    Maddrell, S H; Gardiner, B O

    1976-04-01

    Nicotine is transported at high rates by Malpighian tubules of larvae of Manduca sexta, Pieris brassicae and Rhodnius prolixus and the transport persists in the absence of alkaloid from the diet. In the fluid-secreting portion of Rhodnius tubules this transport is not coupled to ion transport, nor is it dependent on the physiological state of the animal. The transport, which can occur against a steep electrochemical gradient, shows saturation kinetics with a maximal rate of 700 pmol. min-1 per tubule and is half saturated at 2-3 mM. Nicotine transport independent of ion movements also occurs in the lower resorptive parts of Rhodnius tubules. Both portions of Rhodnius tubules can transport morphine and atropine. These alkaloids and nicotine compete with one naother and are presumed to be carried by the smae transport system. Nicotine transport in Rhodnius was unaffected by organic anions, such as amaranth and benzyl penicillin, or by the organic anion transport inhibitor, probenecid. Fluid secretion in 5-HT-stimulated tubules was reduced by atropine and nicotine, probably by blocking the 5-HT receptors. The Malpighian tubules of adult Calliphora erythrocephala and Musca domestica remove nicotine from bathing solutions, an unknown metabolic accumulating in the tubules. Adult P. brassicae and M. sexta do not exhibit transport of nicotine by their Malpighian tubules.

  15. Nonlinear analysis of lipid tubules by nonlocal beam model.

    Science.gov (United States)

    Shen, Hui-Shen

    2011-05-07

    Postbuckling, nonlinear bending and nonlinear vibration analyses are presented for lipid tubules. The lipid tubule is modeled as a nonlocal micro/nano-beam which contains small scale effect. The material properties are assumed to be size-dependent. The governing equation is solved by a two-step perturbation technique. The numerical results reveal that the small scale parameter e₀a reduces the postbuckling equilibrium paths, the static large deflections and natural frequencies of lipid tubules. In contrast, it increases the nonlinear to linear frequency ratios slightly for the lipid tubule with immovable end conditions.

  16. Retroperitoneal unicentric Castleman's disease (giant lymph node hyperplasia: case report

    Directory of Open Access Journals (Sweden)

    Jaques Waisberg

    Full Text Available CONTEXT AND OBJECTIVE: Castleman's disease, or giant lymph node hyperplasia, is a rare disorder of the lymphoid tissue that causes lymph node enlargement. It is considered benign in its localized form, but aggressive in the multicentric type. The definitive diagnosis is based on postoperative pathological findings. The aim here was to describe a case of retroperitoneal unicentric Castleman's disease in the retroperitoneum. CASE REPORT: A 61-year old white male with weight loss and listlessness presented with moderate arterial hypertension and leukopenia. Abdominal tomography revealed a 5 x 4 x 5 cm oval mass of low attenuation, with inner calcification and intense enhancement on intravenous contrast, located in the retroperitoneal region, between the left kidney and the aorta, at the renal hilus. Exploratory laparotomy revealed a non-pulsatile solid oval mass situated in the retroperitoneum, adjacent to the left renal hilus. The retroperitoneal lesion was removed in its entirety. Examination of frozen samples revealed benign lymph node tissue and histopathological examination of the surgical sample revealed hyaline-vascular giant lymph node hyperplasia (Castleman's disease. The patient was discharged on the 12th day without significant events. Two months after the operation, the patient was readmitted with severe cardiac insufficiency, acute renal failure and bronchopneumonia, which progressed to acute respiratory insufficiency, sepsis and death.

  17. Genetics Home Reference: primary macronodular adrenal hyperplasia

    Science.gov (United States)

    ... Genetics Home Health Conditions PMAH primary macronodular adrenal hyperplasia Enable Javascript to view the expand/collapse boxes. ... Open All Close All Description Primary macronodular adrenal hyperplasia ( PMAH ) is a disorder characterized by multiple lumps ( ...

  18. Thymic hyperplasia in Graves′ disease

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    Narendra Kotwal

    2013-01-01

    Full Text Available Graves′ disease is an autoimmune thyroid condition characterized by the production of autoantibodies against the thyrotropin receptor. It is known to be associated with autoimmune conditions such as myasthenia gravis, Addison′s disease, type 1 diabetes mellitus, and vitiligo. We present a case of rare autoimmune association of Graves′ disease with thymic hyperplasia which regressed after treatment with antithyroid drugs. Exact pathophysiology of thymic hyperplasia in Graves′ is not well understood; it is likely to be the result of rather than the cause of Graves′ disease.

  19. Adenomatoid hyperplasia of lower lip

    Directory of Open Access Journals (Sweden)

    Gaganjot Kaur Sharma

    2011-01-01

    Full Text Available Adenomatoid hyperplasia (AH is an uncommon, non-neoplastic swelling on the palate caused due to hyperplasia of the mucinous acini. The lesion clinically presents as a sessile tumor-like nodule resembling pleomorphic adenoma. Histopathologic findings include lobules of enlarged mucinous acini which are filled with secretory granules. The nuclei are squeezed to the basal portions, associated with focal inflammation and ductal dilatation, and a history of trauma is often elicited. Here, we report a rare case of AH of the lower lip in a 20-year-old male patient, which mimics a mucous retention cyst or mucocele.

  20. Focal epithelial hyperplasia: Case report.

    Science.gov (United States)

    Puriene, Alina; Rimkevicius, Arunas; Gaigalas, Mindaugas

    2011-01-01

    The purpose of the present article is to present a 15 year-old patient with focal epithelial hyperplasia and to review the references on the subject-related etiological, pathological, diagnostic and treatment aspects. Focal epithelial hyperplasia is a rare human papilloma virus (HPV) related to oral lesion with very low frequency within our population. Surgical treatment with a biopsy was performed, acanthosis and parakeratosis are consistent histopathological features, since the patient had no history of sexual contact and HIV infection, the virus was probably acquired from environmental sources.

  1. Thymic hyperplasia in Graves' disease.

    Science.gov (United States)

    Kotwal, Narendra; Singh, Yashpal; Menon, Anil; Behera, Vineet

    2013-05-01

    Graves' disease is an autoimmune thyroid condition characterized by the production of autoantibodies against the thyrotropin receptor. It is known to be associated with autoimmune conditions such as myasthenia gravis, Addison's disease, type 1 diabetes mellitus, and vitiligo. We present a case of rare autoimmune association of Graves' disease with thymic hyperplasia which regressed after treatment with antithyroid drugs. Exact pathophysiology of thymic hyperplasia in Graves' is not well understood; it is likely to be the result of rather than the cause of Graves' disease.

  2. A case of giant prostatic hyperplasia

    OpenAIRE

    Luke Wang; Paul Davis; Kevin McMillan

    2016-01-01

    Benign prostatic hyperplasia (BPH) is one of the most common conditions experienced by aging males and a frequent cause of bladder outlet obstruction and macroscopic haematuria. Giant prostatic hyperplasia (GPH) is an extremely rare form of prostatic hyperplasia. We present a case of a patient with GPH of 800 mL. To our knowledge, this is the fourth largest prostatic hyperplasia ever reported in the literature.

  3. A case of giant prostatic hyperplasia

    Directory of Open Access Journals (Sweden)

    Luke Wang

    2016-01-01

    Full Text Available Benign prostatic hyperplasia (BPH is one of the most common conditions experienced by aging males and a frequent cause of bladder outlet obstruction and macroscopic haematuria. Giant prostatic hyperplasia (GPH is an extremely rare form of prostatic hyperplasia. We present a case of a patient with GPH of 800 mL. To our knowledge, this is the fourth largest prostatic hyperplasia ever reported in the literature.

  4. 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 pr

  5. In vitro disinfection of dentinal tubules by various endodontics irrigants.

    Science.gov (United States)

    Buck, R; Eleazer, P D; Staat, R H

    1999-12-01

    Effectiveness of endodontic irrigants within dentinal tubules of human teeth was evaluated. Mid-sections of single-rooted teeth were prepared into dentin wedges. The pulpal sides of the sections were exposed to Micrococcus luteus or Bacillus megaterium that grew into the tubules. Irrigants used in the study included: 0.525% NaOCl, 0.12% chlorhexidine, RC Prep, 0.5% betadine iodine, and sterile H2O (as a control). Pulpal surfaces were exposed to an irrigant and then rinsed in sterile water. The samples were then cracked, exposing a fresh surface. Culture of the exposed dentin surfaces showed that selected irrigants reached to the far ends of the dentinal tubules in a concentration sufficient to kill 100% of the M. luteus. However B. megaterium was neither killed nor apparently inhibited by any irrigant. We conclude that endodontic irrigants permeate throughout dentinal tubules, but their effectiveness is dependent on the type of bacteria found within the tubules.

  6. The early history of tubulation in nerve repair.

    Science.gov (United States)

    IJpma, F F A; Van De Graaf, R C; Meek, M F

    2008-10-01

    The first experiments for bridging peripheral nerve gaps using nerve tubulation emerged in the 19th century. Because Gluck (1853-1942) is said to have performed the first animal experiment of nerve tubulation in 1880, it is interesting to explore the background and veracity of this claim. The original documents on nerve tubulation in the 19th century were studied. We conclude that the conduit that was initially used for nerve tubulation was derived from a resorbable decalcified bone tube developed for wound drainage by Neuber (1850-1932) in 1879. Gluck proposed the use of the bone tube as a guided conduit for regenerating nerves in 1881 but stated briefly that his experiments failed because of scar formation. Vanlair (1839-1914) documented the first successful application of nerve tubulation using a bone tube to bridge a 3 cm sciatic nerve defect in a dog in 1882.

  7. 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.

  8. Phytotherapeutic Agents for Benign Prostatic Hyperplasia: An Overview.

    Science.gov (United States)

    Passi, Neelima Dhingra

    2016-06-20

    Benign prostatic hyperplasia (BPH) the most common condition in aging men is the non malignant enlargement of the prostate gland with increase in numbers of both epithelial and stromal cells within the periurethal transition zone of the prostate. Sources of symptoms in patient with BPH appear to be both static and dynamic component. Management of BPH has undergone a rapid evolution over the past decade to aid men with lower urinary tract symptoms attributed to bladder outlet obstruction. Treatment of clinical BPH aims to improve symptoms, prevent urinary tract infections, avoid renal insult, relief obstruction and improve bladder emptying.Prostate cancer patients and those with benign prostatic hyperplasia are increasingly exploring the use of plant derived non-nutritive compounds with protective or disease preventive properties, especially due to long term side effects of pharmacological treatment and risk of mortality associated with surgical procedures. Phytotherapeutic preparations are plant extracts with different components obtained by different extraction procedures. Numerous mechanisms of action have been postulated for mono and combination plant extracts. This article give a brief account of rationale and efficacy of various existing phytotherapeutic agents in the management of benign prostatic hyperplasia, including the herbs which hold the potential promise are also mentioned , although much research is still required.

  9. Renal elimination of organic anions in cholestasis

    Institute of Scientific and Technical Information of China (English)

    Adriana Mónica Tortes

    2008-01-01

    The disposition of most drugs is highly dependent on specialized transporters.OAT1 and OAT3 are two organic anion transporters expressed in the basolateral membrane of renal proximal tubule cells,identified as contributors to xenobiotic and endogenous organic anion secretion.It is well known that cholestasis may cause renal damage.Impairment of kidney function produces modifications in the renal elimination of drugs.Recent studies have demonstrated that the renal abundance of OAT1 and OAT3 plays an important role in the renal elimination of organic anions in the presence of extrahepatic cholestasis.Time elapsed after obstructive cholestasis has an important impact on the regulation of both types of organic anion transporters.The renal expression of OAT1 and OAT3 should be taken into account in order to improve pharmacotherapeutic efficacy and to prevent drug toxicity during the onset of this hepatic disease.

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

    OpenAIRE

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

    2016-01-01

    Introduction: We experienced two esophageal cancer patients who developed severe acute renal failure after neoadjuvant chemotherapy with cisplatin and 5-fluorourasil. Presentation of case: 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 pati...

  11. Targeting Strategies for Renal Cell Carcinoma: From Renal Cancer Cells to Renal Cancer Stem Cells.

    Science.gov (United States)

    Yuan, Zhi-Xiang; Mo, Jingxin; Zhao, Guixian; Shu, Gang; Fu, Hua-Lin; Zhao, Wei

    2016-01-01

    Renal cell carcinoma (RCC) is a common form of urologic tumor that originates from the highly heterogeneous epithelium of renal tubules. Over the last decade, targeting therapies to renal cancer cells have transformed clinical care for RCC. Recently, it was proposed that renal cancer stem cells (CSCs) isolated from renal carcinomas were responsible for driving tumor growth and resistance to conventional chemotherapy and radiotherapy, according to the theory of CSCs; this has provided the rationale for therapies targeting this aggressive cell population. Precise identification of renal CSC populations and the complete cell hierarchy will accurately inform characterization of disease subtypes. This will ultimately contribute to more personalized and targeted therapies. Here, we summarize potential targeting strategies for renal cancer cells and renal CSCs, including tyrosine kinase inhibitors, mammalian target of rapamycin inhibitors (mTOR), interleukins, CSC marker inhibitors, bone morphogenetic protein-2, antibody drug conjugates, and nanomedicine. In conclusion, targeting therapies for RCC represent new directions for exploration and clinical investigation and they plant a seed of hope for advanced clinical care.

  12. Angiolymphoid hyperplasia with follicular mucinosis

    Directory of Open Access Journals (Sweden)

    Joshi Rajiv

    2007-01-01

    Full Text Available Follicular mucinosis occurring along with angiolymphoid hyperplasia with eosinophils (ALHE has been described in a 54-year-old female. The patient presented with pruritic erythematous papules on the left frontoparietal scalp. Histopathological examination showed prominent blood vessels in the dermis lined by plump histiocytoid endothelial cells that were surrounded by a dense lymphoid infiltrate with numerous eosinophils; these findings are typical of angiolymphoid hyperplasia with eosinophils. Features of follicular mucinosis were observed in the same section with several hyperplastic follicular infundibula containing pools of mucin in the infundibular epithelium. The concurrent occurrence of these two distinct histopathological patterns in the same biopsy specimen has been described in only three cases to date.

  13. Alterações eletrencefalográficas em pacientes com hiperplasia supra-renal congênita secundária à deficiência da 21- hidroxilase Electrocnceplialographic changes in patients with congetinal adrenal hyperplasia due to 21-hydroxylase deficiency

    Directory of Open Access Journals (Sweden)

    Miriam Da Costa Oliveira

    1996-06-01

    Full Text Available Alterações eletrencefalográficas têm sido detectadas em crianças com pubarca precoce. Esse achado poderia ser o reflexo da presença atual ou passada de patologia do sistema nervoso central ou conseqüência do nível aumentado de esteróides sexuais. Com o objetivo de testar essa última hipótese, submetemos à avaliação eletrencefalográfica 10 pacientes (7F, 3M com hyperplasia supra-renal congênita (HSRC por deficiência da 21-hidroxilase, 4 deles com a forma clássica e 6 com a forma não-clássica da doença. O exame neurológico tradicional foi realizado em 7 pacientes, sendo normal em todos, enquanto o exame neurológico evolutivo diagnosticou distúrbio de hiperatividade e déficit de atenção em dois. Em outro paciente, dados de história foram compatíveis com retardo do desenvolvimento neuropsicomotor. A avaliação eletrencefalográfica, quantitativa com mapeamento cerebral nos pacientes com idade superior a 3 anos (n= 9, e tradicional no restante, foi considerada anormal para a idade em 8 pacientes (80%, sendo o traçado em 7 casos caracterizado como lento. A alta freqüência de alterações eletrencefalográficas nessa amostra, bem como na pubarca precoce, sugere que esses achados sejam secundários à presença de níveis androgênicos elevados em faixa etária inapropriada e alerta para a importância da avaliação c acompanhamento neurológico de crianças portadoras de HSRC.Electrocncephalographic changes have been delected in children with premature pubarche. These findings might be the result from past or current central nervous system dysfunction, or from increased sex steroids. In order to test the last assertion we have performed clcctroencephalographic studies in 10 patients (7F, 3M with congenital adrenal hyperplasia (CAH due to 21-hydroxylase deficiency, of whom 4 classic and 6 nonclassic forms of the syndrome. Traditional neurologic examination was performed in 7 patients, the result being considered normal

  14. Diabetes increases facilitative glucose uptake and GLUT2 expression at the rat proximal tubule brush border membrane.

    Science.gov (United States)

    Marks, Joanne; Carvou, Nicolas J C; Debnam, Edward S; Srai, Surjit K; Unwin, Robert J

    2003-11-15

    The mechanism of renal glucose transport involves the reabsorption of filtered glucose from the proximal tubule lumen across the brush border membrane (BBM) via a sodium-dependent transporter, SGLT, and exit across the basolateral membrane via facilitative, GLUT-mediated, transport. The aim of the present study was to determine the effect of streptozotocin-induced diabetes on BBM glucose transport. We found that diabetes increased facilitative glucose transport at the BBM by 67.5 % (P < 0.05)--an effect that was abolished by overnight fasting. Western blotting and immunohistochemistry demonstrated GLUT2 expression at the BBM during diabetes, but the protein was undetectable at the BBM of control animals or diabetic animals that had been fasted overnight. Our findings indicate that streptozotocin-induced diabetes causes the insertion of GLUT2 into the BBM and this may provide a low affinity/high capacity route of entry into proximal tubule cells during hyperglycaemia.

  15. Changes of Apoptosis in Rats of Acute Ischemic Renal Injury under Treatment of Tetrandrine

    Institute of Scientific and Technical Information of China (English)

    钱玲梅; 王笑云; 冷静

    2002-01-01

    ObjectiveTo elucidate the effect of tetrandrine on acute ischemic renal injury and its relation with apoptosis.MethodsA model for bilateral post-ischemic renal injury in rats was developed by clamping renal pedicles for 45 min.Renal tissular DNA fragmentation analysis and renal tissular HE staining were used.Also quantitative analysis of apoptosis in injured renal tubular epithelium was carried out by using TdT-mediated dUTP nick and labeling (TUNEL).ResultsApoptosis of renal tubular epithelium increased in acute ischemic renal injury.Tetrandrine could remarkably decrease the level of apoptosis in injured renal tubule while protecting renal tissue against the ischemic injuries.ConclusionTetrandrine could adjust the level of apoptosis in renal tubular epithelium and alleviate renal tissular injury.``

  16. Changes of Apoptosis in Rats of Acute Ischemic Renal Injury under Treatment of Tetrandrine

    Institute of Scientific and Technical Information of China (English)

    钱玲梅; 王笑云; 等

    2002-01-01

    Objective To elucidate the effect of tetrandrine on acute ischemic renal injury and its relation with apoptosis.Methods A model for bilateral post-ischemic renal injury in rats was developed by clamping renal pedicles for 45 min.Renal tissular DNA fragmentation analysis and renal tissular HE staining were used.Also quantitative analysis of apoptosis in injured renal tubular epithelium was carried out by using TdT-mediated dUTP nick and labeling(TUNEL).Results Apoptosis of renal tubular epithelium increased in acute ischemic renal injury.Tetrandrine could remarkably decrease the level of apoptosis in injured renal tubule while protecting renal tissue against the ischemic injuries.Conclusion Tetrandrine could adjust the level of apoptosis in renal tubular epithelium and alleviate renal tissular injury.

  17. Damage of tubule cells in diabetic nephropathy type 2: Urinary N-acetyl-β-D-glucosaminidasis and γ-glutamil-transferasis

    Directory of Open Access Journals (Sweden)

    Vlatković Vlastimir

    2007-01-01

    Full Text Available Background/Aim. A damage of tubular epithelial cells is followed by the release of cell enzymes and production of proinflammatory compounds, which lead to the tubulointerstitial damage. The aim of this study was to examine the function of renal tubules in the patients with diabetes mellitus type 2 (DM type 2 and the various proteinuria degrees, to establish the damage of the proximal tubule cells caused by DM type 2 by determining urinary N-acetyl-β-D-glucosaminidasis (β-NAG and γ- glutamil-transferasis (γ-GT activity in urine, as well as to compare the obtained results in the examined groups of patients with the values in the healthy examinees. Methods. A complete examination of renal function and selective enzymuria was performed in 37 patients with DM type 2, and 14 healthy examinees as the controls. The patients were divided in three groups according to the degree of proteinuria. The first group consisted of the patients with diabetes without microalbuminuria; the second one consisted of the patients with proteinuria of < 300 mg/24 h, and microalbuminuria of >20 mg/24 h, while the third one included the patients with proteinuria of >300 mg/24 h. Results. In the patients with DM type 2 and the preserved global renal function, fractional excretion of sodium, potassium and phosphates, as well as renal threshold of phosphates concentration, were not sensitive parameters for discovering the damage of the renal tubule function. The determination of β-NAG activity proved to be the most sensitive parameter for early discovering of tubule cells damages. The difference among the examined groups was statistically highly significant. Conclusion. The increased presence of β-NAG in the urine of DM type 2 patients, pointed out an early tubular disorder and damage of cells, while γ-GT was a less sensitive indicator of this damage.

  18. Tubular proteinuria in patients with HNF1α mutations: HNF1α drives endocytosis in the proximal tubule.

    Science.gov (United States)

    Terryn, Sara; Tanaka, Karo; Lengelé, Jean-Philippe; Olinger, Eric; Dubois-Laforgue, Danièle; Garbay, Serge; Kozyraki, Renata; Van Der Smissen, Patrick; Christensen, Erik I; Courtoy, Pierre J; Bellanné-Chantelot, Christine; Timsit, José; Pontoglio, Marco; Devuyst, Olivier

    2016-05-01

    Hepatocyte nuclear factor 1α (HNF1α) is a transcription factor expressed in the liver, pancreas, and proximal tubule of the kidney. Mutations of HNF1α cause an autosomal dominant form of diabetes mellitus (MODY-HNF1A) and tubular dysfunction. To gain insights into the role of HNF1α in the proximal tubule, we analyzed Hnf1a-deficient mice. Compared with wild-type littermates, Hnf1a knockout mice showed low-molecular-weight proteinuria and a 70% decrease in the uptake of β2-microglobulin, indicating a major endocytic defect due to decreased expression of megalin/cubilin receptors. We identified several binding sites for HNF1α in promoters of Lrp2 and Cubn genes encoding megalin and cubilin, respectively. The functional interaction of HNF1α with these promoters was shown in C33 epithelial cells lacking endogenous HNF1α. Defective receptor-mediated endocytosis was confirmed in proximal tubule cells from these knockout mice and could be rescued by transfection of wild-type but not mutant HNF1α. Transfection of human proximal tubule HK2 cells with HNF1α was able to upregulate megalin and cubilin expression and to increase endocytosis of albumin. Low-molecular-weight proteinuria was consistently detected in individuals with HNF1A mutations compared with healthy controls and patients with non-MODY-HNF1A diabetes mellitus. Thus, HNF1α plays a key role in the constitutive expression of megalin and cubilin, hence regulating endocytosis in the proximal tubule of the kidney. These findings provide new insight into the renal phenotype of individuals with mutations of HNF1A.

  19. Acute Tubuler Necrosis Related to Rhabdomyolysis

    Directory of Open Access Journals (Sweden)

    Fatma Sarı DOĞAN

    2014-05-01

    Full Text Available Rhabdomyolysis is a clinical and laboratory syndrome due to traumatic or non-traumatic injury that leads muscle cell contents participation into circulation. Dehydration and acidosis may cause myoglobinuric acute renal failure in patient with rhabdomyolysis. This case presents a 27-year-old male referred to emergency unit with weakness and abdominal ache who has a story of urine decrease and trauma exposure. Diagnosis of rhabdomyolysis in this case highlights the importance of anamnesis in early diagnosis and treatment.

  20. Correlation between serum cystatin C content and renal function in aged patients with benign prostatic hyperplasia%血清胱抑素C含量与老年良性前列腺增生症患者肾功能的相关性

    Institute of Scientific and Technical Information of China (English)

    沈丹; 曹萍; 李睿; 钟亚

    2015-01-01

    目的:探讨老年良性前列腺增生症(BPH)患者血清胱抑素 C(Cys C)的变化,及其与肾功能的相关性。方法:回顾性分析237例老年 BPH 患者的临床资料,按照国际前列腺症状评分(IPSS),分为轻度25例、中度67例、重度145例;纳入同期非前列腺增生患者110例作为正常对照组。检测各组血清 Cys C、血尿素氮(BUN)、肌酐(Scr)、空腹血糖(FBG)、血脂和前列腺特异性抗原(PSA)水平,计算前列腺体积(PV)。结果:与正常对照组比较,BPH 患者的 PV显著增大[(18.94±4.62)ml 比(40.09±12.72)ml],最大尿流率(Qmax )显著降低[(18.67±4.60)ml/s 比(9.93±3.54)ml/s],血清 Cys C 水平显著升高[(1.03±0.23)mg/L 比(1.53±0.61)mg/L],P 均<0.01。亚组分析显示,在轻、中、重度 BPH 组血清 Cys C 水平[(1.32±0.45)mg/L,(1.42±0.32)mg/L,(1.61±0.64)mg/L]均显著高于正常对照组(P 均<0.01);且重度组显著高于轻、中度组(P <0.01或 P <0.05)。Pearson 相关分析显示,血清 Cys C与 BPH 患者的年龄、收缩压、舒张压、FBG、BUN、Scr、PV、IPSS 评分均呈显著正相关(r=0.179~0.580,P <0.05或<0.01),与 Qmax 呈显著负相关(r=-0.243,P <0.05)。结论:血清 Cys C 水平在老年 BPH 患者显著升高,且与前列腺增生程度有关,与肾功能相关,可用于预测老年 BPH 患者的肾功能。%Objective:To explore the correlation between serum cystatin C (Cys C)content and renal function in aged patients with benign prostatic hyperplasia (BPH).Methods:Clinical data of 237 aged BPH patients were retro-spectively analyzed.According to international prostate symptom score (IPSS),they were divided into mild group (n=25),moderate group (n=67)and severe group (n= 145);another 110 patients without prostatic hyperplasia were enrolled as normal control group in the

  1. Renal Toxicities of Targeted Therapies.

    Science.gov (United States)

    Abbas, Anum; Mirza, Mohsin M; Ganti, Apar Kishor; Tendulkar, Ketki

    2015-12-01

    With the incorporation of targeted therapies in routine cancer therapy, it is imperative that the array of toxicities associated with these agents be well-recognized and managed, especially since these toxicities are distinct from those seen with conventional cytotoxic agents. This review will focus on these renal toxicities from commonly used targeted agents. This review discusses the mechanisms of these side effects and management strategies. Anti-vascular endothelial growth factor (VEGF) agents including the monoclonal antibody bevacizumab, aflibercept (VEGF trap), and anti-VEGF receptor (VEGFR) tyrosine kinase inhibitors (TKIs) all cause hypertension, whereas some of them result in proteinuria. Monoclonal antibodies against the human epidermal growth factor receptor (HER) family of receptors, such as cetuximab and panitumumab, cause electrolyte imbalances including hypomagnesemia and hypokalemia due to the direct nephrotoxic effect of the drug on renal tubules. Cetuximab may also result in renal tubular acidosis. The TKIs, imatinib and dasatinib, can result in acute or chronic renal failure. Rituximab, an anti-CD20 monoclonal antibody, can cause acute renal failure following initiation of therapy because of the onset of acute tumor lysis syndrome. Everolimus, a mammalian target of rapamycin (mTOR) inhibitor, can result in proteinuria. Discerning the renal adverse effects resulting from these agents is essential for safe treatment strategies, particularly in those with pre-existing renal disease.

  2. Lipomatosis: a diverse form of hemifacial hyperplasia

    OpenAIRE

    Arora, Preeti Chawla; Umarji, Hemant R.; Arora, Aman; Ramaswami, Easwaran

    2012-01-01

    A case of hemifacial hyperplasia that presented with muscular, skeletal, and dental hyperplasia along with lipomatous infiltration was described. Advanced imaging was useful in identifying the lipomatous infiltration present in the lesion, which raises the possibility of lipomatosis having a diverse presentation in hemifacial hyperplasia. As there was a scarcity of related literature in the field of dentomaxillofacial radiology, this report would make us familiar with its computed tomographic...

  3. Lipomatosis: a diverse form of hemifacial hyperplasia

    Energy Technology Data Exchange (ETDEWEB)

    Arora, Preeti Chawla; Umarji, Hemant R. [Dept. of Oral Medicine, Diagnosis and Radiology, Government Dental College and Hospital, Mumbai (India); Arora, Aman [Dept. of Prosthodontics, Sri Guru Ram Das Institute of Dental Sciences and Research, Amritsar (India); Ramaswami, Easwaran [Oral Medicine, Diagnosis and Radiology, Dr. D.Y. Patil Dental College and Hospital, Navi Mumbai (India)

    2012-09-15

    A case of hemifacial hyperplasia that presented with muscular, skeletal, and dental hyperplasia along with lipomatous infiltration was described. Advanced imaging was useful in identifying the lipomatous infiltration present in the lesion, which raises the possibility of lipomatosis having a diverse presentation in hemifacial hyperplasia. As there was a scarcity of related literature in the field of dentomaxillofacial radiology, this report would make us familiar with its computed tomographic and magnetic resonance image findings.

  4. Unilateral nodular adrenal hyperplasia: Case series

    African Journals Online (AJOL)

    A.F. Kotb

    2016-07-26

    Jul 26, 2016 ... with hyperaldosteronism or Cushing syndrome. Case series: We ... Pathological examination confirmed the diagnosis of nodular hyperplasia. ... Theirpatients were managed by unilateral adrenalectomy and this management.

  5. Human kidney proximal tubule-on-a-chip for drug transport and nephrotoxicity assessment.

    Science.gov (United States)

    Jang, Kyung-Jin; Mehr, Ali Poyan; Hamilton, Geraldine A; McPartlin, Lori A; Chung, Seyoon; Suh, Kahp-Yang; Ingber, Donald E

    2013-09-01

    Kidney toxicity is one of the most frequent adverse events reported during drug development. The lack of accurate predictive cell culture models and the unreliability of animal studies have created a need for better approaches to recapitulate kidney function in vitro. Here, we describe a microfluidic device lined by living human kidney epithelial cells exposed to fluidic flow that mimics key functions of the human kidney proximal tubule. Primary kidney epithelial cells isolated from human proximal tubule are cultured on the upper surface of an extracellular matrix-coated, porous, polyester membrane that splits the main channel of the device into two adjacent channels, thereby creating an apical 'luminal' channel and a basal 'interstitial' space. Exposure of the epithelial monolayer to an apical fluid shear stress (0.2 dyne cm(-2)) that mimics that found in living kidney tubules results in enhanced epithelial cell polarization and primary cilia formation compared to traditional Transwell culture systems. The cells also exhibited significantly greater albumin transport, glucose reabsorption, and brush border alkaline phosphatase activity. Importantly, cisplatin toxicity and Pgp efflux transporter activity measured on-chip more closely mimic the in vivo responses than results obtained with cells maintained under conventional culture conditions. While past studies have analyzed kidney tubular cells cultured under flow conditions in vitro, this is the first report of a toxicity study using primary human kidney proximal tubular epithelial cells in a microfluidic 'organ-on-a-chip' microdevice. The in vivo-like pathophysiology observed in this system suggests that it might serve as a useful tool for evaluating human-relevant renal toxicity in preclinical safety studies.

  6. Insulin uptake across the luminal membrane of the rat proximal tubule in vivo and in vitro.

    Science.gov (United States)

    Kolman, Pavel; Pica, Angelo; Carvou, Nicolas; Boyde, Alan; Cockcroft, Shamshad; Loesch, Andrew; Pizzey, Arnold; Simeoni, Mariadelina; Capasso, Giovambattista; Unwin, Robert J

    2009-05-01

    We visualized insulin uptake in vivo across the apical membrane of the rat proximal tubule (PT) by confocal microscopy; we compared it with in vitro findings in a rat PT cell line (WKPT) using fluorescence microscopy and flow cytometry. Surface tubules were observed in vivo with a 633-nm single laser-illuminated real-time video-rate confocal scanning microscope in upright configuration for optical sectioning below the renal capsule. Fields were selected containing proximal and distal tubules; Cy5-labeled insulin was injected twice (the second time after approximately 140 min) into the right jugular vein, and the fluorescence signal (at 650-670 nm) was recorded. Fluorescence was detected almost immediately at the brush-border membrane (BBM) of PT cells only, moving inside cells within 30-40 min. As a measure of insulin uptake, the ratio of the fluorescence signal after the second injection to the first doubled (ratio: 2.11 +/- 0.26, mean +/- SE, n = 10), indicating a "priming," or stimulating, effect of insulin on its uptake mechanism at the BBM. This effect did not occur after pretreatment with intravenous lysine (ratio: 1.03 +/- 0.07, n = 6; P < 0.01). Cy2- or Cy3-labeled insulin uptake in a PT cell line in vitro was monitored by 488-nm excitation fluorescence microscopy using an inverted microscope. Insulin localized toward the apical membrane of these cells. Semiquantitative analysis of insulin uptake by flow cytometry also demonstrated a priming effect (upregulation) on insulin internalization in the presence of increasing amounts of insulin, as was observed in vivo; moreover, this effect was not seen with, or affected by, the similarly endocytosed ligand beta2-glycoprotein.

  7. FDG PET/CT findings of rebound thymic hyperplasia in oncologic patients with chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Ji Yeon; Kang, Won Jun; Kim, Yu Kyeong; Lee, Chang Hyun; Kang, Keon Wook; Lee, Dong Soo; Chung, June Key; Lee, Myung Chul [Seoul National Univ. College of Medicine, Seoul (Korea, Republic of)

    2007-07-01

    Benign thymic hyperplasia in adult unlike children is a rare condition, however, it could occur, mainly associated with concurrent malignancies or chemotherapy. Rebound thymic hyperplasia in cancer patients could be a cause of great concern for cancer involvement to the thymus. In this study, we characterized the rebound thymic hyperplasia in oncologic patients who received chemotherapy on FDG PET/CT. We reviewed the 1030 PET/CT scans obtained from cancer patients for follow up purpose in Seoul National University Hospital between 2004 and 2006. 21 PET/CT scans of them (2%) revealed thymic enlargement. The scans were obtained from 11 patients (age range: 16-55 yrs) who received chemotherapy for various malignancies (4 breast cancers, 3 lymphomas, and one of each osteosarcoma, rhabdomyosarcoma, hepatocellular carcinoma, renal cell carcinoma). Six cases had more than one follow-up PET/CT, and rebound thymic hyperplasia without malignancy was finally confirmed by clinical observation for follow-up period ranged from 17 to 45 months. The uptake pattern, maximum standardized uptake values (mSUVs), uptake ratio to the liver, and CT findings of thymic hyperplasia on PET/CT were analyzed. In all cases except one, enlarged thymus showed diffuse and relatively homogenous increased FDG uptake. In only one case, nodular increased FDG uptake with mSUV of 2.7 was found. Mean mSUV in the thymus was measured as 1.580.53, and the uptake ratio to the liver was 0.750.26. Decreased thymic metabolism was depicted on follow up PET images, while, resolved thymic enlarged was demonstrated on follow up CT in three of six. Rebound thymic hyperplasia in cancer patients should be distinguished from thymic malignancy. The finding of diffuse and moderate hypermetabolism lesser than liver in the enlarged thymus on follow-up PET/CT in cancer patients may suggest rebound thymic hyperplasia rather than malignancy, especially in condition of the presence of preceding chemotherapy.

  8. MG53 is dispensable for T-tubule maturation but critical for maintaining T-tubule integrity following cardiac stress.

    Science.gov (United States)

    Zhang, Caimei; Chen, Biyi; Wang, Yihui; Guo, Ang; Tang, Yiqun; Khataei, Tahsin; Shi, Yun; Kutschke, William J; Zimmerman, Kathy; Weiss, Robert M; Liu, Jie; Benson, Christopher J; Hong, Jiang; Ma, Jianjie; Song, Long-Sheng

    2017-08-16

    The cardiac transverse (T)-tubule membrane system is the safeguard for cardiac function and undergoes dramatic remodeling in response to cardiac stress. However, the mechanism by which cardiomyocytes repair damaged T-tubule network remains unclear. In the present study, we tested the hypothesis that MG53, a muscle-specific membrane repair protein, antagonizes T-tubule damage to protect against maladaptive remodeling and thereby loss of excitation-contraction coupling and cardiac function. Using MG53-knockout (MG53-KO) mice, we first established that deficiency of MG53 had no impact on maturation of the T-tubule network in developing hearts. Additionally, MG53 ablation did not influence T-tubule integrity in unstressed adult hearts as late as 10months of age. Following left ventricular pressure overload-induced cardiac stress, MG53 protein levels were increased by approximately three-fold in wild-type mice, indicating that pathological stress induces a significant upregulation of MG53. MG53-deficient mice had worsened T-tubule disruption and pronounced dysregulation of Ca(2+) handling properties, including decreased Ca(2+) transient amplitude and prolonged time to peak and decay. Moreover, MG53 deficiency exacerbated cardiac hypertrophy and dysfunction and decreased survival following cardiac stress. Our data suggest MG53 is not required for T-tubule development and maintenance in normal physiology. However, MG53 is essential to preserve T-tubule integrity and thereby Ca(2+) handling properties and cardiac function under pathological cardiac stress. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Na+-H+ exchanger-1 (NHE1) regulation in kidney proximal tubule.

    Science.gov (United States)

    Parker, Mark D; Myers, Evan J; Schelling, Jeffrey R

    2015-06-01

    The ubiquitously expressed plasma membrane Na(+)-H(+) exchanger NHE1 is a 12 transmembrane-spanning protein that directs important cell functions such as homeostatic intracellular volume and pH control. The 315 amino acid cytosolic tail of NHE1 binds plasma membrane phospholipids and multiple proteins that regulate additional, ion-translocation independent functions. This review focuses on NHE1 structure/function relationships, as well as the role of NHE1 in kidney proximal tubule functions, including pH regulation, vectorial Na(+) transport, cell volume control and cell survival. The implications of these functions are particularly critical in the setting of progressive, albuminuric kidney diseases, where the accumulation of reabsorbed fatty acids leads to disruption of NHE1-membrane phospholipid interactions and tubular atrophy, which is a poor prognostic factor for progression to end stage renal disease. This review amplifies the vital role of the proximal tubule NHE1 Na(+)-H(+) exchanger as a kidney cell survival factor.

  10. FISIOPATOLOGÍA DE LA INSUFICIENCIA RENAL AGUDA POR CISPLATINO

    Directory of Open Access Journals (Sweden)

    Rodriguez Macías EL

    2013-09-01

    Full Text Available Cisplatin is one of the major antineoplastic used for treatment of tumors such as testicular, ovarian, cervical, lung, bladder and head, among others. It has been described various types of toxicities induced by cisplatin, but the renal is the main one. This toxicity consist sof an acute reduction in renal plasma flow and a decline in glomerular filtration and installation of a tubular necrosis, with predominant involvement of the distal tubules and accumulation of cellular debris (lumen obstruction. Other mechanisms involved in renal injury are microangiopathy and pro-inflammatory mediators. We conclude that the nephrotoxicity caused by cisplatin can induce renal failure in which tubular structural damage predominates.

  11. Focal epithelial hyperplasia: Heck disease.

    Science.gov (United States)

    Cohen, P R; Hebert, A A; Adler-Storthz, K

    1993-09-01

    Two sisters of Mexican ancestry had focal epithelial hyperplasia (FEH). The lesions on the oral mucosa of the older child were initially misinterpreted as representing sexual abuse. Microscopic evaluation of a hematoxylin and eosin-stained section from a lower lip papule demonstrated the histologic features of FEH. Although human papillomavirus (HPV) type 13 and HPV32 have been most consistently present in FEH lesions, types 6, 11, 13, and 32 were not detected in the paraffin-embedded tissue specimen of our patient using an in situ hybridization technique. The lesions persisted or recurred during management using destructive modalities; subsequently, they completely resolved spontaneously.

  12. Focal epithelial hyperplasia (Heck's disease

    Directory of Open Access Journals (Sweden)

    Parichehr Gheliani

    2011-11-01

    Full Text Available Focal epithelial hyperplasia (Heck is a rare lesion caused by human papilloma virus subtype 13 or 32 and presents as multiple small white or pink papules on the mucosal surface of lips, buccal mucosa and tongue usually seen in children and adolescent of American Indian and Eskimo background. This disease has a genetic basis. The site of new lesions and recurrence are unpredictable. Continued follow up of the patient is often necessary. In this report, a 50-year-old woman is described with benign papillomatous lesions on dorsal surface of tongue for 15 years

  13. 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

    ) 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......% greater in YSHR than YSD and decreased to SD levels in adults. We conclude that there are persistent changes in Na(+) transporter distributions and activity in response to chronic hypertension in SHR that mimic the responses to acute hypertension seen in SD rats and that elevated sodium pump activity per......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...

  14. Renal dopamine receptors and hypertension.

    Science.gov (United States)

    Hussain, Tahir; Lokhandwala, Mustafa F

    2003-02-01

    Dopamine has been recognized as an important modulator of central as well as peripheral physiologic functions in both humans and animals. Dopamine receptors have been identified in a number of organs and tissues, which include several regions within the central nervous system, sympathetic ganglia and postganglionic nerve terminals, various vascular beds, the heart, the gastrointestinal tract, and the kidney. The peripheral dopamine receptors influence cardiovascular and renal function by decreasing afterload and vascular resistance and promoting sodium excretion. Within the kidney, dopamine receptors are present along the nephron, with highest density on proximal tubule epithelial cells. It has been reported that there is a defective dopamine receptor, especially D(1) receptor function, in the proximal tubule of various animal models of hypertension as well as in humans with essential hypertension. Recent reports have revealed the site of and the molecular mechanisms responsible for the defect in D(1) receptors in hypertension. Moreover, recent studies have also demonstrated that the disruption of various dopamine receptor subtypes and their function produces hypertension in rodents. In this review, we present evidence that dopamine and dopamine receptors play an important role in regulating renal sodium excretion and that defective renal dopamine production and/or dopamine receptor function may contribute to the development of various forms of hypertension.

  15. Inhibition of tubular cell proliferation by neutralizing endogenous HGF leads to renal hypoxia and bone marrow-derived cell engraftment in acute renal failure.

    Science.gov (United States)

    Ohnishi, Hiroyuki; Mizuno, Shinya; Nakamura, Toshikazu

    2008-02-01

    During the progression of acute renal failure (ARF), the renal tubular S3 segment is sensitive to ischemic stresses. For reversing tubular damage, resident tubular cells proliferate, and bone marrow-derived cells (BMDC) can be engrafted into injured tubules. However, how resident epithelium or BMDC are involved in tubular repair remains unknown. Using a mouse model of ARF, we examined whether hepatocyte growth factor (HGF) regulates a balance of resident cell proliferation and BMDC recruitment. Within 48 h post-renal ischemia, tubular destruction became evident, followed by two-waved regenerative events: 1) tubular cell proliferation between 2 and 4 days, along with an increase in blood HGF; and 2) appearance of BMDC in the tubules from 6 days postischemia. When anti-HGF IgG was injected in the earlier stage, tubular cell proliferation was inhibited, leading to an increase in BMDC in renal tubules. Under the HGF-neutralized state, stromal cell-derived factor-1 (SDF1) levels increased in renal tubules, associated with the enhanced hypoxia. Administrations of anti-SDF1 receptor IgG into ARF mice reduced the number of BMDC in interstitium and tubules. Thus possible cascades include 1) inhibition of tubular cell proliferation by neutralizing HGF leads to renal hypoxia and SDF1 upregulation; and 2) BMDC are eventually engrafted in tubules through SDF1-mediated chemotaxis. Inversely, administration of recombinant HGF suppressed the renal hypoxia, SDF1 upregulation, and BMDC engraftment in ARF mice by enhancing resident tubular cell proliferation. Thus we conclude that HGF is a positive regulator for eliciting resident tubular cell proliferation, and SDF1 for BMDC engraftment during the repair process of ARF.

  16. Trauma renal Renal trauma

    Directory of Open Access Journals (Sweden)

    Gerson Alves Pereira Júnior

    1999-02-01

    Full Text Available Apresentamos uma revisão sobre trauma renal, com ênfase na avaliação radiológica, particularmente com o uso da tomografia computadorizada, que tem se tornado o exame de eleição, ao invés da urografia excretora e arteriografia. O sucesso no tratamento conservador dos pacientes com trauma renal depende de um acurado estadiamento da extensão da lesão, classificado de acordo com a Organ Injury Scaling do Colégio Americano de Cirurgiões. O tratamento conservador não-operatório é seguro e consiste de observação contínua, repouso no leito, hidratação endovenosa adequada e antibioti- coterapia profilática, evitando-se uma exploração cirúrgica desnecessária e possível perda renal. As indicações para exploração cirúrgica imediata são abdome agudo, rápida queda do hematócrito ou lesões associadas determinadas na avaliação radiológica. Quando indicada, a exploração renal após controle vascular prévio é segura, permitindo cuidadosa inspeção do rim e sua reconstrução com sucesso, reduzindo a probabilidade de nefrectomia.We present a revision of the renal trauma with emphasis in the radiographic evaluation, particularly CT scan that it has largely replaced the excretory urogram and arteriogram in the diagnostic worh-up and management of the patient with renal trauma. The successful management of renal injuries depends upon the accurate assessment of their extent in agreement with Organ Injury Scaling classification. The conservative therapy managed by careful continuous observation, bed rest, appropriate fluid ressuscitation and prophylactic antibiotic coverage after radiographic staging for severely injured kidneys can yield favorable results and save patients from unnecessary exploration and possible renal loss. The indications for immediate exploratory laparotomy were acute abdomen, rapidly dropping hematocrit or associated injuries as determinated from radiologic evaluation. When indicated, renal exploration

  17. Neuronal hyperplasia in the anal canal

    DEFF Research Database (Denmark)

    Fenger, C; Schrøder, H D

    1990-01-01

    In a consecutive series of minor surgical specimens from the anal canal, neuronal hyperplasia was found in nine of 56 haemorrhoidectomy specimens and in four of 23 fibrous polyps. In an additional series of 14 resections of the anal canal, neuronal hyperplasia was present in six cases, of which...

  18. Adenomatoid hyperplasia of palatal minor salivary glands

    OpenAIRE

    Bryant, C. J.; Manisali, M.; Barrett, A. W.

    1996-01-01

    Adenomatoid hyperplasia of palatal minor mucous glands is rare but significant because the clinical appearance mimics malignant disease. The typical history of a painless, indolent palatal swelling, together with the histological picture of benign glandular hyperplasia and hypertrophy, are illustrated in this report.

  19. Computed tomography in untreated congenital adrenal hyperplasia

    Energy Technology Data Exchange (ETDEWEB)

    Harinarayana, C.V.; Renu, G.; Ammini, A.C.; Khurana, M.L.; Ved, P.; Karmarkar, M.G.; Ahuja, M.M.S.; Berry, M. (AIIMS, New Delhi (India))

    1991-02-01

    Six children with untreated congenital adrenal hyperplasia (CAH) were examined by computed tomography (CT). Three cases demonstrated diffuse enlargement of both adrenal glands with preservation of normal configuration and two showed tumorous transformation in one of the enlarged glands. One had equivocal in this group (age 2 years) also showed bilateral hyperplasia. (orig.).

  20. Oral verrucous hyperplasia: a case report.

    Science.gov (United States)

    Navaneetham, Anuradha; Dayanand Saraswathi, M C; Santosh, B S

    2014-09-01

    Oral verrucous hyperplasia is a whitish or pinkinsh elevated pre malignant lesion which occurs rarely. Its is also considered to be an early form of verrucous carcinoma. We have reported a case of verrucous hyperplasia which was diagnosed and treated with buccal fat pad as graft.

  1. Constitutively Active SPAK Causes Hyperkalemia by Activating NCC and Remodeling Distal Tubules.

    Science.gov (United States)

    Grimm, P Richard; Coleman, Richard; Delpire, Eric; Welling, Paul A

    2017-09-01

    Aberrant activation of with no lysine (WNK) kinases causes familial hyperkalemic hypertension (FHHt). Thiazide diuretics treat the disease, fostering the view that hyperactivation of the thiazide-sensitive sodium-chloride cotransporter (NCC) in the distal convoluted tubule (DCT) is solely responsible. However, aberrant signaling in the aldosterone-sensitive distal nephron (ASDN) and inhibition of the potassium-excretory renal outer medullary potassium (ROMK) channel have also been implicated. To test these ideas, we introduced kinase-activating mutations after Lox-P sites in the mouse Stk39 gene, which encodes the terminal kinase in the WNK signaling pathway, Ste20-related proline-alanine-rich kinase (SPAK). Renal expression of the constitutively active (CA)-SPAK mutant was specifically targeted to the early DCT using a DCT-driven Cre recombinase. CA-SPAK mice displayed thiazide-treatable hypertension and hyperkalemia, concurrent with NCC hyperphosphorylation. However, thiazide-mediated inhibition of NCC and consequent restoration of sodium excretion did not immediately restore urinary potassium excretion in CA-SPAK mice. Notably, CA-SPAK mice exhibited ASDN remodeling, involving a reduction in connecting tubule mass and attenuation of epithelial sodium channel (ENaC) and ROMK expression and apical localization. Blocking hyperactive NCC in the DCT gradually restored ASDN structure and ENaC and ROMK expression, concurrent with the restoration of urinary potassium excretion. These findings verify that NCC hyperactivity underlies FHHt but also reveal that NCC-dependent changes in the driving force for potassium secretion are not sufficient to explain hyperkalemia. Instead, a DCT-ASDN coupling process controls potassium balance in health and becomes aberrantly activated in FHHt. Copyright © 2017 by the American Society of Nephrology.

  2. FISIOPATOLOGÍA DE LA INSUFICIENCIA RENAL AGUDA POR CISPLATINO

    OpenAIRE

    Rodriguez Macías EL

    2013-01-01

    Cisplatin is one of the major antineoplastic used for treatment of tumors such as testicular, ovarian, cervical, lung, bladder and head, among others. It has been described various types of toxicities induced by cisplatin, but the renal is the main one. This toxicity consist sof an acute reduction in renal plasma flow and a decline in glomerular filtration and installation of a tubular necrosis, with predominant involvement of the distal tubules and accumulation of cellular debris (lumen...

  3. RENAL HISTOPATHOLOGICAL FINDINGS IN DOGS WITH VISCERAL LEISHMANIASIS

    OpenAIRE

    Rosangela Silva Rigo; Cristiano Marcelo Espínola Carvalho; Michael Robin Honer; Gisele Braziliano de Andrade; Iandara Shetter Silva; Leonardo Rigo; Helen Rezende Figueiredo; Wanessa Teixeira Gomes Barreto

    2013-01-01

    Visceral leishmaniasis affects various organs including the kidneys; which can lead to renal failure and death. In order to verify this renal involvement, material was evaluated from 100 dogs naturally infected and with serological diagnosis of canine visceral leishmaniasis (CVL). Inflammatory changes were present in 25.3% of the tubules, in 67.0% of interstitium and in 52.0% of glomeruli. There was no significant difference (p > 0.05) between the presence of glomerulonephritis in symptomatic...

  4. Renal fructose-metabolizing enzymes: significance in hereditary fructose intolerance.

    Science.gov (United States)

    Kranhold, J F; Loh, D; Morris, R C

    1969-07-25

    In patients with hereditary fructose intolerance, which is characterized by deficient aldolase activity toward fructose-1-phosphate, fructose induces a renal tubular dysfunction that implicates only the proximal convoluted tubule. Because normal metabolism of fructose by way of fructose-1-phosphate requires fructokinase, aldolase "B," and triokinase, the exclusively cortical location of these enzymes indicates that the medulla is not involved in the metabolic abnormality presumably causal of the renal dysfunction.

  5. Imaging Characteristics of Pathologically Proven Thymic Hyperplasia: Identifying Features That Can Differentiate True From Lymphoid Hyperplasia

    Science.gov (United States)

    Araki, Tetsuro; Sholl, Lynette M.; Gerbaudo, Victor H.; Hatabu, Hiroto; Nishino, Mizuki

    2014-01-01

    OBJECTIVE The purpose of this article is to investigate the imaging characteristics of pathologically proven thymic hyperplasia and to identify features that can differentiate true hyperplasia from lymphoid hyperplasia. MATERIALS AND METHODS Thirty-one patients (nine men and 22 women; age range, 20–68 years) with pathologically confirmed thymic hyperplasia (18 true and 13 lymphoid) who underwent preoperative CT (n = 27), PET/CT (n = 5), or MRI (n = 6) were studied. The length and thickness of each thymic lobe and the transverse and anterior-posterior diameters and attenuation of the thymus were measured on CT. Thymic morphologic features and heterogeneity on CT and chemical shift on MRI were evaluated. Maximum standardized uptake values were measured on PET. Imaging features between true and lymphoid hyperplasia were compared. RESULTS No significant differences were observed between true and lymphoid hyperplasia in terms of thymic length, thickness, diameters, morphologic features, and other qualitative features (p > 0.16). The length, thickness, and diameters of thymic hyperplasia were significantly larger than the mean values of normal glands in the corresponding age group (p hyperplasia was significantly higher than that of true hyperplasia among 15 patients with contrast-enhanced CT (median, 47.9 vs 31.4 HU; Wilcoxon p = 0.03). The receiver operating characteristic analysis yielded greater than 41.2 HU as the optimal threshold for differentiating lymphoid hyperplasia from true hyperplasia, with 83% sensitivity and 89% specificity. A decrease of signal intensity on opposed-phase images was present in all four cases with in- and opposed-phase imaging. The mean maximum standardized uptake value was 2.66. CONCLUSION CT attenuation of the thymus was significantly higher in lymphoid hyperplasia than in true hyperplasia, with an optimal threshold of greater than 41.2 HU in this cohort of patients with pathologically confirmed thymic hyperplasia. PMID:24555583

  6. Renal arteriography

    Science.gov (United States)

    ... Read More Acute arterial occlusion - kidney Acute kidney failure Aneurysm Atheroembolic renal disease Blood clots Renal cell carcinoma Renal venogram X-ray Review Date 1/5/2016 Updated by: Jason Levy, ...

  7. Renal Glycosuria without Hyperglycemia in Cyclosporine-Treated Rats

    Directory of Open Access Journals (Sweden)

    Chang Hwa Lee

    2012-06-01

    Conclusion: Glycosuria may occur without hyperglycemia in cyclosporine administration. We suggest that cyclosporine may decrease tubular reabsorption of glucose in renal tubular epithelial cells, and then glycosuria could be induced by the altered glucose transporter expressions. We will analyze the glucose transporters in proximal tubule of rat kidney.

  8. Drosophila provides rapid modeling of renal development, function, and disease.

    Science.gov (United States)

    Dow, Julian A T; Romero, Michael F

    2010-12-01

    The evolution of specialized excretory cells is a cornerstone of the metazoan radiation, and the basic tasks performed by Drosophila and human renal systems are similar. The development of the Drosophila renal (Malpighian) tubule is a classic example of branched tubular morphogenesis, allowing study of mesenchymal-to-epithelial transitions, stem cell-mediated regeneration, and the evolution of a glomerular kidney. Tubule function employs conserved transport proteins, such as the Na(+), K(+)-ATPase and V-ATPase, aquaporins, inward rectifier K(+) channels, and organic solute transporters, regulated by cAMP, cGMP, nitric oxide, and calcium. In addition to generation and selective reabsorption of primary urine, the tubule plays roles in metabolism and excretion of xenobiotics, and in innate immunity. The gene expression resource FlyAtlas.org shows that the tubule is an ideal tissue for the modeling of renal diseases, such as nephrolithiasis and Bartter syndrome, or for inborn errors of metabolism. Studies are assisted by uniquely powerful genetic and transgenic resources, the widespread availability of mutant stocks, and low-cost, rapid deployment of new transgenics to allow manipulation of renal function in an organotypic context.

  9. Renal secondary hyperparathyroidism in dogs.

    Science.gov (United States)

    Stillion, Jenefer R; Ritt, Michelle G

    2009-06-01

    The parathyroid glands secrete parathyroid hormone (PTH), which is important for maintaining calcium homeostasis. Parathyroid gland hyperplasia and subsequent hyperparathyroidism can occur secondary to chronic renal failure in dogs, resulting in significant alterations in calcium metabolism. Renal secondary hyperparathyroidism is a complex, multifactorial syndrome that involves changes in circulating levels of calcium, PTH, phosphorus, and 1,25-dihydroxycholecalciferol (calcitriol). An increased PTH level can have deleterious effects, including soft tissue mineralization, fibrous osteodystrophy, bone marrow suppression, urolithiasis, and neuropathy. Dietary phosphorus restriction, intestinal phosphate binders, and calcitriol supplementation may slow the progression of renal disease and decrease PTH concentrations in animals with secondary hyperparathyroidism; however, the prognosis for these animals is guarded to poor.

  10. Cubilin is an albumin binding protein important for renal tubular albumin reabsorption.

    Science.gov (United States)

    Birn, H; Fyfe, J C; Jacobsen, C; Mounier, F; Verroust, P J; Orskov, H; Willnow, T E; Moestrup, S K; Christensen, E I

    2000-05-01

    Using affinity chromatography and surface plasmon resonance analysis, we have identified cubilin, a 460-kDa receptor heavily expressed in kidney proximal tubule epithelial cells, as an albumin binding protein. Dogs with a functional defect in cubilin excrete large amounts of albumin in combination with virtually abolished proximal tubule reabsorption, showing the critical role for cubilin in the uptake of albumin by the proximal tubule. Also, by immunoblotting and immunocytochemistry we show that previously identified low-molecular-weight renal albumin binding proteins are fragments of cubilin. In addition, we find that mice lacking the endocytic receptor megalin show altered urinary excretion, and reduced tubular reabsorption, of albumin. Because cubilin has been shown to colocalize and interact with megalin, we propose a mechanism of albumin reabsorption mediated by both of these proteins. This process may prove important for understanding interstitial renal inflammation and fibrosis caused by proximal tubule uptake of an increased load of filtered albumin.

  11. DETECTION AND SIGNIFICANCE OF HBV IN RENAL TISSUE OF HBV ASSOCIATED GLOMERULONEPHRITIS PATIENTS

    Institute of Scientific and Technical Information of China (English)

    任淑婷; 于琳华; 徐长福; 李恒力; 党双锁; 成少利; 郑黎明

    2002-01-01

    Objective To study the pathogenesis of hepatitis B virus ( HBV ) on kidney tissues. Methods HBsAg and HBcAg in paraffin-embedded renal biopsy tissues from 27 cases of glomerulonephritis with positive serum HBV markers were observed by using immunohistochemistry. In addition, in situ polymerse chain reaction (IS-PCR) was performed in 5 cases with positive HBsAg and HBcAg in renal tissue of the 27-case glomerulonephritis to reveal the state of renal HBV DNA. Results Twenty cases (20/27,74.07%) were positive with HBAg which were mainly diffusely distributed in epithelial cells of renal tubule. Four cases (4/5,80% ) were positive with HBV DNA whose distribution was the same of that of HBAg. Conclusion Renal lesions due to HBV are not only the results of immunologic response, but also the outcome of direct invasion and duplication of HBV in epithelial cells of renal tubule.

  12. [Oral cavity pathology by renal failure].

    Science.gov (United States)

    Maĭborodin, I V; Minikeev, I M; Kim, S A; Ragimova, T M

    2014-01-01

    The analysis of the scientific literature devoted to organ and tissue changes of oral cavity at the chronic renal insufficiency (CRI)is made. The number of patients in an end-stage of CRI constantly increases and patients receiving renal replacement therapy including hemodialysis, peritoneal dialysis or renal transplantation will comprise an enlarging segment of the dental patient population. Owing to CRI and its treatment there is a set of changes of teeth and oral cavity fabrics which remain even in a end-stage. Renal replacement therapy can affect periodontal tissues including gingival hyperplasia in immune suppressed renal transplantation patients and increased levels of bacterial contamination, gingival inflammation, formation of calculus, and possible increased prevalence and severity of destructive periodontal diseases. Besides, the presence of undiagnosed periodontitis may have significant effects on the medical management of the patients in end-stage of CRI.

  13. Fine structure of the malpighian tubule in Aedes aegypti

    Energy Technology Data Exchange (ETDEWEB)

    Mathew, G.; Rai, K.S.

    1976-07-01

    The malpighian tubule in Aedes aegypti adults is formed by 2 cell types: the principal cell which forms the great bulk of the tubule, and the stellate cell interspersed singly along the tubule. Both cell types possess ultrastructural features characteristic of cells engaged in ion balance and osmoregulation. These include extensive basal infolding and the differentiation of an apical brush border of microvilli. The central area of the cytoplasm of the principal cell is highly vacuolated while in the stellate cell it is finely granular lacking vacuoles. The microvilli in the principal cells enclose elongated, dense mitochondria whereas the stellate cell microvilli lack mitochondria. Excretory granules of an as yet unknown chemical nature accumulate in the principal cell cytoplasm after a blood meal.

  14. MDR1 transporter protects against paraquat-induced toxicity in human and mouse proximal tubule cells.

    Science.gov (United States)

    Wen, Xia; Gibson, Christopher J; Yang, Ill; Buckley, Brian; Goedken, Michael J; Richardson, Jason R; Aleksunes, Lauren M

    2014-10-01

    Paraquat is a herbicide that is highly toxic to the lungs and kidneys following acute exposures. Prior studies have demonstrated that the organic cation transporter 2 and multidrug and toxin extrusion protein 1 contribute to the urinary secretion of paraquat in the kidneys. The purpose of this study was to determine whether the multidrug resistance protein 1 (MDR1/Mdr1, ABCB1, or P-glycoprotein) also participates in the removal of paraquat from the kidneys and protects against renal injury. Paraquat transport and toxicity were quantified in human renal proximal tubule epithelial cells (RPTEC) that endogenously express MDR1, HEK293 cells overexpressing MDR1, and Mdr1a/1b knockout mice. In RPTEC cells, reduction of MDR1 activity using the antagonist PSC833 or siRNA transfection increased the cellular accumulation of paraquat by 50%. Reduced efflux of paraquat corresponded with enhanced cytotoxicity in PSC833-treated cells. Likewise, stable overexpression of the human MDR1 gene in HEK293 cells reduced intracellular levels of paraquat by 50%. In vivo studies assessed the renal accumulation and subsequent nephrotoxicity of paraquat (10 or 30 mg/kg ip) in wild-type and Mdr1a/1b knockout mice. At 4 h after paraquat treatment, renal concentrations of paraquat in the kidneys of Mdr1a/1b knockout mice were 750% higher than wild-type mice. By 72 h, paraquat-treated Mdr1a/1b knockout mice had more extensive tubular degeneration and significantly greater mRNA expression of kidney injury-responsive genes, including kidney injury molecule-1, lipocalin-2, and NAD(P)H quinone oxidoreductase 1, compared with wild-type mice. In conclusion, MDR1/Mdr1 participates in the elimination of paraquat from the kidneys and protects against subsequent toxicity.

  15. Mechanisms of the Effects of Acidosis and Hypokalemia on Renal Ammonia Metabolism

    OpenAIRE

    Han, Ki-Hwan

    2011-01-01

    Renal ammonia metabolism is the predominant component of net acid excretion and new bicarbonate generation. Renal ammonia metabolism is regulated by acid-base balance. Both acute and chronic acid loads enhance ammonia production in the proximal tubule and secretion into the urine. In contrast, alkalosis reduces ammoniagenesis. Hypokalemia is a common electrolyte disorder that significantly increases renal ammonia production and excretion, despite causing metabolic alkalosis. Although the net ...

  16. Focal epithelial hyperplasia - an update.

    Science.gov (United States)

    Said, Ahmed K; Leao, Jair C; Fedele, Stefano; Porter, Stephen R

    2013-07-01

    Focal epithelial hyperplasia (FEH) is an asymptomatic benign mucosal disease, which is mostly observed in specific groups in certain geographical regions. FEH is usually a disease of childhood and adolescence and is generally associated with people who live in poverty and of low socioeconomic status. Clinically, FEH is typically characterized by multiple, painless, soft, sessile papules, plaques or nodules, which may coalesce to give rise to larger lesions. Human papillomavirus (HPV), especially genotypes 13 and 32, have been associated and detected in the majority of FEH lesions. The clinical examination and social history often allow diagnosis, but histopathological examination of lesional tissue is usually required to confirm the exact diagnosis. FEH sometimes resolves spontaneously however, treatment is often indicated as a consequence of aesthetic effects or any interference with occlusion. There remains no specific therapy for FEH, although surgical removal, laser excision or possibly topical antiviral agents may be of benefit. There remains no evidence that FEH is potentially malignant.

  17. Laser tonsillotomy in children with tonsillar hyperplasia.

    Science.gov (United States)

    Baharudin, A; Shahid, H; Rhendra, M Z

    2006-08-01

    Tonsillectomy in children is performed on a regular basis in ENT. The indications are chronic tonsillitis, sleep apnea to deeper structures. The natural history of tonsillar hyperplasia is regression when a child is six years beyond. In children with bilateral tonsillar hyperplasia we studied the use of laser as an alternative procedure to reduce the bulk of the tonsillar mass. Children with symptoms of bilateral tonsillar hyperplasia underwent laser tonsillotomy. The tonsils were dissected using carbon dioxide (CO2) laser. The tonsillar bed was left untouched. Intraoperative and postoperative conditions were noted.

  18. A Pacinian hyperplasia of the foot.

    Science.gov (United States)

    Satge, D; Nabhan, J; Nandiegou, Y; Hermann, B; Goburdhun, J; Labrousse, F

    2001-04-01

    A case of Pacinian hyperplasia of the right great toe is reported. Pacinian hyperplasia is a rare benign and recently recognized painful lesion composed of an excess of well formed or hyperplastic Pacinian corpuscules, normaly involved in sensory innervation. This lesion that is usually observed in the hand, must be distinguished from nerve tumors harboring onion-bulb structure which are not true well formed Pacinian corpuscules and from Morton neuroma. Pacinian hyperplasia is considered a reactive lesion and not a true neoplasm. To our knowledge, this case is the first described in the foot.

  19. Conditional Deletion of Fgfr1 in the Proximal and Distal Tubule Identifies Distinct Roles in Phosphate and Calcium Transport.

    Directory of Open Access Journals (Sweden)

    Xiaobin Han

    Full Text Available A postnatal role of fibroblast growth factor receptor-1 (FGFR1 in the kidney is suggested by its binding to α-Klotho to form an obligate receptor for the hormone fibroblast growth factor-23 (FGF-23. FGFR1 is expressed in both the proximal and distal renal tubular segments, but its tubular specific functions are unclear. In this study, we crossed Fgfr1flox/flox mice with either gamma-glutamyltransferase-Cre (γGT-Cre or kidney specific-Cre (Ksp-Cre mice to selectively create proximal tubule (PT and distal tubule (DT Fgfr1 conditional knockout mice (designated Fgfr1PT-cKO and Fgfr1DT-cKO, respectively. Fgfr1PT-cKO mice exhibited an increase in sodium-dependent phosphate co-transporter expression, hyperphosphatemia, and refractoriness to the phosphaturic actions of FGF-23, consistent with a direct role of FGFR1 in mediating the proximal tubular phosphate responses to FGF-23. In contrast, Fgfr1DT-cKO mice unexpectedly developed hypercalciuria, secondary elevations of parathyroid hormone (PTH, hypophosphatemia and enhanced urinary phosphate excretion. Fgfr1PT-cKO mice also developed a curly tail/spina bifida-like skeletal phenotype, whereas Fgfr1DT-cKO mice developed renal tubular micro-calcifications and reductions in cortical bone thickness. Thus, FGFR1 has dual functions to directly regulate proximal and distal tubule phosphate and calcium reabsorption, indicating a physiological role of FGFR1 signaling in both phosphate and calcium homeostasis.

  20. Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia and Neuroendocrine Hyperplasia of Infancy.

    Science.gov (United States)

    Carr, Laurie L; Kern, Jeffrey A; Deutsch, Gail H

    2016-09-01

    Although incidental reactive pulmonary neuroendocrine cell hyperplasia (PNECH) is seen on biopsy specimens in adults with chronic lung disease, disorders characterized by marked PNECH are rare. Primary hyperplasia of neuroendocrine cells in the lung and obstructive lung disease related to remodeling or physiologic constriction of small airways define diffuse idiopathic neuroendocrine cell hyperplasia (DIPNECH) in the adult and neuroendocrine cell hyperplasia of infancy (NEHI) in children. DIPENCH and NEHI share a similar physiology, typical imaging appearance, and increased neuroendocrine cells on biopsy. However, there are important differences related to the underlying disease mechanisms leading to disparate outcomes.

  1. [Nucleotide receptors and renal function].

    Science.gov (United States)

    Jankowski, Maciej

    2014-01-01

    Kidney plays a key role in homeostasis of human body. It has heterogenic structure and is characterized by complicated vascular beds and numbers of sympathetic nerves endings. Nucleotides receptors are involved in the regulation of blood flow, a fundamental process for renal function. Plasma is filtrated in renal glomerulus and activity of nucleotides receptors located on cells of glomerular filter modifies the physi- cochemical properties of filter and affects the filtration process. Electrolytes, water and low molecular weight molecules are reabsorbed from tubular fluid or secreted into fluid in proximal and distal tubules. Glomerular filtration rate and activity of tubular processes are regulated via nucleotides receptors by glomerulotubularbalance and tubuloglomerular feedback. Nucleotides receptors are involved in systemic regulation of blood pressure and carbohydrate metabolism.

  2. Thiamine uptake into primary proximal tubule cells and MDCK distal tubule cells; Differential effect of ethanol

    Energy Technology Data Exchange (ETDEWEB)

    Pochal, M.A.; Taub, M.; Acara, M. (State Univ. of New York, Buffalo (United States))

    1991-03-11

    Rabbit primary proximal tubule cells (PT) and distal cells from a MDCK cell line (DT) were studied for their ability to accumulate and metabolize {sup 14}C-thiamine and to assess the effect of ethanol on the accumulation. Incubation with 10uM {sup 14}C-thiamine, resulted in a four fold greater accumulation of {sup 14}C in PT compared to DT. Ethanol significantly decreased PT thiamine accumulation to 0.92 {plus minus} 0.09 nmole/mg but had little effect on DT accumulation. Initial thiamine uptake rates were greater in PT than in DT. Ethanol did not produce a significant effect on either initial uptake rate. Ethanol, however, decreased the maximum rate of uptake in PR from 3.20 to 1.75 nmole/mg/min. Although both cell types metabolize {sup 14}C to thiamine phosphates, total amount of metabolite was greater in PT. These data are consistent with cortical slice uptake studies in which thiamine accumulation was associated with its phosphorylation. In these slices both maximal accumulation and metabolism were inhibited by ethanol.

  3. 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.

    Science.gov (United States)

    Esquivel, Carlos J; Cassone, Bryan J; Piermarini, Peter M

    2016-01-01

    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 Malpighian tubules

  4. 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; Weiner, I David

    2016-06-01

    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.

  5. Oxidative stress in benign prostate hyperplasia.

    Science.gov (United States)

    Zabaiou, N; Mabed, D; Lobaccaro, J M; Lahouel, M

    2016-02-01

    To assess the status of oxidative stress in benign prostate hyperplasia, a very common disease in older men which constitutes a public health problem in Jijel, prostate tissues were obtained by transvesical adenomectomy from 10 men with benign prostate hyperplasia. We measured the cytosolic levels of malondialdehyde (MDA) and glutathione (GSH) and cytosolic enzyme activities of superoxide dismutase, catalase, glutathione peroxidase and glutathione S-transferase. The development of benign prostate hyperplasia is accompanied by impaired oxidative status by increasing levels of MDA, depletion of GSH concentrations and a decrease in the activity of all the antioxidant enzymes studied. These results have allowed us to understand a part of the aetiology of benign prostate hyperplasia related to oxidative stress.

  6. 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...

  7. 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...... dramatically at the time of puberty with complete hyalinization of the seminiferous tubules, although a few tubules with spermatogenesis may be present in adult life. Activation of the pituitary-gonadal axis at 3 months of age is seen in Klinefelter boys similar to healthy boys. However, the level...... of testosterone in Klinefelter boys is significantly lower than in controls. After this 'minipuberty', the hormone levels decline to normal prepubertal levels until puberty. In puberty, an initial rise in testosterone, inhibin B, LH and FSH occurs in Klinefelter boys. However, the rise in testosterone levels off...

  8. Gingival enlargement in partial hemifacial hyperplasia

    OpenAIRE

    Jagtap, Rasika Ravindra; Deshpande, Gaurav Shekhar

    2014-01-01

    Hemifacial hypertrophy is a rare developmental disorder, characterized by unilateral enlargement of facial tissues. The hemifacial hyperplasia is classified as true hemifacial hypertrophy and partial hemifacial hypertrophy. It is unilateral enlargement of viscerocranial condition in which not all structures are enlarged. We present a rare case of gingival enlargement in partial hemifacial hyperplasia highlighting the clinical and radiological findings with the corrective treatment offered for...

  9. An uncommon focal epithelial hyperplasia manifestation.

    Science.gov (United States)

    dos Santos-Pinto, Lourdes; Giro, Elisa Maria Aparecida; Pansani, Cyneu Aguiar; Ferrari, Junia; Massucato, Elaine Maria Sgavioli; Spolidório, Luis Carlos

    2009-01-01

    Focal epithelial hyperplasia is a rare, contagious disease associated with infection of the oral mucosa by human papillomavirus types 13 or 32, characterized by multiple soft papules of the same color as the adjacent normal mucosa. It mainly affects the lower lip, buccal mucosa, and tongue. The purpose of this case report was to describe a rare verrucal lesion located in the upper gingiva that was clinically and histologically consistent with focal epithelial hyperplasia.

  10. Oxidative stress in prostate hyperplasia and carcinogenesis

    OpenAIRE

    Udensi K. Udensi; Tchounwou, Paul B.

    2016-01-01

    Prostatic hyperplasia (PH) is a common urologic disease that affects mostly elderly men. PH can be classified as benign prostatic hyperplasia (BPH), or prostate cancer (PCa) based on its severity. Oxidative stress (OS) is known to influence the activities of inflammatory mediators and other cellular processes involved in the initiation, promotion and progression of human neoplasms including prostate cancer. Scientific evidence also suggests that micronutrient supplementation may restore the a...

  11. Bringing together components of the fly renal system.

    Science.gov (United States)

    Denholm, Barry; Skaer, Helen

    2009-10-01

    The function of all animal excretory systems is to rid the body of toxins and to maintain homeostatic balance. Although excretory organs in diverse animal species appear superficially different they are often built on two common principals: filtration and tubular secretion/reabsorbtion. The Drosophila excretory system is composed of filtration nephrocytes and Malpighian (renal) tubules. Here we review recent molecular genetic data on the development and differentiation of nephrocytes and renal tubules. We focus in particular on the molecular mechanisms that underpin key cell and tissue behaviours during morphogenesis, drawing parallels with other species where they exist. Finally we assess the implications of patterned tissue differentiation for the subsequent regulation of renal function. These studies highlight the continuing usefulness of the fly to provide fundamental insights into the complexities of organ formation.

  12. Management of adolescents with congenital adrenal hyperplasia

    Science.gov (United States)

    Merke, Deborah P; Poppas, Dix P

    2014-01-01

    The management of congenital adrenal hyperplasia involves suppression of adrenal androgen production, in addition to treatment of adrenal insufficiency. Management of adolescents with congenital adrenal hyperplasia is especially challenging because changes in the hormonal milieu during puberty can lead to inadequate suppression of adrenal androgens, psychosocial issues often affect adherence to medical therapy, and sexual function plays a major part in adolescence and young adulthood. For these reasons, treatment regimen reassessment is indicated during adolescence. Patients with non-classic congenital adrenal hyperplasia require reassessment regarding the need for glucocorticoid drug treatment. No clinical trials have compared various regimens for classic congenital adrenal hyperplasia in adults, thus therapy is individualised and based on the prevention of adverse outcomes. Extensive patient education is key during transition from paediatric care to adult care and should include education of females with classic congenital adrenal hyperplasia regarding their genital anatomy and surgical history. Common issues for these patients include urinary incontinence, vaginal stenosis, clitoral pain, and cosmetic concerns; for males with classic congenital adrenal hyperplasia, common issues include testicular adrenal rest tumours. Transition from paediatric to adult care is most successful when phased over many years. Education of health-care providers on how to successfully transition patients is greatly needed. PMID:24622419

  13. Natural history of seminiferous tubule degeneration in Klinefelter syndrome.

    Science.gov (United States)

    Aksglaede, Lise; Wikström, Anne M; Rajpert-De Meyts, Ewa; Dunkel, Leo; Skakkebaek, Niels E; Juul, Anders

    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 dramatically at the time of puberty with complete hyalinization of the seminiferous tubules, although a few tubules with spermatogenesis may be present in adult life. Activation of the pituitary-gonadal axis at 3 months of age is seen in Klinefelter boys similar to healthy boys. However, the level of testosterone in Klinefelter boys is significantly lower than in controls. After this 'minipuberty', the hormone levels decline to normal prepubertal levels until puberty. In puberty, an initial rise in testosterone, inhibin B, LH and FSH occurs in Klinefelter boys. However, the rise in testosterone levels off and ends at a low-normal level in young adults. Likewise, serum concentration of inhibin B exhibits a dramatic decline to a low, often undetectable level, concomitantly with a rise in FSH, reflecting the degeneration of the seminiferous tubules. Many hypotheses about the underlying mechanism of the depletion of the germ cells in Klinefelter males have been reported and include insufficient supranumerary X-chromosome inactivation, Leydig cell insufficiency and disturbed regulation of apoptosis of Sertoli and Leydig cells. However, at present, the exact mechanism remains unclear. In this article, we 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.

  14. The effect of exercise training on transverse tubules in normal, remodeled, and reverse remodeled hearts

    OpenAIRE

    Kemi, Ole J.; Hoydal, Morten A; MacQuaide, Niall; Haram, Per M; Koch, Lauren G.; Steven L Britton; Ellingsen, Oyvind; Smith, Godfrey L.; Wisloff, Ulrik

    2011-01-01

    The response of transverse (T)-tubules to exercise training in health and disease remains unclear. Therefore, we studied the effect of exercise training on the density and spacing of left ventricle cardiomyocyte T-tubules in normal and remodeled hearts that associate with detubulation, by confocal laser scanning microscopy. First, exercise training in normal rats increased cardiomyocyte volume by 16% (P < 0.01), with preserved T-tubule density. Thus, the T-tubules adapted to the physiologi...

  15. Early Renal Morphological Changes in High-Cholesterol Diet Rats Model

    Institute of Scientific and Technical Information of China (English)

    YAO Ying; TIAN Xing-kui; LIU Xiao-cheng; SHAO Ju-fang

    2005-01-01

    In rats fed with high-cholesterol (HC) chow, the renal specimens were investigated by microscopy and enzymehistochemistry. The levels of serum lipids, 24 h urinary protein excretion (UPE), N-acetyl-β-D-glucosaminidase (NAG) and Nitric Oxide (NO) were evaluated. Histological examination showed cell swelling, break-down and massive lipid deposition in renal tubules; perivascular and interstitial cell infiltration and mesangial cell proliferation. Enzymehistochemistry demonstrated that lactate dehydrogenase (LDH) activity in proximal tubular epithelial cells increased but succino dehydrogenase (SDH) activity decreased. The NO level in serum, urine and renal cortex were all decreased (p<0.01). Urinary NO, was negatively correlated with urinary NAG and UPE (r is -0.525, -0.529 respectively, p<0.01). This study shows that a HC diet can induce the early morphological changes in the whole kidney, particularly in the renal tubules. The decrease of NO is associated with the pathogenesis of hypercholesterolemia-induced renal injury.

  16. Renal Osteodystrophy

    Directory of Open Access Journals (Sweden)

    Aynur Metin Terzibaşoğlu

    2004-12-01

    Full Text Available Chronic renal insufficiency is a functional definition which is characterized by irreversible and progressive decreasing in renal functions. This impairment is in collaboration with glomeruler filtration rate and serum creatinine levels. Besides this, different grades of bone metabolism disorders develop in chronic renal insufficiency. Pathologic changes in bone tissue due to loss of renal paranchyme is interrelated with calcium, phosphorus vitamine-D and parathyroid hormone. Clinically we can see high turnover bone disease, low turnover bone disease, osteomalacia, osteosclerosis and osteoporosis in renal osteodystropy. In this article we aimed to review pathology of bone metabolism disorders due to chronic renal insufficiency, clinic aspects and treatment approaches briefly.

  17. 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

  18. Gastrointestinal and renal abnormalities in cardio-facio-cutaneous syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Herman, Thomas E.; McAlister, William H. [Washington University School of Medicine, St. Louis Children' s Hospital, Mallinckrodt Institute of Radiology, St. Louis, MO (United States)

    2005-02-01

    Cardio-facio-cutaneous syndrome (CFC) is an uncommon autosomal recessive condition recently distinguished from Noonan syndrome but with more marked growth failure and ectodermal dysplasia. Abdominal symptoms are frequently described but anatomic lesions in CFC have rarely been described. We have found significant anatomic abnormalities in CFC patients including antral foveolar hyperplasia, severe constipation with fecal impaction, nephrocalcinosis and renal cysts. (orig.)

  19. Nocturia and benign prostatic hyperplasia

    Directory of Open Access Journals (Sweden)

    Laketić Darko

    2008-01-01

    Full Text Available Background/Aim. Nocturia often occurs in patients with benign prostate hyperplasia (BPH. The aim of the study was to investigate the frequency of nocturia in patients with BPH. Nocturia and other factors associated with it were also investigated. Methods. Forty patients with the confirmed diagnosis of BPH were studied. Transurethral and transvesical prostatectomy were performed in all the patients. Symptoms were evaluated with the International Prostate Symptom Score before, as well as three and six months after the surgery. All the results were compared with the control group. Results. There was no statistically significant difference between the patients before and after the surgery regarding nocturia. There was, however, a statistically significant difference between the operated patients and the control group regarding nocturia, as well as a statistically significant correlation between noctruia and the age of the patients in both the investigated and the control group. A correlation also existed between nocturia and the prostatic size. Conclusion. There was no statistically significant improvement in symptoms of nocturia after the surgery. It is necessary to be very careful in decision making in patients with nonabsolute indiction for surgery and isolated bothersome symptom of nocturia. Age of a patient should also be considered in the evaluation of favorable result of the surgery because of a significant correlation between noctura and the age of a patient.

  20. cAMP-binding proteins in medullary tubules from rat kidney: effect of ADH

    Energy Technology Data Exchange (ETDEWEB)

    Gapstur, S.M.; Homma, S.; Dousa, T.P.

    1988-08-01

    Little is known of the regulatory steps in the cellular action of vasopressin (AVP) on the renal epithelium, subsequent to the cAMP generation. We studied cAMP-binding proteins in the medullary collecting tubule (MCT) and the thick ascending limb of Henle's loop (MTAL) microdissected from the rat kidney by use of photoaffinity labeling. Microdissected tubules were homogenized and photoaffinity labeled by incubation with 1 microM 32P-labeled 8-azido-adenosine 3',5'-cyclic monophosphate (N3-8-(32P)-cAMP); the incorporated 32P was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography. Both in MCT and MTAL preparations, the analyses showed incorporation of N3-8-(32P)cAMP into two bands (Mr = 49,000 and Mr = 55,000) that comigrated with standards of the cAMP-dependent protein kinase regulatory subunits RI and RII. In MCT, most of the 32P (80%) was incorporated into RI, whereas in MTAL the 32P incorporated into RI and RII was equivalent. When freshly dissected MCT segments were incubated with 10(-12)-10(-6) M AVP, the subsequent photoaffinity labeling of RI with N3-8-(32P)cAMP was markedly diminished in a dose-dependent manner compared with controls. Our results suggest that cAMP binds in MCT and MTAL to regulatory subunits RI and RII of cAMP-dependent protein kinase. However, in MCT the dominant type of cAMP-dependent protein kinase appears to be type I. The outlined procedure is suitable to indirectly measure the occupancy of RI by endogenous cAMP generated in MCT cells in response to physiological levels (10(-12) M) of AVP.

  1. Akt Links Insulin Signaling to Albumin Endocytosis in Proximal Tubule Epithelial Cells.

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    Sam Coffey

    Full Text Available Diabetes mellitus (DM has become an epidemic, causing a significant decline in quality of life of individuals due to its multisystem involvement. Kidney is an important target organ in DM accounting for the majority of patients requiring renal replacement therapy at dialysis units. Microalbuminuria (MA has been a valuable tool to predict end-organ damage in DM but its low sensitivity has driven research efforts to seek other alternatives. Albumin is taken up by albumin receptors, megalin and cubilin in the proximal tubule epithelial cells. We demonstrated that insulin at physiological concentrations induce albumin endocytosis through activation of protein kinase B (Akt in proximal tubule epithelial cells. Inhibition of Akt by a phosphorylation deficient construct abrogated insulin induced albumin endocytosis suggesting a role for Akt in insulin-induced albumin endocytosis. Furthermore we demonstrated a novel interaction between Akt substrate 160kDa (AS160 and cytoplasmic tail of megalin. Mice with type 1 DM (T1D displayed decreased Akt, megalin, cubilin and AS160 expression in their kidneys in association with urinary cubilin shedding preceding significant MA. Patients with T1D who have developed MA in the EDC (The Pittsburgh Epidemiology of Diabetes Complications study demonstrated urinary cubilin shedding prior to development of MA. We hypothesize that perturbed insulin-Akt cascade in DM leads to alterations in trafficking of megalin and cubilin, which results in urinary cubilin shedding as a prelude to MA in early diabetic nephropathy. We propose that utilization of urinary cubilin shedding, as a urinary biomarker, will allow us to detect and intervene in diabetic nephropathy (DN at an earlier stage.

  2. Akt Links Insulin Signaling to Albumin Endocytosis in Proximal Tubule Epithelial Cells.

    Science.gov (United States)

    Coffey, Sam; Costacou, Tina; Orchard, Trevor; Erkan, Elif

    2015-01-01

    Diabetes mellitus (DM) has become an epidemic, causing a significant decline in quality of life of individuals due to its multisystem involvement. Kidney is an important target organ in DM accounting for the majority of patients requiring renal replacement therapy at dialysis units. Microalbuminuria (MA) has been a valuable tool to predict end-organ damage in DM but its low sensitivity has driven research efforts to seek other alternatives. Albumin is taken up by albumin receptors, megalin and cubilin in the proximal tubule epithelial cells. We demonstrated that insulin at physiological concentrations induce albumin endocytosis through activation of protein kinase B (Akt) in proximal tubule epithelial cells. Inhibition of Akt by a phosphorylation deficient construct abrogated insulin induced albumin endocytosis suggesting a role for Akt in insulin-induced albumin endocytosis. Furthermore we demonstrated a novel interaction between Akt substrate 160kDa (AS160) and cytoplasmic tail of megalin. Mice with type 1 DM (T1D) displayed decreased Akt, megalin, cubilin and AS160 expression in their kidneys in association with urinary cubilin shedding preceding significant MA. Patients with T1D who have developed MA in the EDC (The Pittsburgh Epidemiology of Diabetes Complications) study demonstrated urinary cubilin shedding prior to development of MA. We hypothesize that perturbed insulin-Akt cascade in DM leads to alterations in trafficking of megalin and cubilin, which results in urinary cubilin shedding as a prelude to MA in early diabetic nephropathy. We propose that utilization of urinary cubilin shedding, as a urinary biomarker, will allow us to detect and intervene in diabetic nephropathy (DN) at an earlier stage.

  3. New molecular players facilitating Mg(2+) reabsorption in the distal convoluted tubule.

    Science.gov (United States)

    Glaudemans, Bob; Knoers, Nine V A M; Hoenderop, Joost G J; Bindels, René J M

    2010-01-01

    The renal distal convoluted tubule (DCT) has an essential role in maintaining systemic magnesium (Mg(2+)) concentration. The DCT is the final determinant of plasma Mg(2+) levels, as the more distal nephron segments are largely impermeable to Mg(2+). In the past decade, positional candidate strategies in families with inherited forms of hypomagnesemia have led to the identification of genes involved in Mg(2+) handling. A large fraction of this resides in the DCT, namely, (i) the transient receptor potential channel melastatin subtype 6 (TRPM6), a divalent cation-permeable channel located at the luminal membrane of the DCT, facilitates Mg(2+) entry from the pro-urine into the cell; (ii) the epidermal growth factor is a novel hormone regulating active Mg(2+) transport through TRPM6; (iii) the voltage-gated K(+) channel, Kv1.1, establishes a favorable luminal membrane potential for TRPM6-mediated Mg(2+) transport; (iv) the Na(+)/K(+)-ATPase gamma-subunit (gamma-Na(+)/K(+)-ATPase) was identified as mutated protein in a family with isolated dominant hypomagnesemia. The molecular mechanism by which gamma-Na(+)/K(+)-ATPase is involved in DCT Mg(2+) handling remains unknown; (v) a high percentage of patients with mutations in the renal transcription factor HNF1B (hepatocyte nuclear factor 1 homeobox B) gene develop hypomagnesemia; and (vi) Gitelman and EAST/SeSAME syndrome patients suffer from a similar tubulopathy due to mutations in NCC (NaCl cotransporter) and Kir4.1, respectively. In these patients, decreased expression of TRPM6 is proposed to cause hypomagnesemia. Insights into the molecular mechanisms of the identified genes, as well as the identification of novel genes, will further improve our knowledge about renal Mg(2+) handling.

  4. Delineating the Role of Various Factors in Renal Disposition of Digoxin through Application of Physiologically Based Kidney Model to Renal Impairment Populations

    Science.gov (United States)

    Scotcher, Daniel; Jones, Christopher R.; Galetin, Aleksandra

    2017-01-01

    Development of submodels of organs within physiologically-based pharmacokinetic (PBPK) principles and beyond simple perfusion limitations may be challenging because of underdeveloped in vitro-in vivo extrapolation approaches or lack of suitable clinical data for model refinement. However, advantage of such models in predicting clinical observations in divergent patient groups is now commonly acknowledged. Mechanistic understanding of altered renal secretion in renal impairment is one area that may benefit from such models, despite knowledge gaps in renal pathophysiology. In the current study, a PBPK kidney model was developed for digoxin, accounting for the roles of organic anion transporting peptide 4C1 (OATP4C1) and P-glycoprotein (P-gp) in its tubular secretion, with the aim to investigate the impact of age and renal impairment (moderate to severe) on renal drug disposition. Initial PBPK simulations based on changes in glomerular filtration rate (GFR) underestimated the observed reduction in digoxin renal excretion clearance (CLR) in subjects with moderately impaired renal function relative to healthy. Reduction in either proximal tubule cell number or the OATP4C1 abundance in the mechanistic kidney model successfully predicted 59% decrease in digoxin CLR, in particular when these changes were proportional to reduction in GFR. In contrast, predicted proximal tubule concentration of digoxin was only sensitive to changes in the transporter expression/ million proximal tubule cells. Based on the mechanistic modeling, reduced proximal tubule cellularity and OATP4C1 abundance, and inhibition of OATP4C1-mediated transport, are proposed as possible causes of reduced digoxin renal secretion in renally impaired patients. PMID:28057840

  5. '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

  6. SCANNING ELECTRON MICROSCOPIC INVESTIGATION OF DENTINAL TUBULES IN MONKEY DENTIN SCANNING ELECTRON MICROSCOPIC INVESTIGATION OF DENTINAL TUBULES IN Cebus apella DENTIN

    Directory of Open Access Journals (Sweden)

    João Humberto Antoniazzi

    2009-12-01

    Full Text Available

    The aim of the study was to investigate the number and diameter of the Cebus apella dentinal tubules. The roots of the Cebus apella teeth were examined in specific tooth locations: the apical, middle and cervical dentin. The calculations were based on the scanning electron microscope photographs of the fractured surfaces. The results showed that the average number of dentinal tubules for each location was: 74,800 tubules/mm2 for apical root dentin, 90,000 tubules/mm2 for mid-root dentin, 91,600 tubules/mm2 for cervical root dentin. The average diameter was the following: apical root dentin, 4,30µm; mid-root dentin, 4,37µm; cervical root dentin,  5,23µm. These findings demonstrate that the Cebus apella teeth are a suitable substitute for human in endodontics studies. 

    KEY WORDS: Dentin, dentinal tubules, teeth.
    The aim of the study was to investigate the number and diameter of the Cebus apella dentinal tubules. The roots of the Cebus apella teeth were examined in specific tooth locations: the apical, middle and cervical dentin. The calculations were based on the scanning electron microscope photographs of the fractured surfaces. The results showed that the average number of dentinal tubules for each location was: 74,800 tubules/mm2 for apical root dentin, 90,000 tubules/mm2 for mid-root dentin, 91,600 tubules/mm2 for cervical root dentin. The average diameter was the following: apical root dentin, 4,30µm; mid-root dentin, 4,37µm; cervical root dentin,  5,23µm. These findings demonstrate that the Cebus apella teeth are a suitable substitute for human in endodontics studies. 

    KEY WORDS: Dentin, dentinal tubules, teeth.

  7. An experimental study on vascular changes in renal biopsy injury

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Jae Hoon; Han, Man Chung [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    1981-12-15

    An experimental study on the vascular alternations of the kidney following biopsy procedure was carried out in 47 kidneys from 28 rabbits to clarify their nature and frequency by renal arteriography and microangiography together with histopathologic investigation. Renal arteriography and microangiography were performed immediately 2 days, 1 week, and 2 weeks after percutaneous biopsy and the findings were correlated with histological nature. The results are summarized as follows: 1. Important biopsy injuries verified by renal arteriography and microangiography were arterial spasm, perfusion defect, arteriovenous fistula, injury to vasa rectae and renal tubules, intrarenal and extrarenal extravasation of contrast media, and arterial obstruction, in order of frequency. 2. Arterial spasm observed in majority of the cases were relieved during the period of 2 weeks. 3. Detectability of perfusion detect was 57% and 72% angiography and microangiography, respectively, and this perfusion defect seemed to be mostly caused by renal infraction due to vascular injury, such as arteriovenous fistula, arterial obstruction and other vascular injuries. 4. Arteriovenous fistula was detected in 28% by angiography and 50% by microangiography. Many of the arteriovenous fistulae appeared to be closed spontaneous within a week. Above findings suggest that renal biopsy procedure results in various degree of vascular injuries with their sequential modification, and that microangiography is assumed the most effective approach in analysis of biopsy injuries such as small arteriovenous fistula, perfusion defect, injury to vasa recta and renal tubules, overcoming the limitation of traditional angiography.

  8. 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

  9. Dentinal tubules driven wetting of dentin: Cassie-Baxter modelling

    Science.gov (United States)

    Ramos, S. M. M.; Alderete, L.; Farge, P.

    2009-10-01

    We investigate the wetting properties of dentin surfaces submitted to a phosphoric acid etching followed by an air drying procedure, as in clinical situations of adhesive dentistry. The surface topography of the etched surfaces was characterized by AFM, and the wetting properties of water on these rough and heterogeneous surfaces were studied, by contact angle measurements. We showed that the contact angle increases with the acid exposure time and consequently with both surface roughness and the organic-mineral ratio of the dentin components. From the whole results, obtained on dentin and also on synthesized hydroxyapatites samples, we inferred a water contact angle of ˜ 133° on the dentinal tubule. These experimental results may be described by the Cassie-Baxter approach, and it is suggested that small air pockets could be formed inside the dentinal tubules.

  10. Sodium pumps in the Malpighian tubule of Rhodnius sp.

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    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.

  11. Transcriptomic evidence for a dramatic functional transition of the malpighian tubules after a blood meal in the Asian tiger mosquito Aedes albopictus.

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    Carlos J Esquivel

    2014-06-01

    Full Text Available BACKGROUND: The consumption of a vertebrate blood meal by adult female mosquitoes is necessary for their reproduction, but it also presents significant physiological challenges to mosquito osmoregulation and metabolism. The renal (Malpighian tubules of mosquitoes play critical roles in the initial processing of the blood meal by excreting excess water and salts that are ingested. However, it is unclear how the tubules contribute to the metabolism and excretion of wastes (e.g., heme, ammonia produced during the digestion of blood. METHODOLOGY/PRINCIPAL FINDINGS: Here we used RNA-Seq to examine global changes in transcript expression in the Malpighian tubules of the highly-invasive Asian tiger mosquito Aedes albopictus during the first 24 h after consuming a blood meal. We found progressive, global changes in the transcriptome of the Malpighian tubules isolated from mosquitoes at 3 h, 12 h, and 24 h after a blood meal. Notably, a DAVID functional cluster analysis of the differentially-expressed transcripts revealed 1 a down-regulation of transcripts associated with oxidative metabolism, active transport, and mRNA translation, and 2 an up-regulation of transcripts associated with antioxidants and detoxification, proteolytic activity, amino-acid metabolism, and cytoskeletal dynamics. CONCLUSIONS/SIGNIFICANCE: The results suggest that blood feeding elicits a functional transition of the epithelium from one specializing in active transepithelial fluid secretion (e.g., diuresis to one specializing in detoxification and metabolic waste excretion. Our findings provide the first insights into the putative roles of mosquito Malpighian tubules in the chronic processing of blood meals.

  12. Renal metabolism of calcitonin

    Energy Technology Data Exchange (ETDEWEB)

    Simmons, R.E.; Hjelle, J.T.; Mahoney, C.; Deftos, L.J.; Lisker, W.; Kato, P.; Rabkin, R.

    1988-04-01

    The kidneys account for approximately two-thirds of the metabolism of calcitonin, but relatively little is known regarding the details thereof. To further characterize this process, we examined the renal handling and metabolism of human calcitonin (hCT) by the isolated perfused rat kidney. We also studied the degradation of radiolabeled salmon calcitonin (sCT) by subcellular fractions prepared from isolated rabbit proximal tubules. The total renal (organ) clearance of immunoreactive hCT by the isolated kidney was 1.96 +/- 0.18 ml/min. This was independent of the perfusate total calcium concentration from 5.5 to 10.2 mg/dl. Total renal clearance exceeded the glomerular filtration rate (GFR, 0.68 +/- 0.05 ml/min), indicating filtration-independent removal. Urinary calcitonin clearance as a fraction of GFR averaged 2.6%. Gel filtration chromatography of medium from isolated kidneys perfused with /sup 125/I-labeled sCT showed the principal degradation products to be low molecular weight forms eluting with monoiodotyrosine. Intermediate size products were not detected. In the subcellular fractionation experiments, when carried out at pH 5.0, calcitonin hydrolysis exclusively followed the activities of the lysosomal enzyme N-acetyl-beta-glucosaminidase. Typically, at pH 7.5, 42% of total degradation occurred in the region of the brush-border enzyme alanyl aminopeptidase and 29% occurred in the region of the cytosolic enzyme phosphoglucomutase. Although 9% of the calcitonin-degrading activity was associated with basolateral membrane fractions, most of this activity could be accounted for by the presence of brush-border membranes.

  13. Flozins, inhibitors of type 2 renal sodium-glucose co-transporter – not only antihyperglycemic drugs

    OpenAIRE

    Mizerski Grzegorz; Kicinski Pawel; Jaroszynski Andrzej

    2015-01-01

    The kidneys play a crucial role in the regulation of the carbohydrate metabolism. In normal physiological conditions, the glucose that filters through the renal glomeruli is subsequently nearly totally reabsorbed in the proximal renal tubules. Two transporters are engaged in this process: sodium-glucose co-transporter type 1 (SGLT1), and sodium-glucose co-transporter type type 2 (SGLT2) - this being located in the luminal membrane of the renal tubular epithelial cells. It was found that the a...

  14. Prevalence of outer retinal tubulation in eyes with choroidal neovascularization

    OpenAIRE

    Giachetti Filho, Richard Geraldo; Zacharias,Leandro Cabral; Monteiro,Thaís Vera; Preti, Rony Carlos; Pimentel, Sérgio Gianoti

    2016-01-01

    Background Outer retinal tubulations (ORTs) are branching tubular structures located in the outer nuclear layer of the retina. The goal of this study is to determine the prevalence of ORTs observed in eyes with choroidal neovascularization (CNV) undergoing treatment with anti-angiogenic intravitreous injection (IVI) with anti-VEGF (vascular endothelial growth factor) at the Ophthalmology Department of a tertiary hospital in São Paulo, Brazil. Methods This is a descriptive study based on medic...

  15. From cyst to tubule: innovations in vertebrate spermatogenesis.

    Science.gov (United States)

    Yoshida, Shosei

    2016-01-01

    Although vertebrates share many common traits, their germline development and function exhibit significant divergence. In particular, this article focuses on their spermatogenesis. The fundamental elements that constitute vertebrate spermatogenesis and the evolutionary changes that occurred upon transition from water to land will be discussed. The life-long continuity of spermatogenesis is supported by the function of stem cells. Series of mitotic and meiotic germ cell divisions are 'incomplete' due to incomplete cytokinesis, forming syncytia interconnected via intercellular bridges (ICBs). Throughout this process, germ cells are supported by appropriate microenvironments established primarily by somatic Sertoli cells. In anamniotes (fish and amphibians) spermatogenesis progresses in cysts, in which developing germ cell syncytia are individually encapsulated by Sertoli cells. Accordingly, Sertoli cells undergo turnover with germ cells that they nourish. This mode of cystic spermatogenesis is also observed in nonvertebrates as insects. In amniotes (reptiles, birds, and mammals), however, Sertoli cells do not turn over but comprise a persistent structure of seminiferous tubules. Sertoli cells nourish different stages of germ cells simultaneously in distinct regions of their surface. This function of Sertoli cells is spatiotemporally orchestrated, and the seminiferous epithelial cycle and spermatogenic wave make the seminiferous tubules a high-throughput factory for sperm production. Furthermore, contrary to the organized differentiating cells, undifferentiated spermatogonia that comprise the stem cell compartment exhibit active motion over the basal layer of seminiferous tubules and the frequent breakdown of ICBs. Thus, amniote seminiferous tubules represent a typical facultative (or open) niche environment without a stem cell tethering anatomically defined niche. WIREs Dev Biol 2016, 5:119-131. doi: 10.1002/wdev.204 For further resources related to this article

  16. Effect of testicular capsulotomy on lipid droplets in the seminiferous tubules of rats

    Institute of Scientific and Technical Information of China (English)

    Da-Nian QIN; Mary A. Lung

    2001-01-01

    Aim: In order to reveal the histochemical alteration that might occur during the processes of the spermatogenic dis mption induced by testicular capsulotomy, the location and alteration of lipid droplets in the seminiferous tubules were observed in the present study. Methods: Osmium tetroxide was used to demonstrate the lipid droplets in the semi niferous tubules of capsulotomized and sham-operated control testes. Results: In the seminiferous tubules of the sham-operated rat testes, many small lipid droplets were located close to the basement membrane of the seminiferous tubules. But for the capsulotomized testes, the lipid droplets in the seminiferous tubules had increased in size and num ber, with many lipid droplets migrated towards the lumen of the tubules. Conclusion: The results indicated that a progressive fatty degeneration occurred in the seminiferous tubules after testicular capsulotomy.

  17. Renal perfusion scintiscan

    Science.gov (United States)

    Renal perfusion scintigraphy; Radionuclide renal perfusion scan; Perfusion scintiscan - renal; Scintiscan - renal perfusion ... supply the kidneys. This is a condition called renal artery stenosis. Significant renal artery stenosis may be ...

  18. The expression of EPOR in renal cortex during postnatal development.

    Directory of Open Access Journals (Sweden)

    Lu Xiao

    Full Text Available Erythropoietin (EPO, known for its role in erythroid differentiation, has been shown to be an important growth factor for brain and heart. EPO is synthesized by fibroblast-like cells in the renal cortex. Prompted by this anatomical relationship and its significant impact on the maturation process of brain and heart, we asked whether EPO could play a role during the development of renal cortex. The relationship between the development of renal cortex and the change of EPO receptor (EPOR, through which EPO could act as a renotropic cytokine, became interesting to us. In this study, the day of birth was recorded as postnatal day 0(P0. P7, P14, P21, P28, P35, P42 and mature mice (postnatal days>56 were used as the animal model of different developmental stages. Immunohistochemistry and Western blotting were used to detect the expression of EPOR in mouse renal cortex. Results showed that expression of EPOR decreased with the development of renal cortex and became stable when kidney became mature. The expression of EPOR was detected at the renal tubule of all developmental stages and a relatively higher expression was observed at P14. However, at the renal corpuscle the expression was only observed at P7 and quickly became undetectable after that. All these suggested that a translocation of EPOR from renal corpuscle to renal tubule may take place during the developmental process of renal cortex. Also, EPO may be an essential element for the maturation of renal cortex, and the requirement for EPO was changed during postnatal development process.

  19. Dysferlin and myoferlin regulate transverse tubule formation and glycerol sensitivity.

    Science.gov (United States)

    Demonbreun, Alexis R; Rossi, Ann E; Alvarez, Manuel G; Swanson, Kaitlin E; Deveaux, H Kieran; Earley, Judy U; Hadhazy, Michele; Vohra, Ravneet; Walter, Glenn A; Pytel, Peter; McNally, Elizabeth M

    2014-01-01

    Dysferlin is a membrane-associated protein implicated in muscular dystrophy and vesicle movement and function in muscles. The precise role of dysferlin has been debated, partly because of the mild phenotype in dysferlin-null mice (Dysf). We bred Dysf mice to mice lacking myoferlin (MKO) to generate mice lacking both myoferlin and dysferlin (FER). FER animals displayed progressive muscle damage with myofiber necrosis, internalized nuclei, and, at older ages, chronic remodeling and increasing creatine kinase levels. These changes were most prominent in proximal limb and trunk muscles and were more severe than in Dysf mice. Consistently, FER animals had reduced ad libitum activity. Ultrastructural studies uncovered progressive dilation of the sarcoplasmic reticulum and ectopic and misaligned transverse tubules in FER skeletal muscle. FER muscle, and Dysf- and MKO-null muscle, exuded lipid, and serum glycerol levels were elevated in FER and Dysf mice. Glycerol injection into muscle is known to induce myopathy, and glycerol exposure promotes detachment of transverse tubules from the sarcoplasmic reticulum. Dysf, MKO, and FER muscles were highly susceptible to glycerol exposure in vitro, demonstrating a dysfunctional sarcotubule system, and in vivo glycerol exposure induced severe muscular dystrophy, especially in FER muscle. Together, these findings demonstrate the importance of dysferlin and myoferlin for transverse tubule function and in the genesis of muscular dystrophy.

  20. Malpighian tubule development in the red flour beetle (Tribolium castaneum).

    Science.gov (United States)

    King, Benedict; Denholm, Barry

    2014-11-01

    Malpighian tubules (MpTs) are the major organ for excretion and osmoregulation in most insects. MpT development is characterised for Drosophila melanogaster, but not other species. We therefore do not know the extent to which the MpT developmental programme is conserved across insects. To redress this we provide a comprehensive description of MpT development in the beetle Tribolium castaneum (Coleoptera), a species separated from Drosophila by >315 million years. We identify similarities with Drosophila MpT development including: 1) the onset of morphological development, beginning when tubules bud from the gut and proliferate to increase organ size. 2) the tubule is shaped by convergent-extension movements and oriented cell divisions. 3) differentiated tip cells activate EGF-signalling in distal MpT cells through the ligand Spitz. 4) MpTs contain two main cell types - principal and stellate cells, differing in morphology and gene expression. We also describe development of the beetle cryptonephridial system, an adaptation for water conservation, which represents a major modification of the MpT ground plan characterised by intimate association between MpTs and rectum. This work establishes a new model to compare MpT development across insects, and provides a framework to help understand how an evolutionary novelty - the cryptonephridial system - arose during organ evolution.

  1. Brunner's gland hyperplasia in the sand rat (Psammomys obesus).

    Science.gov (United States)

    Steinbach, T J; Kane, J D

    2013-07-01

    Brunner's glands are submucosal glands located in the proximal duodenum. Hyperplasia of the Brunner's gland has been reported rarely in humans and animals. We examined sections of the Brunner's gland from 63 sand rats submitted for necropsy over 2 years. Of the 63 animals necropsied, 45 (71%) had evidence of hyperplasia defined as nodular expansion, dilated ducts, or intraductal papillary proliferation. The hyperplasia was graded as mild in 22 (49%) of the cases, moderate in 15 (33%), and marked in 8 (18%). We found an association with both increased age and evidence of gastric ulceration and hyperplasia of the Brunner's gland. In sand rats with marked hyperplasia, 8 of 8 (100%) had evidence of gastric ulceration, compared to 13 of 18 (72%) in animals with no hyperplasia. Animals with marked hyperplasia were, on average, 8.4 months older than animals with no hyperplasia. There was no association with gender. The lesion in sand rats is histologically similar to that in humans.

  2. What Are the Treatments for Congenital Adrenal Hyperplasia (CAH)?

    Science.gov (United States)

    ... Publications What are the treatments for congenital adrenal hyperplasia (CAH)? Skip sharing on social media links Share ... sees many CAH cases. 6 The Congenital Adrenal Hyperplasia Research, Education & Support (CARES) Foundation strongly recommends delaying ...

  3. Neoplasia versus hyperplasia of the retinal pigment epithelium

    DEFF Research Database (Denmark)

    Heegaard, Steffen; Larsen, J.N.B.; Fledelius, Hans C.

    2001-01-01

    ophthalmology, retinal pigment epithelium, adenoma, tumor-like hyperplasia, histology, immunohistochemistry, tumor, neoplasm, ultrasonography......ophthalmology, retinal pigment epithelium, adenoma, tumor-like hyperplasia, histology, immunohistochemistry, tumor, neoplasm, ultrasonography...

  4. Angiotensin II counteracts the effects of cAMP/PKA on NHE3 activity and phosphorylation in proximal tubule cells.

    Science.gov (United States)

    Crajoinas, Renato O; Polidoro, Juliano Z; Carneiro de Morais, Carla P A; Castelo-Branco, Regiane C; Girardi, Adriana C C

    2016-11-01

    Binding of angiotensin II (ANG II) to the AT1 receptor (AT1R) in the proximal tubule stimulates Na(+)/H(+) exchanger isoform 3 (NHE3) activity through multiple signaling pathways. However, the effects of ANG II/AT1R-induced inihibitory G protein (Gi) activation and subsequent decrease in cAMP accumulation on NHE3 regulation are not well established. We therefore tested the hypothesis that ANG II reduces cAMP/PKA-mediated phosphorylation of NHE3 on serine 552 and, in doing so, stimulates NHE3 activity. Under basal conditions, ANG II stimulated NHE3 activity but did not affect PKA-mediated NHE3 phosphorylation at serine 552 in opossum kidney (OKP) cells. However, in the presence of the cAMP-elevating agent forskolin (FSK), ANG II blocked FSK-induced NHE3 inhibition, reduced intracellular cAMP concentrations, lowered PKA activity, and prevented the FSK-mediated increase in NHE3 serine 552 phosphorylation. All effects of ANG II were blocked by pretreating OKP cells with the AT1R antagonist losartan, highlighting the contribution of the AT1R/Gi pathway in ANG II-mediated NHE3 upregulation under cAMP-elevating conditions. Accordingly, Gi inhibition by pertussis toxin treatment decreased NHE3 activity both in vitro and in vivo and, more importantly, prevented the stimulatory effect of ANG II on NHE3 activity in rat proximal tubules. Collectively, our results suggest that ANG II counteracts the effects of cAMP/PKA on NHE3 phosphorylation and inhibition by activating the AT1R/Gi pathway. Moreover, these findings support the notion that NHE3 dephosphorylation at serine 552 may represent a key event in the regulation of renal proximal tubule sodium handling by ANG II in the presence of natriuretic hormones that promote cAMP accumulation and transporter phosphorylation.

  5. Extensive Focal Epithelial Hyperplasia: A Case Report

    OpenAIRE

    Mansouri, Zahra; Bakhtiari, Sedigheh; Noormohamadi, Robab

    2015-01-01

    Focal epithelial hyperplasia (FEH) or Heck’s disease is a rare viral infection of the oral mucosa caused by human papilloma virus especially subtypes 13 or 32. The frequency of this disease varies widely from one geographic region and ethnic groups to another. This paper reports an Iranian case of extensive focal epithelial hyperplasia. A 35-year-old man with FEH is described, in whom the lesions had persisted for more than 25 years. The lesion was diagnosed according to both clinical and his...

  6. Extensive Focal Epithelial Hyperplasia: A Case Report.

    Science.gov (United States)

    Mansouri, Zahra; Bakhtiari, Sedigheh; Noormohamadi, Robab

    2015-01-01

    Focal epithelial hyperplasia (FEH) or Heck's disease is a rare viral infection of the oral mucosa caused by human papilloma virus especially subtypes 13 or 32. The frequency of this disease varies widely from one geographic region and ethnic groups to another. This paper reports an Iranian case of extensive focal epithelial hyperplasia. A 35-year-old man with FEH is described, in whom the lesions had persisted for more than 25 years. The lesion was diagnosed according to both clinical and histopathological features. Dental practitioner should be aware of these types of lesions and histopathological examination together and a careful clinical observation should be carried out for a definitive diagnosis.

  7. Pseudoepitheliomatous Hyperplasia in a Red Pigment Tattoo

    Science.gov (United States)

    Kazlouskaya, Viktoryia

    2015-01-01

    Red pigment tattoos are known to cause pseudoepitheliomatous hyperplasia in the skin, frequently simulating squamous cell carcinoma or keratoacanthoma. Herein, the authors present two additional cases of red pigment tattoo pseudoepitheliomatous hyperplasia in which they noted a lichenoid tissue reaction. They reviewed the previously published cases and observed a lichenoid reaction in the histopathological images similar to hypertrophic lichen planus. The authors suggest that these reactions might best be referred to as “lichenoid reaction with pseudoepitheliomatous hyperplasia” or “hypertrophic lichen planus-like reaction.” Accordingly, recognition of an inflammatory component may allow additional treatment options. PMID:26705448

  8. Hemorrhagc focal nodular hyperplasia in young men: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jin Hyun; Kwon, Hee Jin; Cho, Jin Han; Oh, Jong Yeong; Nam, Kyung Jin; Roh, Young Hoon; Jeong, Jin Sook [College of Medicine, Dong-A University, Busan (Korea, Republic of)

    2014-04-15

    In general, focal nodular hyperplasia is a hepatic lesion that most frequently affects the healthy women of reproductive age. Focal nodular hyperplasia lesions have a benign natural course; the majority of the cases remain asymptomatic and complications are rare. Spontaneous hemorrhage of focal nodular hyperplasia is a rare disease, and the hemorrhage in young men is even more uncommon. We report a rare case of spontaneous hemorrhage of focal nodular hyperplasia in a 19-year-old man.

  9. [Renal adaptation after experimental nephrectomy in animals: a review].

    Science.gov (United States)

    Rouvellat-Terrade, P; Game, X; de Bonnecaze, G; Beauval, J-B; Mansouri, A; Doumerc, N; Rischmann, P; Malavaud, B

    2013-03-01

    OBJECTIVE AND DATA-GATHERING: We reviewed experimental litterature about kidney adaptation after nephrectomy in mammals. KNOWLEDGE SYNTHESIS: Renal mass increases after nephrectomy thanks to two components, one is immediately due to the rise of glomulary capillary vascular flow, other is linked to cellular modifications with hyperplasia stage which precedes hypertrophy stage. After nephrectomy, young animals show higher renal adaptability than adults. Similarly, the sex influences the remnant kidney parenchyma volume, the increase of glomerular filtration, the hyperplasia's intensity or length, the hypertrophy's metabolic pathways and the glomerular and tubular cells' injury. There is no question that renal compensatory is regulated by hormones such as IGF-1, TGFβ-1 and Ang-II. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  10. Clinical Progress on Acupuncture Treatment of Prostatic Hyperplasia

    Institute of Scientific and Technical Information of China (English)

    李丽会; 张淑静; 徐名一; 黄国琪

    2009-01-01

    @@ Prostatic hyperplasia, also termed benign prostatic hyperplasia (BPH), is a commonly encountered disease in middle-aged and old males. This condition is known as "Retention of Urine" and "Urination Syndrome" in Chinese medicine. Now, the literature from 1998 to 2008 on acupuncture treatment of prostatic hyperplasia are abstracted and reviewed, in order to understand the clinical status of acupuncture treatment for this disease.

  11. Intravenous renal cell transplantation with SAA1-positive cells prevents the progression of chronic renal failure in rats with ischemic-diabetic nephropathy.

    Science.gov (United States)

    Kelly, Katherine J; Zhang, Jizhong; Han, Ling; Wang, Mingsheng; Zhang, Shaobo; Dominguez, Jesus H

    2013-12-15

    Diabetic nephropathy, the most common cause of progressive chronic renal failure and end-stage renal disease, has now reached global proportions. The only means to rescue diabetic patients on dialysis is renal transplantation, a very effective therapy but severely limited by the availability of donor kidneys. Hence, we tested the role of intravenous renal cell transplantation (IRCT) on obese/diabetic Zucker/SHHF F1 hybrid (ZS) female rats with severe ischemic and diabetic nephropathy. Renal ischemia was produced by bilateral renal clamping of the renal arteries at 10 wk of age, and IRCT with genetically modified normal ZS male tubular cells was given intravenously at 15 and 20 wk of age. Rats were euthanized at 34 wk of age. IRCT with cells expressing serum amyloid A had strong and long-lasting beneficial effects on renal function and structure, including tubules and glomeruli. However, donor cells were found engrafted only in renal tubules 14 wk after the second infusion. The results indicate that IRCT with serum amyloid A-positive cells is effective in preventing the progression of chronic kidney disease in rats with diabetic and ischemic nephropathy.

  12. Helical CT angiography of renal arteries: two-years of experience; Angioscanographie helicoidale des arteres renales

    Energy Technology Data Exchange (ETDEWEB)

    Beregi, J.P.; Louvegny, S.; Ceugnart, L.; Willoteaux, S.; Elkohen, M.; Desmoucelle, F.; Deklunder, G.; Wattinne, L. [Centre Hospitalier Universitaire, 59 - Lille (France)

    1997-08-01

    To evaluate the role of helical CT angiography (CTA) in the detection of renal artery stenosis in hypertensive patients. We studied 300 hypertensive patients (50 prospectively and 250 consecutively) with CTA and arteriography (n = 118). Helical acquisition (collimation 3 mm; pitch = 1, 20 seconds acquisition time) was performed 20-45 seconds after contrast injection (300 mgl/ml; 120 ml, 4 ml/sec). Transverse axial views and 3D reconstructions were analysed (360 deg interpolation algorithm, 1 mm overlapped). In the prospective series, CTA sensibility was 100 % for main renal artery stenoses and specificity was 98.2 %; however 7/32 renal accessory arteries were not visualized. In the 300 patients studies, seventy-four stenoses were detected. There were 5 false-positive and 5 false-negative studies. Secondary hypertension was detected in 26 % of patients (including 14 cases of adrenal hyperplasia). CTA is a promising technique for the detection of renal artery stenosis in hypertensive patients. (authors).

  13. Association of systemic hypertension with renal injury in dogs with induced renal failure.

    Science.gov (United States)

    Finco, Delmar R

    2004-01-01

    Systemic hypertension is hypothesized to cause renal injury to dogs. This study was performed on dogs with surgically induced renal failure to determine whether hypertension was associated with altered renal function or morphology. Mean arterial pressure (MAP), heart rate (HR), systolic arterial pressure (SAP), and diastolic arterial pressure (DAP) were measured before and after surgery. Glomerular filtration rate (GFR) and urine protein:creatinine ratios (UPC) were measured at 1, 12, 24, 36, and 56-69 weeks after surgery, and renal histology was evaluated terminally. The mean of weekly MAP, SAP, and DAP measurements for each dog over the 1st 26 weeks was used to rank dogs on the basis of MAP, SAP, or DAP values. A statistically significant association was found between systemic arterial pressure ranking and ranked measures of adverse renal responses. When dogs were divided into higher pressure and lower pressure groups on the basis of SAP, group 1 (higher pressure, n = 9) compared with group 2 (lower pressure, n = 10) had significantly lower GFR values at 36 and 56-69 weeks; higher UPC values at 12 and 56-69 weeks; and higher kidney lesion scores for mesangial matrix, tubule damage, and fibrosis. When dogs were divided on MAP and DAP values, group 1 compared with group 2 had significantly lower GFR values at 12, 24, 36, and 56-69 weeks; higher UPC values at 12 and 56-69 weeks; and higher kidney lesion scores for mesangial matrix, tubule damage, fibrosis, and cell infiltrate. These results demonstrate an association between increased systemic arterial pressure and renal injury. Results from this study might apply to dogs with some types of naturally occurring renal failure.

  14. The Endocytic Receptor Megalin and its Associated Proteins in Proximal Tubule Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Shankhajit De

    2014-07-01

    Full Text Available Receptor-mediated endocytosis in renal proximal tubule epithelial cells (PTECs is important for the reabsorption and metabolization of proteins and other substances, including carrier-bound vitamins and trace elements, in glomerular filtrates. Impairment of this endocytic process results in the loss of such substances and development of proteinuria, which is an important clinical indicator of kidney diseases and is also a risk marker for cardiovascular disease. Megalin, a member of the low-density lipoprotein receptor gene family, is a multiligand receptor expressed in the apical membrane of PTECs and plays a central role in the endocytic process. Megalin interacts with various intracellular adaptor proteins for intracellular trafficking and cooperatively functions with other membrane molecules, including the cubilin-amnionless complex. Evidence suggests that megalin and the cubilin-amnionless complex are involved in the uptake of toxic substances into PTECs, which leads to the development of kidney disease. Studies of megalin and its associated molecules will be useful for future development of novel strategies for the diagnosis and treatment of kidney diseases.

  15. 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.

  16. ZIP8 expression in human proximal tubule cells, human urothelial cells transformed by Cd+2 and As+3 and in specimens of normal human urothelium and urothelial cancer

    OpenAIRE

    Ajjimaporn Amornpan; Botsford Tom; Garrett Scott H; Sens Mary; Zhou Xu; Dunlevy Jane R; Sens Donald A; Somji Seema

    2012-01-01

    Abstract Background ZIP8 functions endogenously as a Zn+2/HCO3- symporter that can also bring cadmium (Cd+2) into the cell. It has also been proposed that ZIP8 participates in Cd-induced testicular necrosis and renal disease. In this study real-time PCR, western analysis, immunostaining and fluorescent localization were used to define the expression of ZIP8 in human kidney, cultured human proximal tubule (HPT) cells, normal and malignant human urothelium and Cd+2 and arsenite (As+3) transform...

  17. Urodynamic implications of benign prostatic hyperplasia

    DEFF Research Database (Denmark)

    Jensen, K M; Andersen, J T

    1990-01-01

    By the age of 60, about 70% of men have developed benign prostatic hyperplasia (BPH), and 85%-95% of these have symptomatic dysfunction of the lower urinary tract, 10%-20% undergoing prostatectomy. Although transurethral resection of the prostate is generally considered to be a safe and effective...

  18. [Focal epithelial hyperplasia. An unusual clinical aspect].

    Science.gov (United States)

    Bodokh, I; Lacour, J P; Rainero, C; Orth, G; Perrin, C; Hoffman, P; Santini, J; Ortonne, J P

    1993-01-01

    We report a case of focal epithelial hyperplasia in a child born in France of Algerian parents. The clinical appearance was unusual in that certain lesions were verrucous and pediculate. A virological study revealed the presence of papillomavirus 32, one of the two types of HPV specifically associated with this entity.

  19. Multifocal epithelial hyperplasia. Report of nine cases.

    Science.gov (United States)

    Ledesma-Montes, Constantino; Vega-Memije, Elisa; Garcés-Ortíz, Maricela; Cardiel-Nieves, Maritza; Juárez-Luna, Claudia

    2005-01-01

    Multifocal epithelial hyperplasia (MEH) is also known as focal epithelial hyperplasia, Heck's disease or multifocal papillomavirus-induced epithelial hyperplasia. It is characterised by the presence of multiple lesions in the oral mucosa of children and it has been associated with the presence of the human papillomavirus. The aim of this study was to determine the clinico-pathological features of the cases diagnosed as MEH in the Service of Dermatology of the Hospital Manuel Gea González (SDHMGG). The files of the SDHMGG were reviewed and all cases diagnosed as MEH were retrieved. Nine MEH cases were found. Most of the patients were 20 year-old or younger (67%) and females were more commonly affected (78%). All patients presented multiple lesions and always, close relatives with similar lesions were found. Lesions were located most commonly in the buccal mucosa, lower lip and commissures. MEH is a soft tissue intraoral condition that needs treatment solely of the traumatised lesions or those with cosmetic problems. Remaining lesions will disappear with the age of the patients. It is suggested that this entity should be named multifocal epithelial hyperplasia since this name describes better the clinico-pathological and microscopic features of the disease.

  20. Puberty and fertility in congenital adrenal hyperplasia.

    NARCIS (Netherlands)

    Otten, B.J.; Stikkelbroeck, M.M.L.; Claahsen-van der Grinten, H.L.; Hermus, A.R.M.M.

    2005-01-01

    Congenital adrenal hyperplasia (CAH) is a disorder of adrenal steroid synthesis. The symptoms and signs of CAH depend on the degree of enzyme deficiency; severe salt-wasting (SW) form, less severe simple virilizing (SV) form and mild nonclassic (NC) form. In this paper, puberty and fertility in CAH

  1. Atypical focal nodular hyperplasia of the liver

    Institute of Scientific and Technical Information of China (English)

    Muhammad Rizwan Khan; Taimur Saleem; Tanveer Ul Haq; Kanwal Aftab

    2011-01-01

    BACKGROUND: Focal nodular hyperplasia, a benign hepatic tumor, is usually asymptomatic. However, rarely the entity can cause symptoms, mandating intervention. METHOD: We present a case of focal nodular hyperplasia of the liver, which caused a considerable diagnostic dilemma due to its atypical presentation. RESULTS: A 29-year-old woman presented with a 15-year history of a progressively increasing mass in the right upper quadrant which was associated with pain and emesis. Examination showed a firm, mobile mass palpable below the right subcostal margin. A computed tomography scan of the abdomen showed an exophytic mass arising from hepatic segments III and IVb. Trucut biopsy of the hepatic mass was equivocal. Angiography showed a vascular tumor that was supplied by a tortuous branch of the proper hepatic artery. Surgical intervention for removal of the mass was undertaken. Intra-operatively, two large discrete tumors were found and completely resected. Histopathological examination showed features consistent with focal nodular hyperplasia. CONCLUSION: This description of an unusual case of focal nodular hyperplasia of the liver highlights the point that the diagnosis of otherwise benign hepatic tumors may be difficult despite extensive work-up in some cases.

  2. Sebaceous hyperplasia in neonates and adults

    Directory of Open Access Journals (Sweden)

    Piotr Brzezinski

    2015-01-01

    Full Text Available Sebaceous hyperplasia is a common benign proliferation of the sebaceous glands seen during the first weeks of life and in middle-aged and elderly people. Clinical picture is quite different in neonatal period compared to adulthood. In neonate the lesions are small, tiny yellow papules distributed on the nose [1].

  3. Benign prostatic hyperplasia: symptoms and objective interpretation

    DEFF Research Database (Denmark)

    Andersen, J T

    1991-01-01

    Considerable new knowledge about benign prostatic hyperplasia has been gained over the past two decades, particularly with regard to its natural history, hydrodynamic changes in the lower urinary tract, and the symptomatic and urodynamic results of treatment. A survey of the literature has been u...

  4. Verrucous hyperplasia: A clinico-pathological study.

    Science.gov (United States)

    Hazarey, Vinay K; Ganvir, Sindhu M; Bodhade, Ashish S

    2011-05-01

    Oral verrucous hyperplasia (OVH) is a premalignant lesion that may transform into an oral cancer. The present retrospective study was carried out to analyze the clinico-pathological features of verrucous hyperplasia (VH). Total 19 diagnosed cases of verrucous hyperplasia were retrospectively analyzed for demographic, clinical and histopathological features including dysplasia. Average age of occurrence of lesion was 4 (th) decade of life, with male predominance (2:1) and common site of occurrence being buccal mucosa. Clinically it present as verrucous exophytic growth with sharp or blunt projections on surface, which corresponds histologically. Tobacco lime quid placement in buccal vestibule was key etiologic factor. Histopathologicaly 68% cases showed dysplasia out of which moderate dysplasia predominates (42%). Moderately dysplastic cases were found to be associated with mixed habit pattern. Maximum cases were treated with excision. Biopsy specimen comprising of adjacent normal epithelium is key in distinguishing verrucous hyperplasia from verrucous carcinoma. Clinical behavior and recurrence potential needs to be assessed with long term follow up studies.

  5. The glomerulo-tubular junction: a target in renal diseases.

    Science.gov (United States)

    Lindop, G B M; Gibson, I W; Downie, T T; Vass, D; Cohen, E P

    2002-05-01

    Both global and segmental glomerulopathies may damage specific areas of the renal glomerulus. Diseases associated with glomerular hyperperfusion cause lesions at the vascular pole, while diseases associated with proteinuria often damage the tubular pole. Atubular glomeruli are now known to be plentiful in a variety of common renal diseases. These glomeruli are disconnected from their tubule at the tubular pole and therefore cannot participate in the production of urine. It is widely believed that the disconnection is a result of external compression by periglomerular fibrosis. However, the variable anatomy and cell populations within both the glomerulus and the beginning of the proximal tubule at the glomerulo-tubular junction may also have important roles to play in the response to damage at this sensitive site of the nephron.

  6. RENAL CRYOABLATION

    Directory of Open Access Journals (Sweden)

    A. V. Govorov

    2012-01-01

    Full Text Available Renal cryoablation is an alternative minimally-invasive method of treatment for localized renal cell carcinoma. The main advantages of this methodology include visualization of the tumor and the forming of "ice ball" in real time, fewer complications compared with other methods of treatment of renal cell carcinoma, as well as the possibility of conducting cryotherapy in patients with concomitant pathology. Compared with other ablative technologies cryoablation has a low rate of repeat sessions and good intermediate oncological results. The studies of long-term oncological and functional results of renal cryoablation are presently under way.

  7. Renal angiomyolipoma

    DEFF Research Database (Denmark)

    Holm-Nielsen, P; Sørensen, Flemming Brandt

    1988-01-01

    lesion. Three cases of renal angiomyolipoma, 2 of which underwent perfusion-fixation, were studied by electron microscopy to clarify the cellular composition of this lesion. In the smooth muscle cells abundant accumulation of glycogen was found, whereas the lipocytes disclosed normal ultrastructural......-specific vesicular structures. These findings suggest a secondary vascular damage, i.e. the thickened vessels may not be a primary, integral part of renal angiomyolipoma. Evidence of a common precursor cell of renal angiomyolipoma was not disclosed. It is concluded that renal angiomyolipoma is a hamartoma composed...

  8. [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.

  9. Natural history of benign prostate hyperplasia

    Institute of Scientific and Technical Information of China (English)

    WU Shi-liang; LI Ning-chen; XIAO Yun-xiang; JIN Jie; QIU Shao-peng; YE Zhang-qun; KONG Chui-ze; SUN Guang; NA Yan-qun

    2006-01-01

    Background Benign prostate hyperplasia is one of the most common diseases affecting the health of the aging males. Watchful waiting is an acceptable management strategy for benign prostate hyperplasia in which the patient is monitored by the physician but receives no active intervention. The epidemiological data on this are lacking in China. Our study was designed to evaluate the changes of signs and symptoms of patients with benign prostate hyperplasia during management by watchful waiting in China.Methods One hundred and forty-five patients with benign prostate hyperplasia aged > 50 years were enrolled in management by watchful waiting. All the patients were visited every 6 months and were given an International Prostate Symptom Score and Quality of Life questionnaire to complete. They also had uroflowmetry and were assessed using ultrasonography to get the volume of prostate, transition zone and amount of residual urine. The Student's t test, the Chi-square test, and variance analysis were used in the statistical analysis.Results All patients were visited after 6 months, the mean volume of transitional zone was found to haveincreased by 1.6 ml (P<0.01), International Prostate Symptom Score was increased by 0.8 (P<0.01) and Quality of Life was increased by 0.2 (P<0.01), and there was no statistical change in other data. Among these patients,17.9% (26/145) visited again after 12 months when the data failed to show a statistically significant difference among the three groups (0, 6, and 12 months).Conclusions After one year's follow-up, the progression of benign prostate hyperplasia was slow and the clinical data did not undergo much change.

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

    DEFF Research Database (Denmark)

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

    1994-01-01

    We tested the hypothesis that proximal tubular Li+ reabsorption is due to passive transport. Clearances of [14C]inulin (CIn) and Li+ (CLi), proximal transepithelial electrical potential difference (PD), and tubular fluid-to-plasma Li+ concentration ratios [(TF/P)Li] were measured in anesthetized...... rats before and after induction of osmotic mannitol diuresis. Late proximal (TF/P)Li was measured after acute intravenous LiCl administration and after addition of LiCl to the diet for 2 days. Glomerular filtration rate (CIn) decreased, whereas CNa and CLi increased during osmotic diuresis. Control...... early proximal PD was -0.6 mV (lumen negative); late proximal PD (PDLP) was 1.1 mV (lumen positive). PDLP decreased by 1.5 mV to -0.4 mV (lumen negative) after mannitol infusion. Late proximal (TF/P)Li was 1.01 after oral Li+, 1.16 after intravenous Li+ (P osmotic diuresis...

  11. Sulfate transport by chick renal tubule brush-border and basolateral membranes

    Energy Technology Data Exchange (ETDEWEB)

    Renfro, J.L.; Clark, N.B.; Metts, R.E.; Lynch, M.A.

    1987-01-01

    Brush-border and basolateral membrane vesicles (BBMV and BLMV, respectively) were prepared from chick kidney by a calcium precipitation method and by centrifugation on an 8% Percoll self-generating gradient, respectively. In BBMV a 100-mM Na gluconate gradient, out>in, caused concentrative (/sup 35/S) sulfate uptake approximately fivefold greater at 1 min than at 60 min (equilibrium) whether or not the membranes were short-circuited with 100 mM K gluconate, in=out, plus 20 ..mu..g valinomycin/mg protein. A 48-mM HCO/sub 3//sup -/ gradient, in>out, stimulated a 2.5-fold higher uptake at 1 min than at 60 min, and short circuiting as above had no effect on the magnitude of this response. Imposition of a H/sup +/ gradient caused concentrative uptake fourfold higher at 1 min than at equilibrium. Short circuiting as above or addition of 0.1 mM carbonyl cyanide m-chlorophenylhydrazone (CCCP) significantly inhibited the pH gradient effect. Creation of an inside positive electrical potential with 100 mM K gluconate, out>in, plus valinomycin, also caused concentrative sulfate uptake. Based on inhibitor/competitor effects, these are distinct sulfate transport processes. In chick BLMV, imposition of an HCO/sub 3//sup -/ gradient, in>out, produced concentrative sulfate uptake. 4-Acetamido-4'-isothiocyanostilbene 2,2'-disulfonic acid disodium at 0.1 mM was an effective inhibitor of BLMV bicarbonate-sulfate exchange.

  12. The cell adhesion molecule Fasciclin2 regulates brush border length and organization in Drosophila renal tubules

    DEFF Research Database (Denmark)

    Halberg, Kenneth Agerlin; Rainey, Stephanie M.; Veland, Iben Rønn

    2016-01-01

    Multicellular organisms rely on cell adhesion molecules to coordinate cell-cell interactions, and to provide navigational cues during tissue formation. In Drosophila, Fasciclin 2 (Fas2) has been intensively studied due to its role in nervous system development and maintenance; yet, Fas2 is most...... role for this well-known cell adhesion molecule, and propose that Fas2-mediated intermicrovillar homophilic adhesion complexes help stabilize the brush border....

  13. Effect of dentinal tubules and resin-based endodontic sealers on fracture properties of root dentin.

    Science.gov (United States)

    Jainaen, Angsana; Palamara, Joseph E A; Messer, Harold H

    2009-10-01

    To investigate the role of dentinal tubules in the fracture properties of human root dentin and whether resin-filled dentinal tubules can enhance fracture resistance. Crack propagation in human root dentin was investigated in 200 microm thick longitudinal samples and examined by light and scanning electron microscopy. 30 maxillary premolar teeth were prepared for work of fracture (Wf) test at different tubule orientations, one perpendicular and two parallel to dentinal tubules. Another 40 single canal premolars were randomly divided into four groups of 10 each: intact dentin, prepared but unobturated canal, canal obturated with epoxy rein (AH Plus/gutta percha), or with UDMA resin sealer (Resilon/RealSeal. The samples were prepared for Wf test parallel to dentinal tubules. Wf was compared under ANOVA with statistical significance set at pcanal preparation nor obturation using epoxy- or UDMA-based resins as sealer cements substantially influenced fracture properties of root dentin, despite extensive infiltration of dentinal tubules by both sealer cements.

  14. 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.

  15. Collectin-11 detects stress-induced L-fucose pattern to trigger renal epithelial injury.

    Science.gov (United States)

    Farrar, Conrad A; Tran, David; Li, Ke; Wu, Weiju; Peng, Qi; Schwaeble, Wilhelm; Zhou, Wuding; Sacks, Steven H

    2016-05-01

    Physiochemical stress induces tissue injury as a result of the detection of abnormal molecular patterns by sensory molecules of the innate immune system. Here, we have described how the recently discovered C-type lectin collectin-11 (CL-11, also known as CL-K1 and encoded by COLEC11) recognizes an abnormal pattern of L-fucose on postischemic renal tubule cells and activates a destructive inflammatory response. We found that intrarenal expression of CL-11 rapidly increases in the postischemic period and colocalizes with complement deposited along the basolateral surface of the proximal renal tubule in association with L-fucose, the potential binding ligand for CL-11. Mice with either generalized or kidney-specific deficiency of CL-11 were strongly protected against loss of renal function and tubule injury due to reduced complement deposition. Ex vivo renal tubule cells showed a marked capacity for CL-11 binding that was induced by cell stress under hypoxic or hypothermic conditions and prevented by specific removal of L-fucose. Further analysis revealed that cell-bound CL-11 required the lectin complement pathway-associated protease MASP-2 to trigger complement deposition. Given these results, we conclude that lectin complement pathway activation triggered by ligand-CL-11 interaction in postischemic tissue is a potent source of acute kidney injury and is amenable to sugar-specific blockade.

  16. A Rare Coexistence of Retroperitoneal Pararenal Castleman's Disease with Focal Nodular Hyperplasia

    Directory of Open Access Journals (Sweden)

    Theodosios Theodosopoulos

    2013-01-01

    Full Text Available Castleman's disease is a distinct form of lymph node hyperplasia divided into a solitary and a multicentric type. The solitary type occurs most commonly in the mediastinum and is usually asymptomatic. We present a patient with Castleman's disease of the hyaline-vascular solitary type located in the retroperitoneum. The patient was a 38-year-old male, who presented to our hospital with fever. The imaging workup revealed a retroperitoneal mass, measuring 4 × 6 cm, located lateral to the aorta, inferior to the left renal artery and vein, and posterior to the left testicular vein. At workup, a solid hepatic lesion, 3 cm in diameter, located in the left lobe of the liver, segment IV, was also identified. Both lesions were surgically excised. The retroperitoneal tumor had the features of angiofollicular hyperplasia (Castleman's disease, hyaline-vascular type, whereas a diagnosis of focal nodular hyperplasia was made for the hepatic lesion. The patient is well at fourty months followup postoperatively. Surgical excision is the treatment of choice for unifocal Castleman's disease.

  17. Nfib Regulates Transcriptional Networks That Control the Development of Prostatic Hyperplasia.

    Science.gov (United States)

    Grabowska, Magdalena M; Kelly, Stephen M; Reese, Amy L; Cates, Justin M; Case, Tom C; Zhang, Jianghong; DeGraff, David J; Strand, Douglas W; Miller, Nicole L; Clark, Peter E; Hayward, Simon W; Gronostajski, Richard M; Anderson, Philip D; Matusik, Robert J

    2016-03-01

    A functional complex consisting of androgen receptor (AR) and forkhead box A1 (FOXA1) proteins supports prostatic development, differentiation, and disease. In addition, the interaction of FOXA1 with cofactors such as nuclear factor I (NFI) family members modulates AR target gene expression. However, the global role of specific NFI family members has yet to be described in the prostate. In these studies, chromatin immunoprecipitation followed by DNA sequencing in androgen-dependent LNCaP prostate cancer cells demonstrated that 64.3% of NFIB binding sites are associated with AR and FOXA1 binding sites. Interrogation of published data revealed that genes associated with NFIB binding sites are predominantly induced after dihydrotestosterone treatment of LNCaP cells, whereas NFIB knockdown studies demonstrated that loss of NFIB drives increased AR expression and superinduction of a subset of AR target genes. Notably, genes bound by NFIB only are associated with cell division and cell cycle. To define the role of NFIB in vivo, mouse Nfib knockout prostatic tissue was rescued via renal capsule engraftment. Loss of Nfib expression resulted in prostatic hyperplasia, which did not resolve in response to castration, and an expansion of an intermediate cell population in a small subset of grafts. In human benign prostatic hyperplasia, luminal NFIB loss correlated with more severe disease. Finally, some areas of intermediate cell expansion were also associated with NFIB loss. Taken together, these results show a fundamental role for NFIB as a coregulator of AR action in the prostate and in controlling prostatic hyperplasia.

  18. Castleman Disease in the Kidney and Retroperitoneum Mimicking Renal Cell Carcinoma with Retroperitoneal Lymphadenopathy: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Ko, Hee Sun; Woo, Ji Young; Hong, Hye Suk; Jung, Ah Young; Yang, Ik; Lee, Yul [Dept. of Radiology, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul (Korea, Republic of)

    2012-09-15

    Castleman disease, or angiofollicular lymph node hyperplasia, is a fairly rare benign tumor of lymphoid origin with unknown etiology. Castleman disease arises mostly in the mediastinum, and some cases of renal and retroperitoneal involvement have been reported. However, Castleman disease that simultaneously involves the kidney and regional lymph nodes has not been reported in radiologic literature. We report a case of renal and pararenal Castleman disease, mimicking renal cell carcinoma with retroperitoneal lymphadenopathy.

  19. The effect of exercise training on transverse tubules in normal, remodeled, and reverse remodeled hearts.

    Science.gov (United States)

    Kemi, Ole J; Hoydal, Morten A; Macquaide, Niall; Haram, Per M; Koch, Lauren G; Britton, Steven L; Ellingsen, Oyvind; Smith, Godfrey L; Wisloff, Ulrik

    2011-09-01

    The response of transverse (T)-tubules to exercise training in health and disease remains unclear. Therefore, we studied the effect of exercise training on the density and spacing of left ventricle cardiomyocyte T-tubules in normal and remodeled hearts that associate with detubulation, by confocal laser scanning microscopy. First, exercise training in normal rats increased cardiomyocyte volume by 16% (P hypertrophy. Next, we studied T-tubules in a rat model of metabolic syndrome with pressure overload-induced concentric left ventricle hypertrophy, evidenced by 15% (P Exercise training further increased cardiomyocyte volume by 8% (P eccentric and concentric hypertrophy and 55% (P Exercise training reversed 50% (P hypertrophy, whereas the T-tubule density increased by 40% (P hypertrophy associated with conserved T-tubule spacing (~1.8-1.9 µm), whereas in pathologic hypertrophy, T-tubules appeared disorganized without regular spacing. In conclusion, cardiomyocytes maintain the relative T-tubule density during physiologic hypertrophy and after mild concentric pathologic hypertrophy, whereas after severe pathologic remodeling with a substantial loss of T-tubules; exercise training reverses the remodeling and partly corrects the T-tubule density.

  20. Number of malpighian tubules in larvae and adults of stingless bees (Hymenoptera: Apidae) from Amazonia.

    Science.gov (United States)

    Barbosa-Costa, K; Kerr, W E; Carvalho-Zilse, G A

    2012-02-01

    The number of Malpighian tubules in larvae and adults of bees is variable. Larvae of Apis mellifera L. have four Malpighian tubules, while adults have 100 tubules. In stingless bees, this number varies from four to eight. The objectives of this study were to provide characteristics of the Malpighian tubules as well as to quantify their number in larvae and adults of six species of Meliponinae, Melipona seminigra merrillae Cockerell, Melipona compressipes manaosensis Schwarz, Melipona rufiventris Lepeletier, Scaptotrigona Moure, Frieseomelitta Ihering, and Trigona williana Friese. Malpighian tubules were dissected from larvae and adults, measured, quantified, and maintained in microtubes with Dietrich's solution. The numbers of Malpighian tubules were constant only for larvae of M. rufiventris (four and eight) and Scaptotrigona sp. (four). The most frequent number of tubules in the Melipona group was seven and eight in larvae, and 70 and 90 in adults. In the Trigona group were four and 20 to 40, for larvae and adults, respectively. The results showed differences in the number of Malpighian tubules among the species analyzed and also between the larvae and adults of the same species. Despite the variation observed, species of the group Melipona always have a larger number and longer Malpighian tubules in both larvae and adults as compared to the Trigona group, which may indicate an evolutionary trend of differentiation between these groups.

  1. Renal cancer

    NARCIS (Netherlands)

    Corgna, Enrichetta; Betti, Maura; Gatta, Gemma; Roila, Fausto; De Mulder, Pieter H. M.

    2007-01-01

    In Europe, renal cancer (that is neoplasia of the kidney, renal pelvis or ureter (ICD-9 189 and ICD-10 C64-C66)) ranks as the seventh most common malignancy in men amongst whom there are 29,600 new cases each year (3.5% of all cancers). Tobacco, obesity and a diet poor in vegetables are all acknowle

  2. Renal fallure

    Institute of Scientific and Technical Information of China (English)

    1992-01-01

    920705 Endothelin and acute renal failure:study on their relationship and possiblemechanisms. LIN Shanyan(林善锬), et al.Renal Res Lab, Huashan Hosp, Shanghai MedUniv, Shanghai, 200040. Natl Med J China 1992;72(4): 201-205. In order to investigate the role of endothelin

  3. Renal cancer.

    NARCIS (Netherlands)

    Corgna, E.; Betti, M.; Gatta, G.; Roila, F.; Mulder, P.H.M. de

    2007-01-01

    In Europe, renal cancer (that is neoplasia of the kidney, renal pelvis or ureter (ICD-9 189 and ICD-10 C64-C66)) ranks as the seventh most common malignancy in men amongst whom there are 29,600 new cases each year (3.5% of all cancers). Tobacco, obesity and a diet poor in vegetables are all

  4. Renal cancer

    NARCIS (Netherlands)

    Corgna, Enrichetta; Betti, Maura; Gatta, Gemma; Roila, Fausto; De Mulder, Pieter H. M.

    2007-01-01

    In Europe, renal cancer (that is neoplasia of the kidney, renal pelvis or ureter (ICD-9 189 and ICD-10 C64-C66)) ranks as the seventh most common malignancy in men amongst whom there are 29,600 new cases each year (3.5% of all cancers). Tobacco, obesity and a diet poor in vegetables are all

  5. 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.)

  6. A dynamic paracellular pathway serves diuresis in mosquito Malpighian tubules.

    Science.gov (United States)

    Beyenbach, Klaus W

    2012-07-01

    Female mosquitoes gorge on vertebrate blood, a rich nutrient source for developing eggs, but gorging meals increase the risk of predation. Mosquitoes are quick to reduce the flight payload with a potent diuresis. Diuretic peptides of the insect kinin family induce a tenfold reduction in the paracellular resistance of Malpighian tubules and increase the paracellular permeation of Cl(-), the counterion of the transepithelial secretion of Na(+) and K(+). As a result, the transepithelial secretion of NaCl and KCl and water increases. Insect kinins signal the opening of the paracellular pathway via G protein-coupled receptors and the elevation of intracellular [Ca(2+)], which leads to the reorganization of the cytoskeleton associated with the septate junction (SJ). The reorganization may affect the septate junctional proteins that control the barrier and permselectivity properties of the paracellular pathway. The proteins involved in the embryonic formation of the SJ and in epithelial polarization are largely known for ectodermal epithelia, but the proteins that form and mediate the dynamic functions of the SJ in Malpighian tubules remain to be determined.

  7. Acute hepatic ischemic-reperfusion injury induces a renal cortical "stress response," renal "cytoresistance," and an endotoxin hyperresponsive state.

    Science.gov (United States)

    Zager, Richard A; Johnson, Ali C M; Frostad, Kirsten B

    2014-10-01

    Hepatic ischemic-reperfusion injury (HIRI) is considered a risk factor for clinical acute kidney injury (AKI). However, HIRI's impact on renal tubular cell homeostasis and subsequent injury responses remain ill-defined. To explore this issue, 30-45 min of partial HIRI was induced in CD-1 mice. Sham-operated or normal mice served as controls. Renal changes and superimposed injury responses (glycerol-induced AKI; endotoxemia) were assessed 2-18 h later. HIRI induced mild azotemia (blood urea nitrogen ∼45 mg/dl) in the absence of renal histologic injury or proteinuria, implying a "prerenal" state. However, marked renal cortical, and isolated proximal tubule, cytoprotective "stress protein" gene induction (neutrophil gelatinase-associated lipocalin, heme oxygenase-1, hemopexin, hepcidin), and increased Toll-like receptor 4 (TLR4) expression resulted (protein/mRNA levels). Ischemia caused release of hepatic heme-based proteins (e.g., cytochrome c) into the circulation. This corresponded with renal cortical oxidant stress (malondialdehyde increases). That hepatic derived factors can evoke redox-sensitive "stress protein" induction was implied by the following: peritoneal dialysate from HIRI mice, soluble hepatic extract, or exogenous cytochrome c each induced the above stress protein(s) either in vivo or in cultured tubule cells. Functional significance of HIRI-induced renal "preconditioning" was indicated by the following: 1) HIRI conferred virtually complete morphologic protection against glycerol-induced AKI (in the absence of hyperbilirubinemia) and 2) HIRI-induced TLR4 upregulation led to a renal endotoxin hyperresponsive state (excess TNF-α/MCP-1 gene induction). In conclusion, HIRI can evoke "renal preconditioning," likely due, in part, to hepatic release of pro-oxidant factors (e.g., cytochrome c) into the systemic circulation. The resulting renal changes can impact subsequent AKI susceptibility and TLR4 pathway-mediated stress.

  8. Gastrin stimulates renal dopamine production by increasing the renal tubular uptake of l-DOPA.

    Science.gov (United States)

    Jiang, Xiaoliang; Zhang, Yanrong; Yang, Yu; Yang, Jian; Asico, Laureano D; Chen, Wei; Felder, Robin A; Armando, Ines; Jose, Pedro A; Yang, Zhiwei

    2017-01-01

    Gastrin is a peptide hormone that is involved in the regulation of sodium balance and blood pressure. Dopamine, which is also involved in the regulation of sodium balance and blood pressure, directly or indirectly interacts with other blood pressure-regulating hormones, including gastrin. This study aimed to determine the mechanisms of the interaction between gastrin and dopamine and tested the hypothesis that gastrin produced in the kidney increases renal dopamine production to keep blood pressure within the normal range. We show that in human and mouse renal proximal tubule cells (hRPTCs and mRPTCs, respectively), gastrin stimulates renal dopamine production by increasing the cellular uptake of l-DOPA via the l-type amino acid transporter (LAT) at the plasma membrane. The uptake of l-DOPA in RPTCs from C57Bl/6J mice is lower than in RPTCs from normotensive humans. l-DOPA uptake in renal cortical slices is also lower in salt-sensitive C57Bl/6J than in salt-resistant BALB/c mice. The deficient renal cortical uptake of l-DOPA in C57Bl/6J mice may be due to decreased LAT-1 activity that is related to its decreased expression at the plasma membrane, relative to BALB/c mice. We also show that renal-selective silencing of Gast by the renal subcapsular injection of Gast siRNA in BALB/c mice decreases renal dopamine production and increases blood pressure. These results highlight the importance of renal gastrin in stimulating renal dopamine production, which may give a new perspective in the prevention and treatment of hypertension. Copyright © 2017 the American Physiological Society.

  9. Bilateral tubulocystic renal cell carcinomas in diabetic end-stage renal disease: first case report with cytogenetic and ultrastructural studies

    Directory of Open Access Journals (Sweden)

    Max Xiangtian Kong

    2013-11-01

    Full Text Available Tubulocystic renal cell carcinoma (TC-RCC is a rare renal tumor composed of well-differentiated tubules and cysts lined by neoplastic cells with eosinophilic cytoplasm and prominent nucleoli. The origin of the tumor cells is still controversial. TC-RCC typically arises unilaterally. Involvement of both kidneys by multifocal TC-RCC has not been reported. In this study we report the first case of bilateral and multifocal TC-RCC. Immunohistochemical, cytogenetic and ultrastructural studies suggest TC-RCC is closely related to papillary RCC.

  10. Myocardial hypertrophy induces carotid body hyperplasia.

    Science.gov (United States)

    Sivridis, Efthimios; Pavlidis, Pavlos; Fiska, Aliki; Pitsiava, Dimitra; Giatromanolaki, Alexandra

    2011-01-01

    The carotid bodies tend to enlarge after long-standing cardiopulmonary disease. Our objective was to investigate whether cardiac hypertrophy is associated with carotid body hyperplasia. Fifteen autopsy cases with combined left and right ventricular hypertrophy were examined and compared with two control groups (16 cases). The study involved a meticulous dissection of carotid bifurcations, thin serial sections, and morphometric analysis of carotid body volume and cell types (progenitor, dark, light, and sustentacular). There was a significant increase in sustentacular cells in all individuals with cardiac hypertrophy, which was not drug-induced, and accompanied by a similar increase in carotid body volume. Dark or light cell accumulation was detected focally and only in three instances. It appears that the generalized sustentacular cell hyperplasia is the result of long-standing hypoxia, while a superimposed focal prominence of dark or light cells may be proliferative or metaplastic in nature and attributed to short-term hypoxia.

  11. Mandibular coronoid hyperplasia in pediatric patients.

    Science.gov (United States)

    Jaskolka, Michael S; Eppley, Barry L; van Aalst, John A

    2007-07-01

    Bilateral coronoid hyperplasia is a relatively rare condition in the pediatric population and yet may be an unrecognized cause of limited mouth opening in children. There are multiple theories as to the causes of the hyperplasia, which include temporalis hyperactivity, hormonal stimulus, and genetic inheritance. The resulting excess growth of the coronoids results in impingement on the zygomatic processes leading to mandibular hypomobility. The diagnosis is confirmed with plain films and computed tomography scans. Treatment involves bilateral coronoidectomies to relieve impingement on the zygoma. Postoperative physical therapy is crucial for success; the therapy focuses on maintaining the mouth opening achieved at the time of surgery. Outcome reports have been variable despite good physical therapy, suggesting that the exact pathology of the condition is not well understood.

  12. Unilateral condylar hyperplasia: a treatment strategy.

    Science.gov (United States)

    Ferreira, Sabrina; da Silva Fabris, André Luis; Ferreira, Gabriel Ramalho; Faverani, Leonardo Perez; Francisconi, Giovanna Barbosa; Souza, Francisley Avila; Garcia, Idelmo Rangel

    2014-05-01

    Condylar hyperplasia (CH) is a pathologic condition that causes overdevelopment of the condylar head and neck as well as the mandible. Slowly progressive unilateral enlargement of the head and the neck of the condyle causes crossbite malocclusion, facial asymmetry, and shifting of the midpoint of the chin to the unaffected side. The etiology and the pathogenesis of CH remain uncertain. The diagnosis is made by clinical and radiologic examinations and bone scintigraph. A difference in uptake of 10% or more between condyles is regarded as indicative of CH, and the affected condyles had a relative uptake of 55% or more. When the diagnosis of active CH is established, the treatment consists of removal of the growth center by a partial condylectomy. The authors present the case of a 46-year-old male patient with right active type II CH or hemimandibular hyperplasia who underwent a high condylectomy.

  13. Epidemiology of clinical benign prostatic hyperplasia

    Directory of Open Access Journals (Sweden)

    Kok Bin Lim

    2017-07-01

    Full Text Available Clinical benign prostatic hyperplasia (BPH is one of the most common diseases in ageing men and the most common cause of lower urinary tract symptoms (LUTS. The prevalence of BPH increases after the age of 40 years, with a prevalence of 8%–60% at age 90 years. Some data have suggested that there is decreased risk among the Asians compared to the western white population. Genetics, diet and life style may play a role here. Recent reports suggest the strong relationship of clinical BPH with metabolic syndrome and erectile dysfunction, as well as the possible role of inflammation as a cause of the prostatic hyperplasia. Lifestyle changes including exercise and diet are important strategies in controlling this common ailment.

  14. Endometrial Stromal Hyperplasia: An Underrecognized Condition

    OpenAIRE

    Efthimios Sivridis; Gerasimos Koutsougeras; Alexandra Giatromanolaki

    2013-01-01

    Hyperplasia of the endometrial stroma is a poorly recognized lesion, lacking widespread recognition with most, if not all, such cases sequestrated in the literature as endometrial stromal nodules or low-grade endometrial stromal sarcomas. In this paper, we describe three examples of “endometrial stromal hyperplasia” which have a remarkable morphological similarity with the normally proliferating endometrial stroma and the endometrial stromal neoplasms, but which also possess subtle, but suffi...

  15. Pseudoepitheliomatous hyperplasia: A review of oral lesions

    Directory of Open Access Journals (Sweden)

    P. Premraj

    2016-05-01

    Full Text Available Pseudoepitheliomatous hyperplasia is a histological reactive pattern of surface epithelium in response to various stimuli from the underlying connective tissue which frequently mimics squamous cell carcinoma. So, differentiation of this entity is of utmost important in the view of treatment planning and approach. This review focuses on those lesions which are encountered in the head and neck region and also the recent concepts related to it.

  16. Classic congenital adrenal hyperplasia: A delayed presentation

    OpenAIRE

    Aziz Siddiqui, Saima; Soomro, Nargis; Ganatra, Ashraf

    2013-01-01

    Congenital adrenal hyperplasia (CAH) is a rare congenital disorder, which in cases of female genotype may result in virilization. Specific enzyme deficiencies in adrenocorticoid hormones biosynthetic pathway lead to excess androgen production causing virilization. Classic type presents early in infant life as salt losing or simple virilizing type, whereas non classic form presents late at puberty or in adult life. Depending on the type of classic CAH, type of adrenocorticoid deficiency, exten...

  17. FOCAL EPITHELIAL HYPERPLASIA: HECK’S DISEASE

    OpenAIRE

    Brzeziński Piotr

    2010-01-01

    Heck's disease (focal epithelial hyperplasia) (FEH) is clinically characterized by multiple circumscribed, soft elevated nodules of the oral mucosa. Papules and plaques are usually the color of normal mucosa, but may be pale or, rarely, white. Disease may persist for years, producing a significant reduction in quality of life. Lessions may be located in the area of mucous membranes of the lips, cheeks and tongue. It is believed that the two virus types are responsible for the FEH, are: HPV 1...

  18. Extensive focal epithelial hyperplasia: case report.

    Science.gov (United States)

    Durso, Braz Campos; Pinto, José Marcelo Vargas; Jorge, Jacks; de Almeida, Oslei Paes

    2005-11-01

    Focal epithelial hyperplasia (FEH) is a rare benign lesion caused by human papillomavirus subtype 13 or 32. The condition occurs in numerous populations and ethnic groups. A higher incidence in close communities and among family members indicates infectious pathogenesis. A 21-year-old woman with FEH is described, in whom the lesions had persisted for 10 years. A literature review is also presented, with emphasis on manifestations in the oral mucosa and histopathological features.

  19. Focal epithelial hyperplasia in a Turkish family.

    Science.gov (United States)

    Gökahmetoğlu, Selma; Ferahbaş, Ayten; Canöz, Özlem

    2014-12-01

    Focal epithelial hyperplasia (FEH) is a benign proliferative condition that is more frequently found in children of certain ethnic groups. Human papillomavirus (HPV) 13 and 32 genotypes has been consistently detected in these lesions. In this study a daughter, mother and father had FEH, and HPV 13 was shown by sequence analysis in the lesions of these patients. Cryotherapy was applied to the lesions and the lesions improved, but did not recover properly. In conclusion, HPV genotyping should be performed in FEH cases.

  20. 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......Hz in which, in addition, there are autonomous oscillations in TGF. Higher amplitude forcings in this band were attenuated by autoregulatory mechanisms, but low-amplitude forcings entrained the autonomous oscillations and provoked amplified oscillations in blood flow, showing an effect of TGF on whole kidney...

  1. Renal teratogens.

    Science.gov (United States)

    Morgan, Thomas M; Jones, Deborah P; Cooper, William O

    2014-09-01

    In utero exposure to certain drugs early in pregnancy may adversely affect nephrogenesis. Exposure to drugs later in pregnancy may affect the renin-angiotensin system, which could have an impact on fetal or neonatal renal function. Reduction in nephron number and renal function could have adverse consequences for the child several years later. Data are limited on the information needed to guide decisions for patients and providers regarding the use of certain drugs in pregnancy. The study of drug nephroteratogenicity has not been systematized, a large, standardized, global approach is needed to evaluate the renal risks of in utero drug exposures.

  2. 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.

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

    Directory of Open Access Journals (Sweden)

    Niranjan Ashok Vatkar

    2016-01-01

    Conclusion: 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.

  4. Mathematical study on robust tissue pattern formation in growing epididymal tubule.

    Science.gov (United States)

    Hirashima, Tsuyoshi

    2016-10-21

    Tissue pattern formation during development is a reproducible morphogenetic process organized by a series of kinetic cellular activities, leading to the building of functional and stable organs. Recent studies focusing on mechanical aspects have revealed physical mechanisms on how the cellular activities contribute to the formation of reproducible tissue patterns; however, the understanding for what factors achieve the reproducibility of such patterning and how it occurs is far from complete. Here, I focus on a tube pattern formation during murine epididymal development, and show that two factors influencing physical design for the patterning, the proliferative zone within the tubule and the viscosity of tissues surrounding to the tubule, control the reproducibility of epididymal tubule pattern, using a mathematical model based on experimental data. Extensive numerical simulation of the simple mathematical model revealed that a spatially localized proliferative zone within the tubule, observed in experiments, results in more reproducible tubule pattern. Moreover, I found that the viscosity of tissues surrounding to the tubule imposes a trade-off regarding pattern reproducibility and spatial accuracy relating to the region where the tubule pattern is formed. This indicates an existence of optimality in material properties of tissues for the robust patterning of epididymal tubule. The results obtained by numerical analysis based on experimental observations provide a general insight on how physical design realizes robust tissue pattern formation.

  5. Non-apoptotic function of apoptotic proteins in the development of Malpighian tubules of Drosophila melanogaster

    Indian Academy of Sciences (India)

    Madhu G Tapadia; Naveen K Gautam

    2011-08-01

    Drosophila metamorphosis is characterized by the histolysis of larval structures by programmed cell death, which paves the way for the establishment of adult-specific structures under the influence of the steroid hormone ecdysone. Malpighian tubules function as an excretory system and are one of the larval structures that are not destroyed during metamorphosis and are carried over to adulthood. The pupal Malpighian tubules evade destruction in spite of expressing apoptotic proteins, Reaper, Hid, Grim, Dronc and Drice. Here we show that in the Malpighian tubules expression of apoptotic proteins commences right from embryonic development and continues throughout the larval stages. Overexpression of these proteins in the Malpighian tubules causes larval lethality resulting in malformed tubules. The number and regular organization of principal and stellate cells of Malpighian tubules is disturbed, in turn disrupting the physiological functioning of the tubules as well. Strikingly, the localization of -tubulin, F-actin and Disclarge (Dlg) is also disrupted. These results suggest that the apoptotic proteins could be having non-apoptotic function in the development of Malpighian tubules.

  6. Intraluminal colonization into the seminiferous tubules in mice

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    Luis Guzmán-Masias

    2011-05-01

    Full Text Available Using the primordial germ cells transplant technique, we could be able preserve and multiply pluripotent cells in the receptor for a long period of time. In this work, We aim to evaluate intraluminal colonization of a cellular gonocyte suspension from 14.5 dpc fetus. Cellular suspension with PGC's were isolated from fetus male mice by two enzymatic digestion steps, and cellular suspensions were transplanted into the rete testis of the receptor animals that were previously injected with Busulfan to decrease their own spermatogenesis. In this research the intraluminal colonization was identified in 13.27%, demonstrating that transplantation of a cellular suspension from gonocytes of fetus of 14.5 dpc containing PGCs can colonize the seminiferous tubules and support the spermatogenesis.

  7. Regional variation in root dentinal tubule infection by Streptococcus gordonii.

    Science.gov (United States)

    Love, R M

    1996-06-01

    The purpose of this study was to investigate the pattern of bacterial invasion of dentinal tubules at different regions in human roots. Specimens were obtained from single-rooted teeth that had their root canals prepared in a standard manner. Roots were then sectioned longitudinally through the canals and the resulting specimens chemically treated to remove the smear layers. Specimens were immersed in a suspension of Streptococcus gordonii for 3 weeks and then prepared for histological analysis. Sections from the cervical, midroot, and apical areas were examined. The pattern of bacterial infection of the cervical and midroot areas was similar, characterized as a heavy infection with bacteria penetrating as deep as 200 microns. Invasion of the apical dentin was significantly different, with a mild infection and maximum penetration of 60 microns.

  8. Static analysis of masonry kilns built with fictile tubules bricks

    Science.gov (United States)

    Olivito, Renato S.; Scuro, Carmelo; Codispoti, Rosamaria

    2016-12-01

    Industrial archeology is a branch that studies all the testimony (tangible and intangible, direct and indirect) related to the process of industrialization since its origins. This technical field is based on an interdisciplinary approach, it has the task of deepening the story, understanding the technological development made by man over the centuries. The present work focused attention on the study and analysis of a masonry kiln, built with the technique of hollow clay fictile tubules. The study, in particular, has been carried out analyzing the stress state caused by the wind on the structure. The kiln is constituted by a particular geometric configuration that develops in height due to the presence of chimney over the dome.

  9. Sarcoidose renal

    Directory of Open Access Journals (Sweden)

    AQUINO MARIA ENEDINA CLAUDINO DE

    2001-01-01

    Full Text Available Em uma mulher de 62 anos, branca, em avaliação pré-operatória de facectomia, foram detectadas alterações urinárias, tendo sido firmados os diagnósticos de calculose renal esquerda e exclusão renal homolateral. No pré-operatório da nefrectomia foram evidenciados processo pulmonar intersticial bilateral e adenopatia torácica, cuja investigação foi adiada para após a cirurgia. No rim retirado foram detectados granulomas epitelióides não necrotizantes, o mesmo ocorrendo posteriormente em biópsia transbrônquica. A paciente foi tratada com metilprednisolona, com discreta melhora pulmonar, o que não ocorreu com a função renal. O diagnóstico final foi de sarcoidose com envolvimento pulmonar, ganglionar torácico e renal.

  10. 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.)

  11. Renal failure

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    2005234 Association between serum fetuin-A and clinical outcome in end-stage renal disease patients. WANG Kai(王开), Dept Renal Dis, Renji Hosp Shanghai, 2nd Med Univ, Shanghai 200001. Chin J Nephrol, 2005;21(2):72-75. Objective: To investigate the change of serum fetuin-A level before and after dialysis, and the association of serum fetuin-A level with clinical parameters

  12. Renal failure

    Institute of Scientific and Technical Information of China (English)

    1995-01-01

    950351 Serum erythropoietin levels in chronic renalinsufficiency.ZHAI Depei(翟德佩),et al.DeptNephrol.General Hosp,Tianjin Med Univ,Tianjin,300000.Tianjin Med J 1995;23(1):19-21.Patients with chronic renal insufficiency(CRI) areoften associated with anemia.The deficiency of EPOproduction in the kidney is thought to be a key factorin the pathogenesis of renal anemia.Serum erythropoi-

  13. Renal failure

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008463 Protective effect of recombination rat augmenter of liver regeneration on kidney in acute renal failure rats. TANG Xiaopeng(唐晓鹏), et al. Dept Nephrol, 2nd Affili Hosp Chongqing Med Univ, Chongqing 400010.Chin J Nephrol 2008;24(6):417-421. Objective To investigate the protective effects of recombination rat augmenter of liver regeneration (rrALR) on tubular cell injury and renal dysfunction

  14. Renal Hemangiopericytoma

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    İbrahim Halil Bozkurt

    2015-03-01

    Full Text Available Hemangiopericytoma is an uncommon perivascular tumor originating from pericytes in the pelvis, head and tneck, and the meninges; extremely rarely in the urinary system. We report a case of incidentally detected renal mass in which radiologic evaluation was suggestive of renal cell carcinoma. First, we performed partial nephrectomy, and then, radical nephrectomy because of positive surgical margins and the pathological examination of the surgical specimen that revealed a hemangiopericytoma. No additional treatment was administered.

  15. 18F-FDG-avid brunner gland hyperplasia.

    Science.gov (United States)

    Park, Seol Hoon; Park, Kwang-Min; Kim, Jae Seung

    2014-08-01

    Brunner gland hyperplasia, a rare duodenal tumor, usually presents with benign features. A 68-year-old man with a history of anemia presented with a polypoid duodenal mass that was detected by CT and esophagogastroduodenoscopy. This mass showed high F-FDG avidity on PET/CT and was histopathologically confirmed as Brunner gland hyperplasia. We suggest that Brunner gland hyperplasia should be considered in the differential diagnosis of F-FDG-avid duodenal tumors.

  16. Unilateral condylar hyperplasia: A case report and review of literature

    OpenAIRE

    Bharathi, Saravana C.; Senthilnathan, S.; Kumar, Lokesh D.; Mohan, Anand C. S.; Taranath, M.

    2014-01-01

    Condylar hyperplasia is (CH) an uncommon malformation of the mandible involving change in size and morphology of the condylar neck and head. CH is an anomaly that usually occurs unilaterally and equally affects in both men and women. Hyperplasia of the condyle ‘differentiated into hemimandibular hyperplasia, hemimandibular elongation and CH. Here, we are presenting a case of 17-year-old male patient with unilateral CH and its review of the literature.

  17. Unilateral condylar hyperplasia: A case report and review of literature.

    Science.gov (United States)

    Bharathi, Saravana C; Senthilnathan, S; Kumar, Lokesh D; Mohan, Anand C S; Taranath, M

    2014-01-01

    Condylar hyperplasia is (CH) an uncommon malformation of the mandible involving change in size and morphology of the condylar neck and head. CH is an anomaly that usually occurs unilaterally and equally affects in both men and women. Hyperplasia of the condyle 'differentiated into hemimandibular hyperplasia, hemimandibular elongation and CH. Here, we are presenting a case of 17-year-old male patient with unilateral CH and its review of the literature.

  18. Denture hyperplasia with areas simulating oral inverted ductal papilloma.

    Science.gov (United States)

    Vargas, Pablo Agustin; Perez, Danyel Elias da Cruz; Jorge, Jacks; Rangel, Ana Lúcia Carrinho Ayrosa; León, Jorge Esquiche; Almeida, Oslei Paes de

    2005-07-01

    Denture hyperplasia is a reactive lesion of the oral mucosa, usually associated to an ill-fitting denture. This lesion is easily diagnosed and in some cases distinct microscopic variations such as osseous, oncocytic and squamous metaplasia may be found. These metaplastic alterations probably are associated with the lymphocytic infiltrate usually present in denture hyperplasia. We present a case of denture hyperplasia containing salivary gland tissue with ductal alterations mimicking an oral inverted ductal papilloma.

  19. A case of neuroleptic malignant syndrome with acute renal failure after the discontinuation of sulpiride and maprotiline.

    Science.gov (United States)

    Kiyatake, I; Yamaji, K; Shirato, I; Kubota, M; Nakayama, S; Tomino, Y; Koide, H

    1991-01-01

    A 46-year-old man developed neuroleptic malignant syndrome with acute myoglobinuric renal failure after the discontinuation of sulpiride and maprotiline treatment. He showed the characteristic features of hyperpyrexia, altered consciousness, muscle rigidity, and autonomic dysfunction. Laboratory data showed lysis of skeletal muscle cells and renal impairment. Muscle biopsy revealed necrosis and regenerative changes in muscle fibers. Renal biopsy showed focal tubulitis and interstitial infiltration of small inflammatory cells. The combination of sulpiride and maprotiline has not previously been reported to be the cause of neuroleptic malignant syndrome and acute myoglobinuric renal failure.

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

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    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.

  1. Acute renal failure following Bull ant mass envenomation in two dogs.

    Science.gov (United States)

    Abraham, L A; Hinkley, C J; Tatarczuch, L; Holloway, S A

    2004-01-01

    Acute renal failure was diagnosed in a German Short Haired Pointer bitch and a Kelpie cross-bred dog following envenomation by Bull ants. Both dogs had been tethered over a Bull ant nest and had experienced mass envenomation. There was local reaction at the envenomation sites and each dog had experienced vomiting that was poorly controlled by symptomatic therapy. Intensive treatment of renal failure was successful in the German Short Haired Pointer and the bitch remains well 19 months after envenomation. The Kelpie cross-bred deteriorated despite intensive treatment and was euthanased 36 hours after presentation. Necropsy examination revealed haemorrhage and necrosis of the small intestine and myocardium, bilateral nephrosis with tubular necrosis, and patchy haemorrhage of the lung alveoli, pancreas and adrenal cortices. Electron microscopy revealed necrosis of the small intestine and hydropic swelling of proximal renal tubules with necrosis of medullary tubules.

  2. Results of surgical treatment of atypical endometrial hyperplasia

    Directory of Open Access Journals (Sweden)

    O. A. Gornykh

    2014-01-01

    Full Text Available The results of surgical treatment in 132 patients with atypical endometrial hyperplasia have been studied. Post-operative diagnosis was: en- dometrial cancer – in 19 %, atypical hyperplasia – in 35 %, simple and complex hyperplasia – in 33 %, only atrophic endometrial changes – in 13 % of patients. The tumor was within the endometrium in 5 patients, the superficial invasion of the myometrium (1–2 mm were in 8 patients, invasion to half of the myometrium – in 9 patients, invasion of more than half of the myometrium – in 3 patients. The questions of tactics of treatment of atypical endometrial hyperplasia is under discussion.

  3. [Nodular regenerative hyperplasia associated with primary antiphospholipid syndrome].

    Science.gov (United States)

    Cadranel, J F; Demontis, R; Guettier, C; Bouraya, D; Dautreaux, M; Ghazali, A; Poux, J M; Coutarel, P; Devergie, B; Fievet, P

    1996-01-01

    Nodular regenerative hyperplasia of the liver is characterized by diffuse nodularity of the hepatic parenchyma without fibrotic septa. It may be related to venous or arterial obstruction in the portal tract. We report a case of primary antiphospholipid syndrome associated with nodular regenerative hyperplasia in a 45-year old woman. The patient had an ischemic stroke, associated with an acute arterial ischemia of the left leg. She had high titers of serum anticardiolipin antibodies. Nodular regenerative hyperplasia of the liver was histologically confirmed and was associated with anicteric cholestasis. This case provides additional evidence that a thrombotic mechanism may play a role in the pathogenesis of nodular regenerative hyperplasia of the liver.

  4. Erdosteine against acetaminophen induced renal toxicity.

    Science.gov (United States)

    Isik, Bunyamin; Bayrak, Reyhan; Akcay, Ali; Sogut, Sadik

    2006-07-01

    Acetaminophen (APAP) induced toxicities have been a major problem in clinical practice. The aim of the present study was to demonstrate a possible protective role of erdosteine, a mucolytic agent having antioxidant properties via its active metabolites, on APAP induced renal damage in rats. Female Wistar Albino rats were divided into groups including control, erdosteine (150 mg/kg, oral), APAP (1 g/kg, oral) APAP+erdosteine (150 mg/kg, oral) and APAP+erdosteine (300 mg/kg, oral). APAP treatment caused lipid peroxidation as well as high NO level in renal tissue. Also, APAP treated rats had decreased activities of CAT and GSH-Px, but not SOD. In addition, tubular epithelial degeneration, vacuolization and cell desquamation were clearly observed in the APAP treated rats. The cellular debris in the proximal tubules and cortical interstitial congestions were prominent in the kidneys of APAP treated rats. BUN and creatinine levels were increased after APAP administration. All these pathological changes were reversed after erdosteine treatments. Erdosteine treated APAP groups showed milder tubular degeneration, epithelial vacuolization in the proximal tubules, lesser cellular desquamation and better morphology when compared with APAP groups. In conclusion, erdosteine may be a choice of preventive treatment against APAP induced nephrotoxicity.

  5. Renal involvement in primary antiphospholipid syndrome.

    Science.gov (United States)

    Marcantoni, Carmelita; Emmanuele, Carmela; Scolari, Francesco

    2016-08-01

    Antiphospholipid syndrome is an autoimmune disorder characterized by recurrent venous or arterial thrombosis and/or pregnancy-related problems associated with persistently elevated levels of antiphospholipid antibodies. The kidney is a major target organ in both primary and secondary antiphospholipid syndrome. This review describes several aspects of the renal involvement in the primary form of the syndrome, in particular the histological pattern of the so-called antiphospholipid syndrome nephropathy (APSN). APSN is a vascular nephropathy characterized by small vessel vaso-occlusive lesions associated with fibrous intimal hyperplasia of interlobular arteries, recanalizing thrombi in arteries and arterioles, and focal atrophy, a constellation of morphological lesions suggestive of primary antiphospholipid syndrome.

  6. Three Dimensional Culture of Human Renal Cell Carcinoma Organoids.

    Directory of Open Access Journals (Sweden)

    Cynthia A Batchelder

    Full Text Available Renal cell carcinomas arise from the nephron but are heterogeneous in disease biology, clinical behavior, prognosis, and response to systemic therapy. Development of patient-specific in vitro models that efficiently and faithfully reproduce the in vivo phenotype may provide a means to develop personalized therapies for this diverse carcinoma. Studies to maintain and model tumor phenotypes in vitro were conducted with emerging three-dimensional culture techniques and natural scaffolding materials. Human renal cell carcinomas were individually characterized by histology, immunohistochemistry, and quantitative PCR to establish the characteristics of each tumor. Isolated cells were cultured on renal extracellular matrix and compared to a novel polysaccharide scaffold to assess cell-scaffold interactions, development of organoids, and maintenance of gene expression signatures over time in culture. Renal cell carcinomas cultured on renal extracellular matrix repopulated tubules or vessel lumens in renal pyramids and medullary rays, but cells were not observed in glomeruli or outer cortical regions of the scaffold. In the polysaccharide scaffold, renal cell carcinomas formed aggregates that were loosely attached to the scaffold or free-floating within the matrix. Molecular analysis of cell-scaffold constructs including immunohistochemistry and quantitative PCR demonstrated that individual tumor phenotypes could be sustained for up to 21 days in culture on both scaffolds, and in comparison to outcomes in two-dimensional monolayer cultures. The use of three-dimensional scaffolds to engineer a personalized in vitro renal cell carcinoma model provides opportunities to advance understanding of this disease.

  7. Parathyroid scintigraphy in chronic renal failure; Exploration scintigraphique des glandes parathyroides au cours de l`insuffisance renale

    Energy Technology Data Exchange (ETDEWEB)

    Baulieu, J.L.; Houlier, S.; Baulieu, F.; Rousseau, C. [Hopital Bretonneau, 37 - Tours (France)

    1995-12-31

    The performances of the scintigraphic localization of parathyroid adenoma have improved with the use of technetium-99m radiolabeled tracers and the development of thyroid subtraction methods. By using methoxy--isobutyl-isonitrile (MIB) alone in two phases, sensitivity and specificity are respectively O.85 and 0.92. The interest of scintigraphy compared with ultrasonography is specially marked in the situations encountered in patients with renal failure: hyperplasia, multiple or ectopic adenoma, association with thyroid nodules. However, the localisation of adenoma remains more difficult in renal failure than in primary hyperthyroidism. Scintigraphy seems to be essential for localizing adenoma and eventually hyperplasia, before surgery in patients in bad conditions or before a second operation. (authors). 26 refs., 3 figs., 2 tabs.

  8. Isolation, growth, and characterization of human renal epithelial cells using traditional and 3D methods.

    Science.gov (United States)

    Gildea, John J; McGrath, Helen E; Van Sciver, Robert E; Wang, Dora Bigler; Felder, Robin A

    2013-01-01

    The kidney is a highly heterogeneous organ that is responsible for fluid and electrolyte balance. Much interest is focused on determining the function of specific renal epithelial cells in humans, which can only be accomplished through the isolation and growth of nephron segment-specific epithelial cells. However, human renal epithelial cells are notoriously difficult to maintain in culture. This chapter describes the isolation, growth, immortalization, and characterization of the human renal proximal tubule cell. In addition, we describe new paradigms in 3D cell culture which allow the cells to maintain more in vivo-like morphology and function.

  9. Renal PET-imaging with 11C-metformin in a transgenic mouse model for chronic kidney disease

    OpenAIRE

    Pedersen, Lea; Jensen, Jonas Brorson; Wogensen, Lise; Munk, Ole Lajord; Jessen, Niels; Frøkiær, Jørgen; Jakobsen, Steen

    2016-01-01

    Background Organic cation transporters (OCTs) in the renal proximal tubule are important for the excretion of both exo- and endogenous compounds, and chronic kidney disease (CKD) alter the expression of OCT. Metformin is a well-known substrate for OCT, and recently, we demonstrated that positron emission tomography (PET) with 11C-labelled metformin (11C-metformin) is a promising approach to evaluate the function of OCT. The aim of this study is therefore to examine renal pharmacokinetics of 1...

  10. 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.

  11. HCMV-infection in a human arterial organ culture model: effects on cell proliferation and neointimal hyperplasia

    Directory of Open Access Journals (Sweden)

    Rössler Wolfgang

    2007-07-01

    Full Text Available Abstract Background The impact of infections with the human cytomegalovirus (HCMV for the development of atherosclerosis and restenosis is still unclear. Both a clear correlation and no correlation at all have been reported in clinical, mostly serological studies. In our study we employed a human non-injury ex vivo organ culture model to investigate the effect of an in vitro permissive HCMV-infection on cell proliferation and neointimal hyperplasia for a period of 56 days. Results During routine-nephrectomies parts of renal arteries from 71 patients were obtained and prepared as human organ cultures. Cell free HCMV infection was performed with the fibroblast adapted HCMV strain AD169, the endotheliotropic strain TB40E, and a clinical isolate (AN 365. After 3, 7, 14, 21, 28, 35, and 56 days in culture staining of HCMV-antigens was carried out and reactive cell proliferation and neointimal thickening were analysed. Successful HCMV-infection was accomplished with all three virus strains studied. During the first 21 days in organ culture no cell proliferation or neointimal hyperplasia was detected. At day 35 and day 56 moderate cell proliferation and neointimal hyperplasia was found both in HCMV-infected segments and mock infected controls. Neointimal hyperplasia in productively HCMV-infected segments was lower than in non infected at day 35 and day 56, but relatively higher after infection with the endotheliotropic TB40E in comparison with the two other strains. Conclusion The data do not support the hypothesis that HCMV-infection triggers restenosis via a stimulatory effect on cell proliferation and neointimal hyperplasia in comparison to non infected controls. Interestingly however, even after lytic infection, a virus strain specific difference was observed.

  12. Parathyroid-specific epidermal growth factor-receptor inactivation prevents uremia-induced parathyroid hyperplasia in mice.

    Science.gov (United States)

    Arcidiacono, Maria Vittoria; Yang, Jing; Fernandez, Elvira; Dusso, Adriana

    2015-03-01

    In chronic kidney disease (CKD), parathyroid hyperplasia contributes to high serum parathyroid hormone (PTH) and also to an impaired suppression of secondary hyperparathyroidism by calcium, vitamin D and fibroblast growth factor 23 (FGF23). In rats, systemic inhibition of epidermal growth factor receptor (EGFR) activation markedly attenuated uremia-induced parathyroid hyperplasia and vitamin D receptor (VDR) loss, hence restoring the response to vitamin D. Therefore, we propose that parathyroid-specific EGFR inactivation should prevent CKD-induced parathyroid hyperplasia. A dominant-negative human EGFR mutant, which forms non-functional heterodimers with full-length endogenous EGFR, was successfully targeted to the parathyroid glands (PTGs) of FVB/N mice, using the 5' regulatory sequence of the PTH promoter. The parathyroid phenotype and serum chemistries of wild-type (WT) and transgenic mice were examined after 14 weeks of either sham operation or 75% renal mass reduction (NX). Both genotypes had similar morphology and body weight, and NX-induction enhanced similarly serum blood urea nitrogen compared with sham-operated controls. However, despite similar serum calcium, phosphate and FGF23 levels in NX mice of both genotypes, parathyroid EGFR inactivation sufficed to completely prevent the marked increases in PTG enlargement, serum PTH and in parathyroid levels of transforming growth factor-α, a powerful EGFR-activator, and the VDR reductions observed in WT mice. In CKD, parathyroid EGFR activation is essential for parathyroid hyperplasia and VDR loss, rendering this transgenic mouse a unique tool to scrutinize the pathogenesis of parathyroid and multiple organ dysfunction of CKD progression unrelated to parathyroid hyperplasia. © The Author 2014. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

  13. In Situ Single Photon Confocal Imaging of Cardiomyocyte T-tubule System from Langendorff-Perfused Hearts

    Directory of Open Access Journals (Sweden)

    Biyi eChen

    2015-05-01

    Full Text Available Transverse tubules (T-tubules are orderly invaginations of the sarcolemma in mammalian cardiomyocytes. The integrity of T-tubule architecture is critical for cardiac excitation-contraction coupling function. T-tubule remodeling is recognized as a key player in cardiac dysfunction. Early studies on T-tubule structure were based on electron microscopy, which uncovered important information about the T-tubule architecture. The advent of fluorescent membrane probes allowed the application of confocal microscopy to investigations of T-tubule structure. Studies have now been extended beyond single cardiomyocytes to examine the T-tubule network in intact hearts through in situ confocal imaging of Langendorff-perfused hearts. This technique has allowed visualization of T-tubule organization in their natural habitat, avoiding the damage induced by isolation of cardiomyocytes. Additionally, it is possible to obtain T-tubule images in different subepicardial regions in a single intact heart. We review how this state-of-the-art imaging technique has provided important mechanistic insights into maturation of T-tubules in developing hearts and defined the role of T-tubule remodeling in development and progression of heart failure.

  14. The kidney and uremic toxin removal: glomerulus or tubule?

    NARCIS (Netherlands)

    Masereeuw, R.; Mutsaers, H.A.M.; Toyohara, T.; Abe, T.; Jhawar, S.; Sweet, D.H.; Lowenstein, J.

    2014-01-01

    Chronic kidney disease (CKD) is a condition that affects approximately 10% of the adult population in developed countries. In patients with CKD adequate renal clearance is compromised, resulting in the accumulation of a plethora of uremic solutes. These uremic retention solutes, also known as uremic

  15. The kidney and uremic toxin removal : glomerulus or tubule?

    NARCIS (Netherlands)

    Masereeuw, Roos; Mutsaers, Henricus A M; Toyohara, Takafumi; Abe, Takaaki; Jhawar, Sachin; Sweet, Douglas H; Lowenstein, Jerome

    2014-01-01

    Chronic kidney disease (CKD) is a condition that affects approximately 10% of the adult population in developed countries. In patients with CKD adequate renal clearance is compromised, resulting in the accumulation of a plethora of uremic solutes. These uremic retention solutes, also known as uremic

  16. Uremic Toxins Induce ET-1 Release by Human Proximal Tubule Cells, which Regulates Organic Cation Uptake Time-Dependently

    Directory of Open Access Journals (Sweden)

    Carolien M. S. Schophuizen

    2015-06-01

    Full Text Available In renal failure, the systemic accumulation of uremic waste products is strongly associated with the development of a chronic inflammatory state. Here, the effect of cationic uremic toxins on the release of inflammatory cytokines and endothelin-1 (ET-1 was investigated in conditionally immortalized proximal tubule epithelial cells (ciPTEC. Additionally, we examined the effects of ET-1 on the cellular uptake mediated by organic cation transporters (OCTs. Exposure of ciPTEC to cationic uremic toxins initiated production of the inflammatory cytokines IL-6 (117 ± 3%, p < 0.001, IL-8 (122 ± 3%, p < 0.001, and ET-1 (134 ± 5%, p < 0.001. This was accompanied by a down-regulation of OCT mediated 4-(4-(dimethylaminostyryl-N-methylpyridinium-iodide (ASP+ uptake in ciPTEC at 30 min (23 ± 4%, p < 0.001, which restored within 60 min of incubation. Exposure to ET-1 for 24 h increased the ASP+ uptake significantly (20 ± 5%, p < 0.001. These effects could be blocked by BQ-788, indicating activation of an ET-B-receptor-mediated signaling pathway. Downstream the receptor, iNOS inhibition by (N(G‐monomethyl‐l‐arginine l-NMMA acetate or aminoguanidine, as well as protein kinase C activation, ameliorated the short-term effects. These results indicate that uremia results in the release of cytokines and ET-1 from human proximal tubule cells, in vitro. Furthermore, ET-1 exposure was found to regulate proximal tubular OCT transport activity in a differential, time-dependent, fashion.

  17. Inflammatory papillary hyperplasia: A systematic review

    Science.gov (United States)

    Gual-Vaqués, Patricia; Jané-Salas, Enric; Egido-Moreno, Sonia; Ayuso-Montero, Raúl; Marí-Roig, Antoni

    2017-01-01

    Introduction Inflammatory papillary hyperplasia (IPH) is a benign lesion of the palatal mucosa. It is usually found in denture-wearers but also has been reported in patients without a history of use of a maxillary prosthesis use. Objetives The aim of this study is to review the literature to assess the prevalence of denture stomatitis and inflammatory papillary hyperplasia and the etiological factors associated. Material and Methods A search was carried out in PubMed (January 2005 to October 2015) with the key words “inflammatory papillary hyperplasia”, “denture stomatitis”, “granular stomatitis” and “Newton’s type III” The inclusion criteria were studies including at least a sample of 50 apparently healthy patients, articles published from 2005 to 2015 written in English. The exclusion criteria were reviews and non-human studies. Results Out of the 190 studies obtained initially from the search 16 articles were selected to be included in our systematic review. The prevalence of denture stomatitis was 29.56% and 4.44% for IPH. We found 5 cases of denture stomatitis among non-denture-wearer individuals. All IPH cases were associated with the use of prosthesis. Smoking and continued use of ill-fitting dentures turned out to be the most frequent risk factors for developing IPH. Conclusions IPH is a rare oral lesion and its pathogenesis still remains unclear. Its presentation among non-denture-wearers is extremely unusual. Key words:Inflammatory papillary hyperplasia, denture stomatitis, prevalence, granular stomatitis, Newton’s type III stomatitis. PMID:27918740

  18. 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...

  19. NonClassic Congenital Adrenal Hyperplasia

    Directory of Open Access Journals (Sweden)

    Azziz Ricardo

    2010-05-01

    Full Text Available Nonclassic congenital adrenal hyperplasia (NCAH due to P450c21 (21-hydroxylase deficiency is a common autosomal recessive disorder. This disorder is due to mutations in the CYP21A2 gene which is located at chromosome 6p21. The clinical features predominantly reflect androgen excess rather than adrenal insufficiency leading to an ascertainment bias favoring diagnosis in females. Treatment goals include normal linear growth velocity and "on-time" puberty in affected children. For adolescent and adult women, treatment goals include regularization of menses, prevention of progression of hirsutism, and fertility. This paper will review key aspects regarding pathophysiology, diagnosis, and treatment of NCAH.

  20. A success story in congenital adrenal hyperplasia.

    Science.gov (United States)

    Kriplani, Alka; Lunkad, Amol; Agarwal, Nutan; Kulshreshtha, Bindu; Ariachery, C Aminni

    2012-12-01

    Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders characterized by enzyme defects in adrenal steroidogenic pathways. CAH due to 21-hydroxylase deficiency accounts for 95 % of cases. This case was diagnosed to have simple virilizing type of CAH and started on dexamethasone, and underwent genitoplasty and clitoroplasty at 25 years of age, then was married 3 years after surgery and conceived spontaneously 2 years after marriage, to deliver a healthy male baby. Thus, proper diagnosis and treatment with steroids and genitoplasty can give females with CAH a normal sexual, normal menstrual, and reproductive function.

  1. Focal epithelial hyperplasia (Heck’s disease)

    OpenAIRE

    Parichehr Gheliani; Atefe Tavangar; Nakissa Torabinia; Laleh Maleki; Tahereh Nosratzehi

    2013-01-01

    Focal epithelial hyperplasia (Heck) is a rare lesion caused by human papilloma virus subtype 13 or 32 and presents as multiple small white or pink papules on the mucosal surface of lips, buccal mucosa and tongue usually seen in children and adolescent of American Indian and Eskimo background. This disease has a genetic basis. The site of new lesions and recurrence are unpredictable. Continued follow up of the patient is often necessary. In this report, a 50-year-old woman is described with be...

  2. FOCAL EPITHELIAL HYPERPLASIA: HECK’S DISEASE

    Directory of Open Access Journals (Sweden)

    Brzeziński Piotr

    2010-10-01

    Full Text Available Heck's disease (focal epithelial hyperplasia (FEH is clinically characterized by multiple circumscribed, soft elevated nodules of the oral mucosa. Papules and plaques are usually the color of normal mucosa, but may be pale or, rarely, white. Disease may persist for years, producing a significant reduction in quality of life. Lessions may be located in the area of mucous membranes of the lips, cheeks and tongue. It is believed that the two virus types are responsible for the FEH, are: HPV 13 and HPV 32. Different therapeutic procedures have been reported: surgical excision, laser ablation, cryotherapy, electrocauterization, interferon, retinoic acid, 5% immiquimod.

  3. Adrenal Steroidogenesis and Congenital Adrenal Hyperplasia

    Science.gov (United States)

    Turcu, Adina F.; Auchus, Richard J.

    2015-01-01

    Synopsis Adrenal steroidogenesis is a dynamic process, reliant on de novo synthesis from cholesterol, under the stimulation of ACTH and other regulators. The syntheses of mineralocorticoids, glucocorticoids and adrenal androgens occur in separate adrenal cortical zones, each expressing specific enzymes. Congenital adrenal hyperplasia (CAH) encompasses a group of autosomal recessive enzymatic defects in cortisol biosynthesis. 21-hydroxylase (21OHD) deficiency accounts for over 90% of CAH cases and when milder or nonclassic forms are included, 21OHD is one of the most common genetic diseases. This review discusses in detail the epidemiology, genetics, diagnostic, clinical aspects and management of 21OHD. PMID:26038201

  4. In vivo model for microbial invasion of tooth root dentinal tubules.

    Science.gov (United States)

    Brittan, Jane L; Sprague, Susan V; Macdonald, Emma L; Love, Robert M; Jenkinson, Howard F; West, Nicola X

    2016-04-01

    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.

  5. The postnatal maturation of efferent tubules in the rat: a light and electron microscopy study.

    Science.gov (United States)

    Francavilla, S; Moscardelli, S; Bruno, B; Barcellona, P S; De Martino, C

    1986-07-01

    The postnatal maturation of the epithelium and tubule wall of efferent tubules in the rat was investigated by light and transmission electron microscopy, from birth to 50 days of age, when sperms were released from the seminiferous tubules and appeared in the genital duct. At the end of the first week of life, an endocytotic apparatus is differentiated in the epithelial cells. During the third week of life, efferent tubules developed specializations for the transport of sperms and fluids, namely the appearance of ciliated elements interspersed among the principal cells of the epithelium, and differentiation of myoid elements in the tubule wall. The appearance of specializations related to endocytosis and fluid transport across the epithelium preceded the canalization of the seminiferous cords which, in fact, is reported to appear at the end of the second week of life in the rat, along with the initial secretion of testicular fluid. This suggested that the maturation of efferent tubules is not triggered by the passage of testicular fluid, as surmised for the postnatal differentiation of caput epididymis. The postnatal maturation of efferent tubules was almost complete 35 days after birth. The appearance of sperms in the genital duct of 50-day-old animals was not associated with any remarkable structural change.

  6. 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.

  7. ImageJ analysis of dentin tubule distribution in human teeth.

    Science.gov (United States)

    Williams, Casia; Wu, Yiching; Bowers, Doria F

    2015-08-01

    Mapping the distribution of dentin tubules is vital to understanding the structure-function relationship of dentin, an important indicator of tooth stability. This study compared the distances between and density of tubules in the external dentin located in the crown region of an adult human incisor and molar to determine if analysis could be conducted using light-level microscopy. Teeth were processed for routine histology, cut in cross-section, images captured using Advanced SPOT Program, and microstructure was analyzed using ImageJ (NIH). Intratubular (peritubular) dentin with or without odontoblast processes were observed and although incisor and molar images appeared visually similar, plot profile graphs differed. Distance-intervals between tubules in the incisor (5.45-7.67 μm) had an overall range of 2.22 μm and in the molar (7.43-8.42 μm) an overall range of 0.99 μm. While molar tubule distribution displayed a tighter overall range, there was a smaller distance between most incisor tubules. The average densities observed in incisors were 15,500 tubules/mm(2), compared with 20,100 tubules/mm(2) in molars. ImageJ analysis of prepared histology microscopic slides provides researchers with a rapid, inexpensive assessment tool when compared with advanced/ultrastructural methodologies. By combining routine histological processing and light microscopic observations followed by ImageJ analysis, tooth structure can be converted into numerical data and easily mastered by laboratory personnel.

  8. Micro- and nano-tubules built from loosely and tightly rolled up thin sheets.

    Science.gov (United States)

    Losensky, Luisa; Goldenbogen, Björn; Holland, Gudrun; Laue, Michael; Petran, Anca; Liebscher, Jürgen; Scheidt, Holger A; Vogel, Alexander; Huster, Daniel; Klipp, Edda; Arbuzova, Anna

    2016-01-14

    Tubular structures built from amphiphilic molecules are of interest for nano-sensing, drug delivery, and structuring of oils. In this study, we characterized the tubules built in aqueous suspensions of a cholesteryl nucleoside conjugate, cholesterylaminouridine (CholAU) and phosphatidylcholines (PCs). In mixtures with unsaturated PCs having chain lengths comparable to the length of CholAU, two different types of tubular structures were observed; nano- and micro-tubules had average diameters in the ranges 50-300 nm and 2-3 μm, respectively. Using cryo scanning electron microscopy (cryo-SEM) we found that nano- and micro-tubules differed in their morphology: the nano-tubules were densely packed, whereas micro-tubules consisted of loosely rolled undulated lamellas. Atomic force microscopy (AFM) revealed that the nano-tubules were built from 4 to 5 nm thick CholAU-rich bilayers, which were in the crystalline state. Solid-state (2)H NMR spectroscopy also confirmed that about 25% of the total CholAU, being about the fraction of CholAU composing the tubules, formed the rigid crystalline phase. We found that CholAU/PC tubules can be functionalized by molecules inserted into lipid bilayers and fluorescently labeled PCs and lipophilic nucleic acids inserted spontaneously into the outer layer of the tubules. The tubular structures could be loaded and cross-linked, e.g. by DNA hybrids, and, therefore, are of interest for further development, e.g. as a depot scaffold for tissue regeneration.

  9. Preoperative and postoperative histopathological findings in patients with endometrial hyperplasia

    OpenAIRE

    Đorđević Biljana; Stanojević Zorica; Živković Vesna; Lalošević Dušan; Gligorijević Jasmina; Krstić Miljan

    2007-01-01

    Introduction. The aim of this study was to analyze and compare the histopathological findings in curettage and hysterectomy specimens, to evaluate the accuracy of histopathological diagnosis in curettage specimens, and to determine the frequency of coexisting endometrial carcinoma in patients with histopathological diagnosis of endometrial hyperplasia. Material and methods. Curettage and hysterectomy specimens of 135 female patients with initially diagnosed endometrial hyperplasia were retros...

  10. Focal epithelial hyperplasia caused by human papillomavirus 13.

    Science.gov (United States)

    Saunders, Natasha R; Scolnik, Dennis; Rebbapragada, Anuradha; Koelink, Eric; Craw, Lindsey; Roth, Sherryn; Aronson, Leya; Perusini, Stephen; Silverman, Michael S

    2010-06-01

    Focal epithelial hyperplasia is a benign, papulo-nodular disease of the oral cavity. It is rare, affecting primarily Native American populations during childhood. It is closely associated with human papillomavirus 13 and 32. This report describes the diagnosis of 2 cases of focal epithelial hyperplasia in children from southern Guyana. The diagnosis was made using clinical criteria, polymerase chain reaction, and DNA sequencing.

  11. Respiratory Syncytial Virus Aggravates Renal Injury through Cytokines and Direct Renal Injury

    Directory of Open Access Journals (Sweden)

    Songhui Zhai

    2016-09-01

    Full Text Available The purpose of this study was to investigate the relationship between renal injury and reinfection that is caused by respiratory syncytial virus (RSV and to analyze the mechanism of renal injury. Rats were repeatedly infected with RSV on days 4, 8, 14, and 28, then sacrificed and examined on day 56 after the primary infection. Renal injury was examined by transmission electron microscopy and histopathology. The F protein of RSV was detected in the renal tissue by indirect immunofluorescence. Proteinuria and urinary glycosaminoglycans (GAGs, serum levels of albumin, urea nitrogen, and creatinine, secretion of cytokines, T lymphocyte population and subsets, and dendritic cell (DC activation state were examined. The results showed that renal injury was more serious in the reinfection group than in the primary infection group. At a higher infection dose, 6×106 PFU, the renal injury was more severe, accompanied by higher levels of proteinuria and urinary GAGs excretion, and lower levels of serum albumin. Podocyte foot effacement was more extensive, and hyperplasia of mesangial cells and proliferation of mesangial matrix were observed. The maturation state of DCs was specific, compared with the primary infection. There was also a decrease in the ratio of CD4+ to CD8+T lymphocytes, due to an increase in the percentage of CD8+T lymphocytes and a decrease in the percentage of CD4+T lymphocytes, and a dramatic increase in the levels of IL-6 and IL-17. In terms of the different reinfection times, the day 14 reinfection group yielded the most serious renal injury and the most significant change in immune function. RSV F protein was still expressed in the glomeruli 56 days after RSV infection. Altogether, these results reveal that RSV infection could aggravate renal injury, which might be due to direct renal injury caused by RSV and the inflammatory lesions caused by the anti-virus response induced by RSV.

  12. Nephron proximal tubule patterning and corpuscles of Stannius formation are regulated by the sim1a transcription factor and retinoic acid in zebrafish.

    Science.gov (United States)

    Cheng, Christina N; Wingert, Rebecca A

    2015-03-01

    The mechanisms that establish nephron segments are poorly understood. The zebrafish embryonic kidney, or pronephros, is a simplified yet conserved genetic model to study this renal development process because its nephrons contain segments akin to other vertebrates, including the proximal convoluted and straight tubules (PCT, PST). The zebrafish pronephros is also associated with the corpuscles of Stannius (CS), endocrine glands that regulate calcium and phosphate homeostasis, but whose ontogeny from renal progenitors is largely mysterious. Initial patterning of zebrafish renal progenitors in the intermediate mesoderm (IM) involves the formation of rostral and caudal domains, the former being reliant on retinoic acid (RA) signaling, and the latter being repressed by elevated RA levels. Here, using expression profiling to gain new insights into nephrogenesis, we discovered that the gene single minded family bHLH transcription factor 1a (sim1a) is dynamically expressed in the renal progenitors-first marking the caudal domain, then becoming restricted to the proximal segments, and finally exhibiting specific CS expression. In loss of function studies, sim1a knockdown expanded the PCT and abrogated both the PST and CS populations. Conversely, overexpression of sim1a modestly expanded the PST and CS, while it reduced the PCT. These results show that sim1a activity is necessary and partially sufficient to induce PST and CS fates, and suggest that sim1a may inhibit PCT fate and/or negotiate the PCT/PST boundary. Interestingly, the sim1a expression domain in renal progenitors is responsive to altered levels of RA, suggesting that RA regulates sim1a, directly or indirectly, during nephrogenesis. sim1a deficient embryos treated with exogenous RA formed nephrons that were predominantly composed of PCT segments, but lacked the enlarged PST observed in RA treated wild-types, indicating that RA is not sufficient to rescue the PST in the absence of sim1a expression. Alternately

  13. 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.

  14. Testicular adrenal rest tumor in infertile man with congenital adrenal hyperplasia: case report and literature review

    Directory of Open Access Journals (Sweden)

    Giovanni Scala Marchini

    Full Text Available CONTEXT: Synthesis of cortisol and aldosterone is impaired in patients with congenital adrenal hyperplasia (CAH because of 21-hydroxylase deficiency. Men with CAH have low fertility rates compared with the normal population, and this is related to testicular adrenal rest tumors. Findings of azoospermia in combination with a testicular tumor on ultrasound are likely to have a mechanical cause, especially when in the testicular mediastinum. The preferred treatment method consists of intensive corticoid therapy. However, when the tumor is unresponsive to steroid therapy, surgical treatment should be considered. CASE REPORT: We present the case of a male patient with CAH due to 21-hydroxylase deficiency who presented a testicular tumor and azoospermia. Treatment with low daily corticoid doses had previously been started by an endocrinologist, but after 12 months, no significant change in sperm count was found. Although the adrenocorticotrophic hormone and 17-hydroxyprogesterone levels returned to normal values, the follicle-stimulating hormone (FSH, luteinizing hormone and testosterone levels remained unchanged. Ultrasound examination confirmed that the testicles were small and heterogenous bilaterally, and revealed a mosaic area at the projection of the testis network bilaterally. Magnetic resonance imaging confirmed the finding. Testicular biopsy revealed the presence of preserved spermatogenesis and spermiogenesis in 20% of the seminiferous tubules in the right testicle. The patient underwent testis-sparing tumor resection. After 12 months of follow-up, there was no tumor recurrence but the patient still presented azoospermia and joined an intracytoplasmic sperm injection program.

  15. Intraoperative identification of adrenal-renal fusion

    Science.gov (United States)

    Boll, Griffin; Rattan, Rishi; Yilmaz, Osman; Tarnoff, Michael E

    2015-01-01

    Adrenal - renal fusion is a rare entity defined as incomplete encapsulation of the adrenal gland and kidney with histologically adjacent functional tissue. This report describes the first published intraoperative identification of this anomaly during laparoscopic adrenalectomy. The patient was a 59-year-old man with chronic hypertension refractory to multiple antihypertensives found to be caused by a right-sided aldosterone-producing adrenal adenoma in the setting of bilateral adrenal hyperplasia. During laparoscopic adrenalectomy, the normal avascular plane between the kidney and adrenal gland was absent. Pathologic evaluation confirmed adrenal - renal fusion without adrenal heterotopia. Identified intraoperatively, this may be misdiagnosed as invasive malignancy, and thus awareness of this anomaly may help prevent unnecessarily morbid resection. PMID:26195881

  16. Cadmium and cisplatin damage erythropoietin-producing proximal renal tubular cells

    Energy Technology Data Exchange (ETDEWEB)

    Horiguchi, Hyogo; Oguma, Etsuko; Kayama, Fujio [Jichi Medical School, Division of Environmental Medicine, Center for Community Medicine, Tochigi (Japan); Core Research for Evolutional Science and Technology, Japan Science Technology Corporation (CREST-JST), Saitama (Japan)

    2006-10-15

    The concomitant manifestations of proximal renal tubular dysfunction and anemia with erythropoietin (Epo) deficiency observed in chronic cadmium (Cd) intoxication, such as Itai-itai disease, suggest a close local correlation between the Cd-targeted tubular cells and Epo-producing cells in the kidney. Therefore, we investigated the local relationship between hypoxia-induced Epo production and renal tubular injury in rats injected with Cd at 2 mg/kg twice a week for 8 months. Anemia due to insufficient production of Epo was observed in Cd-intoxicated rats. In situ hybridization detected Epo mRNA expression in the proximal renal tubular cells of hypoxic rats without Cd intoxication, and the Cd-intoxicated rats showed atrophy of Epo-expressing renal tubules and replacement of them with fibrotic tissue. A single dose of cisplatin at 8 mg/kg, which can induce clinical manifestations similar to those of Cd including renal tubular damage along with Epo-deficient anemia, resulted in Epo-expressing renal tubule destruction on day 4. These data indicate that Cd and cisplatin would induce anemia through the direct injury of the proximal renal tubular cells that are responsible for Epo production. (orig.)

  17. Therapeutic options for management of endometrial hyperplasia.

    Science.gov (United States)

    Chandra, Vishal; Kim, Jong Joo; Benbrook, Doris Mangiaracina; Dwivedi, Anila; Rai, Rajani

    2016-01-01

    Endometrial hyperplasia (EH) comprises a spectrum of changes in the endometrium ranging from a slightly disordered pattern that exaggerates the alterations seen in the late proliferative phase of the menstrual cycle to irregular, hyperchromatic lesions that are similar to endometrioid adenocarcinoma. Generally, EH is caused by continuous exposure of estrogen unopposed by progesterone, polycystic ovary syndrome, tamoxifen, or hormone replacement therapy. Since it can progress, or often occur coincidentally with endometrial carcinoma, EH is of clinical importance, and the reversion of hyperplasia to normal endometrium represents the key conservative treatment for prevention of the development of adenocarcinoma. Presently, cyclic progestin or hysterectomy constitutes the major treatment option for EH without or with atypia, respectively. However, clinical trials of hormonal therapies and definitive standard treatments remain to be established for the management of EH. Moreover, therapeutic options for EH patients who wish to preserve fertility are challenging and require nonsurgical management. Therefore, future studies should focus on evaluation of new treatment strategies and novel compounds that could simultaneously target pathways involved in the pathogenesis of estradiol-induced EH. Novel therapeutic agents precisely targeting the inhibition of estrogen receptor, growth factor receptors, and signal transduction pathways are likely to constitute an optimal approach for treatment of EH.

  18. Torus hyperplasia of the pyloric antrum.

    Science.gov (United States)

    Kim, Chi-Hun; Han, Hye Seung; Lee, Sun-Young; Kim, Byung Kook; Sung, In-Kyung; Seong, Moo Kyung; Lee, Kyung Yung

    2010-01-01

    Primary or idiopathic hypertrophy of the pyloric muscle in adult, so called torus hyperplasia, is an infrequent but an established entity. It is caused by a circular muscle hypertrophy affecting the lesser curvature near the pylorus. Since most of the lesions are difficult to differentiate from tumor, distal gastrectomy is usually preformed to rule out most causes of pyloric lesions including neoplastic ones through a pathological study. A 56-yr-old man with a family history of gastric cancer presented with abdominal discomfort of 1 month duration. Upper gastrointestinal endoscopy showed a 1.0 cm sized irregular submucosal lesion proximal to the pylorus to the distal antrum on the lesser curvature. On colonoscopy examination, a 1.5 cm sized protruding mass was noticed on the appendiceal orifice. Gastrectomy and cecectomy were done, and histological section revealed marked hypertrophy of the distal circular pyloric musculature and an appendiceal mucocele. To the best of our knowledge, this is the first case of torus hyperplasia with appendiceal mucocele which is found incidentally.

  19. Therapeutic options for management of endometrial hyperplasia

    Science.gov (United States)

    2016-01-01

    Endometrial hyperplasia (EH) comprises a spectrum of changes in the endometrium ranging from a slightly disordered pattern that exaggerates the alterations seen in the late proliferative phase of the menstrual cycle to irregular, hyperchromatic lesions that are similar to endometrioid adenocarcinoma. Generally, EH is caused by continuous exposure of estrogen unopposed by progesterone, polycystic ovary syndrome, tamoxifen, or hormone replacement therapy. Since it can progress, or often occur coincidentally with endometrial carcinoma, EH is of clinical importance, and the reversion of hyperplasia to normal endometrium represents the key conservative treatment for prevention of the development of adenocarcinoma. Presently, cyclic progestin or hysterectomy constitutes the major treatment option for EH without or with atypia, respectively. However, clinical trials of hormonal therapies and definitive standard treatments remain to be established for the management of EH. Moreover, therapeutic options for EH patients who wish to preserve fertility are challenging and require nonsurgical management. Therefore, future studies should focus on evaluation of new treatment strategies and novel compounds that could simultaneously target pathways involved in the pathogenesis of estradiol-induced EH. Novel therapeutic agents precisely targeting the inhibition of estrogen receptor, growth factor receptors, and signal transduction pathways are likely to constitute an optimal approach for treatment of EH. PMID:26463434

  20. Renal tubular acidosis.

    Science.gov (United States)

    Rothstein, M; Obialo, C; Hruska, K A

    1990-12-01

    Renal tubular acidosis refers to a group of disorders that result from pure tubular damage without concomitant glomerular damage. They could be hereditary (primary) or acquired (secondary to various disease states like sickle cell disease, obstructive uropathy, postrenal transplant, autoimmune disease, or drugs). The hallmark of the disorder is the presence of hyperchloremic metabolic acidosis with, or without, associated defects in potassium homeostasis, a UpH greater than 5.5 in the presence of systemic acidemia, and absence of an easily identifiable cause of the acidemia. There are three physiologic types whose basic defects are impairment of or a decrease in acid excretion, i.e., type 1 (dRTA); a failure in bicarbonate reabsorption, i.e., type 2 (pRTA); and deficiency of buffer or impaired generation of NH4+, i.e., type 4 RTA. Several pathophysiologic mechanisms have been postulated for these various types. pRTA is the least common of all in the adult population. It rarely occurs as an isolated defect. It is frequently accompanied by diffuse proximal tubule transport defects with aminoaciduria, glycosuria, hyperphosphaturia, and so forth (Fanconi syndrome). dRTA is associated with a high incidence of nephrolithiasis, nephrocalcinosis, osteodystrophy, and growth retardation (in children). Osteodystrophy also occurs in pRTA to a lesser degree and is believed to be secondary to hypophosphatemia. Patients with type 4 RTA usually have mild renal insufficiency from either diabetes mellitus or interstitial nephritis. Acute bicarbonate loading will result in a high fractional excretion of bicarbonate greater than 15% (FEHCO3- greater than 15%) in patients with pRTA, but FEHCO3- less than 3% in patients with dRTA. Type I patients will also have a low (U - B) PCO2 with bicarbonate loading. They are also unable to lower their urine pH to less than 5.5 with NH4Cl loading. The treatment of these patients involves avoidance of precipitating factors when possible, treatment

  1. Renal Cysts

    Science.gov (United States)

    ... as “simple” cysts, meaning they have a thin wall and contain water-like fluid. Renal cysts are fairly common in ... simple kidney cysts, meaning they have a thin wall and only water-like fluid inside. They are fairly common in ...

  2. Renal failure

    Institute of Scientific and Technical Information of China (English)

    1997-01-01

    970363 Effect on serum PTH and 1, 25(OH)2 D3levels of rapid correction of metabolic acidosis in CRFpatients with secondary hyperparathyroidism. YUANQunsheng(袁群生), et al. Renal Div, PUMC Hosp,Beijing, 100730. Chin J Nephrol 1996; 12(6): 328-331.

  3. Renal Cortical Lactate Dehydrogenase: A Useful, Accurate, Quantitative Marker of In Vivo Tubular Injury and Acute Renal Failure.

    Directory of Open Access Journals (Sweden)

    Richard A Zager

    Full Text Available Studies of experimental acute kidney injury (AKI are critically dependent on having precise methods for assessing the extent of tubular cell death. However, the most widely used techniques either provide indirect assessments (e.g., BUN, creatinine, suffer from the need for semi-quantitative grading (renal histology, or reflect the status of residual viable, not the number of lost, renal tubular cells (e.g., NGAL content. Lactate dehydrogenase (LDH release is a highly reliable test for assessing degrees of in vitro cell death. However, its utility as an in vivo AKI marker has not been defined. Towards this end, CD-1 mice were subjected to graded renal ischemia (0, 15, 22, 30, 40, or 60 min or to nephrotoxic (glycerol; maleate AKI. Sham operated mice, or mice with AKI in the absence of acute tubular necrosis (ureteral obstruction; endotoxemia, served as negative controls. Renal cortical LDH or NGAL levels were assayed 2 or 24 hrs later. Ischemic, glycerol, and maleate-induced AKI were each associated with striking, steep, inverse correlations (r, -0.89 between renal injury severity and renal LDH content. With severe AKI, >65% LDH declines were observed. Corresponding prompt plasma and urinary LDH increases were observed. These observations, coupled with the maintenance of normal cortical LDH mRNA levels, indicated the renal LDH efflux, not decreased LDH synthesis, caused the falling cortical LDH levels. Renal LDH content was well maintained with sham surgery, ureteral obstruction or endotoxemic AKI. In contrast to LDH, renal cortical NGAL levels did not correlate with AKI severity. In sum, the above results indicate that renal cortical LDH assay is a highly accurate quantitative technique for gauging the extent of experimental acute ischemic and toxic renal injury. That it avoids the limitations of more traditional AKI markers implies great potential utility in experimental studies that require precise quantitation of tubule cell death.

  4. Drug-induced renal injury

    African Journals Online (AJOL)

    Drugs can cause acute renal failure by causing pre-renal, intrinsic or post-renal toxicity. Pre-renal ... incidence of drug dose adjustment in renal impairment in the SAMJ. ... Fever, haemolytic anaemia, thrombocytopenia, renal impairment and.

  5. Inhibitory effects of Tripterygium wilfordii multiglycoside on benign prostatic hyperplasia in rats.

    Science.gov (United States)

    Shen, Hai-Nan; Xu, Yuan; Jiang, Zhen-Zhou; Huang, Xin; Zhang, Lu-Yong; Wang, Tao

    2015-06-01

    The present study was designed to evaluate the inhibitory effects of Tripterygium wilfordii multiglycoside (GTW) against testosterone-induced benign prostatic hyperplasia (BPH) in rats. A total of 45 rats were randomly divided into five groups: Group I, vehicle control group (sham-operated and treated with vehicle); Group II, BPH group; Group III, BPH rats treated with finasteride at a dose of 5 mg·kg(-1); and Groups IV and V, BPH rats treated with GTW at dose levels of 10 and 20 mg·kg(-1), respectively. The drugs were administered orally once a day for 14 days. Prostate weight, prostatic index, and the testosterone and dihydrotestosterone (DHT) levels in serum and prostate, and the serum prostate specific antigen (PSA) levels were measured; prostate tissues were taken for histopathological examination; and serum biochemical analysis was also performed. The BPH rats displayed an increase in prostate weight, prostatic index with increased testosterone and DHT levels in both the serum and prostate, and increased serum PSA levels. GTW treatment at both doses resulted in significant reductions in prostate weight, prostatic index, testosterone and DHT levels in both the serum and prostate, and serum PSA levels, compared with BPH group. Histopathological examination also indicated that GTW treatment at both doses inhibited testosterone-induced prostatic hyperplasia. Serum biochemical analysis showed that the liver and renal functions were normal. In conclusion, GTW inhibited testosterone-induced prostatic hyperplasia in rats, without host toxicity, providing a basis for the development of GTW as a novel therapy for BPH.

  6. Regulatory pathways for ATP-binding cassette transport proteins in kidney proximal tubules

    NARCIS (Netherlands)

    Masereeuw, R.; Russel, F.G.M.

    2012-01-01

    The ATP-binding cassette transport proteins (ABC transporters) represent important determinants of drug excretion. Protective or excretory tissues where these transporters mediate substrate efflux include the kidney proximal tubule. Regulation of the transport proteins in this tissue requires elabor

  7. Effect of depth and tubule direction on ultimate tensile strength of human coronal dentin.

    Science.gov (United States)

    Inoue, Satoshi; Pereira, Patricia N R; Kawamoto, Chiharu; Nakajima, Masatoshi; Koshiro, Kenichi; Tagami, Junji; Carvalho, Ricardo M; Pashley, David H; Sano, Hidehiko

    2003-03-01

    The purpose of this study was to evaluate the effect of dentin depth and tubule direction on the ultimate tensile strength (UTS) of human dentin. Dentin slabs of 0.5-mm thickness were trimmed either from the mesial and distal (for specimens with the tubules parallel to the tensile force; parallel group) or from the occlusal and pulpal surfaces (perpendicular group) to reduce the cross-sectional area of the superficial, middle, and deep regions to 0.25 mm2, and subjected to microtensile testing. From SEM photomicrographs of the fractured specimens of the parallel group, the tubule density was investigated. For both parallel and perpendicular groups, superficial dentin showed a significantly higher UTS than deep dentin. The tubule density of superficial dentin was significantly lower than that of middle and deep dentin. When performing the microtensile bond test to deep dentin, it is possible that cohesive failure of dentin can occur at relatively low tensile stresses.

  8. Purine transport by malpighian tubules of pteridine-deficient eye color mutants of Drosophila melanogaster.

    Science.gov (United States)

    Sullivan, D T; Bell, L A; Paton, D R; Sullivan, M C

    1979-06-01

    Uptakes of guanine into Malpighian tubules of wild-type Drosophila and the eye color mutants white (w), brown (bw), and pink-peach (pp) have been compared. Tubules for each of these mutants are unable to concentrate guanine intracellularly. The transport of xanthine and riboflavin is also deficient in w tubules. The transport of guanosine, adenine, hypoxanthine, and guanosine monophosphate is similar in wild-type and white Malpighian tubules. These data and other information about these mutants make it likely that these pteridine-deficient eye color mutants do not produce pigments because of the inability to transport a pteridine precursor. This view supports the hypothesis that mutants which lack both pteridine and ommochromes do so because precursors to both classes of pigments share a common transport system.

  9. RENAL HISTOPATHOLOGICAL FINDINGS IN DOGS WITH VISCERAL LEISHMANIASIS

    Directory of Open Access Journals (Sweden)

    Rosangela Silva Rigo

    2013-04-01

    Full Text Available Visceral leishmaniasis affects various organs including the kidneys; which can lead to renal failure and death. In order to verify this renal involvement, material was evaluated from 100 dogs naturally infected and with serological diagnosis of canine visceral leishmaniasis (CVL. Inflammatory changes were present in 25.3% of the tubules, in 67.0% of interstitium and in 52.0% of glomeruli. There was no significant difference (p > 0.05 between the presence of glomerulonephritis in symptomatic and oligosymptomatic dogs. The membranous and membranoproliferative glomerulonephritis were the most frequent, both with 18.0% frequency, followed by focal segmental glomerulosclerosis with 14.0%. Changes such as cylindruria, tubular and fibrosis hypertrophy, periglomerular inflammatory infiltrate, and multifocal and diffuse peritubular inflammatory infiltrate were observed. The findings are consistent with those of other authors indicating that renal involvement is common in CVL and the standards of membranous and membranoploriferative glomerulonephritis, as well as the tubulointerstitial involvement, are frequent.

  10. Renal histopathological findings in dogs with visceral leishmaniasis.

    Science.gov (United States)

    Rigo, Rosangela Silva; Carvalho, Cristiano Marcelo Espínola; Honer, Michael Robin; Andrade, Gisele Braziliano de; Silva, Iandara Shetter; Rigo, Leonardo; Figueiredo, Helen Rezende; Barreto, Wanessa Teixeira Gomes

    2013-01-01

    Visceral leishmaniasis affects various organs including the kidneys; which can lead to renal failure and death. In order to verify this renal involvement, material was evaluated from 100 dogs naturally infected and with serological diagnosis of canine visceral leishmaniasis (CVL). Inflammatory changes were present in 25.3% of the tubules, in 67.0% of interstitium and in 52.0% of glomeruli. There was no significant difference (p > 0.05) between the presence of glomerulonephritis in symptomatic and oligosymptomatic dogs. The membranous and membranoproliferative glomerulonephritis were the most frequent, both with 18.0% frequency, followed by focal segmental glomerulosclerosis with 14.0%. Changes such as cylindruria, tubular and fibrosis hypertrophy, periglomerular inflammatory infiltrate, and multifocal and diffuse peritubular inflammatory infiltrate were observed. The findings are consistent with those of other authors indicating that renal involvement is common in CVL and the standards of membranous and membranoploriferative glomerulonephritis, as well as the tubulointerstitial involvement, are frequent.

  11. An angiotensin-(1-7) peptidase in the kidney cortex, proximal tubules, and human HK-2 epithelial cells that is distinct from insulin-degrading enzyme.

    Science.gov (United States)

    Wilson, Bryan A; Cruz-Diaz, Nildris; Marshall, Allyson C; Pirro, Nancy T; Su, Yixin; Gwathmey, TanYa M; Rose, James C; Chappell, Mark C

    2015-03-15

    Angiotensin 1-7 [ANG-(1-7)] is expressed within the kidney and exhibits renoprotective actions that antagonize the inflammatory, fibrotic, and pro-oxidant effects of ANG II. We previously identified an peptidase that preferentially metabolized ANG-(1-7) to ANG-(1-4) in the brain medulla and cerebrospinal fluid (CSF) of sheep (Marshall AC, Pirro NT, Rose JC, Diz DI, Chappell MC. J Neurochem 130: 313-323, 2014); thus the present study established the expression of the peptidase in the kidney. Utilizing a sensitive HPLC-based approach, we demonstrate a peptidase activity that hydrolyzed ANG-(1-7) to ANG-(1-4) in the sheep cortex, isolated tubules, and human HK-2 renal epithelial cells. The peptidase was markedly sensitive to the metallopeptidase inhibitor JMV-390; human HK-2 cells expressed subnanomolar sensitivity (IC50 = 0.5 nM) and the highest specific activity (123 ± 5 fmol·min(-1)·mg(-1)) compared with the tubules (96 ± 12 fmol·min(-1)·mg(-1)) and cortex (107 ± 9 fmol·min(-1)·mg(-1)). The peptidase was purified 41-fold from HK-2 cells; the activity was sensitive to JMV-390, the chelator o-phenanthroline, and the mercury-containing compound p-chloromercuribenzoic acid (PCMB), but not to selective inhibitors against neprilysin, neurolysin and thimet oligopeptidase. Both ANG-(1-7) and its endogenous analog [Ala(1)]-ANG-(1-7) (alamandine) were preferentially hydrolyzed by the peptidase compared with ANG II, [Asp(1)]-ANG II, ANG I, and ANG-(1-12). Although the ANG-(1-7) peptidase and insulin-degrading enzyme (IDE) share similar inhibitor characteristics of a metallothiolendopeptidase, we demonstrate marked differences in substrate specificity, which suggest these peptidases are distinct. We conclude that an ANG-(1-7) peptidase is expressed within the renal proximal tubule and may play a potential role in the renal renin-angiotensin system to regulate ANG-(1-7) tone.

  12. 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...

  13. Resin Adaptation of Radicular Dentin Tubules after Endodontic Instrumentation and Acid Etching.

    Science.gov (United States)

    1983-02-01

    intracanal irrigant . After completion of the Carson L. Mader 15 -1 endodontic instrumentation, the canals were flushed with 25 ml. of sterile saline...I RD-Ai26 872 RESIN ADAPTATION OF RADICULAR DENTIN TUBULES AFTER / I ENDODONTIC INSTRUMENTATION AND ACID ETCHING(U) WALTER I REED ARMY INST OF...Adaptation to Radicular Dentin Tubules SbisoofpeAfter Endodontic Instrumentation and Acid Etching 1982-1983 6. PERFORMING ORG. REPORTNUMBER -, AUTHOR(a) S

  14. Length Is Associated with Pain: Jellyfish with Painful Sting Have Longer Nematocyst Tubules than Harmless Jellyfish.

    Science.gov (United States)

    Kitatani, Ryuju; Yamada, Mayu; Kamio, Michiya; Nagai, Hiroshi

    2015-01-01

    A large number of humans are stung by jellyfish all over the world. The stings cause acute pain followed by persistent pain and local inflammation. Harmful jellyfish species typically cause strong pain, whereas harmless jellyfish cause subtle or no pain. Jellyfish sting humans by injecting a tubule, contained in the nematocyst, the stinging organ of jellyfish. The tubule penetrates into the skin leading to venom injection. The detailed morphology of the nematocyst tubule and molecular structure of the venom in the nematocyst has been reported; however, the mechanism responsible for the difference in pain that is caused by harmful and harmless jellyfish sting has not yet been explored or explained. Therefore, we hypothesized that differences in the length of the nematocyst tubule leads to different degrees of epithelial damage. The initial acute pain might be generated by penetration of the tubule, which stimulates pain receptor neurons, whilst persistent pain might be caused by injection of venom into the epithelium. To test this hypothesis we compared the lengths of discharged nematocyst tubules from harmful and harmless jellyfish species and evaluated their ability to penetrate human skin. The results showed that the harmful jellyfish species, Chrysaora pacifica, Carybdea brevipedalia, and Chironex yamaguchii, causing moderate to severe pain, have nematocyst tubules longer than 200 μm, compared with a jellyfish species that cause little or no pain, Aurelia aurita. The majority of the tubules of harmful jellyfishes, C. yamaguchii and C. brevipedalia, were sufficiently long to penetrate the human epidermis and physically stimulate the free nerve endings of Aδ pain receptor fibers around plexuses to cause acute pain and inject the venom into the human skin epithelium to cause persistent pain and inflammation.

  15. Effects of ammonium hexafluorosilicate concentration on dentin tubule occlusion and composition of the precipitate.

    Science.gov (United States)

    Suge, Toshiyuki; Kawasaki, Akiko; Ishikawa, Kunio; Matsuo, Takashi; Ebisu, Shigeyuki

    2010-01-01

    Ammonium hexafluorosilicate [SiF: (NH(4))(2)SiF(6)] was prepared in order to overcome the tooth discoloration caused by diamine silver fluoride [AgF: (NH(3))(2)AgF] application. We employed a single concentration of SiF solution in our previous study; therefore, it is still unclear how the concentration of SiF solution affects the occlusion of dentin tubules and composition of the precipitate. The aim of this study was to evaluate the effects of changing the concentration of SiF on its clinical use as a dentin hypersensitivity treatment. To simulate dentin tubules subject to dentin hypersensitivity, dentin disks were treated with EDTA for 2 min. Then, the disks were treated with several concentrations of SiF solution (from 100 to 19,400 ppm) for 3 min. The occlusion of dentin tubules was evaluated using scanning electron microscopy (SEM), and the composition of the precipitate formed in the tubules after SiF treatment was assessed using energy dispersive X-ray analysis (EDXA). SEM photographs demonstrated that dentin tubules after treatment with SiF were occluded homogeneously and fully regardless of the concentration of SiF solution. The Ca/P molar ratio of the precipitate formed in dentin tubules after SiF treatment was increased with the concentration of SiF solution. It was concluded that the capacity to occlude dentin tubules was the same regardless of the concentration of SiF solution. However, the composition of the precipitate formed in the tubules was dependent on the concentration of SiF solution.

  16. Renal failure (chronic)

    OpenAIRE

    Clase, Catherine

    2011-01-01

    Chronic renal failure is characterised by a gradual and sustained decline in renal clearance or glomerular filtration rate (GFR). Continued progression of renal failure will lead to renal function too low to sustain healthy life. In developed countries, such people will be offered renal replacement therapy in the form of dialysis or renal transplantation. Requirement for dialysis or transplantation is termed end-stage renal disease (ESRD).Diabetes, glomerulonephritis, hypertension, pyelone...

  17. Renal pathology and urinary protein excretion in a 14-month-old Bernese mountain dog with chronic renal failure.

    Science.gov (United States)

    Raila, J; Aupperle, H; Raila, G; Schoon, H-A; Schweigert, F J

    2007-04-01

    The renal pathology and urinary protein pattern of a 14-month-old female Bernese mountain dog with chronic renal failure was investigated. Sodium dodecyl sulphate-polyacrylamid gel electrophoresis and subsequent Western blot analysis of urine showed the presence of heavy and light chains of immunoglobulin, transferrin, albumin, vitamin D-binding protein, transthyretin and retinol-binding protein (RBP), but no excretion of Tamm-Horsfall protein (THP). Histopathological examinations of the kidneys revealed severe membranous glomerulonephritis accompanied by tubular dilatation, tubular atrophy and interstitial fibrosis. The renal expression of megalin, the main endocytic receptor for the re-uptake of proteins in proximal tubules, RBP and THP was reduced or completely absent, indicating severe tubular dysfunction. The identified urinary proteins may be of interest as additional markers for the diagnosis of juvenile nephropathy in Bernese mountain dogs.

  18. Reno-invasive fungal infection presenting as acute renal failure: importance of renal biopsy for early diagnosis.

    Science.gov (United States)

    Ranjan, Priyadarshi; Chipde, Saurabh Sudhir; Vashistha, Saurabh; Kumari, Neeraj; Kapoor, Rakesh

    2014-11-01

    Renal zygomycosis, caused by invasive fungi, is a rare and potentially fatal infection. The patient usually presents with non-specific symptoms and renal failure. A 34-year-old male non-diabetic and without any predisposing factors for systemic fungal infection presented to the emergency department with diffuse abdominal pain, high-grade fever and acute renal failure with a serum creatinine of 6.5. A computed tomography showed bilateral diffuse globular nephromegaly. A urine smear for fungal examination showed right angle branching hyphae and kidney biopsy showed fungal hyphae within the glomeruli, tubules and interstitium. Although radiological investigations can give us a clue, the definitive diagnosis can only be made by kidney biopsy. A high index of suspicion and timely diagnosis is important for a proper management.

  19. Investigation of dentinal tubule occlusion using FIB-SEM milling and EDX.

    Science.gov (United States)

    Earl, J S; Ward, M B; Langford, R M

    2010-01-01

    The aim of this study was to evaluate in vitro the dentin tubule occluding effect of an 8% strontium acetate dentifrice (Sensodyne Rapid Relief) compared to patent dentin tubules using modern sample preparation, imaging, and analysis techniques. Etched dentin discs, either untreated or treated with the dentifrice, were analyzed by preparing cross-sections using focused ion beam scanning electron microscopy (FIB-SEM) milling, and the strontium presence mapped using energy dispersive X-ray spectroscopy (EDX). Surface imaging showed the dentifrice had coated the treated sample. Sub-surface information gained by preparing longitudinal cross-sections of the treated samples showed the tubule openings to be plugged, and EDX mapping of the cross-section confirmed enhanced strontium levels within the tubules several microns below the treatment surface. The combination of modern sample preparation, imaging, and analysis techniques employed in this study has shown that the 8% strontium acetate dentifrice occludes dentin tubules. EDX analysis has shown the presence of strontium within the dentin tubules, with elemental maps illustrating how the strontium has been incorporated into the dentin.

  20. Eps 15 Homology Domain (EHD)-1 Remodels Transverse Tubules in Skeletal Muscle.

    Science.gov (United States)

    Demonbreun, Alexis R; Swanson, Kaitlin E; Rossi, Ann E; Deveaux, H Kieran; Earley, Judy U; Allen, Madison V; Arya, Priyanka; Bhattacharyya, Sohinee; Band, Hamid; Pytel, Peter; McNally, Elizabeth M

    2015-01-01

    We previously showed that Eps15 homology domain-containing 1 (EHD1) interacts with ferlin proteins to regulate endocytic recycling. Myoblasts from Ehd1-null mice were found to have defective recycling, myoblast fusion, and consequently smaller muscles. When expressed in C2C12 cells, an ATPase dead-EHD1 was found to interfere with BIN1/amphiphysin 2. We now extended those findings by examining Ehd1-heterozygous mice since these mice survive to maturity in normal Mendelian numbers and provide a ready source of mature muscle. We found that heterozygosity of EHD1 was sufficient to produce ectopic and excessive T-tubules, including large intracellular aggregates that contained BIN1. The disorganized T-tubule structures in Ehd1-heterozygous muscle were accompanied by marked elevation of the T-tubule-associated protein DHPR and reduction of the triad linker protein junctophilin 2, reflecting defective triads. Consistent with this, Ehd1-heterozygous muscle had reduced force production. Introduction of ATPase dead-EHD1 into mature muscle fibers was sufficient to induce ectopic T-tubule formation, seen as large BIN1 positive structures throughout the muscle. Ehd1-heterozygous mice were found to have strikingly elevated serum creatine kinase and smaller myofibers, but did not display findings of muscular dystrophy. These data indicate that EHD1 regulates the maintenance of T-tubules through its interaction with BIN1 and links T-tubules defects with elevated creatine kinase and myopathy.

  1. EHD1 mediates vesicle trafficking required for normal muscle growth and tubule development

    Science.gov (United States)

    Posey, Avery D.; Swanson, Kaitlin E.; Alvarez, Manuel G.; Krishnan, Swathi; Earley, Judy E.; Band, Hamid; Pytel, Peter; McNally, Elizabeth M.; Demonbreun, Alexis R.

    2014-01-01

    EHD proteins have been implicated in intracellular trafficking, especially endocytic recycling, where they mediate receptor and lipid recycling back to the plasma membrane. Additionally, EHDs help regulate cytoskeletal reorganization and induce tubule formation. It was previously shown that EHD proteins bind directly to the C2 domains in myoferlin, a protein that regulates myoblast fusion. Loss of myoferlin impairs normal myoblast fusion leading to smaller muscles in vivo but the intracellular pathways perturbed by loss of myoferlin function are not well known. We now characterized muscle development in EHD1-null mice. EHD1-null myoblasts display defective receptor recycling and mislocalization of key muscle proteins, including caveolin-3 and Fer1L5, a related ferlin protein homologous to myoferlin. Additionally, EHD1-null myoblast fusion is reduced. We found that loss of EHD1 leads to smaller muscles and myofibers in vivo. In wildtype skeletal muscle EHD1 localizes to the transverse tubule (T-tubule), and loss of EHD1 results in overgrowth of T-tubules with excess vesicle accumulation in skeletal muscle. We provide evidence that tubule formation in myoblasts relies on a functional EHD1 ATPase domain. Moreover, we extended our studies to show EHD1 regulates BIN1 induced tubule formation. These data, taken together and with the known interaction between EHD and ferlin proteins, suggests that the EHD proteins coordinate growth and development likely through mediating vesicle recycling and the ability to reorganize the cytoskeleton. PMID:24440153

  2. Eps 15 Homology Domain (EHD-1 Remodels Transverse Tubules in Skeletal Muscle.

    Directory of Open Access Journals (Sweden)

    Alexis R Demonbreun

    Full Text Available We previously showed that Eps15 homology domain-containing 1 (EHD1 interacts with ferlin proteins to regulate endocytic recycling. Myoblasts from Ehd1-null mice were found to have defective recycling, myoblast fusion, and consequently smaller muscles. When expressed in C2C12 cells, an ATPase dead-EHD1 was found to interfere with BIN1/amphiphysin 2. We now extended those findings by examining Ehd1-heterozygous mice since these mice survive to maturity in normal Mendelian numbers and provide a ready source of mature muscle. We found that heterozygosity of EHD1 was sufficient to produce ectopic and excessive T-tubules, including large intracellular aggregates that contained BIN1. The disorganized T-tubule structures in Ehd1-heterozygous muscle were accompanied by marked elevation of the T-tubule-associated protein DHPR and reduction of the triad linker protein junctophilin 2, reflecting defective triads. Consistent with this, Ehd1-heterozygous muscle had reduced force production. Introduction of ATPase dead-EHD1 into mature muscle fibers was sufficient to induce ectopic T-tubule formation, seen as large BIN1 positive structures throughout the muscle. Ehd1-heterozygous mice were found to have strikingly elevated serum creatine kinase and smaller myofibers, but did not display findings of muscular dystrophy. These data indicate that EHD1 regulates the maintenance of T-tubules through its interaction with BIN1 and links T-tubules defects with elevated creatine kinase and myopathy.

  3. Membrane tubule formation by banana-shaped proteins with or without transient network structure

    Science.gov (United States)

    Noguchi, Hiroshi

    2016-02-01

    In living cells, membrane morphology is regulated by various proteins. Many membrane reshaping proteins contain a Bin/Amphiphysin/Rvs (BAR) domain, which consists of a banana-shaped rod. The BAR domain bends the biomembrane along the rod axis and the features of this anisotropic bending have recently been studied. Here, we report on the role of the BAR protein rods in inducing membrane tubulation, using large-scale coarse-grained simulations. We reveal that a small spontaneous side curvature perpendicular to the rod can drastically alter the tubulation dynamics at high protein density, whereas no significant difference is obtained at low density. A percolated network is intermediately formed depending on the side curvature. This network suppresses tubule protrusion, leading to the slow formation of fewer tubules. Thus, the side curvature, which is generated by protein-protein and membrane-protein interactions, plays a significant role in tubulation dynamics. We also find that positive surface tensions and the vesicle membrane curvature can stabilize this network structure by suppressing the tubulation.

  4. EHD1 mediates vesicle trafficking required for normal muscle growth and transverse tubule development.

    Science.gov (United States)

    Posey, Avery D; Swanson, Kaitlin E; Alvarez, Manuel G; Krishnan, Swathi; Earley, Judy U; Band, Hamid; Pytel, Peter; McNally, Elizabeth M; Demonbreun, Alexis R

    2014-03-15

    EHD proteins have been implicated in intracellular trafficking, especially endocytic recycling, where they mediate receptor and lipid recycling back to the plasma membrane. Additionally, EHDs help regulate cytoskeletal reorganization and induce tubule formation. It was previously shown that EHD proteins bind directly to the C2 domains in myoferlin, a protein that regulates myoblast fusion. Loss of myoferlin impairs normal myoblast fusion leading to smaller muscles in vivo but the intracellular pathways perturbed by loss of myoferlin function are not well known. We now characterized muscle development in EHD1-null mice. EHD1-null myoblasts display defective receptor recycling and mislocalization of key muscle proteins, including caveolin-3 and Fer1L5, a related ferlin protein homologous to myoferlin. Additionally, EHD1-null myoblast fusion is reduced. We found that loss of EHD1 leads to smaller muscles and myofibers in vivo. In wildtype skeletal muscle EHD1 localizes to the transverse tubule (T-tubule), and loss of EHD1 results in overgrowth of T-tubules with excess vesicle accumulation in skeletal muscle. We provide evidence that tubule formation in myoblasts relies on a functional EHD1 ATPase domain. Moreover, we extended our studies to show EHD1 regulates BIN1 induced tubule formation. These data, taken together and with the known interaction between EHD and ferlin proteins, suggests that the EHD proteins coordinate growth and development likely through mediating vesicle recycling and the ability to reorganize the cytoskeleton. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. So-called embryonal hyperplasia of Bowman's capsular epithelium: an immunohistochemical and ultrastructural study.

    Science.gov (United States)

    Ogata, K; Hajikano, H; Sakaguchi, H

    1991-01-01

    The so-called embryonal hyperplasia of Bowman's capsular epithelium (EHBCE) is a rather specific lesion occurring in kidneys of patients maintained on chronic dialysis. It consists of poorly differentiated cells proliferating around sclerosed or obsolescent glomeruli. In this study, immunohistochemical and ultrastructural characterization of EHBCE was performed. The poorly differentiated cells in the lesion exhibited a positive reaction for vimentin and a negative one for cytokeratin (PKK 1) and epithelial membrane antigen. On ultrastructural examination, specialized junctions between adjoining cells, microvilli-like structures on their surfaces, and immature basal folds were observed. These observations suggest that the cells of EHBCE may be associated with the anlage of glomerular epithelium. The background in which neoplasms like renal cell carcinoma or atypical epithelium of cyst wall develop in end-stage kidneys of adult patients on long-term dialysis may cause such a proliferation of poorly differentiated cells in young or paediatric age group patients.

  6. GLOMERULAR CAPILLARY GROWTH AND CELLULAR HYPERPLASIA IN A MODEL OF FOCAL AND SEGMENTAL GLOMERULOSCLEROSIS

    Directory of Open Access Journals (Sweden)

    John F Bertram

    2011-05-01

    Full Text Available Focal and segmental glomerulosclerosis (FSGS is a chronic renal disorder characterized by segmental glomerular lesions and widespread podocyte foot process effacement. We have previously shown that glomerular enlargement (hypertrophy precedes the development of FSGS in an animal model not previously thought to involve glomerular hypertrophy. This hypertrophy involved growth of glomerular capillaries. The aim of the present study was to determine whether the capillary growth involved an increase in the number of capillaries per glomerulus, or lengthening of existing capillaries. In addition, we examined the contribution of glomerular cell hyperplasia to the hypertrophy. We found that glomerular capillary growth in this model appears to primarily involve lengthening of existing capillaries rather that sprouting of new capillaries, and that glomerular cell proliferation contributes to the glomerular hypertrophy.

  7. Giant fibroadenomatoid hyperplasia of the breast: a case report.

    Science.gov (United States)

    Zhang, Hao; Wang, Xin-Lu; Ren, Wei-Dong; Shi, Tie-Mei

    2014-01-01

    Fibroadenomatoid hyperplasia of the breast (FAHB) is a rare benign breast lesion and its clinical features are similar to fibroadenoma and fibrocystic changes. FAHB has been previously termed sclerosing lobular hyperplasia, fibroadenomatosis, fibroadenomatoid change, or fibroadenomatoid mastopathy. Typically, FAHB is derived from stroma and epithelia. The pathologic characteristics of FAHB are microfocal lobulocentric proliferation of stroma accompanied by epithelial and myoepithelial components resembling similar histological changes, as found in fibroadenoma, apocrine hyperplasia, intraductal hyperplasia, and lobular hyperplasia. FAHB could be present as a localized or diffused pattern in pathology. Most cases show no well-circumscribed mass lesions and no apparent capsules; it is usually identified as an incidental finding in other benign lesions or in random sampling in cancerous breast tissues. FAHB is categorized as a benign proliferative breast disease and it has previously been reported; however, the authors believe this study may be the first case with two giant masses reported. Fiber adenoma hyperplasia is a rare cystic hyperplasia of breast pathology and its ultrasonographic manifestations are easily confused with breast cancer. Comparative MRI ultrasound analysis will help make the differential diagnosis.

  8. Treatment of dentinal tubules by Nd:YAG laser

    Science.gov (United States)

    Chmelíčkova, Hana; Zapletalova, Zdeňka; Peřina, Jan, Jr.; Novotný, Radko; Kubínek, Roman; Stranyánek, Martin

    2005-08-01

    Symptom of cervical dentine hypersensitivity attacks from 10% to 15% of population and causes an uncomfortable pain during contact with any matter. Sealing of open dentinal tubules is one of the methods to reach insensibility. Laser as a source of coherent radiation is used to melt dentine surface layers. Melted dentine turns to hard mass with a smooth, non-porous surface. Simulation of this therapy was made in vitro by means of LASAG Nd:YAG pulsed laser system KLS 246-102. Eighty human extracted teeth were cut horizontally to obtain samples from 2 mm to 3 mm thick. First experiments were done on cross section surfaces to find an optimal range of laser parameters. A wide range of energies from 30 mJ to 210 mJ embedded in 0,3 ms long pulse was tested. Motion in X and Y axes was ensured by a CNC driven table and the pulse frequency 15 Hz was chosen to have a suitable overlap of laser spots. Some color agents were examined with the aim to improve surface absorption. Scanning Electron Microscopy was used to evaluate all samples and provided optimal values of energies around 50 J.cm-2. Next experiments were done with the beam oriented perpendicularly to a root surface, close to the real situation. Optical fibers with the diameter of 0,6 mm and 0,2 mm were used to guide a laser beam to teeth surfaces. Laser processing heads with lens F = 100 mm and F = 50 mm were used. The best samples were investigated by means of the Atomic Force Microscopy.

  9. Anti-hyperplasia effects of Rosa rugosa polyphenols in rats with hyperplasia of mammary gland.

    Science.gov (United States)

    Chen, Tao; Li, Jingjing; Chen, Jinglou; Song, Hongping; Yang, Chuhao

    2015-03-01

    Rosa rugosa (Thunb.) is used in Chinese traditional medicine with the functions of promoting blood circulation, relieving the depressed liver and attenuating breast disorders. This study was to investigate the anti-hyperplasia effects of the polyphenols-rich fraction from R. rugosa (FRR) in rat. Rat model of hyperplasia of mammary gland (HMG) was induced by intramuscularly injected with estrogen (0.5mg/kg/d) for 25 days, and followed with progestogen (5mg/kg/d) for another 5 days. Meanwhile, FRR was orally given for 30 days. Then, the levels of estradiol and oxidative stress were assessed. The mammary expressions of AKT and JNK were evaluated by Western blot analysis. The expressions of NFκB-p65, COX-2 and VEGF were measured by immunohistochemical analysis. The whole results indicated that FRR could exert anti-hyperplasia effects in rat via modulating the mammary expression of JNK and AKT, as well as alleviating the NFκB related oxidative stress and inflammatory responses.

  10. Renal aquaporins and sodium transporters with special focus on urinary tract obstruction

    DEFF Research Database (Denmark)

    Frøkiaer, Jørgen; Li, Chunling; Shi, Yimin

    2003-01-01

    seven aquaporins are expressed at distinct sites in the kidney and 4 members of this family (AQP1-4) have been demonstrated to play pivotal roles in the physiology and pathophysiology for renal regulation of body water balance. Osmotic equilibration via renal aquaporins is maintained by active transport...... of NaCl. The major sodium transporters and channels in the individual renal tubule segments have been identified and the regulation of these transporters and channels are fundamental for renal sodium reabsorption and for establishing the driving force. In this mini-review the role of renal aquaporins...... and sodium transporters and channels is briefly described and their key role for the impaired urinary concentrating capacity in response to urinary tract obstruction is reviewed. Thus this review updates previous detailed reviews (1-5)....

  11. Focal Epithelial Hyperplasia. A Case Report

    Directory of Open Access Journals (Sweden)

    Rafael Pila Pérez

    2014-02-01

    Full Text Available Focal epithelial hyperplasia, also known as Heck's disease, is relatively rare, occurring mostly in children and adolescents. A case of a 20 year-old female patient treated at the Manuel Ascunce Domenech University Hospital in Camagüey due to papular lesions, which had evolved for ten months, is presented. Other viral diseases were ruled out; however based on histological studies, it was concluded that she suffered from Heck disease, which is frequently treated by dentists, but little known among pediatricians, internists and dermatologists. Because of its etiology, many cases are related to human papilloma virus infection. When the disease evolves, treatment can involve excision, laser surgery or cryotherapy. The latter method was used in this patient with satisfactory results, as she is completely asymptomatic.

  12. Mice lacking neurofibromin develop gastric hyperplasia

    Science.gov (United States)

    Lin, Lu; Chen, Jian; Richardson, James A.

    2009-01-01

    Gastrointestinal (GI) neoplasms are among many manifestations of the genetic disease neurofibromatosis type 1 (NF1). However, the physiological and pathological functions of the Nf1 gene in the GI system have not been fully studied, possibly because of a lack of mouse models. In this study, we generated conditional knockout mice with Nf1 deficiency in the GI tract. These mice develop gastric epithelial hyperplasia and inflammation together with increased cell proliferation and apoptosis. The gastric phenotypes observed in these mutant mice seem to be the consequence of loss of Nf1 in gastric fibroblasts, resulting in paracrine hyperactivation of the ERK pathway in the gastric epithelium. These mice provide a useful model to study the pathogenesis of GI lesions in a subset of patients with NF1 and to investigate the role of the Nf1 gene in the development of GI neoplasms. PMID:19661150

  13. Risk stratification for benign prostatic hyperplasia.

    Science.gov (United States)

    Zattoni, Fabio; Ficarra, Vincenzo; Novara, Giacomo

    2017-03-18

    Benign prostatic hyperplasia (BPH) represents an important public health problem in ageing men due to frequently associated lower urinary tract symptoms (LUTS), which may impair quality of life. BPH is also a progressive disease, mainly characterized by a worsening of LUTS over time, and in some patients by the occurrence of serious outcomes such as acute urinary retention and need for BPH-related surgery. The management of BPH and LUTS in men should move forward its focus on symptom control only. Indeed, the goals of therapy for BPH are not only to improve bothersome LUTS but also to identify those patients at risk of unfavourable outcomes in order to optimize their management and reduce complications. Risk stratification and tailored treatment should improve the reductions in both symptoms and the long-term consequences of BPH and BPH treatments. To do this, clinicians need to know possible factors that may support the develop of PBH and possible risks due to the BPH itself.

  14. Papillary endothelial hyperplasia (Masson's tumor) in children.

    Science.gov (United States)

    Liné, A; Sanchez, J; Jayyosi, L; Birembaut, P; Ohl, X; Poli-Mérol, M-L; François, C

    2016-06-23

    The intravascular papillary endothelial hyperplasia (IPEH/Masson's tumor) is a rare benign tumor of the skin and subcutaneous vessels. We report, in four pediatric cases, clinical presentation, care (diagnostic and surgical) of Masson's tumor in children. Two boys (two years) and two girls (four and six years) showed a pain subcutaneous tumor (one to five centimeters). They were in the transverse abdominal muscle, between two metatarsals, at the front of thigh and in the axilla. Imaging performed (MRI, Doppler ultrasound) evoked either a hematoma, a lymphangioma or hemangioma. The indication for removal was selected from pain and/or parental concern. The diagnosis was histologically. A lesion persisted in residual form (incomplete initial resection), and is currently not scalable for eleven years.

  15. Pulmonary Atypical Adenomatous Hyperplasia And Bronchioloalveolar Carcinoma

    Institute of Scientific and Technical Information of China (English)

    MeilinXu; XiaYang; ZhiyaoZhang

    2004-01-01

    OBJECTIVE To study the relationship between atypical adenomatous hyperplasia (AAH) and bronchioloalveolar carcinoma (BAC). METHODS Morphometric, immunohistochemical and ultrastructural analyses were performed in 4 patients with low grade AAH, 5 with high grade AAH and 7 with BAC. RESULTS The mean nuclear areas of high grade AAH and BAC were greater than those of low grade AAH (P<0.05); p53 protein expression was negative in 4 cases of low grade AAH,while the positive rates in high grade AAH and BAC were 40% (2/5) and 57% (4/7), respectively. CONCLUSION The development of BAC is stepwise. AAH appears to be a lesion closely related with BAC, probably as its genuine precursor.

  16. Congenital adrenal hyperplasia: Treatment and outcomes.

    Science.gov (United States)

    Kamoun, Mahdi; Feki, Mouna Mnif; Sfar, Mohamed Habib; Abid, Mohamed

    2013-10-01

    Congenital adrenal hyperplasia (CAH) describes a group of autosomal recessive disorders where there is impairment of cortisol biosynthesis. CAH due to 21-hydroxylase deficiency accounts for 95% of cases and shows a wide range of clinical severity. Glucocorticoid and mineralocorticoid replacement therapies are the mainstays of treatment of CAH. The optimal treatment for adults with CAH continues to be a challenge. Important long-term health issues for adults with CAH affect both men and women. These issues may either be due to the disease or to steroid treatment and may affect final height, fertility, cardiometabolic risk, bone metabolism, neuro-cognitive development and the quality-of-life. Patients with CAH should be regularly followed-up from childhood to adulthood by multidisciplinary teams who have knowledge of CAH. Optimal replacement therapy, close clinical and laboratory monitoring, early life-style interventions, early and regular fertility assessment and continuous psychological management are needed to improve outcome.

  17. Congenital adrenal hyperplasia: Treatment and outcomes

    Directory of Open Access Journals (Sweden)

    Mahdi Kamoun

    2013-01-01

    Full Text Available Congenital adrenal hyperplasia (CAH describes a group of autosomal recessive disorders where there is impairment of cortisol biosynthesis. CAH due to 21-hydroxylase deficiency accounts for 95% of cases and shows a wide range of clinical severity. Glucocorticoid and mineralocorticoid replacement therapies are the mainstays of treatment of CAH. The optimal treatment for adults with CAH continues to be a challenge. Important long-term health issues for adults with CAH affect both men and women. These issues may either be due to the disease or to steroid treatment and may affect final height, fertility, cardiometabolic risk, bone metabolism, neuro-cognitive development and the quality-of-life. Patients with CAH should be regularly followed-up from childhood to adulthood by multidisciplinary teams who have knowledge of CAH. Optimal replacement therapy, close clinical and laboratory monitoring, early life-style interventions, early and regular fertility assessment and continuous psychological management are needed to improve outcome.

  18. Microwave Treatment of Prostate Cancer and Hyperplasia

    Science.gov (United States)

    Arndt, G. Dickey; Ngo, Phong; Carl, J. R.; Raffoul, George

    2005-01-01

    Microwave ablation in the form of microwave energy applied to a heart muscle by a coaxial catheter inserted in a vein in the groin area can be used to heat and kill diseased heart cells. A microwave catheter has been developed to provide deep myocardial ablation to treat ventricular tachycardia by restoring appropriate electrical activity within the heart and eliminating irregular heartbeats. The resulting microwave catheter design, which is now being developed for commercial use in treating ventricular tachycardia, can be modified to treat prostate cancer and benign prostatic hyperplasia (BPH). Inasmuch as the occurrence of BPH is increasing currently 350,000 operations per year are performed in the United States alone to treat this condition this microwave catheter has significant commercial potential.

  19. Pseudoangiomatous stromal hyperplasia causing massive breast enlargement.

    Science.gov (United States)

    Bourke, Anita Geraldine; Tiang, Stephen; Harvey, Nathan; McClure, Robert

    2015-10-16

    Pseudoangiomatous stromal hyperplasia (PASH) of the breast is a benign mesenchymal proliferative process, initially described by Vuitch et al. We report an unusual case of a 46-year-old woman who presented with a 6-week history of bilateral massive, asymmetrical, painful enlargement of her breasts, without a history of trauma. On clinical examination, both breasts were markedly enlarged and oedematous, but there were no discrete palpable masses. Preoperative image-guided core biopsies and surgery showed PASH. PASH is increasingly recognised as an incidental finding on image-guided core biopsy performed for screen detected lesions. There are a few reported cases of PASH presenting as rapid breast enlargement. In our case, the patient presented with painful, asymmetrical, massive breast enlargement. Awareness needs to be raised of this entity as a differential diagnosis in massive, painful breast enlargement.

  20. Verrucous Hyperplasia: Case report and differential diagnosis.

    Science.gov (United States)

    Grover, Sonal; Jha, Mihir; Sharma, Bhushan; Kapoor, Shekhar; Mittal, Kumud; Parakkat, Nithin K; Shivappa, Anil B; Kaur, Ravleen

    2017-02-01

    Verrucous hyperplasia (VH) is a rare exophytic oral mucosal lesion which can transform into verrucous carcinoma (VC), its malignant but clinically similar counterpart. These entities can be distinguished by the lack of invasive growth in VH cases; as such, it is essential to include a margin with adequate depth when performing a biopsy of the epithelium of the lesion. We report an 80-year-old male patient who presented to the Bapuji Dental College & Hospital, Davangere, Karanataka, India, in 2011 with a warty whitish-pink growth on the inside of his cheek. The patient was treated with wide surgical excision of the lesion and a diagnosis of VH was made based on histopathological features. There was no evidence of recurrence at a five-year follow-up. This report highlights the histological variations, pathogenesis and differential diagnosis of VH.

  1. 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

  2. Fibroadenoma with "immature-like" type of usual ductal hyperplasia.

    Science.gov (United States)

    Bezić, Joško; Karaman, Ivana; Kunac, Nenad

    2016-01-01

    We herein report a case of the breast fibroadenoma with foci of so-called immature variant of the conventional ductal hyperplasia. This type of usual ductal hyperplasia is histologically characterised by encircling intraductal proliferation of large cells with pale to amphophilic cytoplasm and large nuclei which vary in shape and in staining quality of the chromatin. We showed here, using the cytokeratin immunohistochemistry, that the proliferating cells were not of immature but rather mature immunohistochemical phenotype. Because of the presented discordance between immature histology and mature immunohistological profile we suggest that this rare type of usual ductal hyperplasia should be called "immature-like".

  3. Maxillary sinus marrow hyperplasia in sickle cell anemia

    Energy Technology Data Exchange (ETDEWEB)

    Fernandez, M. [Dept. of Imaging, Children`s Hospital of Michigan, Detroit, MI (United States); Slovis, T.L. [Dept. of Imaging, Children`s Hospital of Michigan, Detroit, MI (United States); Whitten-Shurney, W. [Dept. of Pediatrics, Children`s Hospital of Michigan, Detroit, MI (United States)

    1995-11-01

    Marrow hyperplasia is a sequela of sickle cell anemia (SCA) and may be seen in the skull in children after 5 years of age. The facial bones, except for the mandible and orbits, are usually not involved. We report an unusual case of a 28-month-old black boy with SCA who presented with extensive marrow hyperplasia of the maxillary sinuses in addition to severe calvarial and mandibular changes. The imaging characteristics on CT (similar to other sites of marrow hyperplasia) and MR (low signal on both T{sub 1} and T{sub 2} sequences) should aid in making the correct diagnosis. (orig.)

  4. Role of renal DJ-1 in the pathogenesis of hypertension associated with increased reactive oxygen species production.

    Science.gov (United States)

    Cuevas, Santiago; Zhang, Yanrong; Yang, Yu; Escano, Crisanto; Asico, Laureano; Jones, John E; Armando, Ines; Jose, Pedro A

    2012-02-01

    The D(2) dopamine receptor (D(2)R) is important in the pathogenesis of essential hypertension. We have already reported that systemic deletion of the D(2)R gene in mice results in reactive oxygen species (ROS)-dependent hypertension, suggesting that the D(2)R has antioxidant effects. However, the mechanism of this effect is unknown. DJ-1 is a protein that has antioxidant properties. D(2)R and DJ-1 are expressed in the mouse kidney and colocalize and coimunoprecipitate in mouse renal proximal tubule cells. We hypothesized that D(2)Rs regulate renal ROS production in the kidney through regulation of DJ-1 expression or function. Heterozygous D(2)(+/-) mice have increased blood pressure, urinary 8-isoprostanes, and renal Nox 4 expression, but decreased renal DJ-1 expression. Silencing D(2)R expression in mouse renal proximal tubule cells increases ROS production and decreases the expression of DJ-1. Conversely, treatment of these cells with a D(2)R agonist increases DJ-1 expression and decreases Nox 4 expression and NADPH oxidase activity, effects that are partially blocked by a D(2)R antagonist. Silencing DJ-1 expression in mouse renal proximal tubule cells increases ROS production and Nox 4 expression. Selective renal DJ-1 silencing by the subcapsular infusion of DJ-1 siRNA in mice increases blood pressure, renal Nox4 expression, and NADPH oxidase activity. These results suggest that the inhibitory effects of D(2)R on renal ROS production are at least, in part, mediated by a positive regulation of DJ-1 expression/function and that DJ-1 may have a role in the prevention of hypertension associated with increased ROS production.

  5. Renale Osteopathie

    OpenAIRE

    Horn S

    2001-01-01

    Die renale Osteopathie umfaßt Erkrankungen des Knochens, die bei Patienten mit chronischen Nierenerkrankungen auftreten, wie den sekundären bzw. tertiären Hyperparathyreoidismus, die adynamische Knochenerkrankung und die Osteopathie nach Nierentransplantation. Durch die Identifikation des Kalzium-Sensing-Rezeptors bzw. des Vitamin D-Rezeptors hat sich unser Verständnis der Zusammenhänge in den letzten Jahren erheblich verbessert. Neue Medikamente versprechen effizientere Prophylaxe- und Thera...

  6. Renale Knochenerkrankungen

    Directory of Open Access Journals (Sweden)

    Mayer G

    2008-01-01

    Full Text Available Störungen des Mineral- und Knochenstoffwechsels sind bei fast allen Patienten mit chronischen Nierenerkrankungen anzutreffen. Pathogenetisch spielt eine Neigung zur Phosphatretention bei einer Reduktion der glomerulären Filtrationsrate die zentrale Rolle. Neben typischen, aber sehr variablen Veränderungen der Knochenstruktur (renale Osteopathie besteht auch eine sehr enge Assoziation zwischen diesen Störungen und dem massiv erhöhten kardiovaskulären Risiko der Patienten.

  7. Obesity and renal hemodynamics

    NARCIS (Netherlands)

    Bosma, R. J.; Krikken, J. A.; van der Heide, J. J. Homan; de Jong, P. E.; Navis, G. J.

    2006-01-01

    Obesity is a risk factor for renal damage in native kidney disease and in renal transplant recipients. Obesity is associated with several renal risk factors such as hypertension and diabetes that may convey renal risk, but obesity is also associated with an unfavorable renal hemodynamic profile

  8. Obesity and renal hemodynamics

    NARCIS (Netherlands)

    Bosma, R. J.; Krikken, J. A.; van der Heide, J. J. Homan; de Jong, P. E.; Navis, G. J.

    2006-01-01

    Obesity is a risk factor for renal damage in native kidney disease and in renal transplant recipients. Obesity is associated with several renal risk factors such as hypertension and diabetes that may convey renal risk, but obesity is also associated with an unfavorable renal hemodynamic profile inde

  9. 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;

    2016-01-01

    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...... (PHA-1) symptoms already on a standard diet. In the present study, we further examined the importance of αENaC in the CNT. Knock-out mice with αENaC deleted primarily in a part of the CNT (CNT-KO) were generated using Scnn1a(lox/lox) mice and Atp6v1b1::Cre mice. On a standard diet, plasma [Na...... and showed lower food intake and relative body weight, lower plasma [Na(+)], higher fractional excretion (FE) of Na(+), higher plasma [K(+)], and lower FE of K(+). The higher FE of Na(+) coincided with lower abundance and phosphorylation of the Na(+)-Cl(-) cotransporter, NCC. In conclusion, reducing ENa...

  10. Evaluation of “Dream Herb,” Calea zacatechichi, for Nephrotoxicity Using Human Kidney Proximal Tubule Cells

    Directory of Open Access Journals (Sweden)

    Miriam E. Mossoba

    2016-01-01

    Full Text Available A recent surge in the use of dietary supplements, including herbal remedies, necessitates investigations into their safety profiles. “Dream herb,” Calea zacatechichi, has long been used in traditional folk medicine for a variety of purposes and is currently being marketed in the US for medicinal purposes, including diabetes treatment. Despite the inherent vulnerability of the renal system to xenobiotic toxicity, there is a lack of safety studies on the nephrotoxic potential of this herb. Additionally, the high frequency of diabetes-associated kidney disease makes safety screening of C. zacatechichi for safety especially important. We exposed human proximal tubule HK-2 cells to increasing doses of this herb alongside known toxicant and protectant control compounds to examine potential toxicity effects of C. zacatechichi relative to control compounds. We evaluated both cellular and mitochondrial functional changes related to toxicity of this dietary supplement and found that even at low doses evidence of cellular toxicity was significant. Moreover, these findings correlated with significantly elevated levels of nephrotoxicity biomarkers, lending further support for the need to further scrutinize the safety of this herbal dietary supplement.

  11. Evaluation of “Dream Herb,” Calea zacatechichi, for Nephrotoxicity Using Human Kidney Proximal Tubule Cells

    Science.gov (United States)

    Flynn, Thomas J.; Vohra, Sanah; Wiesenfeld, Paddy; Sprando, Robert L.

    2016-01-01

    A recent surge in the use of dietary supplements, including herbal remedies, necessitates investigations into their safety profiles. “Dream herb,” Calea zacatechichi, has long been used in traditional folk medicine for a variety of purposes and is currently being marketed in the US for medicinal purposes, including diabetes treatment. Despite the inherent vulnerability of the renal system to xenobiotic toxicity, there is a lack of safety studies on the nephrotoxic potential of this herb. Additionally, the high frequency of diabetes-associated kidney disease makes safety screening of C. zacatechichi for safety especially important. We exposed human proximal tubule HK-2 cells to increasing doses of this herb alongside known toxicant and protectant control compounds to examine potential toxicity effects of C. zacatechichi relative to control compounds. We evaluated both cellular and mitochondrial functional changes related to toxicity of this dietary supplement and found that even at low doses evidence of cellular toxicity was significant. Moreover, these findings correlated with significantly elevated levels of nephrotoxicity biomarkers, lending further support for the need to further scrutinize the safety of this herbal dietary supplement. PMID:27703475

  12. 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

    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......-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...... 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...

  13. 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 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.

  14. Structural and cellular changes in fetal renal papilla during development

    Directory of Open Access Journals (Sweden)

    Laura Vinci

    2017-02-01

    Full Text Available The mature renal papilla is characterized by medullary collecting ducts, Henle’s loops, vasa recta and the interstitium. Cortical and medullary stromal cells are essential for the regulation of urine concentration and other specialized kidney functions. Mechanisms that direct the renal papilla development are not clearly understood. In recent years, the renal papilla has been identified as a niche for renal stem/progenitor cells in the adult mouse. Studies on experimental animals evidenced a probably common interstitial progenitor for the medullary and cortical stromal cells, characterized by the Foxd1+/PAX2- phenotype. Moreover, Hox10 and Hox11 expression is required for differentiation and patterning of the multiple subtypes of developing medullary interstitial cells. Given the scarcity of morphological and molecular studies on the human renal papilla, this work aimed to evidence morphological changes during human gestation, both in the architecture of the medullary interstitium and in cell types differentiating between the collecting tubules and the Henle’s loops. Future immunohistochemical studies are needed to better identify different interstitial cell types giving rise to the mature interstitium of the renal papilla.

  15. Saethre-Chotzen syndrome presenting with incomplete renal Fanconi syndrome.

    Science.gov (United States)

    Oktenli, Cagatay; Saglam, Mutlu; Zafer, Emre; Gül, Davut

    2002-10-01

    Here we report on a patient with findings of acrocephaly, craniosynostosis, low frontal hairline, ptosis of eyelids, deviated nasal septum, broad great toes, moderate hallux valgus, bilateral symmetrical complete soft tissue syndactyly of toes 2 and 3, and partial soft tissue syndactyly of toes 4 and 5 consistent with the diagnosis of Saethre-Chotzen syndrome. Additionally, the patient had some unusual findings as part of generalized dysfunction of the renal tubules including hypophosphatemia with renal phosphate wasting, normocalcemic hypercalciuria, hypomagnesemia with renal magnesium wasting, low-molecular-weight proteinuria, decreased serum PTH levels, osteopenia, and nephrolithiasis. In the light of these findings, the diagnosis of incomplete renal Fanconi syndrome was made. In conclusion, on the basis of the present findings, it is difficult to say whether renal tubular dysfunction are somehow connected to the Saethre-Chotzen syndrome or not. Therefore, we consider that this is probably just a coincident. However, further studies may show the connection between renal tubular dysfunction and Saethre-Chotzen syndrome.

  16. Cinnabar Induces Renal Inflammation and Fibrogenesis in Rats

    Directory of Open Access Journals (Sweden)

    Ying Wang

    2015-01-01

    Full Text Available The purpose of this study was to investigate whether cinnabar causes renal inflammation and fibrosis in rats. Rats were dosed orally with cinnabar (1 g/kg/day for 8 weeks or 12 weeks. The control rats were treated with solvent (5% carboxymethylcellulose solution over the same time periods, respectively. Renal mercury (RHg, urinary mercury (UHg, serum creatinine (SCr, urine kidney injury molecule 1 (KIM-1, renal pathology, and renal mediators were examined. At both 8 weeks and 12 weeks, RHg, UHg, and urine KIM-1 were significantly higher in the cinnabar group than in the control group, although SCr was unchanged. Kidney lesions in the cinnabar-treated rats occurred mainly in the tubules and interstitium, including vacuolization, protein casts, infiltration of inflammatory cells, and slight increase in interstitial collagen. In addition, mild mesangial proliferation was observed in glomeruli. Moreover, the expression of inflammatory and fibrogenic mediators was upregulated in the cinnabar group. In conclusion, cinnabar may cause kidney damage due to the accumulation of mercury, and renal inflammation and slight fibrogenesis may occur in rats. In the clinic, the potential risk of renal injury due to the prolonged consumption of cinnabar should be considered even though the agent is relatively nontoxic.

  17. Assessment of mitochondrial membrane potential in proximal tubules after hypoxia-reoxygenation.

    Science.gov (United States)

    Feldkamp, Thorsten; Kribben, Andreas; Weinberg, Joel M

    2005-06-01

    Proximal tubules develop a severe energetic deficit during hypoxia-reoxygenation (H/R) that previous studies using fluorescent potentiometric probes have suggested is characterized by sustained, partial mitochondrial deenergization. To validate the primary occurrence of mitochondrial deenergization in the process, optimize approaches for estimating changes in mitochondrial membrane potential (DeltaPsim) in the system, and clarify the mechanisms for the defect, we further investigated the behavior of 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazocarbocyanine iodide (JC-1) in these cells and introduce a more dynamic and quantitative approach employing safranin O for use with the tubule system. Although use of JC-1 can be complicated by decreases in the plasma membrane potential that limit cellular uptake of JC-1 and such behavior was demonstrated in ouabain-treated tubules, changes in DeltaPsim entirely accounted for the decreases in the formation of red fluorescent JC-1 aggregates and in the ratio of red/green fluorescence observed after H/R. The red JC-1 aggregates did not readily dissociate when tubules were deenergized after JC-1 uptake, making it unsuitable for dynamic studies of energization. Safranin O uptake by digitonin-permeabilized tubules required very small numbers of tubules, permitted measurements of DeltaPsim for relatively prolonged periods after the end of the experimental maneuvers, was rapidly reversible during deenergization, and allowed for direct assessment of both substrate-dependent, electron transport-mediated DeltaPsim, and ATP hydrolysis-supported DeltaPsim. Both types of energization measured using safranin O in tubules permeabilized after H/R were impaired, but combining substrates and ATP substantially restored DeltaPsim.

  18. Maturational changes in connexin 43 expression in the seminiferous tubules may depend on thyroid hormone action

    Science.gov (United States)

    Marchlewska, Katarzyna; Kula, Krzysztof; Walczak-Jedrzejowska, Renata; Kula, Wojciech; Oszukowska, Elzbieta; Filipiak, Eliza; Moszura, Tomasz

    2013-01-01

    Introduction Connexin 43 (Cx43) mediates the effect of thyroid hormone on Sertoli cell maturation in vitro. We investigated the influence of triiodothyronine (T3) administration on Cx43 expression in relation to the progress in seminiferous tubule maturation. Material and methods Male rats were daily injected with 100 µg T3/kg body weight from birth until postnatal day (pnd) 5 (transient treatment – tT3) or until pnd 15 (continuous treatment – cT3) or solvent – control (C). On pnd 16 serum hormone levels, body and testes weight, seminiferous tubule morphometry, Cx43 immunostaining and germ cell degeneration were investigated. Cx43 expression was also assessed in six 50-day-old adult untreated rats. Result tT3 increased 2.6-fold serum level of T3, testes weight, and seminiferous tubule diameter, and induced maturation-like dislocation of Cx43 expression from the apical to the peripheral region of Sertoli cell cytoplasm. In addition, incidence of Cx43-positive tubules declined from 86% in C to 46% after tT3, being similar to the adult value (30% of tubules Cx43-positive). In turn, cT3 increased serum T3 level 12-fold, and decreased body weight. Seminiferous tubules became shortened and distended, Sertoli cell cytoplasm vacuolated, Cx43 expression had minimal intensity and germ cell degeneration increased. Conclusions Cx43 might intermediate a short and transient stimulatory effect of T3 on seminiferous tubule maturation that disappeared together with exposure to the toxic effect of a continuously high level of the hormone. PMID:23515877

  19. New Developments in Our Understanding of Neointimal Hyperplasia.

    Science.gov (United States)

    Lee, Timmy; Ul Haq, Naveed

    2015-11-01

    The vascular access remains the lifeline for the hemodialysis patient. The most common etiology of vascular access dysfunction is venous stenosis at the vein-artery anastomosis in arteriovenous fistula and at the vein-graft anastomosis in arteriovenous grafts (AVG). This stenotic lesion is typically characterized on histology as aggressive venous neointimal hyperplasia in both arteriovenous fistula and AVG. In recent years, we have advanced our knowledge and understanding of neointimal hyperplasia in vascular access and begun testing several novel therapies. This article will (1) review recent developments in our understanding of the pathophysiology of neointimal hyperplasia development in AVG and fistula failure, (2) discuss atypical factors leading to neointimal hyperplasia development, (3) highlight key novel therapies that have been evaluated in clinical trials, and (4) discuss future opportunities and challenges to improve our understanding of vascular access dysfunction and translate this knowledge into novel and innovative therapies.

  20. Rare Posterior Pharyngeal Mass: Atypical Marginal Zone Hyperplasia.

    Science.gov (United States)

    Eliçora, Sultan Şevik; Güven, Mehmet; Varli, Ali F; Yilmaz, Mahmut S; Alponat, Selin

    2016-03-01

    Cases of posterior pharyngeal masses are quite rare, and are typically derived from schwannoma or encephalocele, or are of vascular or infectious origin. They are clinically significant due to their tendency to cause airway obstruction. The aim of this study was to present a rare atypical marginal hyperplasia case of a posterior pharyngeal wall mass. A 10-year-old male was admitted to our clinic with dyspnea. A plane-surfaced 4 × 3 × 3 cm mass was observed on the posterior pharyngeal wall upon physical examination. The patient underwent magnetic resonance imaging and surgical treatment. Following excision of material from the patient's mass, a pathologic diagnosis of atypical marginal zone hyperplasia was made. Atypical marginal zone hyperplasia of the posterior pharyngeal wall has not yet been reported in the literature. Marginal zone hyperplasia associated with a lymphoproliferative disease should be considered when making differential diagnoses of posterior pharyngeal wall masses.

  1. Axon and muscle spindle hyperplasia in the myostatin null mouse.

    Science.gov (United States)

    Elashry, Mohamed I; Otto, Anthony; Matsakas, Antonios; El-Morsy, Salah E; Jones, Lisa; Anderson, Bethan; Patel, Ketan

    2011-02-01

    Germline deletion of the myostatin gene results in hyperplasia and hypertrophy of the tension-generating (extrafusal) fibres in skeletal muscle. As this gene is expressed predominantly in myogenic tissues it offers an excellent model with which to investigate the quantitative relationship between muscle and axonal development. Here we show that skeletal muscle hyperplasia in myostatin null mouse is accompanied by an increase in nerve fibres in major nerves of both the fore- and hindlimbs. We show that axons within these nerves undergo hypertrophy. Furthermore, we provide evidence that the age-related neural atrophic process is delayed in the absence of myostatin. Finally, we show that skeletal muscle hyperplasia in the myostatin null mouse is accompanied by an increase in the number of muscle spindles (also called stretch receptors or proprioceptors). However, our work demonstrates that the mechanisms regulating intrafusal fibre hyperplasia and hypertrophy differ from those that control the aetiology of extrafusal fibres.

  2. Ortho-surgical management of condylar hyperplasia: Rare case reports.

    Science.gov (United States)

    Singh, Virendra; Verma, Ajay; Attresh, Gyanander; Batra, Jitender

    2014-01-01

    Condylar hyperplasia of the mandible is a clinical condition of over-development and growth because of excessive cellular growth of one condylar part of the mandible leading to facial asymmetry, mandibular deviation and enlargement of condyle. The elongation of the condylar neck in turn leads to malocclusion and articular dysfunction. In the past the interceptive and corrective procedures of growth and deformity in condylar hyperplasia were either condylectomy or high condylotomy. However, the deformity ceases after growth is completed. Therefore, other surgical procedures have to be undertaken to correct the manifested deformity of condylar hyperplasia. Further it has to be stressed that no single procedure can completely correct the deformity. So in addition to condylectomy, other orthognathic surgical procedures both on body and ramus and also on maxilla can be undertaken to correct the canting of occlusion. Two rare cases of unilateral hyperplasia encountered in our hospital are presented which required different lines of treatment.

  3. Bilateral Renal Mass-Renal Disorder: Tuberculosis

    Directory of Open Access Journals (Sweden)

    Ozlem Tiryaki

    2013-01-01

    Full Text Available A 30-year-old woman has presented complaining of weakness and fatigue to her primary care physician. The renal sonography is a routine step in the evaluation of new onset renal failure. When the renal masses have been discovered by sonography in this setting, the functional imaging may be critical. We reported a case about bilateral renal masses in a young female patient with tuberculosis and renal insufficiency. Magnetic resonance (MR has revealed the bilateral renal masses in patient, and this patient has been referred to our hospital for further management. The patient’s past medical and surgical history was unremarkable.

  4. Distal renal tubular acidosis

    Science.gov (United States)

    Renal tubular acidosis - distal; Renal tubular acidosis type I; Type I RTA; RTA - distal; Classical RTA ... excreting it into the urine. Distal renal tubular acidosis (Type I RTA) is caused by a defect ...

  5. Proximal renal tubular acidosis

    Science.gov (United States)

    Renal tubular acidosis - proximal; Type II RTA; RTA - proximal; Renal tubular acidosis type II ... by alkaline substances, mainly bicarbonate. Proximal renal tubular acidosis (Type II RTA) occurs when bicarbonate is not ...

  6. Reversible hard palate hyperplasia associated with amlodipine use: case report.

    Science.gov (United States)

    Wang, Xinwen; Liu, Qing; Dong, Guangying; Wang, Qintao

    2016-09-01

    Calcium channel blockers (CCBs) are medications often used in the clinical management of hypertension and coronary artery disease. Gingival enlargement is a common side effect of CCB administration with no other oral tissue hyperplasia being reported. Thus, gingival enlargement is considered to be a tissue-specific side effect of CCBs. Here, we report for the first time a case of CCB-related palate hyperplasia in a patient suffering from oral lichen planus and the possible reasons for its occurrence.

  7. Clinical associations of hepatic stellate cell (HSC) hyperplasia.

    Science.gov (United States)

    Mounajjed, Taofic; Graham, Rondell P; Sanderson, Schuyler O; Smyrk, Thomas C

    2014-07-01

    Hepatic stellate cell (HSC) hyperplasia has been principally attributed to hypervitaminosis A. There are sporadic reports of HSC hyperplasia in other conditions such as chronic biliary disease and hepatitis C, but clinical associations of this entity have not been studied in detail. We aimed to investigate the clinical associations of HSC hyperplasia aside from hypervitaminosis A. We identified 34 patients whose liver histology showed HSC hyperplasia. We reviewed the liver samples; additional histologic findings in addition to HSC hyperplasia were consolidated into a histologic diagnosis. We collected clinical, laboratory, and radiologic data; the histologic diagnosis was combined with this data to reach an "overall diagnosis." Four patients had hypervitaminosis A (all native livers). In native livers (n = 24), HSC hyperplasia also occurred in association with drug-induced hepatitis [n = 6, niacin was the most common inducing agent (n = 3)], reactive hepatitis (n = 4), chronic hepatitis C (n = 4), autoimmune hepatitis (n = 3), steatohepatitis (n = 1), chronic biliary disease (n = 1), and portal venopathy (n = 1). In liver allografts (n = 10), HSC hyperplasia was seen in protocol biopsies without other significant abnormalities (n = 5), chronic biliary disease (n = 4), and acute cellular rejection (n = 1). All patients used medications (total of 99) and 82 % were on multiple medications. HSC hyperplasia is an uncommon and relatively nonspecific finding that most commonly occurs in multimedicated patients, often in the absence of hypervitaminosis A. Associated conditions include drug toxicity (such as niacin), post-liver transplant setting, reactive hepatitis (due to systemic illness or inflammatory disorders of the gastrointestinal tract), and chronic liver disease.

  8. Paediatric cyclical Cushing's disease due to corticotroph cell hyperplasia.

    LENUS (Irish Health Repository)

    Noctor, E

    2015-06-01

    Cushing\\'s disease is very rare in the paediatric population. Although uncommon, corticotroph hyperplasia causing Cushing\\'s syndrome has been described in the adult population, but appears to be extremely rare in children. Likewise, cyclical cortisol hypersecretion, while accounting for 15 % of adult cases of Cushing\\'s disease, has only rarely been described in the paediatric population. Here, we describe a very rare case of a 13-year old boy with cyclical cortisol hypersecretion secondary to corticotroph cell hyperplasia.

  9. A Rare Case of Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia

    OpenAIRE

    Godwin Ofikwu; Mani, Vishnu R.; Ajai Rajabalan; Albert Adu; Leaque Ahmed; Dennis Vega

    2015-01-01

    Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a rare clinical condition with only about 100 cases reported in the literature. It is characterized by primary hyperplasia of pulmonary neuroendocrine cells (PNECs) which are specialized epithelial cells located throughout the entire respiratory tract, from the trachea to the terminal airways. DIPNECH appears in various forms that include diffuse proliferation of scattered neuroendocrine cells, small nodules, or a linea...

  10. Proteus syndrome: MRI characteristics of plantar cerebriform hyperplasia

    Energy Technology Data Exchange (ETDEWEB)

    Vanhoenacker, F.M.; Beuckeleer, L.H. de; Schepper, A.M. de [Dept. of Radiology, University Hospital Antwerp, Edegem (Belgium); Deprettere, A. [Dept. of Pediatrics, University Hospital Antwerp, Edegem (Belgium); Moor, A. de [Dept. of Dermatology, Univ. Hospital Antwerp, Edegem (Belgium)

    2000-02-01

    Proteus syndrome is a rare congenital hamartomatous syndrome with a variety of abnormalities. It shares many features with other congenital hamartomatous disorders, but cerebriform hyperplasia of the soles and the palms is known as a quite distinctive characteristic in the dermatologic literature. The purpose of this case report is to demonstrate the MRI features of plantar cerebriform hyperplasia in a 9-year-old boy with known Proteus syndrome. (orig.)

  11. Oral focal epithelial hyperplasia: report of five cases

    OpenAIRE

    Borborema-Santos,Cristina Maria; Castro,Maria Marta de; Santos,Paulo José Benevides dos; Talhari,Sinésio; Astolfi-Filho, Spartaco

    2006-01-01

    Focal epithelial hyperplasia or Heck's disease is a rare contagious disease caused by human papillomavirus types 13 or 32, initially described among Native American populations. This condition is characterized by the occurrence of multiple small papules or nodules in oral cavity, especially on labial and buccal mucosa and tongue. This report describes the diagnosis of focal epithelial hyperplasia in five Central Amazonian Indians who sought treatment at the Amazonas State Foundation of Tropic...

  12. Focal epithelial hyperplasia. A rare disease in our area.

    Science.gov (United States)

    Segura-Saint-Gerons, Rafael; Toro-Rojas, Mariano; Ceballos-Salobreña, Alejandro; Aparicio-Soria, Jose Luis; Fuentes-Vaamonde, Helena

    2005-01-01

    Focal epithelial hyperplasia is a benign, asymptomatic disease, occurring with very low frequency within our population. It appears as papules, principally on the lower lip, although it can also be found on the retro-commissural mucosa and tongue, and less frequently on the upper lip, gingiva and palate. We present the clinical case of a 9-year-old Saharan girl with lesions that clinically and histologically corresponded to a focal epithelial hyperplasia.

  13. Role of claudins in renal calcium handling

    Directory of Open Access Journals (Sweden)

    Armando Luis Negri

    2015-07-01

    Full Text Available Paracellular channels occurring in tight junctions play a major role in transepithelial ionic flows. This pathway includes a high number of proteins, such as claudins. Within renal epithelium, claudins result in an ionic selectivity in tight junctions. Ascending thick limb of loop of Henle (ATLH is the most important segment for calcium reabsorption in renal tubules. Its cells create a water-proof barrier, actively transport sodium and chlorine through a transcellular pathway, and provide a paracellular pathway for selective calcium reabsorption. Several studies have led to a model of paracellular channel consisting of various claudins, particularly claudin-16 and 19. Claudin-16 mediates cationic paracellular permeability in ATLH, whereas claudin-19 increases cationic selectivity of claudin-16 by blocking anionic permeability. Recent studies have shown that claudin-14 promoting activity is only located in ATLH. When co-expressed with claudin-16, claudin-14 inhibits the permeability of claudin-16 and reduces paracellular permeability to calcium. Calcium reabsorption process in ATLH is closely regulated by calcium sensor receptor (CaSR, which monitors circulating Ca levels and adjusts renal excretion rate accordingly. Two microRNA, miR-9 and miR-374, are directly regulated by CaSR. Thus, miR-9 and miR-374 suppress mRNA translation for claudin-14 and induce claudin-14 decline.

  14. Effect of YM218, a nonpeptide vasopressin V(1A) receptor-selective antagonist, on rat mesangial cell hyperplasia and hypertrophy.

    Science.gov (United States)

    Tahara, Atsuo; Tsukada, Junko; Tomura, Yuichi; Suzuki, Takeshi; Yatsu, Takeyuki; Shibasaki, Masayuki

    2007-06-01

    Mesangial cell growth constitutes a key feature of progressive glomerular injury. Vasopressin (AVP), a potent peptide vasoconstrictor, acts on mesangial cells through the V(1A) receptors, inducing contraction and cell proliferation. This study examined the effects of YM218, a nonpeptide AVP V(1A) receptor-selective antagonist, on the mitogenic and hypertrophic effects of AVP in rat mesangial cells. When added to mesangial cells whose growth was arrested, AVP concentration-dependently induced hyperplasia and hypertrophy. YM218 potently prevented AVP-induced hyperplasia and hypertrophy of these cells. Furthermore, AVP stimulated endothelin (ET)-1 secretion from mesangial cells in a concentration-dependent manner and this effect was potently inhibited by YM218. ET-1 also induced hyperplasia and hypertrophy in mesangial cells and this effect was completely abolished by ET(A) receptor-selective antagonist YM598. In addition, AVP-induced hyperplasia and hypertrophy were partly inhibited by YM598. These results suggest that AVP may modulate mesangial cell growth not only by its direct action but also through the stimulation of ET-1 secretion. YM218 displays high potency in inhibiting the AVP-induced physiologic responses of mesangial cells via the V(1A) receptors and is a potent pharmacologic probe for investigating the physiologic and pathophysiologic roles of AVP in several renal diseases.

  15. Renal tuberculosis

    Directory of Open Access Journals (Sweden)

    Džamić Zoran

    2016-01-01

    Full Text Available Tuberculosis is still a significant health problem in the world, mostly in developing countries. The special significance lies in immunocompromised patients, particularly those suffering from the HIV. Urogenital tuberculosis is one of the most common forms of extrapulmonary tuberculosis, while the most commonly involved organ is the kidney. Renal tuberculosis occurs by hematogenous dissemination of mycobacterium tuberculosis from a primary tuberculosis foci in the body. Tuberculosis is characterized by the formation of pathognomonic lesions in the tissues - granulomata. These granulomata may heal spontaneously or remain stable for years. In certain circumstances in the body associated with immunosuppression, the disease may be activated. Central caseous necrosis occurs within tuberculoma, leading to formation of cavities that destroy renal parenchyma. The process may gain access to the collecting system, forming the caverns. In this way, infection can be spread distally to renal pelvis, ureter and bladder. Scaring of tissue by tuberculosis process may lead to development of strictures of the urinary tract. The clinical manifestations are presented by nonspecific symptoms and signs, so tuberculosis can often be overlooked. Sterile pyuria is characteristic for urinary tuberculosis. Dysuric complaints, flank pain or hematuria may be presented in patients. Constitutional symptoms of fever, weight loss and night sweats are presented in some severe cases. Diagnosis is made by isolation of mycobacterium tuberculosis in urine samples, by cultures carried out on standard solid media optimized for mycobacterial growth. Different imaging studies are used in diagnostics - IVU, CT and NMR are the most important. Medical therapy is the main modality of tuberculosis treatment. The first line anti-tuberculosis drugs include isoniazid, rifampicin, pyrazinamide and ethambutol. Surgical treatment is required in some cases, to remove severely damaged kidney, if

  16. Renal stem cells and their implications for kidney cancer.

    Science.gov (United States)

    Axelson, Håkan; Johansson, Martin E

    2013-02-01

    The renal cell carcinomas (RCC) denote a diverse set of neoplasias with unique genetic and histological features. The RCCs emanate from the renal tubule, a highly heterogeneous epithelial structure, and depending on which cell is malignified the resulting cancer displays unique characteristics. Notwithstanding this, the cells of origin for the RCC forms are far from established, and only inferred by the accumulated weight of marker similarities, not always providing an unequivocal picture. The tubular epithelium is normally mitotically quiescent, but demonstrates a considerable regenerative capacity upon renal injury. Recently the hypothesis that regeneration is driven by adult stem cells has been added experimental support, providing further complexity to the issue of renal carcinogenesis. Whether these cells are linked to RCC is an open question. In the present review we therefore present the prevailing theories regarding kidney regeneration, since a better understanding of this process might be of relevance when considering the different malignancies that arise from kidney epithelium. Our own results show that papillary renal cell carcinoma displays considerable similarities to proximal tubular progenitor cells and we suggest that this tumor form may develop in a multi-step fashion via benign renal adenomas. The putative connection between renal stem cells and carcinomas is, however, not clarified, since the current understanding of the renal stem cell system is not complete. It is clear that the efforts to isolate and characterize renal progenitor/stem cells suffer from numerous technical limitations and that it remains likely that the kidney harbors different stem cell pools with a restricted differentiation potential.

  17. Role of megalin and cubilin in renal physiology and pathophysiology.

    Science.gov (United States)

    Christensen, E I; Nielsen, R

    2007-01-01

    Megalin and cubilin are endocytic receptors highly expressed in the endocytic apparatus of the renal proximal tubule. These receptors appear to be responsible for the tubular clearance of most proteins filtered in the glomeruli. Cubilin is a peripheral membrane protein, and therefore it does not have an endocytosis signaling sequence. It appears that megalin is responsible for internalization of cubilin and its ligands in addition to internalizing its own ligands. The proteinuria observed in megalin-deficient mice, in dogs lacking functional cubilin, and in patients with distinct mutations of the cubilin gene illustrates the importance of the receptors.

  18. Renale Osteopathie

    Directory of Open Access Journals (Sweden)

    Horn S

    2001-01-01

    Full Text Available Die renale Osteopathie umfaßt Erkrankungen des Knochens, die bei Patienten mit chronischen Nierenerkrankungen auftreten, wie den sekundären bzw. tertiären Hyperparathyreoidismus, die adynamische Knochenerkrankung und die Osteopathie nach Nierentransplantation. Durch die Identifikation des Kalzium-Sensing-Rezeptors bzw. des Vitamin D-Rezeptors hat sich unser Verständnis der Zusammenhänge in den letzten Jahren erheblich verbessert. Neue Medikamente versprechen effizientere Prophylaxe- und Therapiemöglichkeiten. Wir beeinflussen dadurch nicht nur die Morbidität und Lebensqualität, sondern auch die Mortalität unserer Patienten.

  19. Segment-specific Ca(2+) transport by isolated Malpighian tubules of Drosophila melanogaster: A comparison of larval and adult stages.

    Science.gov (United States)

    Browne, Austin; O'Donnell, Michael J

    2016-04-01

    Haemolymph calcium homeostasis in insects is achieved through the regulation of calcium excretion by Malpighian tubules in two ways: (1) sequestration of calcium within biomineralized granules and (2) secretion of calcium in soluble form within the primary urine. Using the scanning ion-selective electrode technique (SIET), basolateral Ca(2+) transport was measured at the distal, transitional, main and proximal tubular segments of anterior tubules isolated from both 3rd instar larvae and adults of the fruit fly Drosophila melanogaster. Basolateral Ca(2+) transport exceeded transepithelial secretion by 800-fold and 11-fold in anterior tubules of larvae and adults, respectively. The magnitude of Ca(2+) fluxes across the distal tubule of larvae and adults were larger than fluxes across the downstream segments by 10 and 40 times, respectively, indicating a dominant role for the distal segment in whole animal Ca(2+) regulation. Basolateral Ca(2+) transport across distal tubules of Drosophila varied throughout the life cycle; Ca(2+) was released by distal tubules of larvae, taken up by distal tubules of young adults and was released once again by tubules of adults ⩾ 168 h post-eclosion. In adults and larvae, SIET measurements revealed sites of both Ca(2+) uptake and Ca(2+) release across the basolateral surface of the distal segment of the same tubule, indicating that Ca(2+) transport is bidirectional. Ca(2+) uptake across the distal segment of tubules of young adults and Ca(2+) release across the distal segment of tubules of older adults was also suggestive of reversible Ca(2+) storage. Our results suggest that the distal tubules of D. melanogaster are dynamic calcium stores which allow efficient haemolymph calcium regulation through active Ca(2+) sequestration during periods of high dietary calcium intake and passive Ca(2+) release during periods of calcium deficiency.

  20. Renal disease in pregnancy.

    Science.gov (United States)

    Thorsen, Martha S; Poole, Judith H

    2002-03-01

    Anatomic and physiologic adaptations within the renal system during pregnancy are significant. Alterations are seen in renal blood flow and glomerular filtration, resulting in changes in normal renal laboratory values. When these normal renal adaptations are coupled with pregnancy-induced complications or preexisting renal dysfunction, the woman may demonstrate a reduction of renal function leading to an increased risk of perinatal morbidity and mortality. This article will review normal pregnancy adaptations of the renal system and discuss common pregnancy-related renal complications.