WorldWideScience

Sample records for renal sodium-phosphate cotransporters

  1. Autosomal recessive hypophosphataemic rickets with hypercalciuria is not caused by mutations in the type II renal sodium/phosphate cotransporter gene.

    NARCIS (Netherlands)

    Heuvel, L.P.W.J. van den; Koul, K. Op de; Knots, E.; Knoers, N.V.A.M.; Monnens, L.A.H.

    2001-01-01

    BACKGROUND: At present the genetic defect for autosomal recessive and autosomal dominant hypophosphataemic rickets with hypercalciuria (HHRH) is unknown. Type II sodium/phosphate cotransporter (NPT2) gene is a serious candidate for being the causative gene in either or both autosomal recessive and

  2. Functional interaction between CFTR and the sodium-phosphate co-transport type 2a in Xenopus laevis oocytes.

    Directory of Open Access Journals (Sweden)

    Naziha Bakouh

    Full Text Available A growing number of proteins, including ion transporters, have been shown to interact with Cystic Fibrosis Transmembrane conductance Regulator (CFTR. CFTR is an epithelial chloride channel that is involved in Cystic Fibrosis (CF when mutated; thus a better knowledge of its functional interactome may help to understand the pathophysiology of this complex disease. In the present study, we investigated if CFTR and the sodium-phosphate co-transporter type 2a (NPT2a functionally interact after heterologous expression of both proteins in Xenopus laevis oocytes.NPT2a was expressed alone or in combination with CFTR in X. laevis oocytes. Using the two-electrode voltage-clamp technique, the inorganic phosphate-induced current (IPi was measured and taken as an index of NPT2a activity. The maximal IPi for NPT2a substrates was reduced when CFTR was co-expressed with NPT2a, suggesting a decrease in its expression at the oolemna. This was consistent with Western blot analysis showing reduced NPT2a plasma membrane expression in oocytes co-expressing both proteins, whereas NPT2a protein level in total cell lysate was the same in NPT2a- and NPT2a+CFTR-oocytes. In NPT2a+CFTR- but not in NPT2a-oocytes, IPi and NPT2a surface expression were increased upon PKA stimulation, whereas stimulation of Exchange Protein directly Activated by cAMP (EPAC had no effect. When NPT2a-oocytes were injected with NEG2, a short amino-acid sequence from the CFTR regulatory domain that regulates PKA-dependent CFTR trafficking to the plasma membrane, IPi values and NPT2a membrane expression were diminished, and could be enhanced by PKA stimulation, thereby mimicking the effects of CFTR co-expression.We conclude that when both CFTR and NPT2a are expressed in X. laevis oocytes, CFTR confers to NPT2a a cAMPi-dependent trafficking to the membrane. This functional interaction raises the hypothesis that CFTR may play a role in phosphate homeostasis.

  3. Kidney injury after sodium phosphate solution beyond the acute renal failure.

    Science.gov (United States)

    Fernández-Juárez, Gema; Parejo, Leticia; Villacorta, Javier; Tato, Ana; Cazar, Ramiro; Guerrero, Carmen; Marin, Isabel Martinez; Ocaña, Javier; Mendez-Abreu, Angel; López, Katia; Gruss, Enrique; Gallego, Eduardo

    2016-01-01

    Screening colonoscopy with polipectomy reduces colonorectal cancer incidence and mortality. An adequate bowel cleansing is one of the keys to achieving best results with this technique. Oral sodium phosphate solution (OSP) had a widespread use in the 90s decade. Its efficacy was similar to polyethylene glycol (PEG) solution, but with less cost and convenient administration. Series of patients with acute renal failure due to OSP use have been reported. However, large cohorts of patients found no difference in the incidence of renal damage between these two solutions. From 2006 to 2009 we identified twelve cases of phosphate nephropathy after colonoscopy prepared with OSP. All patients were followed up to six months. All patients had received just a single dose. We analyzed 12 cases with phosphate nephropathy; three patients debuted with AKI and nine patients had chronic renal injury. Four cases were confirmed with renal biopsy. One patient with AKI needed hemodialysis at diagnosis without subsequent recovery. Two patients (both with chronic damage) fully recovered their previous renal function. The remaining patients (nine) had an average loss of estimated glomerular filtration rate of 24ml/min/1.73m(2). The use of OSP can lead to both acute and chronic renal damage. However, chronic injury was the most common pattern. Both forms of presentation imply a significant and irreversible loss of renal function. Further studies analyzing renal damage secondary to bowel cleaning should consider these two different patterns of injury. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

  4. Hemodialysis for near-fatal sodium phosphate toxicity in a child receiving sodium phosphate enemas.

    Science.gov (United States)

    Becknell, Brian; Smoyer, William E; O'Brien, Nicole F

    2014-11-01

    This study aimed to demonstrate the importance of considering hemodialysis as a treatment option in the management of sodium phosphate toxicity. This is a case report of a 4-year-old who presented to the emergency department with shock, decreased mental status, seizures, and tetany due to sodium phosphate toxicity from sodium phosphate enemas. Traditional management of hyperphosphatemia with aggressive hydration and diuretics was insufficient to reverse the hemodynamic and neurological abnormalities in this child. This is the first report of the use of hemodialysis in a child without preexisting renal failure for the successful management of near-fatal sodium phosphate toxicity. Hemodialysis can safely be used as an adjunctive therapy in sodium phosphate toxicity to rapidly reduce serum phosphate levels and increase serum calcium levels in children not responding to conventional management.

  5. Water transport by the renal Na(+)-dicarboxylate cotransporter

    DEFF Research Database (Denmark)

    Meinild, A K; Loo, D D; Pajor, A M

    2000-01-01

    . This solute-coupled influx of water took place in the absence of, and even against, osmotic gradients. There was a strict stoichiometric relationship between Na(+), substrate, and water transport of 3 Na(+), 1 dicarboxylate, and 176 water molecules/transport cycle. These results indicate that the renal Na......This study investigated the ability of the renal Na(+)-dicarboxylate cotransporter, NaDC-1, to transport water. Rabbit NaDC-1 was expressed in Xenopus laevis oocytes, cotransporter activity was measured as the inward current generated by substrate (citrate or succinate), and water transport...... was monitored by the changes in oocyte volume. In the absence of substrates, oocytes expressing NaDC-1 showed an increase in osmotic water permeability, which was directly correlated with the expression level of NaDC-1. When NaDC-1 was transporting substrates, there was a concomitant increase in oocyte volume...

  6. Human Sodium Phosphate Transporter 4 (hNPT4/SLC17A3) as a Common Renal Secretory Pathway for Drugs and Urate*

    Science.gov (United States)

    Jutabha, Promsuk; Anzai, Naohiko; Kitamura, Kenichiro; Taniguchi, Atsuo; Kaneko, Shuji; Yan, Kunimasa; Yamada, Hideomi; Shimada, Hidetaka; Kimura, Toru; Katada, Tomohisa; Fukutomi, Toshiyuki; Tomita, Kimio; Urano, Wako; Yamanaka, Hisashi; Seki, George; Fujita, Toshiro; Moriyama, Yoshinori; Yamada, Akira; Uchida, Shunya; Wempe, Michael F.; Endou, Hitoshi; Sakurai, Hiroyuki

    2010-01-01

    The evolutionary loss of hepatic urate oxidase (uricase) has resulted in humans with elevated serum uric acid (urate). Uricase loss may have been beneficial to early primate survival. However, an elevated serum urate has predisposed man to hyperuricemia, a metabolic disturbance leading to gout, hypertension, and various cardiovascular diseases. Human serum urate levels are largely determined by urate reabsorption and secretion in the kidney. Renal urate reabsorption is controlled via two proximal tubular urate transporters: apical URAT1 (SLC22A12) and basolateral URATv1/GLUT9 (SLC2A9). In contrast, the molecular mechanism(s) for renal urate secretion remain unknown. In this report, we demonstrate that an orphan transporter hNPT4 (human sodium phosphate transporter 4; SLC17A3) was a multispecific organic anion efflux transporter expressed in the kidneys and liver. hNPT4 was localized at the apical side of renal tubules and functioned as a voltage-driven urate transporter. Furthermore, loop diuretics, such as furosemide and bumetanide, substantially interacted with hNPT4. Thus, this protein is likely to act as a common secretion route for both drugs and may play an important role in diuretics-induced hyperuricemia. The in vivo role of hNPT4 was suggested by two hyperuricemia patients with missense mutations in SLC17A3. These mutated versions of hNPT4 exhibited reduced urate efflux when they were expressed in Xenopus oocytes. Our findings will complete a model of urate secretion in the renal tubular cell, where intracellular urate taken up via OAT1 and/or OAT3 from the blood exits from the cell into the lumen via hNPT4. PMID:20810651

  7. Effects of 1alpha-hydroxycholecalciferol on growth performance, parameters of tibia and plasma, meat quality, and type IIb sodium phosphate cotransporter gene expression of one- to twenty-one-day-old broilers.

    Science.gov (United States)

    Han, J C; Yang, X D; Zhang, T; Li, H; Li, W L; Zhang, Z Y; Yao, J H

    2009-02-01

    This experiment was conducted to investigate the effects of 1alpha-hydroxycholecalciferol (1alpha-OH D3) on the growth performance, tibia and plasma parameters, nutrient utilization, meat quality of the breast and thigh, and type IIb sodium phosphate cotranspoter gene expression of broilers. A total of 96 males of 1-d-old Arbor Acres broilers were randomly assigned to 8 cages of 12 birds each. Two dietary treatments were applied to 4 cages each. Diet 1 was prepared as the basal diet (nonphytate phosphorus, 0.21%), whereas diet 2 was the basal diet supplemented with 5 microg/kg of 1alpha-OH D3. Results showed that supplementation of the basal diet with 1alpha-OH D3 increased growth performance, tibia ash and strength, plasma inorganic phosphate concentration, utilization of total phosphorus and nonphytate phosphorus, lightness and yellowness of the breast and thigh meat, and intestinal type IIb sodium phosphate cotranspoter mRNA expression, whereas it decreased the shear force and water-holding capacity of the thigh meat. These data suggest that the addition of 1alpha-OH D3 might improve growth performance, tibia development, and meat quality in 1- to 21-d-old broilers by increasing the absorption and retention of phosphorus.

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

    Science.gov (United States)

    Rojas-Vega, Lorena; Gamba, Gerardo

    2016-01-01

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

  9. Oral sodium phosphate solution: a review of its use as a colorectal cleanser.

    Science.gov (United States)

    Curran, Monique P; Plosker, Greg L

    2004-01-01

    with bowel obstructions, small intestinal disorders, poor gut motilderly and those with bowel obstructions, small intestinal disorders, poor gut motility, renal insufficiency, cardiovascular disease or taking concomitant medication) or in patients ingesting more than the recommended dosage. Changes in the colonic mucosa have been reported in patients treated with oral sodium phosphate solution; however, the exact role of this agent in the appearance of these changes has not been fully clarified. The tolerability profile of oral sodium phosphate solution was similar to, or significantly better than, that of PEG or other colorectal cleansing regimens. Oral sodium phosphate solution was generally significantly more acceptable than PEG or other colorectal cleansing regimens. Oral sodium phosphate solution had similar tolerability, but was considered to be more acceptable than commercially available oral sodium phosphate tablets prior to colonoscopy (data from one study).

  10. Renal glucose handling in diabetes and sodium glucose cotransporter 2 inhibition

    Directory of Open Access Journals (Sweden)

    Resham Raj Poudel

    2013-01-01

    Full Text Available The kidneys play a major role in glucose homeostasis through its utilization, gluconeogenesis, and reabsorption via sodium glucose cotransporters (SGLTs. The defective renal glucose handling from upregulation of SGLTs, mainly the SGLT2, plays a fundamental role in the pathogenesis of type 2 diabetes mellitus. Genetic mutations in a SGLT2 isoform that results in benign renal glycosuria, as well as clinical studies with SGLT2 inhibitors in type 2 diabetes support the potential of this approach. These studies indicate that inducing glycosuria by suppressing SGLT2 can reduce plasma glucose and A1c levels, as well as decrease weight, resulting in improved β-cell function and enhanced insulin sensitivity in liver and muscle. Because the mechanism of SGLT2 inhibition is independent of insulin secretion and sensitivity, these agents can be combined with other antidiabetic agents, including exogenous insulin. This class represents a novel therapeutic approach with potential for the treatment of both type 2 and type 1 diabetes.

  11. Lowering Plasma Glucose Concentration by Inhibiting Renal Sodium-Glucose Co-Transport

    Science.gov (United States)

    Abdul-Ghani, Muhammad A; DeFronzo, Ralph A

    2017-01-01

    Maintaining normoglycaemia not only reduces the risk of diabetic microvascular complications but also corrects the metabolic abnormalities that contribute to the development and progression of hyperglycaemia (i.e. insulin resistance and beta-cell dysfunction). Progressive beta-cell failure, in addition to the multiple side effects associated with many current antihyperglycaemic agents (e.g., hypoglycaemia and weight gain) presents major obstacle to the achievement of the recommended goal of glycaemic control in patients with diabetes mellitus (DM). Thus, novel effective therapies are needed for optimal glucose control in subjects with DM. Recently, specific inhibitors of renal sodium glucose cotransporter 2 (SGLT2) have been developed to produce glucosuria and lower the plasma glucose concentration. Because of their unique mechanism of action (which is independent of the secretion and action of insulin), these agents are effective in lowering the plasma glucose concentration in all stages of DM and can be combined with all other antidiabetic agents. In this review, we summarize the available data concerning the mechanism of action, efficacy and safety of this novel class of antidiabetic agent. PMID:24690096

  12. Renal sodium-glucose cotransporter inhibition in the management of type 2 diabetes mellitus

    Science.gov (United States)

    Abdul-Ghani, Muhammad A.; Norton, Luke

    2015-01-01

    Hyperglycemia is the primary factor responsible for the microvascular, and to a lesser extent macrovascular, complications of diabetes. Despite this well-established relationship, approximately half of all type 2 diabetic patients in the US have a hemoglobin A1c (HbA1c) ≥7.0%. This is associated in part with the side effects, i.e., weight gain and hypoglycemia, of currently available antidiabetic agents and in part with the failure to utilize medications that reverse the basic pathophysiological defects present in patients with type 2 diabetes. The kidney has been shown to play a central role in the development of hyperglycemia by excessive production of glucose throughout the sleeping hours and enhanced reabsorption of filtered glucose by the renal tubules secondary to an increase in the threshold at which glucose spills into the urine. Recently, a new class of antidiabetic agents, the sodium-glucose cotransporter 2 (SGLT2) inhibitors, has been developed and approved for the treatment of patients with type 2 diabetes. In this review, we examine their mechanism of action, efficacy, safety, and place in the therapeutic armamentarium. Since the SGLT2 inhibitors have a unique mode of action that differs from all other oral and injectable antidiabetic agents, they can be used at all stages of the disease and in combination with all other antidiabetic medications. PMID:26354881

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

    Science.gov (United States)

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

    2016-09-01

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

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

    Directory of Open Access Journals (Sweden)

    Mizerski Grzegorz

    2015-09-01

    Full Text Available 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 administration of dapagliflozin, a selective SGLT2 inhibitor, in patients with type 2 diabetes, is associated with the reduction of HbA1c concentration by 0.45-1.11%. Additional benefits from the treatment with dapagliflozin are the reduction of arterial blood pressure and a permanent reduction of body weight. This outcome is related to the effect of osmotic diuresis and to the considerable loss of the glucose load by way of urine excretion. Dapagliflozin may be successfully applied in type 2 diabetes monotherapy, as well as in combined therapy (including insulin, where it is equally effective as other oral anti-diabetic drugs. Of note: serious adverse effects of dapagliflozin administration are rarely observed. What is more, episodes of severe hypoglycaemia related with the treatment occur only sporadically, most often in the course of diabetes polytherapy. The most frequent effects of the SGLT2 inhibitors are inseparably associated with the mechanism of their action (the glucuretic effect, and cover urogenital infections with a mild clinical course. At present, clinical trials are being continued of the administration of several subsequent drugs from this group, the most advanced of these being the use of canagliflozin and empagliflozin.

  15. Cloning and expression of sheep renal K-CI cotransporter-1.

    Science.gov (United States)

    Zhang, Jin J; Misri, Sandeep; Adragna, Norma C; Gagnon, Kenneth B E; Fyffe, Robert E W; Lauf, Peter K

    2005-01-01

    Sheep K-Cl cotransporter-1(shKCC1) cDNA was cloned from kidney by RT-PCR with an open reading frame of 3258 base pairs exhibiting 92%, 90%, 88% and 87% identity with pig, rabbit and human, rat and mouse KCC1 cDNAs, respectively, encoding an approximately 122 kDa polypeptide of 1086-amino acids. Hydropathy analysis reveals the familiar KCC1 topology with 12 transmembrane domains (TMDs) and the hydrophilic NH2-terminal (NTD) and COOH-terminal (CTD) domains both at the cytoplasmic membrane face. However, shKCC1 has two rather than one large extracellular loops (ECL): ECL3 between TMDs 5 and 6, and ECL6, between TMDs 11 and 12. The translated shKCC1 protein differs in 12 amino acid residues from other KCC1s, mainly within the NTD, ECL3, ICL4, ECL6, and CTD. Notably, a tyrosine residue at position 996 replaces aspartic acid conserved in all other species. Human embryonic kidney (HEK293) cells and mouse NIH/3T3 fibroblasts, transiently transfected with shKCCI-cDNA, revealed the glycosylated approximately 150 kDa proteins by Western blots and positive immunofluorescence-staining with polyclonal rabbit anti-ratKCC1 antibodies. ShKCC1 was functionally expressed in NIH/3T3 cells by an elevated basal Cl-dependent K influx measured with Rb as K-congener that was stimulated three-fold by the KCC-activator N-ethylmaleimide. Copyright (c) 2005 S. Karger AG, Basel.

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

    Science.gov (United States)

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

    2017-01-01

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

  17. Hemodynamic and renal implications of sodium-glucose cotransporter- 2 inhibitors in type 2 diabetes mellitus.

    Science.gov (United States)

    Tejedor Jorge, Alberto

    2016-11-01

    In DM2, there is increased expression of the proximal glucose transporter SGLT2. The increased glucose reabsorption from the urine to the proximal tubule and subsequently to the bloodstream, has three direct effects on the prognosis of patients with DM2: a) it increases the daily glucose load by raising the renal threshold for glucose, thus augmenting requirements for oral antidiabetics and insulin. This progressive increase occurs throughout the course of the disease and in parallel with the increase in renal mass (renal hypertrophy); b) because of the greater glucose reabsorption, glycosuria is lower than the level corresponding to glycaemia, decreasing the stimulus on the tubuloglomerular feedback system of the distal nephron. As a result, the glomerular vasodilation caused by hyperglycaemia is not arrested, maintaining glomerular hyperfiltration, and c) the excess glucose transported to the proximal tubular cells modifies their redox status, increasing local production of glycosylating products and activating local production of proinflammatory and profibrotic proliferative mediators. These mediators are responsible for the direct free radical damage to proximal tubular cells, for increased SGLT2 expression, increased production of collagen IV and extracellular matrix, and activation of monocyte/macrophages able to cause endothelial injury. The use of SGLT2 inhibitors not only reduces the reabsorption of glucose from the glomerular filtrate back into the circulationthus improving metabolic control in diabetesbut also restores tubuloglomerular feedback by increasing glycosuria and distal urinary flow. However, the most notable effect is due to inhibition of glucose entry to the proximal tubular cells. Glycosuria is toxic to the kidney: it harms glucosetransporting cells, that is, the proximal cells, which contain SGLT2. In animal models, SGLT2 inhibition reduces local production of oxygen-free radicals, the formation of mesangial matrix and collagen IV

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

    Science.gov (United States)

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

    2015-12-01

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

  19. Purification of Sodium Phosphates as by Product of Rirang Ore Decomposition Process

    International Nuclear Information System (INIS)

    Sugeng-Walujo; Hafni-LN; Susilaningtyas; Mukhlis; Budi-Sarono; Widowati

    2004-01-01

    The aim of this experiment is to get purification condition of sodium phosphates from the filtration result of mixing mother liquor and filtrate of washing residue from Rirang monazite decomposition by alkaline. The method of purification which has been used is dissolved the precipitation of sodium phosphates into agitated water 5 minutes and solution settling for 12 hours until appear of sodium phosphate crystals. The variable of experiment included dissolution time and ratio of the amount precipitate sodium phosphate volume of water to solvent. Experimental data shown that the good temperature of dissolution is 70 o C with the ratio of precipitate sodium phosphate is 80 gram/ 40 ml to water. The recovery of sodium phosphate crystallisation is 87.4314 % with 54.0105 % pure of Na 3 PO 4 , U content is 0.0004%, NaOH content and other impurities is 45.9889%. (author)

  20. Acute renal failure with sodium-glucose-cotransporter-2 inhibitors: Analysis of the FDA adverse event report system database.

    Science.gov (United States)

    Perlman, A; Heyman, S N; Matok, I; Stokar, J; Muszkat, M; Szalat, A

    2017-12-01

    Sodium-glucose-cotransporter-2 (SGLT2) inhibitors have recently been approved for the treatment of type II diabetes mellitus (T2DM). It has been proposed that these agents could induce acute renal failure (ARF) under certain conditions. This study aimed to evaluate the association between SGLT2-inhibitors and ARF in the FDA adverse event report system (FAERS) database. We analyzed adverse event cases submitted to FAERS between January 2013 and September 2016. ARF cases were identified using a structured medical query. Medications were identified using both brand and generic names. During the period evaluated, 18,915 reports (out of a total of 3,832,015 registered in FAERS) involved the use of SGLT2-inhibitors. SGLT2-inhibitors were reportedly associated with ARF in 1224 of these cases (6.4%), and were defined as the "primary" or "secondary" cause of the adverse event in 96.8% of these cases. The proportion of reports with ARF among reports with SGLT2 inhibitor was almost three-fold higher compared to reports without these drugs (ROR 2.88, 95% CI 2.71-3.05, p SGLT2-inhibitors was significantly greater than the proportion of ARF among cases with T2DM without SGLT2-inhibitors (ROR 1.68, 95% CI 1.57-1.8, p SGLT2-inhibitors, canagliflozin was associated with a higher proportion of reports of renal failure (7.3%), compared to empagliflozin and dapagliflozin (4.7% and 4.8% respectively, p SGLT2-inhibitors are associated with an increase in the proportion of reports of ARF compared to other medications. SGLT2-inhibitor agents may differ from one another in their respective risk for ARF. Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

  1. Sodium glucose co-transporter 2 inhibitors: blocking renal tubular reabsorption of glucose to improve glycaemic control in patients with diabetes.

    Science.gov (United States)

    Jabbour, S A; Goldstein, B J

    2008-08-01

    The kidney plays a central role in the regulation of plasma glucose levels, although until recently this has not been widely appreciated or considered a target for therapeutic intervention. The sodium glucose co-transporter type 2 (SGLT2) located in the plasma membrane of cells lining the proximal tubule mediates the majority of renal glucose reabsorption from the tubular fluid, which normally prevents the loss of glucose in the urine. Competitive inhibitors of SGLT2 that provoke the renal excretion of glucose have been discovered, thereby providing a unique mechanism to potentially lower the elevated blood glucose levels in patients with diabetes. To explore the physiology of SGLT2 action and discuss several SGLT2 inhibitors that have entered early clinical development. All publicly available data were identified by searching the internet for 'SGLT2' and 'SGLT2 inhibitor' through 1 November 2007. Published articles, press releases and abstracts presented at national and international meetings were considered. Sodium glucose co-transporter type 2 inhibition is a novel treatment option for diabetes, which has been studied in preclinical models and a few potent and selective SGLT2 inhibitors have been reported and are currently in clinical development. These agents appear to be safe and generally well tolerated, and will potentially be a beneficial addition to the growing battery of oral antihyperglycaemic agents.

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

    Science.gov (United States)

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

    2018-01-01

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

  3. EFFECT OF SODIUM PHOSPHATES ON SELECTED FOOD GRADE BACTERIA

    Directory of Open Access Journals (Sweden)

    Stanislav Kráčmar

    2011-04-01

    Full Text Available The aim of this study was to examine the inhibitory effect in vitro of selected sodium phosphates (under the corporate names Hexa 68, Hexa 70, Trikrystal, FST, Pyro 52, KPS, Didi on selected gram-positive and gram-negative bacteria. Seven different concentrations of each phosphate were used. Sensitivity of the bacterial strains to phosphates was observed in broth supplemented with salts. In vitro was showed a negative effect of various phosphates on growth of selected gram-positive bacteria. Orthophosphates and diphosphates (pyrophosphates did not have significant inhibitory effect on tested bacteria at neutral pH. With the exception of phosphate Trikrystal has not been found in vitro significant inhibitory effects on gram-negative bacteria.doi:10.5219/141

  4. Effect of Sodium-Glucose Co-Transporter 2 Inhibitor, Dapagliflozin, on Renal Renin-Angiotensin System in an Animal Model of Type 2 Diabetes.

    Science.gov (United States)

    Shin, Seok Joon; Chung, Sungjin; Kim, Soo Jung; Lee, Eun-Mi; Yoo, Young-Hye; Kim, Ji-Won; Ahn, Yu-Bae; Kim, Eun-Sook; Moon, Sung-Dae; Kim, Myung-Jun; Ko, Seung-Hyun

    2016-01-01

    Renal renin-angiotensin system (RAS) activation is one of the important pathogenic mechanisms in the development of diabetic nephropathy in type 2 diabetes. The aim of this study was to investigate the effects of a sodium-glucose co-transporter 2 (SGLT-2) inhibitor, dapagliflozin, on renal RAS in an animal model with type 2 diabetes. Dapagliflozin (1.0 mg/kg, OL-DA) or voglibose (0.6 mg/kg, OL-VO, diabetic control) (n = 10 each) was administered to Otsuka Long-Evans Tokushima Fatty (OLETF) rats for 12 weeks. We used voglibose, an alpha-glucosidase inhibitor, as a comparable counterpart to SGLT2 inhibitor because of its postprandial glucose-lowering effect without proven renoprotective effects. Control Long-Evans Tokushima Otsuka (LT) and OLETF (OL-C) rats received saline (n = 10, each). Changes in blood glucose, urine albumin, creatinine clearance, and oxidative stress were measured. Inflammatory cell infiltration, mesangial widening, and interstitial fibrosis in the kidney were evaluated by histological analysis. The effects of dapagliflozin on renal expression of the RAS components were evaluated by quantitative RT-PCR in renal tissue. After treatment, hyperglycemia and urine microalbumin levels were attenuated in both OL-DA and OL-VO rather than in the OL-C group (P renal RAS component expression, oxidative stress and interstitial fibrosis in OLETF rats. We suggest that, in addition to control of hyperglycemia, partial suppression of renal RAS with an SGLT2 inhibitor would be a promising strategy for the prevention of treatment of diabetic nephropathy.

  5. Sodium Phosphate Supplementation and Time Trial Performance in Female Cyclists

    Directory of Open Access Journals (Sweden)

    Christopher L. Buck

    2014-09-01

    Full Text Available This study investigated the effects of three doses of sodium phosphate (SP supplementation on cycling 500 kJ (119.5 Kcal time trial (TT performance in female cyclists. Thirteen cyclists participated in a randomised, Latin-square design study where they completed four separate trials after ingesting either a placebo, or one of three different doses (25, 50 or 75 mg·kg-1 fat free mass: FFM of trisodium phosphate dodecahydrate which was split into four equal doses a day for six days. On the day after the loading phase, the TT was performed on a cycle ergometer. Serum phosphate blood samples were taken at rest both before and after each loading protocol, while a ~21 day washout period separated each loading phase. No significant differences in TT performance were observed between any of the supplementation protocols (p = 0.73 with average completion times for the 25, 50 or 75 mg·kg-1 FFM being, 42:21 ± 07:53, 40:55 ± 07:33 and 40:38 ± 07:20 min respectively, and 40:39 ± 07:51 min for the placebo. Likewise, average and peak power output did not significantly differ between trials (p = 0.06 and p = 0.46, respectively. Consequently, 500 kJ cycling TT performance was not different in any of the supplementation protocols in female cyclists.

  6. Sodium phosphate as a solid catalyst for biodiesel preparation

    Directory of Open Access Journals (Sweden)

    S. T. Jiang

    2010-03-01

    Full Text Available Sodium phosphate (Na3PO4 was chosen as catalyst for biodiesel preparation from rapeseed oil. The effects of mass ratio of catalyst to oil, molar ratio of methanol to oil, reaction temperature and rotation speed on biodiesel yield were investigated. For a mass ratio of catalyst to oil of 3%, molar ratio of methanol to oil of 9:1, reaction temperature of 343K and rotation speed of 600rpm, the transesterification was nearly completed within 20 minutes. Na3PO4 has a similar activity to homogeneous catalysts. Na3PO4 could be used repeatedly for 8 runs without any activation treatment and no obvious activity loss was observed. The concentrations of catalyst in biodiesel ranged from 0.6 to 0.7 mg/g. Compared to Na3PO4, Na3PO4.10H2O was cheaper, but the final yield was 71.3%, much lower than that of Na3PO4 at 99.7%.

  7. Metabolic and hemodynamic effects of sodium-dependent glucose cotransporter 2 inhibitors on cardio-renal protection in the treatment of patients with type 2 diabetes mellitus.

    Science.gov (United States)

    Kashiwagi, Atsunori; Maegawa, Hiroshi

    2017-07-01

    The specific sodium-glucose cotransporter 2 inhibitors (SGLT2 inhibitors) inhibit glucose reabsorption in proximal renal tubular cells, and both fasting and postprandial glucose significantly decrease because of urinary glucose loss. As a result, pancreatic β-cell function and peripheral insulin action significantly improve with relief from glucose toxicity. Furthermore, whole-body energy metabolism changes to relative glucose deficiency and triggers increased lipolysis in fat cells, and fatty acid oxidation and then ketone body production in the liver during treatment with SGLT2 inhibitors. In addition, SGLT2 inhibitors have profound hemodynamic effects including diuresis, dehydration, weight loss and lowering blood pressure. The most recent findings on SGLT2 inhibitors come from results of the Empagliflozin, Cardiovascular Outcomes and Mortality in Type 2 Diabetes trial. SGLT2 inhibitors exert extremely unique and cardio-renal protection through metabolic and hemodynamic effects, with long-term durability on the reduction of blood glucose, bodyweight and blood pressure. Although a site of action of SGLT2 inhibitors is highly specific to inhibit renal glucose reabsorption, whole-body energy metabolism, and hemodynamic and renal functions are profoundly modulated during the treatment of SGLT2 inhibitors. Previous studies suggest multifactorial clinical benefits and safety concerns of SGLT2 inhibitors. Although ambivalent clinical results of this drug are still under active discussion, the present review summarizes promising recent evidence on the cardio-renal and metabolic benefits of SGLT2 inhibitors in the treatment of type 2 diabetes. © 2017 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

  8. Nephrotic syndrome induced by dibasic sodium phosphate injections for twenty-eight days in rats.

    Science.gov (United States)

    Tsuchiya, Noriko; Torii, Mikinori; Narama, Isao; Matsui, Takane

    2009-04-01

    Sprague-Dawley rats received once daily tail-vein injections of 360 mM dibasic sodium phosphate solution at 8 mL/kg for fourteen or twenty-eight days. Clinical examination revealed persistent proteinuria from three days after the first dosing and thereafter severe proteinuria from eight days or later in the phosphate-treated groups. Proteinuria developed without remission even after fourteen-day withdrawal in the fourteen-day dosed group. Phosphate-treated animals developed lipemia, hypercholesterolemia, anemia, higher serum fibrinogen levels, and lower serum albumin/globulin ratios on day 29. Renal weight increased significantly compared with control animals, and the kidneys appeared pale and enlarged with a rough surface. Histopathologically, glomerular changes consisted of mineralization in whole glomeruli, glomerular capillary dilatation, partial adhesion of glomerular tufts to Bowman's capsule, and mesangiolysis. Ultrastructural lesions such as an increased number of microvilli, effacement of foot processes, and thickening of the glomerular basement membrane, and immunocytochemical changes in podocytes, mainly decreased podoplanin-positive cells and increased desmin expression, were also conspicuous in the phosphate-treated rats for twenty-eight days. Marked tubulointerstitial lesions were tubular regeneration and dilatation, protein casts, mineralization in the basement membrane, focal interstitial inflammation, and fibrosis in the cortex. These clinical and morphological changes were similar to features of human nephrotic syndrome.

  9. Interactions of [14C]phosphonoformic acid with renal cortical brush-border membranes. Relationship to the Na+-phosphate co-transporter

    International Nuclear Information System (INIS)

    Szczepanska-Konkel, M.; Yusufi, A.N.; Dousa, T.P.

    1987-01-01

    Since phosphonoformic acid (PFA) acts as a specific competitive inhibitor of Na+-Pi co-transport across renal brush-border membrane (BBM), we employed the [ 14 C]PFA as a probe to determine the mechanism of its interaction with rat renal BBM. The binding of [ 14 C]PFA to BBM vesicles (BBMV), with Na+ present in extravesicular medium (Na+o), was time- and temperature-dependent. The replacement of Na+o with other monovalent cations reduced the PFA binding by -80%. Cl- was the most effective accompanying monovalent anion as NaCl for maximum PFA binding. The Na+o increased the apparent affinity of BBMV for [ 14 C]PFA binding, but it did not change the maximum binding capacity. The maximum [ 14 C]PFA binding was achieved at Na+o approximately equal to 50 mM. The extent of Na+-dependent [ 14 C]PFA binding correlated with percent inhibition by an equimolar dose of PFA of the dependent BBMV uptake of 32Pi. Intravesicular Na+ (Na+i) decreased [ 14 C]PFA binding, on BBMV, and this inhibition by Na+i was dependent on the presence of Na+o. The increase in Na+i, at constant [Na+]o, decreased the Vmax, but not the Km, for [ 14 C]PFA binding on BBMV. Bound [ 14 C]PFA was displaced from BBMV by phosphonocarboxylic acids proportionally to their ability to inhibit gradient-dependent Pi transport, whereas other monophosphonates, diphosphonates, L-proline, or D-glucose did not influence the [ 14 C]PFA binding. The Na+-dependent binding of [ 14 C]PFA and of [ 3 H]phlorizin by BBMV was 10 times higher than binding of these ligands to renal basolateral membranes and to mitochondria. [ 14 C]PFA probably binds onto the same locus on the luminal surface of BBM, where Pi and Na+ form a ternary complex with the Na+-Pi co-transporter

  10. Evaluation of intestinal phosphate binding to improve the safety profile of oral sodium phosphate bowel cleansing.

    Directory of Open Access Journals (Sweden)

    Stef Robijn

    Full Text Available Prior to colonoscopy, bowel cleansing is performed for which frequently oral sodium phosphate (OSP is used. OSP results in significant hyperphosphatemia and cases of acute kidney injury (AKI referred to as acute phosphate nephropathy (APN; characterized by nephrocalcinosis are reported after OSP use, which led to a US-FDA warning. To improve the safety profile of OSP, it was evaluated whether the side-effects of OSP could be prevented with intestinal phosphate binders. Hereto a Wistar rat model of APN was developed. OSP administration (2 times 1.2 g phosphate by gavage with a 12h time interval induced bowel cleansing (severe diarrhea and significant hyperphosphatemia (21.79 ± 5.07 mg/dl 6h after the second OSP dose versus 8.44 ± 0.97 mg/dl at baseline. Concomitantly, serum PTH levels increased fivefold and FGF-23 levels showed a threefold increase, while serum calcium levels significantly decreased from 11.29 ± 0.53 mg/dl at baseline to 8.68 ± 0.79 mg/dl after OSP. OSP administration induced weaker NaPi-2a staining along the apical proximal tubular membrane. APN was induced: serum creatinine increased (1.5 times baseline and nephrocalcinosis developed (increased renal calcium and phosphate content and calcium phosphate deposits on Von Kossa stained kidney sections. Intestinal phosphate binding (lanthanum carbonate or aluminum hydroxide was not able to attenuate the OSP induced side-effects. In conclusion, a clinically relevant rat model of APN was developed. Animals showed increased serum phosphate levels similar to those reported in humans and developed APN. No evidence was found for an improved safety profile of OSP by using intestinal phosphate binders.

  11. Norepinephrine-evoked salt-sensitive hypertension requires impaired renal sodium chloride cotransporter activity in Sprague-Dawley rats.

    Science.gov (United States)

    Walsh, Kathryn R; Kuwabara, Jill T; Shim, Joon W; Wainford, Richard D

    2016-01-15

    Recent studies have implicated a role of norepinephrine (NE) in the activation of the sodium chloride cotransporter (NCC) to drive the development of salt-sensitive hypertension. However, the interaction between NE and increased salt intake on blood pressure remains to be fully elucidated. This study examined the impact of a continuous NE infusion on sodium homeostasis and blood pressure in conscious Sprague-Dawley rats challenged with a normal (NS; 0.6% NaCl) or high-salt (HS; 8% NaCl) diet for 14 days. Naïve and saline-infused Sprague-Dawley rats remained normotensive when placed on HS and exhibited dietary sodium-evoked suppression of peak natriuresis to hydrochlorothiazide. NE infusion resulted in the development of hypertension, which was exacerbated by HS, demonstrating the development of the salt sensitivity of blood pressure [MAP (mmHg) NE+NS: 151 ± 3 vs. NE+HS: 172 ± 4; P salt-sensitive animals, increased NE prevented dietary sodium-evoked suppression of peak natriuresis to hydrochlorothiazide, suggesting impaired NCC activity contributes to the development of salt sensitivity [peak natriuresis to hydrochlorothiazide (μeq/min) Naïve+NS: 9.4 ± 0.2 vs. Naïve+HS: 7 ± 0.1; P salt-sensitive component of NE-mediated hypertension, while chronic ANG II type 1 receptor antagonism significantly attenuated NE-evoked hypertension without restoring NCC function. These data demonstrate that increased levels of NE prevent dietary sodium-evoked suppression of the NCC, via an ANG II-independent mechanism, to stimulate the development of salt-sensitive hypertension. Copyright © 2016 the American Physiological Society.

  12. [Optimization of riboflavin sodium phosphate loading to calcium alginate floating microspheres by response surface methodology].

    Science.gov (United States)

    Zhang, An-yang; Fan, Tian-yuan

    2009-12-18

    To investigate the preparation, optimization and in vitro properties of riboflavin sodium phosphate floating microspheres. The floating microspheres composed of riboflavin sodium phosphate and calcium alginate were prepared using ion gelatin-oven drying method. The properties of the microspheres were investigated, including the buoyancy, release, appearance and entrapment efficiency. The formulation was optimized by response surface methodology (RSM). The optimized microspheres were round. The entrapment efficiency was 57.49%. All the microspheres could float on the artificial gastric juice over 8 hours. The release of the drug from the microspheres complied with Fick's diffusion.

  13. Simultaneous Determination of Ciprofloxacin Hydrochloride and Dexamethasone Sodium Phosphate in Eye Drops by HPLC

    Directory of Open Access Journals (Sweden)

    Prakash Katakam

    2012-01-01

    Full Text Available A liquid chromatographic method was developed and validated for the simultaneous determination of ciprofloxacin hydrochloride and dexamethasone sodium phosphate in bulk and pharmaceutical formulations. Optimum separation was achieved in less than 5 min using a C18 column (250 mmx4.6 mm i.d, 5μ particle size by isocratic elution. The mobile phase consisting of a mixture of mixed phosphate buffer (pH 4 and acetonitrile (65:35, v/v was used. Column effluents were monitored at 254 nm at a flow rate of 1ml/min. Retention times of ciprofloxacin hydrochloride and dexamethasone sodium phosphate were 2.0 and 3.16 min respectively. The linearity of ciprofloxacin hydrochloride and dexamethasone sodium phosphate was in the range of 3-18 μg/ml and 1-6 μg/ml respectively. Developed method was economical in terms of the time taken and amount of solvent consumed for each analysis. The method was validated and successfully applied to the simultaneous determination of ciprofloxacin hydrochloride and dexamethasone sodium phosphate in bulk and pharmaceutical formulations.

  14. A minor role of WNK3 in regulating phosphorylation of renal NKCC2 and NCC co-transporters in vivo

    Directory of Open Access Journals (Sweden)

    Katsuyuki Oi

    2012-02-01

    Mutations in WNK1 and WNK4 kinase genes have been shown to cause a human hereditary hypertensive disease, pseudohypoaldosteronism type II (PHAII. We previously discovered that WNK kinases phosphorylate and activate OSR1/SPAK kinases that regulate renal SLC12A family transporters such as NKCC2 and NCC, and clarified that the constitutive activation of this cascade causes PHAII. WNK3, another member of the WNK kinase family, was reported to be a strong activator of NCC/NKCC2 when assayed in Xenopus oocytes, suggesting that WNK3 also plays a major role in regulating blood pressure and sodium reabsorption in the kidney. However, it remains to be determined whether WNK3 is in fact involved in the regulation of these transporters in vivo. To clarify this issue, we generated and analyzed WNK3 knockout mice. Surprisingly, phosphorylation and expression of OSR1, SPAK, NKCC2 and NCC did not decrease in knockout mouse kidney under normal and low-salt diets. Similarly, expression of epithelial Na channel and Na/H exchanger 3 were not affected in knockout mice. Na+ and K+ excretion in urine in WNK3 knockout mice was not affected under different salt diets. Blood pressure in WNK3 knockout mice was not lower under normal diet. However, lower blood pressure was observed in WNK3 knockout mice fed low-salt diet. WNK4 and WNK1 expression was slightly elevated in the knockout mice under low-salt diet, suggesting compensation for WNK3 knockout by these WNKs. Thus, WNK3 may have some role in the WNK-OSR1/SPAK-NCC/NKCC2 signal cascade in the kidney, but its contribution to total WNK kinase activity may be minimal.

  15. Hideout and hideout return of tri-sodium phosphate in PWR steam generators

    International Nuclear Information System (INIS)

    Feron, D.; You, D.; Turluer, G.

    2002-01-01

    Tri-sodium phosphate is used as a chemical conditioner of several sub-systems in secondary circuits of PWR. As confirmed by the international experience feedback of the secondary water chemistry, it can appear as a pollutant of the secondary water circuits, whereby it can concentrate in some areas of restricted flow or deposits in the steam generators. The issues raised by those occurrences prompted the safety French authorities (IPSN) to develop a model boiler investigation programme to assess the respective sodium/phosphate behaviour as a result of hideout and hideout return processes. Hideout and hideout return experiments have been performed with three model boilers in order to investigate the behaviour of tri-sodium phosphate pollution with three different configurations: only tube-tube support plate crevices, only sludge at the bottom of the tubes, or with only ''free'' tube surfaces. Obtained results, with discontinuous pollutions at some mg.kg -1 , can be summarised as follow: low hideout on the free surface of the tubes (less than 10%), hideout is more important when tube-tube support plate crevices are present (10 to 30%), maximum hideout is obtained when there is some sludge at the bottom of the tubes (30 to 90%), Hideout return data are always very low compared to the hideout quantities, due to the formation of solid compound with alumina and silica. (authors)

  16. Efficacy and tolerance of sodium phosphates oral solution after diet liberalization.

    Science.gov (United States)

    Scott, Sherrie R; Raymond, Patricia L; Thompson, William O; Galt, Deborah J B

    2005-01-01

    Bowel cleansing regimens commonly require adherence to liquid diets for 24 to 48 hours before examination, which often leads to poor compliance, reduced cleansing, and ultimately inadequate examinations. The authors investigated the efficacy and tolerability of diet liberalization before bowel cleansing with sodium phosphates oral solution. Two hundred patients were randomized into two treatment groups. One group received the standard light breakfast followed by clear liquids the day before colonoscopy; the second had a normal breakfast followed by a low-residue lunch the day before colonoscopy. Both groups had the same bowel preparation with sodium phosphates oral solution (2 x 45-mL, 7 p.m./6 a.m.). There was no difference in clinical efficacy between the two diet regimens (excellent/good in 93% standard, 95% low-residue). Fewer patients receiving the low-residue diet reported hunger, and more patients receiving the low-residue regimen reported energy to perform usual activities. This study supports offering patients a regular breakfast and a low-residue lunch before bowel cleansing with sodium phosphates oral solution.

  17. Hideout and hideout return of tri-sodium phosphate in PWR steam generators

    Energy Technology Data Exchange (ETDEWEB)

    Feron, D.; You, D. [CEA/DEN - Laboratoire d' Etude de la Corrosion Aqueuse, Saclay (France); Turluer, G. [CEA/IPSN-Service d' Analyse des Materiels et des Structures, Fontenay-aux-Roses (France)

    2002-07-01

    Tri-sodium phosphate is used as a chemical conditioner of several sub-systems in secondary circuits of PWR. As confirmed by the international experience feedback of the secondary water chemistry, it can appear as a pollutant of the secondary water circuits, whereby it can concentrate in some areas of restricted flow or deposits in the steam generators. The issues raised by those occurrences prompted the safety French authorities (IPSN) to develop a model boiler investigation programme to assess the respective sodium/phosphate behaviour as a result of hideout and hideout return processes. Hideout and hideout return experiments have been performed with three model boilers in order to investigate the behaviour of tri-sodium phosphate pollution with three different configurations: only tube-tube support plate crevices, only sludge at the bottom of the tubes, or with only ''free'' tube surfaces. Obtained results, with discontinuous pollutions at some mg.kg{sup -1}, can be summarised as follow: low hideout on the free surface of the tubes (less than 10%), hideout is more important when tube-tube support plate crevices are present (10 to 30%), maximum hideout is obtained when there is some sludge at the bottom of the tubes (30 to 90%), Hideout return data are always very low compared to the hideout quantities, due to the formation of solid compound with alumina and silica. (authors)

  18. EFFECTS OF SODIUM PHOSPHATE LOADING ON AEROBIC POWER AND CAPACITY IN OFF ROAD CYCLISTS

    Directory of Open Access Journals (Sweden)

    Scott Woska

    2009-12-01

    Full Text Available The main aim of this paper was to evaluate the effects of short- term (6 days phosphate loading, as well as prolonged (21 days intake of sodium phosphate on aerobic capacity in off-road cyclists. Nineteen well-trained cyclists were randomly divided into a supplemental (S and control group (C. Group S was supplemented for 6 days with tri-sodium phosphate, in a dose of 50 mg·kg-1 of FFM/d, while a placebo was provided for the C group. Additionally, group S was further subjected to a 3-week supplementation of 25 mg·kg-1 FFM/d, while group C received 2g of glucose. The results indicate a significant (p < 0.05 increase in VO2max, VEmax, and O2/HR, due to sodium phosphate intake over 6 days. Also a significant (p < 0.05 decrease in HRrest and HRmax occurred. The supplementation procedure caused a significant increase (p < 0.05 in Pmax and a shift of VAT towards higher loads. There were no significant changes in the concentration of 2,3-DPG, acid-base balance and lactate concentration, due to phosphate salt intake

  19. Role of Klotho in Osteoporosis and Renal Osteodystrophy

    Science.gov (United States)

    2014-10-01

    proximal tubules of the kidney. This is an important finding because prior to these data it was unclear how Fgf23 could downregulate the sodium phosphate...downregulates the sodium phosphate co-transporters (NaPi2a, Napi2c) and inhibits expression of 1α(OH)ase. We are interested in determining if there are any...7-day adaptation phase to the casein diet without addition of adenine. Then 8-week old Prx1cre;Klotho fl/fl and Klotho fl/fl mice were randomized

  20. Sodium Phosphate

    Science.gov (United States)

    ... through such as water, flavored water, lemonade without pulp, apple juice, and ginger ale. Do not drink ... a heart attack, chest pain, seizures, inflammatory bowel disease (IBD; a group of conditions in which all ...

  1. Treatment of cows with parturient paresis using intravenous calcium and oral sodium phosphate.

    Science.gov (United States)

    Braun, U; Grob, D; Hässig, M

    2016-09-01

    The goal of this study was to investigate whether intravenous infusion of 1000 ml 40% calcium borogluconate combined with the oral adminstration of 500 g sodium phosphate leads to a better cure rate and longer-lasting normocalcaemia and normophosphataemia than standard intravenous treatment with 500 ml calcium borogluconate in cows with parturient paresis. Forty recumbent cows with hypocalcaemia and hypophosphataemia were alternately allocated to group A or B. Cows of both groups were treated intravenously with 500 ml 40% calcium borogluconate, and cows of group B additionally received another 500 ml calcium borogluconate via slow intravenous infusion and 500 g sodium phosphate administered via an orogastric tube. Thirty-two cows stood within 8 hours after the start of treatment and 8 did not; of the 32 cows that stood, 18 belonged to group A and 14 to group B (90% of group A vs. 70% of group B; P = 0.23). Seven cows relapsed; of these and the 8 that did not respond to initial treatment, 10 stood after two standard intravenous treatments. Downer cow syndrome occurred in 5 cows, 3 of which recovered after aggressive therapy. The overall cure rate did not differ significantly between groups A and B. Twelve (60%) cows of group A and 14 (70%) cows of group B were cured after a single treatment and of the remaining 14, 11 were cured after two or more treatments. Two downer cows were euthanized and one other died of heart failure during treatment. Serum calcium concentrations during the first eight hours after the start of treatment were significantly higher in group B than in group A, and oral sodium phosphate caused a significant and lasting increase in inorganic phosphate. More cows of group B than group A were cured after a single treatment (P > 0.05). These findings, although not statistically significant, are promising and should be verified using a larger number of cows.

  2. Simultaneous Determination of Ciprofloxacin Hydrochloride and Dexamethasone Sodium Phosphate in Eye Drops by HPLC

    OpenAIRE

    Katakam, Prakash; Sireesha, Karanam R.

    2012-01-01

    A liquid chromatographic method was developed and validated for the simultaneous determination of ciprofloxacin hydrochloride and dexamethasone sodium phosphate in bulk and pharmaceutical formulations. Optimum separation was achieved in less than 5 min using a C18 column (250 mmx4.6 mm i.d, 5μ particle size) by isocratic elution. The mobile phase consisting of a mixture of mixed phosphate buffer (pH 4) and acetonitrile (65:35, v/v) was used. Column effluents were monitored at 254 nm at a flow...

  3. Compatibility and stability of aloxi (palonosetron hydrochloride) admixed with dexamethasone sodium phosphate.

    Science.gov (United States)

    Trissel, Lawrence A; Zhang, Yanping

    2004-01-01

    The purpose of this study was to evaluate the physical and chemical stability of palonosetron hydrochloride 0.25 mg admixed with dexamethasone (as sodium phophate) 10 mg or 20 mg in 5% dextrose injection or 0.9% sodium chloride injection in polyvinylchloride minibags, and also admixed with dexamethasone (as sodium phosphate) 3.3 mg in 5% dextrose injection or 0.9% sodium chloride injection in polypropylene syringes, at 4 deg C stored in the dark for 14 days, and at 23 deg C exposed to normal laboratory fluorescent light over 48 hours. Test samples of palonosetron hydrochloride 5 micrograms/mL with dexamethasone (as sodium phosphate) 0.2 mg/mL and also 0.4 mg/mL were prepared in polyvinylchloride minibags of each infusion solution. Additionally, palonosetron hydrochloride 25 micrograms/mL with dexamethasone (as sodium phosphate) 0.33 mg/mL in each infusion solution were prepared as 10 mL of test solution in 20-mL polypropylene syringes. Evaluations for physical and chemical stability were performed on samples taken initially and after 1, 3, 7 and 14 days of storage at 4 deg C and after 1, 4, 24 and 48 hours at 23 deg C. Physical stability was assessed using visual observation in normal room light and using a high-intensity monodirectional light beam. In addition, turbidity and particle content were measured electronically. Chemical stability of the drug was evaluated by using a stability-indicating high-performance liquid chromatographic analytical technique. All samples were physically compatible throughout the study. The solutions remained clear and showed little or no change in particulate burden and haze level. Additionally, little or no loss of palonosetron hydrochloride and dexamethasone occurred in any of the samples at either temperature throughout the entire study period. Admixtures of palonosetron hydrochloride with dexamethasone sodium phosphate in 5% dextrose injection or in 0.9% sodium chloride injection packaged in polyvinylchloride minibags or in

  4. Spectral-luminescence properties of trivalent titanium in aluminum-sodium phosphate glass

    International Nuclear Information System (INIS)

    Sukhanov, S.B.; Batyaev, I.M.

    1992-01-01

    Since development of the first crystal laser, Al 2 O 3 crystals remain the most widely used in quantum electronics. In the present work, the aluminum-sodium phosphate glass, Al 2 O 3 -Na 2 O 3 -P 2 O 5 , was studied with different proportions of components. A luminescence medium is obtained based on phosphate glass doped by Ti 3+ ions with intense emission in the 700-900-nm spectral range. This glass is a promising lasing medium for tunable solid-state lasers. 12 refs., 2 figs

  5. [Sodium-glucose co-transporter-2 inhibitors: from the bark of apple trees and familial renal glycosuria to the treatment of type 2 diabetes mellitus].

    Science.gov (United States)

    Mauricio, Dídac

    2013-09-01

    The therapeutic armamentarium for the treatment of hyperglycemia in type 2 diabetes mellitus is still inadequate. We are currently witnessing the introduction of a new mode of hypoglycemic treatment through induction of glycosuria to decrease the availability of the metabolic substrate, i.e. glucose. Clinical trials have shown that sodium-glucose co-transporter-2 (SGLT2) inhibitors are as efficacious as other oral hypoglycemic drugs. This article discusses the basic features of this new treatment concept and the efficacy and safety of this new drug group. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  6. Renal-Specific Silencing of TNF (Tumor Necrosis Factor) Unmasks Salt-Dependent Increases in Blood Pressure via an NKCC2A (Na+-K+-2Cl- Cotransporter Isoform A)-Dependent Mechanism.

    Science.gov (United States)

    Hao, Shoujin; Hao, Mary; Ferreri, Nicholas R

    2018-06-01

    We tested the hypothesis that TNF (tumor necrosis factor)-α produced within the kidney and acting on the renal tubular system is part of a regulatory mechanism that attenuates increases in blood pressure in response to high salt intake. Intrarenal administration of a lentivirus construct, which specifically silenced TNF in the kidney, did not affect baseline blood pressure. However, blood pressure increased significantly 1 day after mice with intrarenal silencing of TNF ingested 1% NaCl in the drinking water. The increase in blood pressure, which was continuously observed for 11 days, promptly returned to baseline levels when mice were switched from 1% NaCl to tap water. Silencing of renal TNF also increased NKCC2 (Na + -K + -2Cl - cotransporter) phosphorylation and induced a selective increase in NKCC2A (NKCC2 isoform A) mRNA accumulation in both the cortical and medullary thick ascending limb of Henle loop that was neither associated with a compensatory decrease of NKCC2F in the medulla nor NKCC2B in the cortex. The NaCl-mediated increases in blood pressure were completely absent when NKCC2A, using a lentivirus construct that did not alter expression of NKCC2F or NKCC2B, and TNF were concomitantly silenced in the kidney. Moreover, the decrease in urine volume and NaCl excretion induced by renal TNF silencing was abolished when NKCC2A was concurrently silenced, suggesting that this isoform contributes to the transition from a salt-resistant to salt-sensitive phenotype. Collectively, the data are the first to demonstrate a role for TNF produced by the kidney in the modulation of sodium homeostasis and blood pressure regulation. © 2018 American Heart Association, Inc.

  7. Compatibility and Stability of Rolapitant Injectable Emulsion Admixed with Dexamethasone Sodium Phosphate.

    Science.gov (United States)

    Wu, George; Yeung, Stanley; Chen, Frank

    2017-01-01

    Neurokinin-1 receptor antagonist, 5-hydroxytryptamine-3 receptor antagonist, and dexamethasone combination therapy is the standard of care for the prevention of chemotherapy-induced nausea and vomiting. Herein, we describe the physical and chemical stability of an injectable emulsion of the Neurokinin-1 receptor antagonist rolapitant 185 mg in 92.5 mL (free base, 166.5 mg in 92.5 mL) admixed with either 2.5 mL of dexamethasone sodium phosphate (10 mg) or 5 mL of dexamethasone sodium phosphate (20 mg). Admixtures were prepared and stored in two types of container closures (glass and Crystal Zenith plastic bottles) and four types of intravenous administration tubing sets (or intravenous tubing sets). The assessment of the physical and chemical stability was conducted on admixtures packaged in bottled samples stored at room temperature (20°C to 25°C under fluorescent light) and evaluated at 0, 1, and 6 hours. For admixtures in intravenous tubing sets, the assessment of physicochemical stability was performed after 0 and 7 hours of storage at 20°C to 25°C, and then after 20 hours (total 27 hours) under refrigeration (2°C to 8°C) and protected from light. Physical stability was assessed by visually examining the bottle contents under normal room light and measuring turbidity and particulate matter. Chemical stability was assessed by measuring the pH of the admixture and determining drug concentrations through high-performance liquid chromatographic analysis. Results showed that all samples were physically compatible throughout the duration of the study. The admixtures stayed within narrow and acceptable ranges in pH, turbidity, and particulate matter. Admixtures of rolapitant and dexamethasone were chemically stable when stored in glass and Crystal Zenith bottles for at least 6 hours at room temperature, as well as in the four selected intravenous tubing sets for 7 hours at 20°C to 25°C and then for 20 (total 27 hours) hours at 2°C to 8°C. No loss of potency

  8. Copper(II) oxide solubility behavior in aqueous sodium phosphate solutions at elevated temperatures

    International Nuclear Information System (INIS)

    Ziemniak, S.E.; Jones, M.E.; Combs, K.E.S.

    1990-02-01

    A platinum-lined, flowing autoclave facility is used to investigate the solubility behavior of copper(II) oxide (CuO) in aqueous sodium phosphate solutions at temperatures between 292 and 535 K. Copper solubilities are observed to increase continuously with temperature and phosphate concentration. The measured solubility is examined via a Cu(II) ion hydrolysis/complexing model and thermodynamic functions for the hydrolysis/complexing reactions are obtained from a least- squares analysis of the data. Altogether, thermochemical properties are established for five anionic complexes: Cu(OH) 3 - , Cu(OH) 4 = , Cu(OH) 2 (HPO 4 ) = , Cu(OH) 3 (H 2 PO 4 ) = , and Cu(OH) 2 (PO 4 ) ≡ . Precise thermochemical parameters are also derived for the Cu(OH) + hydroxocomplex based on CuO solubility behavior previously observed in pure water (*) at elevated temperatures. The relative ease of Cu(II) ion hydrolysis is such that Cu(OH) 3 - species become the preferred hydroxocomplex for pH ≥ 9.4. 20 refs., 8 figs., 6 tabs

  9. Host sensitized near-infrared emission in Nd3+ doped different alkaline-sodium-phosphate phosphors

    Science.gov (United States)

    Balakrishna, A.; Swart, H. C.; Kroon, R. E.; Ntwaeaborwa, O. M.

    2018-04-01

    Near-infrared (NIR) emitting phosphors of different alkaline based sodium-phosphate (MNa[PO4], where M = Mg, Ca, Sr and Ba were prepared by a conventional solution combustion method with fixed doping concentration of Nd3+ (1.0 mol%). The phosphors were characterized by powder X-ray diffraction, field emission scanning electron microscope, Fourier transform infrared spectroscopy, UV-vis spectroscopy and fluorescent spectrophotometry. The optical properties including reflectance, excitation and emission were investigated. The excitation spectra of the phosphors were characterized by a broadband extending from 450 to 900 nm. Upon excitation with a wavelength of 580 nm, the phosphor emits intensely infrared region at 872 nm, 1060 nm and 1325 nm which correspond to the 4F3/2 → 4I9/2, 4F3/2 → 4I11/2 and 4F3/2 → 4I13/2 transitions of Nd3+ ions and were found to vary for the different hosts. The strongest emission wavelength reaches 1060 nm. The most intense emission of Nd3+ was observed from Ca2+ incorporated host. The down conversion emissions of the material fall in the NIR region suggesting that the prepared phosphors have potential application in the development of photonic devices emitting in the NIR.

  10. Electron beam-induced radiation damage: the bubbling response in amorphous dried sodium phosphate buffer.

    Science.gov (United States)

    Massover, William H

    2010-06-01

    Irradiation of an amorphous layer of dried sodium phosphate buffer (pH = 7.0) by transmission electron microscopy (100-120 kV) causes rapid formation of numerous small spherical bubbles [10-100 A (= 1-10 nm)] containing an unknown gas. Bubbling is detected even with the first low-dose exposure. In a thin layer (ca. 100-150 A), bubbling typically goes through nucleation, growth, possible fusion, and end-state, after which further changes are not apparent; co-irradiated adjacent areas having a slightly smaller thickness never develop bubbles. In moderately thicker regions (ca. over 200 A), there is no end-state. Instead, a complex sequence of microstructural changes is elicited during continued intermittent high-dose irradiation: nucleation, growth, early simple fusions, a second round of extensive multiple fusions, general reduction of matrix thickness (producing flattening and expansion of larger bubbles, occasional bubble fission, and formation of very large irregularly-shaped bubbles by a third round of compound fusion events), and slow shrinkage of all bubbles. The ongoing lighter appearance of bubble lumens, maintenance of their rounded shape, and extensive changes in size and form indicate that gas content continues throughout their surprisingly long lifetime; the thin dense boundary layer surrounding all bubbles is proposed to be the main mechanism for their long lifetime.

  11. Renal and Cardiovascular Effects of sodium–glucose cotransporter 2 (SGLT2) inhibition in combination with loop Diuretics in diabetic patients with Chronic Heart Failure (RECEDE-CHF): protocol for a randomised controlled double-blind cross-over trial

    Science.gov (United States)

    Mordi, Natalie A; Mordi, Ify R; Singh, Jagdeep S; Baig, Fatima; Choy, Anna-Maria; McCrimmon, Rory J; Struthers, Allan D; Lang, Chim C

    2017-01-01

    Introduction Type 2 diabetes (T2D) and heart failure (HF) are a frequent combination, where treatment options remain limited. There has been increasing interest around the sodium–glucose cotransporter 2 (SGLT2) inhibitors and their use in patients with HF. Data on the effect of SGLT2 inhibitor use with diuretics are limited. We hypothesise that SGLT2 inhibition may augment the effects of loop diuretics and the benefits of SGLT2 inhibitors may extend beyond those of their metabolic (glycaemic parameters and weight loss) and haemodynamic parameters. The effects of SGLT2 inhibitors as an osmotic diuretic and on natriuresis may underlie the cardiovascular and renal benefits demonstrated in the recent EMPA-REG study. Methods and analysis To assess the effect of SGLT2 inhibitors when used in combination with a loop diuretic, the RECEDE-CHF (Renal and Cardiovascular Effects of SGLT2 inhibition in combination with loop Diuretics in diabetic patients with Chronic Heart Failure) trial is a single-centre, randomised, double-blind, placebo-controlled, cross-over trial conducted in a secondary care setting within NHS Tayside, Scotland. 34 eligible participants, aged between 18 and 80 years, with stable T2D and CHF will be recruited. Renal physiological testing will be performed at two points (week 1 and week 6) on each arm to assess the effect of 25 mg empagliflozin, on the primary and secondary outcomes. Participants will be enrolled in the trial for a total period between 14 and 16 weeks. The primary outcome will assess the effect of empagliflozin versus placebo on urine output. The secondary outcomes are to assess the effect of empagliflozin on glomerular filtration rate, cystatin C, urinary sodium excretion, urinary protein/creatinine ratio and urinary albumin/creatinine ratio when compared with placebo. Ethics and dissemination Ethics approval was obtained by the East of Scotland Research Ethics Service. Results of the trial will be submitted for publication in a peer

  12. A randomized prospective triaI comparing oral sodium phosphate with magnesium citrate in preparing of patients for double contrast barium enema

    International Nuclear Information System (INIS)

    Lee, Eun Joo; Lee, Sung Woo; Lee, Hyeon Kyeong; Yang, Chang Hun; Kim, Soon; Oh, Yoen Hee; Kim, Seung Hyeon

    2004-01-01

    The purpose of this study was to compare two bowel preparation agents, sodium phosphate solution with magnesium citrate solution. A total of 94 subjects that underwent a double-contrast barium enema were included in this study. Bowel preparation before performing the barium study was done by using a sodium phosphate solution in 47 subjects and by using a magnesium citrate solution in the other 47 subjects. We evaluated the presence or absence of side effects when using these bowel preparation agents. Two radiologist who were blinded to the type of bowel preparation evaluated the quality of bowel preparation at the colonic segments (ascending, descending, and sigmoid colon) on the radiographs obtained by double-contrast barium enema, with regard to stool cleansing, water retention, barium coating and bubble formation. The side effects, such as abdominal clamping pain, nausea, hunger pain and chill occurred more frequently in the sodium phosphate group than in the magnesium citrate group (p< 0.001). Stool retention was more frequently found in the magnesium citrate group (p< 0.001). However, no statistical difference was noted on the status of water retention and barium coating between two groups. Gas bubble formation was more commonly seen in the sodium phosphate group (p< 0.001). The sodium phosphate solution appeared to be more effective in cleansing the right colon (p=0.001). Sodium phosphate solution appears to be more effective for colonic cleansing, with a lower incidence of side effects, than when using magnesium citrate solution

  13. Effects of sodium phosphate and caffeine ingestion on repeated-sprint ability in male athletes.

    Science.gov (United States)

    Kopec, Benjamin J; Dawson, Brian T; Buck, Christopher; Wallman, Karen E

    2016-03-01

    To assess the effects of sodium phosphate (SP) and caffeine supplementation on repeated-sprint performance. Randomized, double-blind, Latin-square design. Eleven team-sport males participated in four trials: (1) SP (50mgkg(-1) of free fat-mass daily for six days) and caffeine (6mgkg(-1) ingested 1h before exercise); SP+C, (2) SP and placebo (for caffeine), (3) caffeine and placebo (for SP) and (4) placebo (for SP and caffeine). After loading, participants performed a simulated team-game circuit (STGC) consisting of 2×30min halves, with 6×20-m repeated-sprint sets performed at the start, half-time and end of the STGC. There were no interaction effects between trials for first-sprint (FS), best-sprint (BS) or total-sprint (TS) times (p>0.05). However, SP resulted in the fastest times for all sprints, as supported by moderate to large effect sizes (ES; d=0.51-0.83) and 'likely' to 'very likely' chances of benefit, compared with placebo. Compared with caffeine, SP resulted in 'possible' to 'likely' chances of benefit for FS, BS and TS for numerous sets and a 'possible' chance of benefit compared with SP+C for BS (set 2). Compared with placebo, SP+C resulted in moderate ES (d=0.50-0.62) and 'possible' to 'likely' benefit for numerous sprints, while caffeine resulted in a moderate ES (d=0.63; FS: set 3) and 'likely' chances of benefit for a number of sets. While not significant, ES and qualitative analysis results suggest that SP supplementation may improve repeated-sprint performance when compared with placebo. Copyright © 2015 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

  14. Effects of sodium-glucose co-transporter 2 (SGLT2 inhibition on renal function and albuminuria in patients with type 2 diabetes: a systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Lubin Xu

    2017-06-01

    Full Text Available Aim To evaluate the effects of sodium-glucose co-transporter 2 (SGLT2 inhibition on renal function and albuminuria in patients with type 2 diabetes. Methods We conducted systematic searches of PubMed, Embase and Cochrane Central Register of Controlled Trials up to June 2016 and included randomized controlled trials of SGLT2 inhibitors in adult type 2 diabetic patients reporting estimated glomerular filtration rate (eGFR and/or urine albumin/creatinine ratio (ACR changes. Data were synthesized using the random-effects model. Results Forty-seven studies with 22,843 participants were included. SGLT2 inhibition was not associated with a significant change in eGFR in general (weighted mean difference (WMD, −0.33 ml/min per 1.73 m2, 95% CI [−0.90 to 0.23] or in patients with chronic kidney disease (CKD (WMD −0.78 ml/min per 1.73 m2, 95% CI [−2.52 to 0.97]. SGLT2 inhibition was associated with eGFR reduction in short-term trials (WMD −0.98 ml/min per 1.73 m2, 95% CI [−1.42 to −0.54], and with eGFR preservation in long-term trials (WMD 2.01 ml/min per 1.73 m2, 95% CI [0.86 to 3.16]. Urine ACR reduction after SGLT2 inhibition was not statistically significant in type 2 diabetic patients in general (WMD −7.24 mg/g, 95% CI [−15.54 to 1.06], but was significant in patients with CKD (WMD −107.35 mg/g, 95% CI [−192.53 to −22.18]. Conclusions SGLT2 inhibition was not associated with significant changes in eGFR in patients with type 2 diabetes, likely resulting from a mixture of an initial reduction of eGFR and long-term renal function preservation. SGLT2 inhibition was associated with statistically significant albuminuria reduction in type 2 diabetic patients with CKD.

  15. SIMULTANEOUS ESTIMATION OF MOXIFLOXACIN HYDROCHLORIDE AND DEXAMETHASONE SODIUM PHOSPHATE IN BULK AND IN OPHTHALMIC SOLUTION BY RP- HPLC

    OpenAIRE

    DHUMAL, D. M; SHIRKHEDKAR, A. A; NERKAR, P. P; SURANA, S. J

    2012-01-01

    A new simple, precise, accurate and selective RP-HPLC method has been developed and validated for simultaneous estimation of Moxifloxacin Hydrochloride (MOX) and Dexamethasone Sodium Phosphate (DSP) in Ophthalmic Solution. The method was carried out on a Qualisil RP C-8 (250 mm x 4.6 mm, 5 µm) column with a mobile phase consisting of Methanol: Water (75:25 v/v) pH adjusted to 3.0 with ortho-phosphoric acid of aqueous phase and flow rate of 1.0 mL min¹. Detection was carried out at 240 nm. The...

  16. Renal tubular NHE3 is required in the maintenance of water and sodium chloride homeostasis.

    Science.gov (United States)

    Fenton, Robert A; Poulsen, Søren B; de la Mora Chavez, Samantha; Soleimani, Manoocher; Dominguez Rieg, Jessica A; Rieg, Timo

    2017-08-01

    The sodium/proton exchanger isoform 3 (NHE3) is expressed in the intestine and the kidney, where it facilitates sodium (re)absorption and proton secretion. The importance of NHE3 in the kidney for sodium chloride homeostasis, relative to the intestine, is unknown. Constitutive tubule-specific NHE3 knockout mice (NHE3 loxloxCre) did not show significant differences compared to control mice in body weight, blood pH or bicarbonate and plasma sodium, potassium, or aldosterone levels. Fluid intake, urinary flow rate, urinary sodium/creatinine, and pH were significantly elevated in NHE3 loxloxCre mice, while urine osmolality and GFR were significantly lower. Water deprivation revealed a small urinary concentrating defect in NHE3 loxloxCre mice on a control diet, exaggerated on low sodium chloride. Ten days of low or high sodium chloride diet did not affect plasma sodium in control mice; however, NHE3 loxloxCre mice were susceptible to low sodium chloride (about -4 mM) or high sodium chloride intake (about +2 mM) versus baseline, effects without differences in plasma aldosterone between groups. Blood pressure was significantly lower in NHE3 loxloxCre mice and was sodium chloride sensitive. In control mice, the expression of the sodium/phosphate co-transporter Npt2c was sodium chloride sensitive. However, lack of tubular NHE3 blunted Npt2c expression. Alterations in the abundances of sodium/chloride cotransporter and its phosphorylation at threonine 58 as well as the abundances of the α-subunit of the epithelial sodium channel, and its cleaved form, were also apparent in NHE3 loxloxCre mice. Thus, renal NHE3 is required to maintain blood pressure and steady-state plasma sodium levels when dietary sodium chloride intake is modified. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  17. Partitioning of L-methionine in aqueous two-phase systems containing poly(propylene glycol) and sodium phosphate salts

    Energy Technology Data Exchange (ETDEWEB)

    Salabat, Alireza, E-mail: a-salabat@araku.ac.ir [Chemistry Department, Arak University, P.O. Box 38156-879, Arak (Iran, Islamic Republic of); Sadeghi, Rahmat [Department of Chemistry, University of Kurdistan, Sanandaj, Kurdistan 66135 (Iran, Islamic Republic of); Moghadam, Somayeh Tiani [Chemistry Department, Arak University, P.O. Box 38156-879, Arak (Iran, Islamic Republic of); Jamehbozorg, Bahman [Department of Chemistry, University of Kurdistan, Sanandaj, Kurdistan 66135 (Iran, Islamic Republic of)

    2011-10-15

    Highlights: > Thermodynamics parameters for partitioning of L-methionine in ATPS. > Investigation of different effects on partition coefficient of the amino acid. > Propose the best condition for L-methionine partitioning. - Abstract: The partitioning behavior of L-methionine has been studied in aqueous two-phase systems of (poly(propylene glycol) + sodium phosphate salts + H{sub 2}O) at different temperatures. The salts used were sodium di-hydrogen phosphate (NaH{sub 2}PO{sub 4}), di-sodium hydrogen phosphate (Na{sub 2}HPO{sub 4}) and tri-sodium phosphate (Na{sub 3}PO{sub 4}). The effects of tie line length, salt type, and temperature on the partition coefficient of this amino acid have been studied. In addition, thermodynamic parameters ({Delta}H{sup o}, {Delta}S{sup o} and {Delta}G{sup o}) as a function of temperature were calculated. The results showed that increasing tie line length led to decreasing of the partition coefficient. We also showed that the partition coefficients of the amino acid in the systems containing Na{sub 3}PO{sub 4} are greater than the other two salts. Moreover, it is verified that increasing temperature led to decreasing the partition coefficient. The experimental partition coefficient data are correlated using a modified virial-type model.

  18. Partitioning of L-methionine in aqueous two-phase systems containing poly(propylene glycol) and sodium phosphate salts

    International Nuclear Information System (INIS)

    Salabat, Alireza; Sadeghi, Rahmat; Moghadam, Somayeh Tiani; Jamehbozorg, Bahman

    2011-01-01

    Highlights: → Thermodynamics parameters for partitioning of L-methionine in ATPS. → Investigation of different effects on partition coefficient of the amino acid. → Propose the best condition for L-methionine partitioning. - Abstract: The partitioning behavior of L-methionine has been studied in aqueous two-phase systems of (poly(propylene glycol) + sodium phosphate salts + H 2 O) at different temperatures. The salts used were sodium di-hydrogen phosphate (NaH 2 PO 4 ), di-sodium hydrogen phosphate (Na 2 HPO 4 ) and tri-sodium phosphate (Na 3 PO 4 ). The effects of tie line length, salt type, and temperature on the partition coefficient of this amino acid have been studied. In addition, thermodynamic parameters (ΔH o , ΔS o and ΔG o ) as a function of temperature were calculated. The results showed that increasing tie line length led to decreasing of the partition coefficient. We also showed that the partition coefficients of the amino acid in the systems containing Na 3 PO 4 are greater than the other two salts. Moreover, it is verified that increasing temperature led to decreasing the partition coefficient. The experimental partition coefficient data are correlated using a modified virial-type model.

  19. In vitro bioactivity of soda lime borate glasses with substituted SrO in sodium phosphate solution

    Directory of Open Access Journals (Sweden)

    Mohamed A. Marzouk

    2014-09-01

    Full Text Available Borate glasses with the basic composition 0.6B2O3·0.2Na2O·0.2CaO and SrO progressively substituting CaO were prepared and characterized for their bone-bonding ability. The obtained glasses were thermally treated and converted to their glass-ceramic derivatives. In this study, FTIR spectral analyses were done for the prepared glasses and glass-ceramics before and after immersion in a sodium phosphate solution for extended times. The appearance of two IR bands within the spectral range 550–680 cm-1 after immersion confirms the formation of hydroxyapatite. X-ray diffraction studies and scanning electron microscope analysis supported the obtained infrared spectroscopy results. The solubility test (measurements of the weight loss in aqueous sodium phosphate solution was conducted for measuring the dissolution of both glassy and crystalline derivatives to find out the role of SrO. The corrosion behaviour of the glasses and glass-ceramics indicate the increase of weight loss with the increase of SrO content. Different suggested proposals were introduced to explain this abnormal behaviour.

  20. Effect of poly(lactide-co-glycolide) molecular weight on the release of dexamethasone sodium phosphate from microparticles.

    Science.gov (United States)

    Jaraswekin, Saowanee; Prakongpan, Sompol; Bodmeier, Roland

    2007-03-01

    The objective of this study was to investigate the effect of poly(lactide-co-glycolide) (PLGA) molecular weight (Resomer RG 502H, RG 503H, and RG 504H) on the release behavior of dexamethasone sodium phosphate-loaded microparticles. The microparticles were prepared by three modifications of the solvent evaporation method (O/W-cosolvent, O/W-dispersion, and W/O/W-methods). The encapsulation efficiency of microparticles prepared by the cosolvent- and W/O/W-methods increased from approximately 50% to >90% upon addition of NaCl to the external aqueous phase, while the dispersion method resulted in lower encapsulation efficiencies. The release of dexamethasone sodium phosphate from PLGA microparticles (>50 microm) was biphasic. The initial burst release correlated well with the porosity of the microparticles, both of which increased with increasing polymer molecular weight (RG 504H > 503H > 502H). The burst was also dependent on the method of preparation and was in the order of dispersion method > WOW method > consolvent method. In contrast to the higher molecular weight PLGA microparticles, the release from RG 502H microparticles prepared by cosolvent method was not affected by volume of organic solvent (1.5-3.0 ml) and drug loading (4-13%). An initial burst of approximately 10% followed by a 5-week sustained release phase was obtained. Microparticles with a size <50 microm released in a triphasic manner; an initial burst was followed by a slow release phase and then by a second burst.

  1. Stability-Indicating HPLC Method for Simultaneous Determination of Chloramphenicol, Dexamethasone Sodium Phosphate and Tetrahydrozoline Hydrochloride in Ophthalmic Solution.

    Science.gov (United States)

    AlAani, Hashem; Alnukkary, Yasmin

    2016-03-01

    A simple stability-indicating RP-HPLC assay method was developed and validated for quantitative determination of Chloramphenicol, Dexamethasone Sodium Phosphate and Tetrahydrozoline Hydrochloride in ophthalmic solution in the presence of 2-amino-1-(4-nitrophenyl)propane-1,3-diol, a degradation product of Chloramphenicol, and Dexamethasone, a degradation product of Dexamethasone Sodium Phosphate. Effective chromatographic separation was achieved using C18 column (250 mm, 4.6 mm i.d., 5 μm) with isocratic mobile phase consisting of acetonitrile - phosphate buffer (pH 4.0; 0.05 M) (30:70, v/v) at a flow rate of 1 mL/minute. The column temperature was maintained at 40°C and the detection wavelength was 230 nm. The proposed HPLC procedure was statistically validated according to the ICH guideline, and was proved to be stability-indicating by resolution of the APIs from their forced degradation products. The developed method is suitable for the routine analysis as well as stability studies.

  2. Stability of Diphenhydramine Hydrochloride, Lorazepam, and Dexamethasone Sodium Phosphate in 0.9% Sodium Chloride Stored in Polypropylene Syringes.

    Science.gov (United States)

    Anderson, Collin R; Halford, Zachery; MacKay, Mark

    2015-01-01

    Chemotherapy induced nausea and vomiting is problematic for many patients undergoing chemotherapy. Multiple-drug treatments have been developed to mitigate chemotherapy induced nausea and vomiting. A patient-controlled infusion of diphenhydramine hydrochloride, lorazepam, and dexamethasone sodium phosphate has been studied in patients who are refractory to first-line therapy. Unfortunately, the physical and chemical compatibility of this three-drug combination is not available in the published literature. Chemical compatibility was evaluated using high-performance liquid chromatography with ultraviolet detection. Visual observation was employed to detect change in color, clarity, or gas evolution. Turbidity and pH measurements were performed in conjunction with visual observation at hours 0, 24, and 48. Results showed that diphenhydramine hydrochloride 4 mg/mL, lorazepam 0.16 mg/mL, and dexamethasone sodium phosphate 0.27 mg/mL in 0.9% sodium chloride stored in polypropylene syringes were compatible, and components retained greater than 95% of their original concentration over 48 hours when stored at room temperature.

  3. Cotransporters as molecular water pumps

    DEFF Research Database (Denmark)

    Zeuthen, Thomas; MacAulay, Nanna

    2002-01-01

    Molecular water pumps are membrane proteins of the cotransport type in which a flux of water is coupled to substrate fluxes by a mechanism within the protein. Free energy can be exchanged between the fluxes. Accordingly, the flux of water may be relatively independent of the external water chemical...

  4. Vasopressin induces phosphorylation of the thiazide-sensitive sodium chloride cotransporter in the distal convoluted tubule

    DEFF Research Database (Denmark)

    Pedersen, Nis Borbye; Hofmeister, Marlene Vind; Rosenbaek, Lena L

    2010-01-01

    The thiazide-sensitive Na(+)-Cl(-) cotransporter (NCC) is important for renal electrolyte balance and its phosphorylation causes an increase in its transport activity and cellular localization. Here, we generated phospho-specific antibodies against two conserved N-terminal phosphorylation sites...

  5. Structural and luminescence studies of Ho{sup 3+}-doped zinc-aluminium-sodium-phosphate (ZANP) glasses

    Energy Technology Data Exchange (ETDEWEB)

    Brahmachary, K.; Rajesh, D.; Ratnakaram, Y. C., E-mail: ratnakaramsvu@gmail.com [Department of Physics, Sri Venkateswara University, Tirupati-517502 (India)

    2015-06-24

    Trivalent holmium doped zinc-aluminium-sodium-phosphate (ZANP) glasses were prepared by conventional melt-quenching technique and characterized for their structural and luminescence properties. The amorphous nature, elemental analysis and thermal stability of the glasses were studied by using X-ray diffraction, energy dispersive spectrum and differential scanning calorimetry analysis, respectively. The absorption and fluorescence spectra have been recorded at room temperature. Based on the absorption spectra, the Judd-Ofelt parameters and radiative parameters such as spontaneous transition probabilities (A{sub R}), branching ratios (β{sub R}), radiative lifetimes (τ{sub R}) were calculated and discussed. From the emission spectra emission peak positions (λ{sub P}), effective bandwidths (Δλ{sub eff}) and stimulated emission cross-sections (σ{sub P}) were calculated for the observed emission transitions,{sup 5}S{sub 2} ({sup 5}F{sub 4}→{sup 5}I{sub 8}) and {sup 5}F{sub 5}→{sup 5}I{sub 8} in all the glass samples. The stimulated emission cross-section is higher for ZANPHo10 glass matrix and so it may be useful for laser excitation.

  6. Comparative study of layer-by-layer deposition techniques for poly(sodium phosphate) and poly(allylamine hydrochloride).

    Science.gov (United States)

    Elosua, Cesar; Lopez-Torres, Diego; Hernaez, Miguel; Matias, Ignacio R; Arregui, Francisco J

    2013-12-20

    An inorganic short chain polymer, poly(sodium phosphate), PSP, together with poly(allylamine hydrochloride), PAH, is used to fabricate layer-by-layer (LbL) films. The thickness, roughness, contact angle, and optical transmittance of these films are studied depending on three parameters: the precursor solution concentrations (10-3 and 10-4 M), the number of bilayers deposited (20, 40, 60, 80, and 100 bilayers), and the specific technique used for the LbL fabrication (dipping or spraying). In most cases of this experimental study, the roughness of the nanofilms increases with the number of bilayers. This contradicts the basic observations made in standard LbL assemblies where the roughness decreases for thicker coatings. In fact, a wide range of thickness and roughness was achieved by means of adjusting the three parameters mentioned above. For instance, a roughness of 1.23 or 205 nm root mean square was measured for 100 bilayer coatings. Contact angles close to 0 were observed. Moreover, high optical transmittance is also reported, above 90%, for 80 bilayer films fabricated with the 10-4 M solutions. Therefore, these multilayer structures can be used to obtain transparent superhydrophilic surfaces.

  7. Thermal inactivation of Salmonella Enteritidis on chicken skin previously exposed to acidified Sodium chlorite or tri-sodium phosphate.

    Science.gov (United States)

    Karuppasamy, K; Yadav, Ajit S; Saxena, Gaurav K

    2015-12-01

    Thermal inactivation of normal and starved cells of Salmonella Enteritidis on chicken skin previously exposed to different concentrations of acidified sodium chlorite (ASC) or tri-sodium phosphate (TSP) was investigated. Inoculated skin was pretreated with different concentration of ASC or TSP, packaged in bags, and then immersed in a circulating water bath at 60 to 68 °C. The recovery medium was Hektoen enteric agar. D-values, determined by linear regression, for normal cells on chicken skin, were 2.79, 1.17 and 0.53 min whereas D-values for starved cells were 4.15, 1.83 and 0.66 at 60, 64 and 68 °C, respectively. z-values for normal cells were 3.54 and for starved cells were 2.29. Pretreatment of Salmonella Enteritidis cells with 0 to 200 ppm of ASC or 0 to 1.0 % TSP resulted in lower D-values at all temperatures. Sensory results indicated no significance differences for control and treatments. Thus, results of this study indicated that pretreatment of chicken skin with ASC or TSP increased sensitivity of Salmonella Enteritidis to heat without affecting organoleptic quality of chicken meat.

  8. Stability of i.v. admixture containing metoclopramide, diphenhydramine hydrochloride, and dexamethasone sodium phosphate in 0.9% sodium chloride injection.

    Science.gov (United States)

    Kintzel, Polly E; Zhao, Ting; Wen, Bo; Sun, Duxin

    2014-12-01

    The chemical stability of a sterile admixture containing metoclopramide 1.6 mg/mL, diphenhydramine hydrochloride 2 mg/mL, and dexamethasone sodium phosphate 0.16 mg/mL in 0.9% sodium chloride injection was evaluated. Triplicate samples were prepared and stored at room temperature without light protection for a total of 48 hours. Aliquots from each sample were tested for chemical stability immediately after preparation and at 1, 4, 8, 24, and 48 hours using liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Metoclopramide, diphenhydramine hydrochloride, and dexamethasone sodium phosphate were selectively monitored using multiple-reaction monitoring. Samples were diluted differently for quantitation using three individual LC-MS/MS methods. To determine the drug concentration of the three compounds in the samples, three calibration curves were constructed by plotting the peak area or the peak area ratio versus the concentration of the calibration standards of each tested compound. Apixaban was used as an internal standard. Linearity of the calibration curve was evaluated by the correlation coefficient r(2). Constituents of the admixture of metoclopramide 1.6 mg/mL, diphenhydramine hydrochloride 2 mg/mL, and dexamethasone sodium phosphate 0.16 mg/mL in 0.9% sodium chloride injection retained more than 90% of their initial concentrations over 48 hours of storage at room temperature without protection from light. The observed variability in concentrations of these three compounds was within the limits of assay variability. An i.v. admixture containing metoclopramide 1.6 mg/mL, diphenhydramine hydrochloride 2 mg/mL, and dexamethasone sodium phosphate 0.16 mg/mL in 0.9% sodium chloride injection was chemically stable for 48 hours when stored at room temperature without light protection. Copyright © 2014 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

  9. Effect of sodium phosphate salts on the thermodynamic properties of aqueous solutions of poly(ethylene oxide) 6000 at different temperatures

    International Nuclear Information System (INIS)

    Sadeghi, Rahmat; Hosseini, Rahim; Jamehbozorg, Bahman

    2008-01-01

    Precise density, sound velocity, water activity, and phase diagram measurements have been carried out on polyethylene oxide (PEO) in aqueous solutions of sodium di-hydrogen phosphate, di-sodium hydrogen phosphate, and tri-sodium phosphate over a range of temperatures at atmospheric pressure. The experimental density and sound velocity data are used to calculate the apparent specific volume and isentropic compressibility as a function of temperature and concentration. It was found that both of the apparent specific volume and isentropic compressibility of PEO in aqueous solutions increase by increasing temperature and charge on the anion of electrolytes. The results show that the slope of constant water activity lines increased with increasing the temperature and charge on the anion of electrolytes and the vapour pressure depression for an aqueous (PEO + sodium phosphate) system is more than the sum of those for the corresponding binary solutions. Furthermore, the effect of temperature and type of anion of salt on the salting-out effect of polyethylene oxide by sodium phosphate salts has been studied

  10. Effect of sodium phosphate salts on the thermodynamic properties of aqueous solutions of poly(ethylene oxide) 6000 at different temperatures

    Energy Technology Data Exchange (ETDEWEB)

    Sadeghi, Rahmat [Department of Chemistry, University of Kurdistan, Sanandaj (Iran, Islamic Republic of)], E-mail: rahsadeghi@yahoo.com; Hosseini, Rahim; Jamehbozorg, Bahman [Department of Chemistry, University of Kurdistan, Sanandaj (Iran, Islamic Republic of)

    2008-09-15

    Precise density, sound velocity, water activity, and phase diagram measurements have been carried out on polyethylene oxide (PEO) in aqueous solutions of sodium di-hydrogen phosphate, di-sodium hydrogen phosphate, and tri-sodium phosphate over a range of temperatures at atmospheric pressure. The experimental density and sound velocity data are used to calculate the apparent specific volume and isentropic compressibility as a function of temperature and concentration. It was found that both of the apparent specific volume and isentropic compressibility of PEO in aqueous solutions increase by increasing temperature and charge on the anion of electrolytes. The results show that the slope of constant water activity lines increased with increasing the temperature and charge on the anion of electrolytes and the vapour pressure depression for an aqueous (PEO + sodium phosphate) system is more than the sum of those for the corresponding binary solutions. Furthermore, the effect of temperature and type of anion of salt on the salting-out effect of polyethylene oxide by sodium phosphate salts has been studied.

  11. Bowel Preparation for Colonoscopy with Sodium Phosphate Solution versus Polyethylene Glycol-Based Lavage: A Multicenter Trial

    Directory of Open Access Journals (Sweden)

    S. Schanz

    2008-01-01

    Full Text Available Background: Adequate bowel preparation is essential for accurate colonoscopy. Both oral sodium phosphate (NaP and polyethylene glycol-based lavage (PEG-ELS are used predominantly as bowel cleansing modalities. NaP has gained popularity due to low drinking volume and lower costs. The purpose of this randomized multicenter observer blinded study was to compare three groups of cleansing (NaP, NaP + sennosides, PEG-ELS + sennosides in reference to tolerability, acceptance, and cleanliness. Patient and Methods: 355 outpatients between 18 and 75 years were randomized into three groups (A, B, C receiving NaP = A, NaP, and sennosides = B or PEG-ELS and sennosides = C. Gastroenterologists performing colonoscopies were blinded to the type of preparation. All patients documented tolerance and adverse events. Vital signs, premedication, completeness, discomfort, and complications were recorded. A quality score (0–4 of cleanliness was generated. Results: The three groups were similar with regard to age, sex, BMI, indication for colonoscopy, and comorbidity. Drinking volumes (L (A = 4.33 + 1.2, B = 4.56 + 1.18, C = 4.93 + 1.71 were in favor of NaP (P = .005. Discomfort from ingested fluid was recorded in A = 39.8% (versus C: P = .015, B = 46.6% (versus C: P = .147, and C = 54.6%. Differences in tolerability and acceptance between the three groups were statistically not significant. No differences in adverse events and the cleanliness effects occurred in the three groups (P = .113. The cleanliness quality scores 0–2 were calculated in A: 77.7%, B: 86.7%, and C: 85.2%. Conclusions: These data fail to demonstrate significant differences in tolerability, acceptance, and preparation quality between the three types of bowel preparation for colonoscopy. Cleansing with NaP was not superior to PEG-ELS.

  12. Spectrophotometric and chemometric methods for determination of imipenem, ciprofloxacin hydrochloride, dexamethasone sodium phosphate, paracetamol and cilastatin sodium in human urine

    Science.gov (United States)

    El-Kosasy, A. M.; Abdel-Aziz, Omar; Magdy, N.; El Zahar, N. M.

    2016-03-01

    New accurate, sensitive and selective spectrophotometric and chemometric methods were developed and subsequently validated for determination of Imipenem (IMP), ciprofloxacin hydrochloride (CIPRO), dexamethasone sodium phosphate (DEX), paracetamol (PAR) and cilastatin sodium (CIL) in human urine. These methods include a new derivative ratio method, namely extended derivative ratio (EDR), principal component regression (PCR) and partial least-squares (PLS) methods. A novel EDR method was developed for the determination of these drugs, where each component in the mixture was determined by using a mixture of the other four components as divisor. Peak amplitudes were recorded at 293.0 nm, 284.0 nm, 276.0 nm, 257.0 nm and 221.0 nm within linear concentration ranges 3.00-45.00, 1.00-15.00, 4.00-40.00, 1.50-25.00 and 4.00-50.00 μg mL- 1 for IMP, CIPRO, DEX, PAR and CIL, respectively. PCR and PLS-2 models were established for simultaneous determination of the studied drugs in the range of 3.00-15.00, 1.00-13.00, 4.00-12.00, 1.50-9.50, and 4.00-12.00 μg mL- 1 for IMP, CIPRO, DEX, PAR and CIL, respectively, by using eighteen mixtures as calibration set and seven mixtures as validation set. The suggested methods were validated according to the International Conference of Harmonization (ICH) guidelines and the results revealed that they were accurate, precise and reproducible. The obtained results were statistically compared with those of the published methods and there was no significant difference.

  13. Radiative properties and luminescence spectra of Sm{sup 3+} ion in zinc–aluminum–sodium-phosphate (ZANP) glasses

    Energy Technology Data Exchange (ETDEWEB)

    Brahmachary, K.; Rajesh, D.; Ratnakaram, Y.C., E-mail: ratnakaramsvu@gmail.com

    2015-05-15

    The fluorescence properties of different concentrations of Sm{sup 3+} doped zinc–aluminum–sodium-phosphate (ZANP) glasses were studied by the XRD, SEM, FTIR, TG–DTA, optical absorption, photoluminescence and decay cure analysis. X-ray diffraction profiles and SEM images confirmed the amorphous nature of the glass samples. Structural information of these glass matrices was provided by FTIR spectrum. Judd–Ofelt (J–O) theory was applied to the experimental oscillator strengths to evaluate three phenomenological J–O intensity parameters, Ω{sub λ} (λ=2, 4 and 6). Using J–O intensity parameters and emission spectra, various radiative parameters such as radiative transition probabilities (A{sub R}), radiative lifetimes (τ{sub R}), calculated and measured branching ratios (β{sub R} and β{sub m}), effective bandwidths (Δλ{sub eff}) and stimulated emission cross-sections (σ{sub P}) were calculated for observed emission transitions. The intensity of emission transitions with the variation of Sm{sup 3+} ion concentration was studied. The nature of decay curves of {sup 4}G{sub 5/2} level for different Sm{sup 3+} ion concentrations in ZANP glass was analyzed and obtained measured lifetimes (τ{sub exp}). Quantum efficiency of {sup 4}G{sub 5/2} level was calculated based on experimental and measured radiative lifetimes (τ{sub exp} and τ{sub R}). - Highlights: • The amorphous nature of glasses was confirmed due to lack of sharp peaks in the XRD profiles. • Higher covalency and rigidity were obtained in ZANPSm05 and ZANPSm15 glass matrices respectively. • The symmetric nature present in ZANP glass matrix is confirmed from MD transition, {sup 4}G{sub 5/2}→{sup 6}H{sub 7/2} of Sm{sup 3+} ion. • The decrease of intensity of emission transitions beyond 0.5 mol% is attributed to dipole–dipole interactions. • Among all the glass matrices studied, all the spectroscopic parameters are higher in ZANPSm05 glass matrix.

  14. Characterization of a novel phosphorylation site in the sodium-chloride cotransporter, NCC

    DEFF Research Database (Denmark)

    Rosenbaek, L L; Assentoft, M; Pedersen, N B

    2012-01-01

    The sodium-chloride cotransporter, NCC, is essential for renal electrolyte balance. NCC function can be modulated by protein phosphorylation. In this study, we characterized the role and physiological regulation of a novel phosphorylation site in NCC at Ser124 (S124). Novel phospho-specific antib......The sodium-chloride cotransporter, NCC, is essential for renal electrolyte balance. NCC function can be modulated by protein phosphorylation. In this study, we characterized the role and physiological regulation of a novel phosphorylation site in NCC at Ser124 (S124). Novel phospho......-related proline-alanine-rich kinase and oxidative stress-response kinases (SPAK and OSR1) were not able to phosphorylate NCC at S124. Protein kinase arrays identified multiple kinases that were able to bind to the region surrounding S124. Four of these kinases (IRAK2, CDK6/Cyclin D1, NLK and m...

  15. Positioning of sodium-glucose cotransporter-2 inhibitors in national and international guidelines.

    Science.gov (United States)

    Morillas, Carlos

    2016-11-01

    Sodium-glucose cotransporter-2 inhibitors (SGLT2-i) selectively and reversibly inhibit sodium-glucose cotransporter-2 (SGLT2), promoting renal glucose excretion and reducing plasma glycaemia. By increasing renal glucose excretion, these drugs favour a negative energy balance, leading to weight loss. Their glucoselowering effect is independent of insulin. Although these drugs have only recently been developed, they have been included in all the main national and international guidelines since 2014. The present review summarises the most important recommendations on the use of SGLT2 in patients with DM2 contained in the most recently published guidelines and consensus statements. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  16. Compatibility and Stability of VARUBI (Rolapitant) Injectable Emulsion Admixed with Intravenous Palonosetron Hydrochloride Injection and Dexamethasone Sodium Phosphate Injection.

    Science.gov (United States)

    Wu, George; Powers, Dan; Yeung, Stanley; Chen, Frank

    2018-01-01

    Prophylaxis or therapy with a combination of a neurokinin 1 (NK-1) receptor antagonist (RA), a 5-hydroxytryptamine-3 (5-HT3) RA, and dexamethasone is recommended by international antiemesis guidelines for the prevention of chemotherapy-induced nausea and vomiting for patients receiving highly emetogenic chemotherapy and for selected patients receiving moderately emetogenic chemotherapy. VARUBI (rolapitant) is a substance P/NK-1 RA that was recently approved by the U.S. Food and Drug Administration as an injectable emulsion in combination with other antiemetic agents in adults for the prevention of delayed nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy, including, but not limited to, highly emetogenic chemotherapy. Palonosetron is one of the 5-HT3 RAs indicated for the prevention of nausea and/or vomiting associated with initial and repeat courses of emetogenic cancer therapy, including high-dose cisplatin. Herein, we describe the physical and chemical compatibility and stability of VARUBI injectable emulsion (166.5 mg/92.5 mL [1.8 mg/mL, free base], equivalent to 185 mg of rolapitant hydrochloride) admixed with palonosetron injection 0.25 mg free base in 5 mL (equivalent to 0.28 mg hydrochloride salt) and with either 5 mL (20 mg) or 2.5 mL (10 mg) of dexamethasone sodium phosphate. Admixtures were prepared and stored in VARUBI injectable emulsion ready-to-use glass vials as supplied by the rolapitant manufacturer and in four types of commonly used intravenous administration (tubing) sets. Assessment of the physical and chemical compatibility and stability of the admixtures in the VARUBI ready-to-use vials stored at room temperature (20°C to 25°C) under fluorescent light and under refrigeration (2°C to 8°C protected from light) was conducted at 0, 1, 6, 24, and 48 hours, and that of the admixtures in the intravenous tubing sets was evaluated at 0, 2, and 6 hours of storage at 20°C to 25°C. Physical stability

  17. XANES analysis of calcium and sodium phosphates and silicates and hydroxyapatite-Bioglass (registered) 45S5 co-sintered bioceramics

    International Nuclear Information System (INIS)

    Demirkiran, Hande; Hu Yongfeng; Zuin, Lucia; Appathurai, Narayana; Aswath, Pranesh B.

    2011-01-01

    Bioglass (registered) 45S5 was co-sintered with hydroxyapatite at 1200 deg. C. When small amounts ( 5 (PO 4 ) 2 SiO 4 and Na 3 Ca 6 (PO 4 ) 5 in an amorphous silicate matrix respectively. These chemistries show improved bioactivity compared to hydroxyapatite and are the subject of this study. The structure of several crystalline calcium and sodium phosphates and silicates as well as the co-sintered hydroxyapatite-Bioglass (registered) 45S5 bioceramics were examined using XANES spectroscopy. The nature of the crystalline and amorphous phases were studied using silicon (Si) and phosphorus (P) K- and L 2,3 -edge and calcium (Ca) K-edge XANES. Si L 2,3 -edge spectra of sintered bioceramic compositions indicates that the primary silicates present in these compositions are sodium silicates in the amorphous state. From Si K-edge spectra, it is shown that the silicates are in a similar structural environment in all the sintered bioceramic compositions with 4-fold coordination. Using P L 2,3 -edge it is clearly shown that there is no evidence of sodium phosphate present in the sintered bioceramic compositions. In the P K-edge spectra, the post-edge shoulder peak at around 2155 eV indicates that this shoulder to be more defined for calcium phosphate compounds with decreasing solubility and increasing thermodynamic stability. This shoulder peak is more noticeable in hydroxyapatite and β-TCP indicating greater stability of the phosphate phase. The only spectra that does not show a noticeable peak is the composition with Na 3 Ca 6 (PO 4 ) 5 in a silicate matrix indicating that it is more soluble compared to the other compositions.

  18. XANES analysis of calcium and sodium phosphates and silicates and hydroxyapatite-Bioglass (registered) 45S5 co-sintered bioceramics

    Energy Technology Data Exchange (ETDEWEB)

    Demirkiran, Hande [Graduate Student, Materials Science and Engineering Department, University of Texas at Arlington, Arlington, TX (United States); Hu Yongfeng; Zuin, Lucia [Beamline Scientist, Canadian Light Source, Saskatoon, SK (Canada); Appathurai, Narayana [Beamline Scientist, Synchrotron Radiation Center, Madison, WI (United States); Aswath, Pranesh B., E-mail: aswath@uta.edu [Materials Science and Engineering Department, University of Texas at Arlington, Arlington, TX (United States)

    2011-03-12

    Bioglass (registered) 45S5 was co-sintered with hydroxyapatite at 1200 deg. C. When small amounts (< 5 wt.%) of Bioglass (registered) 45S5 was added it behaved as a sintering aid and also enhanced the decomposition of hydroxyapatite to {beta}-tricalcium phosphate. However when 10 wt.% and 25 wt.% Bioglass (registered) 45S5 was used it resulted in the formation of Ca{sub 5}(PO{sub 4}){sub 2}SiO{sub 4} and Na{sub 3}Ca{sub 6}(PO{sub 4}){sub 5} in an amorphous silicate matrix respectively. These chemistries show improved bioactivity compared to hydroxyapatite and are the subject of this study. The structure of several crystalline calcium and sodium phosphates and silicates as well as the co-sintered hydroxyapatite-Bioglass (registered) 45S5 bioceramics were examined using XANES spectroscopy. The nature of the crystalline and amorphous phases were studied using silicon (Si) and phosphorus (P) K- and L{sub 2,3}-edge and calcium (Ca) K-edge XANES. Si L{sub 2,3}-edge spectra of sintered bioceramic compositions indicates that the primary silicates present in these compositions are sodium silicates in the amorphous state. From Si K-edge spectra, it is shown that the silicates are in a similar structural environment in all the sintered bioceramic compositions with 4-fold coordination. Using P L{sub 2,3}-edge it is clearly shown that there is no evidence of sodium phosphate present in the sintered bioceramic compositions. In the P K-edge spectra, the post-edge shoulder peak at around 2155 eV indicates that this shoulder to be more defined for calcium phosphate compounds with decreasing solubility and increasing thermodynamic stability. This shoulder peak is more noticeable in hydroxyapatite and {beta}-TCP indicating greater stability of the phosphate phase. The only spectra that does not show a noticeable peak is the composition with Na{sub 3}Ca{sub 6}(PO{sub 4}){sub 5} in a silicate matrix indicating that it is more soluble compared to the other compositions.

  19. Functionalized silica nanoparticles as a carrier for Betamethasone Sodium Phosphate: Drug release study and statistical optimization of drug loading by response surface method.

    Science.gov (United States)

    Ghasemnejad, M; Ahmadi, E; Mohamadnia, Z; Doustgani, A; Hashemikia, S

    2015-11-01

    Mesoporous silica nanoparticles with a hexagonal structure (SBA-15) were synthesized and modified with (3-aminopropyl) triethoxysilane (APTES), and their performance as a carrier for drug delivery system was studied. Chemical structure and morphology of the synthesized and modified SBA-15 were characterized by SEM, BET, TEM, FT-IR and CHN technique. Betamethasone Sodium Phosphate (BSP) as a water soluble drug was loaded on the mesoporous silica particle for the first time. The response surface method was employed to obtain the optimum conditions for the drug/silica nanoparticle preparation, by using Design-Expert software. The effect of time, pH of preparative media, and drug/silica ratio on the drug loading efficiency was investigated by the software. The maximum loading (33.69%) was achieved under optimized condition (pH: 1.8, time: 3.54 (h) and drug/silica ratio: 1.7). The in vitro release behavior of drug loaded particles under various pH values was evaluated. Finally, the release kinetic of the drug was investigated using the Higuchi and Korsmeyer-Peppas models. Cell culture and cytotoxicity assays revealed the synthesized product doesn't have any cytotoxicity against human bladder cell line 5637. Accordingly, the produced drug-loaded nanostructures can be applied via different routes, such as implantation and topical or oral administration. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Bond strength and interfacial morphology of orthodontic brackets bonded to eroded enamel treated with calcium silicate-sodium phosphate salts or resin infiltration.

    Science.gov (United States)

    Costenoble, Aline; Vennat, Elsa; Attal, Jean-Pierre; Dursun, Elisabeth

    2016-11-01

     To investigate the shear bond strength (SBS) of orthodontic brackets bonded to eroded enamel treated with preventive approaches and to examine the enamel/bracket interfaces.  Ninety-one brackets were bonded to seven groups of enamel samples: sound; eroded; eroded+treated with calcium silicate-sodium phosphate salts (CSP); eroded+infiltrated by ICON ® ; eroded+infiltrated by ICON ® and brackets bonded with 1-month delay; eroded+infiltrated by an experimental resin; and eroded+infiltrated by an experimental resin and brackets bonded with 1-month delay. For each group, 12 samples were tested in SBS and bond failure was assessed with the adhesive remnant index (ARI); one sample was examined using scanning electron microscopy (SEM).  Samples treated with CSP or infiltration showed no significant differences in SBS values with sound samples. Infiltrated samples followed by a delayed bonding showed lower SBS values. All of the values remained acceptable. The ARI scores were significantly higher for sound enamel, eroded, and treated with CSP groups than for all infiltrated samples. SEM examinations corroborated the findings.  Using CSP or resin infiltration before orthodontic bonding does not jeopardize the bonding quality. The orthodontic bonding should be performed shortly after the resin infiltration.

  1. High temperature aqueous potassium and sodium phosphate solutions: two-liquid-phase boundaries and critical phenomena, 275-4000C; potential applications for steam generators

    International Nuclear Information System (INIS)

    Marshall, W.L.

    1981-12-01

    Two-liquid-phase boundaries at temperatures between 275 and 400 0 C were determined for potassium phosphate and sodium phosphate aqueous solutions for compositions from 0 to 60 wt % dissolved salt. The stoichiometric mole ratios, K/PO 4 or Na/PO 4 , were varied from 1.00 to 2.12 and from 1.00 to 2.16 for the potassium and sodium systems, respectively. Liquid-vapor critical temperatures were also determined for most of the dilute liquid phases that formed. The minimum temperatures (below which a single solution existed) of two-liquid-phase formation were 360 0 C for the potassium system and 279 0 C for the sodium system at mole ratios of 2.00 and 2.16, respectively. For the sodium system at mole ratios greater than 2.16, solids crystallized at lower temperatures as expected from earlier studies. In contrast, potassium solutions that were explored at mole ratios from 2.12 to 3.16 and at temperatures below 360 0 C did not produce solid phases nor liquid-liquid immiscibilities. Aside from the generally unusual observations of two immiscible liquids in an aqueous inorganic salt system, the results could possibly be applied to the use of phosphate additives in steam power generators. 16 refs

  2. Passive water and ion transport by cotransporters

    DEFF Research Database (Denmark)

    Loo, D D; Hirayama, B A; Meinild, A K

    1999-01-01

    the Lp of control oocytes. Passive Na+ transport (Na+ leak) was obtained from the blocker-sensitive Na+ currents in the absence of substrates (glucose and GABA). 2. Passive Na+ and water transport through SGLT1 were blocked by phlorizin with the same sensitivity (inhibitory constant (Ki), 3-5 micro......1. The rabbit Na+-glucose (SGLT1) and the human Na+-Cl--GABA (GAT1) cotransporters were expressed in Xenopus laevis oocytes, and passive Na+ and water transport were studied using electrical and optical techniques. Passive water permeabilities (Lp) of the cotransporters were determined from......M). When Na+ was replaced with Li+, phlorizin also inhibited Li+ and water transport, but with a lower affinity (Ki, 100 microM). When Na+ was replaced by choline, which is not transported, the SGLT1 Lp was indistinguishable from that in Na+ or Li+, but in this case water transport was less sensitive...

  3. Preformulation and characterization of a lidocaine hydrochloride and dexamethasone sodium phosphate thermo-reversible and bioadhesive long-acting gel for intraperitoneal administration.

    Science.gov (United States)

    Arbelaez-Camargo, Diana; Suñé-Negre, Josep Maria; Roig-Carreras, Manel; García-Montoya, Encarna; Pérez-Lozano, Pilar; Miñarro-Carmona, Montserrat; Ticó-Grau, Josep Ramon

    2016-02-10

    The search for new formulations of anaesthetic agents that allow a localized administration and provide a prolonged effect is of great interest in the multimodal management of postoperative pain. The pre-formulation and characterization of a lidocaine and dexamethasone thermosensitive and bioadhesive long-acting gel for intraperitoneal administration was done as a tool in the management of pain in abdominal surgeries. The pre-formulation process was conducted by a systematic variation of the concentration of the different polymers, until setting it, in a suitable concentration that allowed an adequate gelation temperature. The poloxamer 407 (P407) was used as the main polymer; hydroxypropyl methylcellulose (HPMC) as the bioadhesive agent and polyvinyl pyrrolidone (PVP) to adjust the gelation temperature and physicochemical properties. The formulations were characterized by gelation temperature, pH, viscosity at 25°C and 37°C, gelation time, density and osmolality. Gelation temperature was decreased when increasing the concentration of hydroxypropyl methylcellulose and poloxamer 407, this effect was also observed when adding lidocaine hydrochloride and dexamethasone sodium phosphate to the formulations. The gelation temperature did not have statistically significant relation with the PVP concentration (P-value of 0.6797), even though, there is a tendency in the gelation temperature by varying it. Between the developed formulations, the 12.5/3.3/0.4% (P407/HPMC/PVP) formulation presents an appropriate gelation temperature, a suitable viscosity for administration by syringe, an adequate and stable pH and osmolality to prevent tissue damage and a correct gelation time that allowed the formation of a prolonged release implant. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Controlled transdermal iontophoresis for poly-pharmacotherapy: Simultaneous delivery of granisetron, metoclopramide and dexamethasone sodium phosphate in vitro and in vivo.

    Science.gov (United States)

    Cázares-Delgadillo, Jennyfer; Ganem-Rondero, Adriana; Merino, Virginia; Kalia, Yogeshvar N

    2016-03-31

    Iontophoresis has been used to deliver small molecules, peptides and proteins into and across the skin. In principle, it provides a controlled, non-invasive method for poly-pharmacotherapy since it is possible to formulate and to deliver multiple therapeutic agents simultaneously from the anodal and cathodal compartments. The objective of this proof-of-principle study was to investigate the simultaneous anodal iontophoretic delivery of granisetron (GST) and metoclopramide (MCL) and cathodal iontophoresis of dexamethasone sodium phosphate (DEX-P). In addition to validating the hypothesis, these are medications that are routinely used in combination to treat chemotherapy-induced emesis. Two preliminary in vitro studies using porcine skin were performed: Study 1 - effect of formulation composition on anodal co-iontophoresis of GST and MCL and Study 2 - combined anodal iontophoresis of GST (10mM) and MCL (110 mM) and cathodal iontophoresis of DEX-P (40 mM). The results from Study 1 demonstrated the dependence of GST/MCL transport on the respective drug concentrations when co-iontophoresed at 0.3 mA·cm(-2). Although they possess similar physicochemical properties, MCL seemed to be a more efficient charge carrier (JMCL=0.0591∗CMCLvs JGST=0.0414∗CGST). In Study 2, MCL permeation was markedly superior to that of GST (2324.83 ± 307.85 and 209.83 ± 24.84 μg·cm(-2), respectively); this was consistent with the difference in their relative concentrations; DEX-P permeation was 336.94 ± 71.91 μg·cm(-2). The in vivo studies in Wistar rats (10mM GST, 110 mM MCL and 40 mM DEX-P (0.5 mA·cm(-2) for 5h with Ag/AgCl electrodes and salt bridges) demonstrated that significant drug levels were achieved rapidly for each drug. This was most noticeable for dexamethasone (DEX) where relatively constant plasma levels were obtained from the 1 to 5h time-points; DEX-P was not detected in the plasma since it was completely hydrolyzed to the active metabolite. The calculated input

  5. Intra-individual comparison of magnesium citrate and sodium phosphate for bowel preparation at CT colonography: Automated volumetric analysis of residual fluid for quality assessment

    International Nuclear Information System (INIS)

    Bannas, P.; Bakke, J.; Munoz del Rio, A.; Pickhardt, P.J.

    2014-01-01

    Aim: To perform an objective, intra-individual comparison of residual colonic fluid volume and attenuation associated with the current front-line laxative magnesium citrate (MgC) versus the former front-line laxative sodium phosphate (NaP) at CT colonography (CTC). Materials and methods: This retrospective Health Insurance and Portability and Accountability Act-compliant study had institutional review board approval; informed consent was waived. The study cohort included 250 asymptomatic adults (mean age at index 56.1 years; 124 male/126 female) who underwent CTC screening twice over a 5 year interval. Colon catharsis at initial and follow-up screening employed single-dose NaP and double-dose MgC, respectively, allowing for intra-patient comparison. Automated volumetric analysis of residual colonic fluid volume and attenuation was performed on all 500 CTC studies. Colonic fluid volume <200 ml and mean attenuation between 300–900 HU were considered optimal. Paired t-test and McNemar's test were used to compare differences. Results: Residual fluid volumes <200 ml were recorded in 192 examinations (76.8%) following MgC and in 204 examinations (81.6%) following NaP (p = 0.23). The mean total residual fluid volume was 155 ± 114 ml for MgC and 143 ± 100 ml for NaP (p = 0.01). The attenuation range of 300–900 HU was significantly more frequent for MgC (n = 220, 88%) than for NaP (n = 127, 50.8%; p < 0.001). Mean fluid attenuation was significantly lower for MgC (700 ± 165 HU) than for NaP (878 ± 155 HU; p < 0.001). Concomitant presence of both optimal fluid volume and attenuation was significantly more frequent for MgC 65.2% than for NaP (38%; p < 0.001). Conclusions: Objective intra-individual comparison using automated volumetric analysis suggests that the replacement of NaP by MgC as the front-line laxative for CTC has not compromised overall examination quality. - Highlights: • Automated volumetric analysis provides

  6. Nanomaterials-Based Approaches for the Modulation of Sodium Bicarbonate Cotransporters

    Directory of Open Access Journals (Sweden)

    Jeong Hee Hong

    2015-01-01

    Full Text Available HCO3- and fluid secretion are major functions of all epithelia, and alterations in HCO3- secretion by sodium bicarbonate cotransporters are associated with many epithelial diseases, such as renal, ocular, and dental abnormalities. Electrolyte and fluid exits are synergistically mediated by the intracellular second messengers, cAMP and Ca2+, and this raises the possibility that ion transporters are involved in simple secretion and more complicated forms of regulation. Evidence indicates that HCO3- transport is regulated by the assemblage of Na+-HCO3- cotransporters (NBCs into complexes by multiple regulatory factors. Recently the specific regulatory functions of factors that interact with NBCe1, especially NBCe1-B, have been elucidated. In this review, I focus on the structural characteristics of electrogenic NBCe1, pathophysiology of NBCe1, and molecular mechanisms responsible for transporter regulation. Moreover I propose the possibility to apply nanomaterials combined with regulatory factors for modulating the activity of NBC transporters as a potential development of therapeutic drug.

  7. Activation of thiazide-sensitive co-transport by angiotensin II in the cyp1a1-Ren2 hypertensive rat.

    Directory of Open Access Journals (Sweden)

    Ali Ashek

    Full Text Available Transgenic rats with inducible expression of the mouse Ren2 gene were used to elucidate mechanisms leading to the development of hypertension and renal injury. Ren2 transgene activation was induced by administration of a naturally occurring aryl hydrocarbon, indole-3-carbinol (100 mg/kg/day by gastric gavage. Blood pressure and renal parameters were recorded in both conscious and anesthetized (butabarbital sodium; 120 mg/kg IP rats at selected time-points during the development of hypertension. Hypertension was evident by the second day of treatment, being preceded by reduced renal sodium excretion due to activation of the thiazide-sensitive sodium-chloride co-transporter. Renal injury was evident after the first day of transgene induction, being initially limited to the pre-glomerular vasculature. Mircoalbuminuria and tubuloinsterstitial injury developed once hypertension was established. Chronic treatment with either hydrochlorothiazide or an AT1 receptor antagonist normalized sodium reabsorption, significantly blunted hypertension and prevented renal injury. Urinary aldosterone excretion was increased ≈ 20 fold, but chronic mineralocorticoid receptor antagonism with spironolactone neither restored natriuretic capacity nor prevented hypertension. Spironolactone nevertheless ameliorated vascular damage and prevented albuminuria. This study finds activation of sodium-chloride co-transport to be a key mechanism in angiotensin II-dependent hypertension. Furthermore, renal vascular injury in this setting reflects both barotrauma and pressure-independent pathways associated with direct detrimental effects of angiotensin II and aldosterone.

  8. The effects of sodium-glucose co-transporter 2 inhibitors in patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Storgaard, Heidi; Gluud, Lise Lotte; Christensen, Mikkel

    2014-01-01

    INTRODUCTION: Sodium-glucose co-transporter 2 inhibitors (SGLT-2i) increase urinary glucose excretion through a reduced renal glucose reabsorption. We plan to perform a systematic review of SGLT-2i for treatment of type 2 diabetes. METHODS AND ANALYSIS: A systematic review with meta-analyses of r......INTRODUCTION: Sodium-glucose co-transporter 2 inhibitors (SGLT-2i) increase urinary glucose excretion through a reduced renal glucose reabsorption. We plan to perform a systematic review of SGLT-2i for treatment of type 2 diabetes. METHODS AND ANALYSIS: A systematic review with meta......-analyses of randomised clinical trials on SGLT-2i versus placebo, other oral glucose lowering drugs or insulin for patients with type 2 diabetes will be performed. The primary end point will be the glycated haemoglobin. Secondary end points will include changes in body weight, body mass index, fasting plasma glucose......, plasma cholesterol, kidney and liver blood tests, blood pressure and adverse events. Electronic (the Cochrane Library, MEDLINE, EMBASE and the Science Citation Index) and manual searches will be performed. Meta-analyses will be performed and the results presented as mean differences for continuous...

  9. Cotransport of water by Na¿-K¿-2Cl¿ cotransporters expressed in Xenopus oocytes

    DEFF Research Database (Denmark)

    Zeuthen, Thomas; Macaulay, Nanna

    2012-01-01

    The NKCC1 and NKCC2 isoforms of the mammalian Na¿–K¿–2Cl¿ cotransporter were expressed in Xenopus oocytes and the relation between external ion concentration and water fluxes determined.Water fluxes were determined from changes in the oocytes volume and ion fluxes from 86Rb+ uptake. Isotonic...

  10. Cotransport of water by the Na+-K+-2Cl(-) cotransporter NKCC1 in mammalian epithelial cells

    DEFF Research Database (Denmark)

    Hamann, Steffen; Herrera-Perez, José J; Zeuthen, Thomas

    2010-01-01

    Water transport by the Na+-K+-2Cl(-) cotransporter (NKCC1) was studied in confluent cultures of pigmented epithelial (PE) cells from the ciliary body of the fetal human eye. Interdependence among water, Na+ and Cl(-) fluxes mediated by NKCC1 was inferred from changes in cell water volume, monitored...

  11. Urine concentrating mechanism: impact of vascular and tubular architecture and a proposed descending limb urea-Na+ cotransporter

    Science.gov (United States)

    Dantzler, William H.; Pannabecker, Thomas L.

    2012-01-01

    We extended a region-based mathematical model of the renal medulla of the rat kidney, previously developed by us, to represent new anatomic findings on the vascular architecture in the rat inner medulla (IM). In the outer medulla (OM), tubules and vessels are organized around tightly packed vascular bundles; in the IM, the organization is centered around collecting duct clusters. In particular, the model represents the separation of descending vasa recta from the descending limbs of loops of Henle, and the model represents a papillary segment of the descending thin limb that is water impermeable and highly urea permeable. Model results suggest that, despite the compartmentalization of IM blood flow, IM interstitial fluid composition is substantially more homogeneous compared with OM. We used the model to study medullary blood flow in antidiuresis and the effects of vascular countercurrent exchange. We also hypothesize that the terminal aquaporin-1 null segment of the long descending thin limbs may express a urea-Na+ or urea-Cl− cotransporter. As urea diffuses from the urea-rich papillary interstitium into the descending thin limb luminal fluid, NaCl is secreted via the cotransporter against its concentration gradient. That NaCl is then reabsorbed near the loop bend, raising the interstitial fluid osmolality and promoting water reabsorption from the IM collecting ducts. Indeed, the model predicts that the presence of the urea-Na+ or urea- Cl− cotransporter facilitates the cycling of NaCl within the IM and yields a loop-bend fluid composition consistent with experimental data. PMID:22088433

  12. Rationale, design and baseline characteristics of the CANagliflozin cardioVascular Assessment Study-Renal (CANVAS-R) : A randomized, placebo-controlled trial

    NARCIS (Netherlands)

    Neal, Bruce; Perkovic, Vlado; Matthews, David R.; Mahaffey, Kenneth W.; Fulcher, Greg; Meininger, Gary; Erondu, Ngozi; Desai, Mehul; Shaw, Wayne; Vercruysse, Frank; Yee, Jacqueline; Deng, Hsiaowei; de Zeeuw, Dick

    Aims: The primary aim of the CANagliflozin cardioVascular Assessment Study-Renal (CANVAS-R) is to determine whether the favourable effects of inhibition of the sodium glucose co-transporter 2 (SGLT2) on blood glucose, blood pressure and body weight are accompanied by protection against adverse renal

  13. Two-liquid-phase boundaries and critical phenomena at 275 to 4000C for high-temperature aqueous potassium phosphate and sodium phosphate solutions. Potential applications for steam generators

    International Nuclear Information System (INIS)

    Marshall, W.L.

    1982-01-01

    Two-liquid-phase boundaries at temperatures between 275 and 400 0 C were determined for potassium phosphate and sodium phosphate aqueous solutions for compositions from 0 to 60 wt % dissolved salt. The stoichiometric mole ratios, K/PO 4 or Na/PO 4 , were varied from 1.00 to 2.12 and from 1.00 to 2.16 for the potassium and sodium systems, respectively. Liquid-vapor critical temperatures were also determined for most of the dilute liquid phases that formed. The minimum temperatures (below which a single solution existed) of two-liquid-phase formation were 360 0 C for the potassium system and 279 0 C for the sodium system at mole ratios of 2.00 and 2.16, respectively. For the sodium system at mole ratios greater than 2.16, solids crystallized at lower temperatures as expected from earlier studies. In contrast, potassium solutions that were explored at mole ratios from 2.12 to 3.16 and at temperatures below 360 0 C did not produce solid phases or liquid-liquid immisibilities. Aside from the generally unusual observations of two immiscible liquids in an aqueous inorganic salt system, the results could possibly be applied to the use of phosphate additives in steam power generators

  14. Nonclinical safety of the sodium-glucose cotransporter 2 inhibitor empagliflozin.

    Science.gov (United States)

    Bogdanffy, Matthew S; Stachlewitz, Robert F; van Tongeren, Susan; Knight, Brian; Sharp, Dale E; Ku, Warren; Hart, Susan Emeigh; Blanchard, Kerry

    2014-01-01

    Empagliflozin, a selective inhibitor of the renal tubular sodium-glucose cotransporter 2, was developed for treatment of type 2 diabetes mellitus. Nonclinical safety of empagliflozin was studied in a battery of tests to support global market authorization. Safety pharmacology studies indicated no effect of empagliflozin on measures of respiratory or central nervous system function in rats or cardiovascular safety in telemeterized dogs. In CD-1 mouse, Wistar Han rat, or beagle dogs up to 13, 26, or 52 weeks of treatment, respectively, empagliflozin exhibited a toxicity profile consistent with secondary supratherapeutic pharmacology related to glucose loss and included decreased body weight and body fat, increased food consumption, diarrhea, dehydration, decreased serum glucose and increases in other serum parameters reflective of increased protein catabolism, gluconeogenesis, and electrolyte imbalances, and urinary changes such as polyuria and glucosuria. Microscopic changes were consistently observed in kidney and included tubular nephropathy and interstitial nephritis (dog), renal mineralization (rat) and tubular epithelial cell karyomegaly, single cell necrosis, cystic hyperplasia, and hypertrophy (mouse). Empagliflozin was not genotoxic. Empagliflozin was not carcinogenic in female mice or female rats. Renal adenoma and carcinoma were induced in male mice only at exposures 45 times the maximum clinical dose. These tumors were associated with a spectrum of nonneoplastic changes suggestive of a nongenotoxic, cytotoxic, and cellular proliferation-driven mechanism. In male rats, testicular interstitial cell tumors and hemangiomas of the mesenteric lymph node were observed; both tumors are common in rats and are unlikely to be relevant to humans. These studies demonstrate the nonclinical safety of empagliflozin. © The Author(s) 2014.

  15. Cardiovascular effects of sodium glucose cotransporter 2 inhibitors

    Directory of Open Access Journals (Sweden)

    Santos Cavaiola T

    2018-04-01

    Full Text Available Tricia Santos Cavaiola, Jeremy Pettus Division of Endocrinology and Metabolism, University of California San Diego, San Diego, CA, USA Abstract: As the first cardiovascular (CV outcome trial of a glucose-lowering agent to demonstrate a reduction in the risk of CV events in patients with type 2 diabetes mellitus (T2DM, the EMPAgliflozin Removal of Excess Glucose: Cardiovascular OUTCOME Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME® trial, which investigated the sodium glucose cotransporter 2 (SGLT2 inhibitor empagliflozin, has generated great interest among health care professionals. CV outcomes data for another SGLT2 inhibitor, canagliflozin, have been published recently in the CANagliflozin CardioVascular Assessment Study (CANVAS Program, as have CV data from the retrospective real-world study Comparative Effectiveness of Cardiovascular Outcomes in New Users of Sodium-Glucose Cotransporter-2 Inhibitors (CVD-REAL, which compared SGLT2 inhibitors with other classes of glucose-lowering drugs. This review discusses the results of these three studies and, with a focus on EMPA-REG OUTCOME, examines the possible mechanisms by which SGLT2 inhibitors may reduce CV risk in patients with T2DM. Keywords: canagliflozin, cardiovascular outcomes, dapagliflozin, empagliflozin, mechanisms, sodium glucose cotransporter 2 inhibitors

  16. KCl cotransport regulation and protein kinase G in cultured vascular smooth muscle cells.

    Science.gov (United States)

    Adragna, N C; Zhang, J; Di Fulvio, M; Lincoln, T M; Lauf, P K

    2002-05-15

    K-Cl cotransport is activated by vasodilators in erythrocytes and vascular smooth muscle cells and its regulation involves putative kinase/phosphatase cascades. N-ethylmaleimide (NEM) activates the system presumably by inhibiting a protein kinase. Nitrovasodilators relax smooth muscle via cGMP-dependent activation of protein kinase G (PKG), a regulator of membrane channels and transporters. We investigated whether PKG regulates K-Cl cotransport activity or mRNA expression in normal, PKG-deficient-vector-only-transfected (PKG-) and PKG-catalytic-domain-transfected (PKG+) rat aortic smooth muscle cells. K-Cl cotransport was calculated as the Cl-dependent Rb influx, and mRNA was determined by semiquantitative RT-PCR. Baseline K-Cl cotransport was higher in PKG+ than in PKG- cells (p <0.01). At 0.5 mM, NEM stimulated K-Cl cotransport by 5-fold in PKG- but not in PKG+ cells. However, NEM was more potent although less effective to activate K-Cl cotransport in normal (passage 1-3) and PKG+ than in PKG- cells. In PKG- cells, [(dihydroindenyl) oxy] alkanoic acid (300 mM) but not furosemide (1 mM) inhibited K-Cl cotransport. Furthermore, no difference in K-Cl cotransport mRNA expression was observed between these cells. In conclusion, this study shows that manipulation of PKG expression in vascular smooth muscle cells affects K-Cl cotransport activity and its activation by NEM.

  17. Diabetic Ketoacidosis in a Patient with Type 2 Diabetes After Initiation of Sodium-Glucose Cotransporter 2 Inhibitor Treatment

    DEFF Research Database (Denmark)

    Storgaard, Heidi; Bagger, Jonatan I; Knop, Filip K

    2016-01-01

    Sodium-glucose cotransporter 2 inhibitors (SGLT2i) were recently introduced for the treatment of type 2 diabetes (T2D). SGLT2i lower plasma glucose by inhibiting the renal reuptake of glucose leading to glucosuria. Generally, these drugs are considered safe to use. However, recently, SGLT2i have...... been suggested to predispose to ketoacidosis. Here, we present a case of diabetic ketoacidosis (DKA) developed in an obese, poorly controlled male patient with T2D treated with the SGLT2i dapagliflozin. He was admitted with DKA 5 days after the initiation of treatment with the SGLT2i dapagliflozin...... 72 hr with insulin as the only glucose-lowering therapy. After 1 month, dapagliflozin was reintroduced as add-on to insulin with no recurrent signs of ketoacidosis. During acute illness or other conditions with increased insulin demands in diabetes, SGLT2i may predispose to the formation of ketone...

  18. The effects of sodium-glucose co-transporter 2 inhibitors in patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Storgaard, Heidi; Gluud, Lise Lotte; Christensen, Mikkel

    2014-01-01

    INTRODUCTION: Sodium-glucose co-transporter 2 inhibitors (SGLT-2i) increase urinary glucose excretion through a reduced renal glucose reabsorption. We plan to perform a systematic review of SGLT-2i for treatment of type 2 diabetes. METHODS AND ANALYSIS: A systematic review with meta......-analyses of randomised clinical trials on SGLT-2i versus placebo, other oral glucose lowering drugs or insulin for patients with type 2 diabetes will be performed. The primary end point will be the glycated haemoglobin. Secondary end points will include changes in body weight, body mass index, fasting plasma glucose...... to the knowledge regarding the beneficial and harmful effects of SGLT-2i in patients with type 2 diabetes. We plan to publish the study irrespective of the results. RESULTS: The study will be disseminated by peer-review publication and conference presentation. TRIAL REGISTRATION NUMBER: PROSPERO CRD42014008960...

  19. Sodium glucose co-transporter 2 (SGLT2) inhibitors: novel antidiabetic agents.

    Science.gov (United States)

    Washburn, William N

    2012-05-01

    Maintenance of glucose homeostasis in healthy individuals involves SGLT2 (sodium glucose co-transporter 2)-mediated recovery of glucose from the glomerular filtrate which otherwise would be excreted in urine. Clinical studies indicate that SGLT2 inhibitors provide an insulin-independent means to reduce the hyperglycemia that is the hallmark of type 2 diabetes mellitus (T2DM) with minimal risk of hypoglycemia. The pharmacophore common to the SGLT2 inhibitors currently in development is a diarylmethane C-glucoside which is discussed in this review. The focus is how this pharmacophore was further modified as inferred from the patents publishing from 2009 to 2011. The emphasis is on the strategy that each group employed to circumvent the constraints imposed by prior art and how the resulting SGLT2 potency and selectivity versus SGLT1 compared with that of the lead clinical compound dapagliflozin. SGLT2 inhibitors offer a new fundamentally different approach for treatment of diabetes. To date, the clinical results suggest that for non-renally impaired patients this class of inhibitors could be safely used at any stage of T2DM either alone or in combination with other marketed antidiabetic medications.

  20. Potassium Supplementation Prevents Sodium Chloride Cotransporter Stimulation During Angiotensin II Hypertension.

    Science.gov (United States)

    Veiras, Luciana C; Han, Jiyang; Ralph, Donna L; McDonough, Alicia A

    2016-10-01

    Angiotensin II (AngII) hypertension increases distal tubule Na-Cl cotransporter (NCC) abundance and phosphorylation (NCCp), as well as epithelial Na(+) channel abundance and activating cleavage. Acutely raising plasma [K(+)] by infusion or ingestion provokes a rapid decrease in NCCp that drives a compensatory kaliuresis. The first aim tested whether acutely raising plasma [K(+)] with a single 3-hour 2% potassium meal would lower NCCp in Sprague-Dawley rats after 14 days of AngII (400 ng/kg per minute). The potassium-rich meal neither decreased NCCp nor increased K(+) excretion. AngII-infused rats exhibited lower plasma [K(+)] versus controls (3.6±0.2 versus 4.5±0.1 mmol/L; Pblood pressure did not significantly decrease. Epithelial Na(+) channel subunit abundance and cleavage increased 1.5- to 3-fold in both A1K and A2K; ROMK (renal outer medulla K(+) channel abundance) abundance was unaffected by AngII or dietary K(+) In summary, the accumulation and phosphorylation of NCC seen during chronic AngII infusion hypertension is likely secondary to potassium deficiency driven by epithelial Na(+) channel stimulation. © 2016 American Heart Association, Inc.

  1. Sodium-glucose co-transporter 2 (SGLT2 inhibitors: a growing class of anti-diabetic agents

    Directory of Open Access Journals (Sweden)

    Eva M Vivian

    2014-12-01

    Full Text Available Although several treatment options are available to reduce hyperglycemia, only about half of individuals with diagnosed diabetes mellitus (DM achieve recommended glycemic targets. New agents that reduce blood glucose concentrations by novel mechanisms and have acceptable safety profiles are needed to improve glycemic control and reduce the complications associated with type 2 diabetes mellitus (T2DM. The renal sodium-glucose co-transporter 2 (SGLT2 is responsible for reabsorption of most of the glucose filtered by the kidney. Inhibitors of SGLT2 lower blood glucose independent of the secretion and action of insulin by inhibiting renal reabsorption of glucose, thereby promoting the increased urinary excretion of excess glucose. Canagliflozin, dapagliflozin, and empagliflozin are SGLT2 inhibitors approved as treatments for T2DM in the United States, Europe, and other countries. Canagliflozin, dapagliflozin, and empagliflozin increase renal excretion of glucose and improve glycemic parameters in patients with T2DM when used as monotherapy or in combination with other antihyperglycemic agents. Treatment with SGLT2 inhibitors is associated with weight reduction, lowered blood pressure, and a low intrinsic propensity to cause hypoglycemia. Overall, canagliflozin, dapagliflozin, and empagliflozin are well tolerated. Cases of genital infections and, in some studies, urinary tract infections have been more frequent in canagliflozin-, dapagliflozin-, and empagliflozin-treated patients compared with those receiving placebo. Evidence from clinical trials suggests that SGLT2 inhibitors are a promising new treatment option for T2DM.

  2. Effect of co-transporter blockers on non-synaptic epileptiform activity—computational simulation

    Science.gov (United States)

    Rodrigues Lopes, Mariana; Canton Santos, Luiz Eduardo; Márcio Rodrigues, Antônio; Antônio Duarte, Mario; Catelli Infantosi, Antonio Fernando; Alexandre Scorza, Fulvio; Arida, Ricardo Mario; Madureira, Ana Paula; Amaral da Silveira, Gilcélio; dos Santos, Ivans Carlos; Abrão Cavalheiro, Esper; Guimarães de Almeida, Antônio-Carlos

    2013-10-01

    The important role of cation-chloride co-transporters in epilepsy is being supported by an increasing number of investigations. However, enormous complexity is involved since the action of these co-transporters has effects on the ionic homeostasis influencing directly the neuronal excitability and the tissue propensity to sustain seizure. To unravel the complex mechanisms involving the co-transporters action during seizure, this paper shows simulations of non-synaptic epileptiform activity and the effect of the blockage of the two different types of cation-chloride co-transporters present in the brain: Na, K and 2Cl co-transporter (NKCC) and K and Cl co-transporter (KCC). The simulations were performed with an electrochemical model representing the non-synaptic structure of the granule cell layer of the dentate gyrus (DG) of the rat hippocampus. The simulations suggest: (i) the potassium clearance is based on the systemic interplay between the Na/K pump and the NKCC co-transporters; (ii) the simultaneous blockage of the NKCC of the neurons and KCC of glial cells acts efficiently suppressing the epileptiform activities; and (iii) the simulations show that depending on the combined blockage of the co-transporters, the epileptiform activities may be suppressed or enhanced.

  3. Characterization of glial cell K-Cl cotransport.

    Science.gov (United States)

    Gagnon, Kenneth B E; Adragna, Norma C; Fyffe, Robert E W; Lauf, Peter K

    2007-01-01

    The molecular mechanism of K-Cl cotransport (KCC) consists of at least 4 isoforms, KCC 1, 2, 3, and 4 which, in multiple combinations, exist in most cells, including erythrocytes and neuronal cells. We utilized reverse-transcriptase-polymerase chain reaction (RT-PCR) and ion flux studies to characterize KCC activity in an immortalized in vitro cell model for fibrous astrocytes, the rat C6 glioblastoma cell. Isoform-specific sets of oligonucleotide primers were synthesized for NKCC1, KCC1, KCC2, KCC3, KCC4, and also for NKCC1 and actin. K-Cl cotransport activity was determined by measuring either the furosemide-sensitive, or the Cl(-)-dependent bumetanide-insensitive Rb(+) (a K(+) congener) influx in the presence of the Na/K pump inhibitor ouabain. Rb(+) influx was measured at a fixed external Cl concentrations, [Cl(-)](e), as a function of varying external Rb concentrations, [Rb(+)](e), and at a fixed [Rb(+)](e) as a function of varying [Cl(-)](e), and with equimolar Cl replacement by anions of the chaotropic series. RT-PCR of C6 glioblastoma (C6) cells identified mRNA for three KCC isoforms (1, 3, and 4). NKCC1 mRNA was also detected. The apparent K(m) for KCC-mediated Rb(+) influx was 15 mM [Rb(+)](e), and V(max) 12.5 nmol Rb(+) * mg protein(-1) * minute(-1). The calculated apparent K(m) for external Cl(-) was 13 mM and V(max) 14.4 nmol Rb(+) * mg protein(-1) * minute(-1). The anion selectivity sequence of the furosemide-sensitive Rb(+) influx was Cl(-)>Br-=NO(3)(-)>I(-)=SCN(-)>Sfm(-) (sulfamate). Established activators of K-Cl cotransport, hyposmotic shock and N-ethylmaleimide (NEM) pretreatment, stimulated furosemide-sensitive Rb(+) influx. A ñ50% NEM-induced loss of intracellular K(+) was prevented by furosemide. We have identified by RT-PCR the presence of three distinct KCC isoforms (1, 3, and 4) in rat C6 glioblastoma cells, and functionally characterized the anion selectivity and kinetics of their collective sodium-independent cation-chloride cotransport

  4. Clinical potential of sodium-glucose cotransporter 2 inhibitors in the management of type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Kim Y

    2012-08-01

    Full Text Available Yoojin Kim, Ambika R BabuDivision of Endocrinology, John Stroger Jr Hospital of Cook County and Rush University, Chicago, IL, USABackground: The kidney plays an important role in glucose metabolism, and has been considered a target for therapeutic intervention. The sodium-glucose cotransporter type 2 (SGLT2 mediates most of the glucose reabsorption from the proximal renal tubule. Inhibition of SGLT2 leads to glucosuria and provides a unique mechanism to lower elevated blood glucose levels in diabetes. The purpose of this review is to explore the physiology of SGLT2 and discuss several SGLT2 inhibitors which have clinical data in patients with type 2 diabetes.Methods: We performed a PubMed search using the terms "SGLT2" and "SGLT2 inhibitor" through April 10, 2012. Published articles, press releases, and abstracts presented at national and international meetings were considered.Results: SGLT2 inhibitors correct a novel pathophysiological defect, have an insulin-independent action, are efficacious with glycosylated hemoglobin reduction ranging from 0.5% to 1.5%, promote weight loss, have a low incidence of hypoglycemia, complement the action of other antidiabetic agents, and can be used at any stage of diabetes. They are generally well tolerated. However, due to side effects, such as repeated urinary tract and genital infections, increased hematocrit, and decreased blood pressure, appropriate patient selection for drug initiation and close monitoring after initiation will be important. Results of ongoing clinical studies of the effect of SGLT2 inhibitors on diabetic complications and cardiovascular safety are crucial to determine the risk-benefit ratio. A recent decision by the Committee for Medicinal Products for Human Use of the European Medicines Agency has recommended approval of dapagliflozin for the treatment of type 2 diabetes as an adjunct to diet and exercise, in combination with other glucose-lowering medicinal products, including

  5. X-ray diffraction studies on merohedrally twinned Δ1–62NtNBCe1-A crystals of the sodium/bicarbonate cotransporter

    International Nuclear Information System (INIS)

    Gill, Harindarpal S.; Dutcher, Lauren; Boron, Walter F.; Patel, Samir; Guay-Woodford, Lisa M.

    2013-01-01

    A truncated mutant missing the first 62 residues of the N-terminal, cytoplasmic domain of the sodium-bicarbonate NBCe1-A cotransporter crystallizes in space group P3 1 with pseudo-P3 1 21 symmetry and a hemihedral twin fraction of 33.0%. Twinned fractions and twin-pair statistics over binned resolutions confirm that the calculated twin fraction is associated with hemihedral twinning and not to non-crystallographic symmetry. NBCe1-A membrane-embedded macromolecules that cotransport sodium and bicarbonate ions across the bilayer serve to maintain acid–base homeostasis throughout the body. Defects result in a number of renal and eye disorders, including type-II renal tubular acidosis and cataracts. Here, crystals of a human truncated mutant of the cytoplasmic N-terminal domain of NBCe1 (Δ1–62NtNBCe1-A) are reported that diffract X-rays to 2.4 Å resolution. The crystal symmetry of Δ1–62NtNBCe1-A is of space group P3 1 with pseudo-P3 1 21 symmetry and it has a hemihedral twin fraction of 33.0%. The crystals may provide insight into the pathogenic processes observed in a subset of patients with truncating and point mutations in the gene encoding NBCe1

  6. X-ray diffraction studies on merohedrally twinned Δ1-62NtNBCe1-A crystals of the sodium/bicarbonate cotransporter.

    Science.gov (United States)

    Gill, Harindarpal S; Dutcher, Lauren; Boron, Walter F; Patel, Samir; Guay-Woodford, Lisa M

    2013-07-01

    NBCe1-A membrane-embedded macromolecules that cotransport sodium and bicarbonate ions across the bilayer serve to maintain acid-base homeostasis throughout the body. Defects result in a number of renal and eye disorders, including type-II renal tubular acidosis and cataracts. Here, crystals of a human truncated mutant of the cytoplasmic N-terminal domain of NBCe1 (Δ1-62NtNBCe1-A) are reported that diffract X-rays to 2.4 Å resolution. The crystal symmetry of Δ1-62NtNBCe1-A is of space group P31 with pseudo-P3121 symmetry and it has a hemihedral twin fraction of 33.0%. The crystals may provide insight into the pathogenic processes observed in a subset of patients with truncating and point mutations in the gene encoding NBCe1.

  7. Substrate specificity of the electrogenic sodium/bicarbonate cotransporter NBCe1-A (SLC4A4, variant A) from humans and rabbits.

    Science.gov (United States)

    Lee, Seong-Ki; Boron, Walter F; Parker, Mark D

    2013-04-01

    In the basolateral membrane of proximal-tubule cells, NBCe1-A (SLC4A4, variant A), operating with an apparent Na(+):HCO(3)(-) stoichiometry of 1:3, contributes to the reclamation of HCO(3)(-) from the glomerular filtrate, thereby preventing whole body acidosis. Others have reported that NBCe1-like activity in human, rabbit, and rat renal preparations is substantially influenced by lithium, sulfite, oxalate, and harmaline. These data were taken as evidence for the presence of distinct Na(+) and CO(3)(2-) binding sites in NBCe1-A, favoring a model of 1 Na(+):1 HCO(3)(-):1 CO(3)(2-). Here, we reexamine these findings by expressing human or rabbit NBCe1-A clones in Xenopus oocytes. In oocytes, NBCe1-A exhibits a 1:2 stoichiometry and could operate in one of five thermodynamically equivalent transport modes: 1) cotransport of Na(+) + 2 HCO(3)(-), 2) cotransport of Na(+) + CO(3)(2-), 3) transport of NaCO(3)(-), 4) exchange of Na(+) + HCO(3)(-) for H(+), or 5) HCO(3)(-)-activated exchange of Na(+) for 2 H(+). In contrast to the behavior of NBCe1-like activity in renal preparations, we find that cloned NBCe1-A is only slightly stimulated by Li(+), not at all influenced by sulfite or oxalate, and only weakly inhibited by harmaline. These negative data do not uniquely support any of the five models above. In addition, we find that NBCe1-A mediates a small amount of Na(+)-independent NO(3)(-) transport and that NBCe1-A is somewhat inhibited by extracellular benzamil. We suggest that the features of NBCe1-like activity in renal preparations are influenced by yet-to-be-identified renal factors. Thus the actual ionic substrates of NBCe1 remain to be identified.

  8. Cardiovascular effects of sodium glucose cotransporter 2 inhibitors

    Science.gov (United States)

    Cavaiola, Tricia Santos; Pettus, Jeremy

    2018-01-01

    As the first cardiovascular (CV) outcome trial of a glucose-lowering agent to demonstrate a reduction in the risk of CV events in patients with type 2 diabetes mellitus (T2DM), the EMPAgliflozin Removal of Excess Glucose: Cardiovascular OUTCOME Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME®) trial, which investigated the sodium glucose cotransporter 2 (SGLT2) inhibitor empagliflozin, has generated great interest among health care professionals. CV outcomes data for another SGLT2 inhibitor, canagliflozin, have been published recently in the CANagliflozin CardioVascular Assessment Study (CANVAS) Program, as have CV data from the retrospective real-world study Comparative Effectiveness of Cardiovascular Outcomes in New Users of Sodium-Glucose Cotransporter-2 Inhibitors (CVD-REAL), which compared SGLT2 inhibitors with other classes of glucose-lowering drugs. This review discusses the results of these three studies and, with a focus on EMPA-REG OUTCOME, examines the possible mechanisms by which SGLT2 inhibitors may reduce CV risk in patients with T2DM. PMID:29695924

  9. Water transport by the Na+/glucose cotransporter under isotonic conditions

    DEFF Research Database (Denmark)

    Zeuthen, T; Meinild, A K; Klaerke, D A

    1997-01-01

    Solute cotransport in the Na+/glucose cotransporter is directly coupled to significant water fluxes. The water fluxes are energized by the downhill fluxes of the other substrates by a mechanism within the protein itself. In the present paper we investigate the Na+/glucose cotransporter expressed ...... of water molecules and the number of Na+ ions transported, equivalent to 390 water molecules per glucose molecule. Unstirred layer effects are ruled out on the basis of experiments on native oocytes incubated with the ionophores gramicidin D or nystatin.......Solute cotransport in the Na+/glucose cotransporter is directly coupled to significant water fluxes. The water fluxes are energized by the downhill fluxes of the other substrates by a mechanism within the protein itself. In the present paper we investigate the Na+/glucose cotransporter expressed...... in Xenopus oocytes. We present a method which allows short-term exposures to sugar under voltage clamp conditions. We demonstrate that water is cotransported with the solutes despite no osmotic differences between the external and intracellular solutions. There is a fixed ratio of 195:1 between the number...

  10. Structural and functional significance of water permeation through cotransporters

    DEFF Research Database (Denmark)

    Zeuthen, Thomas; Gorraitz, Edurne; Her, Ka

    2016-01-01

    Membrane transporters, in addition to their major role as specific carriers for ions and small molecules, can also behave as water channels. However, neither the location of the water pathway in the protein nor their functional importance is known. Here, we map the pathway for water and urea...... through the intestinal sodium/glucose cotransporter SGLT1. Molecular dynamics simulations using the atomic structure of the bacterial transporter vSGLT suggest that water permeates the same path as Na+ and sugar. On a structural model of SGLT1, based on the homology structure of vSGLT, we identified...... to be due to alterations in steric hindrance to water and urea, and/or changes in protein folding caused by mismatching of side chains in the water pathway. Water permeation through SGLT1 and other transporters bears directly on the structural mechanism for the transport of polar solutes through...

  11. K-Cl cotransporters, cell volume homeostasis, and neurological disease.

    Science.gov (United States)

    Kahle, Kristopher T; Khanna, Arjun R; Alper, Seth L; Adragna, Norma C; Lauf, Peter K; Sun, Dandan; Delpire, Eric

    2015-08-01

    K(+)-Cl(-) cotransporters (KCCs) were originally characterized as regulators of red blood cell (RBC) volume. Since then, four distinct KCCs have been cloned, and their importance for volume regulation has been demonstrated in other cell types. Genetic models of certain KCCs, such as KCC3, and their inhibitory WNK-STE20/SPS1-related proline/alanine-rich kinase (SPAK) serine-threonine kinases, have demonstrated the evolutionary necessity of these molecules for nervous system cell volume regulation, structure, and function, and their involvement in neurological disease. The recent characterization of a swelling-activated dephosphorylation mechanism that potently stimulates the KCCs has pinpointed a potentially druggable switch of KCC activity. An improved understanding of WNK/SPAK-mediated KCC cell volume regulation in the nervous system might reveal novel avenues for the treatment of multiple neurological diseases. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Sodium glucose co-transporter 2 (SGLT2) inhibitors: new among antidiabetic drugs.

    Science.gov (United States)

    Opie, L H

    2014-08-01

    Type 2 diabetes is characterized by decreased insulin secretion and sensitivity. The available oral anti-diabetic drugs act on many different molecular sites. The most used of oral anti-diabetic agents is metformin that activates glucose transport vesicles to the cell surface. Others are: the sulphonylureas; agents acting on the incretin system; GLP-1 agonists; dipetidylpeptidase-4 inhibitors; meglinitide analogues; and the thiazolidinediones. Despite these many drugs acting by different mechanisms, glycaemic control often remains elusive. None of these drugs have a primary renal mechanism of action on the kidneys, where almost all glucose excreted is normally reabsorbed. That is where the inhibitors of glucose reuptake (sodium-glucose cotransporter 2, SGLT2) have a unique site of action. Promotion of urinary loss of glucose by SGLT2 inhibitors embodies a new principle of control in type 2 diabetes that has several advantages with some urogenital side-effects, both of which are evaluated in this review. Specific approvals include use as monotherapy, when diet and exercise alone do not provide adequate glycaemic control in patients for whom the use of metformin is considered inappropriate due to intolerance or contraindications, or as add-on therapy with other anti-hyperglycaemic medicinal products including insulin, when these together with diet and exercise, do not provide adequate glycemic control. The basic mechanisms are improved β-cell function and insulin sensitivity. When compared with sulphonylureas or other oral antidiabetic agents, SGLT2 inhibitors provide greater HbA1c reduction. Urogenital side-effects related to the enhanced glycosuria can be troublesome, yet seldom lead to discontinuation. On this background, studies are analysed that compare SGLT2 inhibitors with other oral antidiabetic agents. Their unique mode of action, unloading the excess glycaemic load, contrasts with other oral agents that all act to counter the effects of diabetic

  13. The Effect of WNK4 on the Na+-Cl- Cotransporter Is Modulated by Intracellular Chloride.

    Science.gov (United States)

    Bazúa-Valenti, Silvana; Chávez-Canales, María; Rojas-Vega, Lorena; González-Rodríguez, Xochiquetzal; Vázquez, Norma; Rodríguez-Gama, Alejandro; Argaiz, Eduardo R; Melo, Zesergio; Plata, Consuelo; Ellison, David H; García-Valdés, Jesús; Hadchouel, Juliette; Gamba, Gerardo

    2015-08-01

    It is widely recognized that the phenotype of familial hyperkalemic hypertension is mainly a consequence of increased activity of the renal Na(+)-Cl(-) cotransporter (NCC) because of altered regulation by with no-lysine-kinase 1 (WNK1) or WNK4. The effect of WNK4 on NCC, however, has been controversial because both inhibition and activation have been reported. It has been recently shown that the long isoform of WNK1 (L-WNK1) is a chloride-sensitive kinase activated by a low Cl(-) concentration. Therefore, we hypothesized that WNK4 effects on NCC could be modulated by intracellular chloride concentration ([Cl(-)]i), and we tested this hypothesis in oocytes injected with NCC cRNA with or without WNK4 cRNA. At baseline in oocytes, [Cl(-)]i was near 50 mM, autophosphorylation of WNK4 was undetectable, and NCC activity was either decreased or unaffected by WNK4. A reduction of [Cl(-)]i, either by low chloride hypotonic stress or coinjection of oocytes with the solute carrier family 26 (anion exchanger)-member 9 (SLC26A9) cRNA, promoted WNK4 autophosphorylation and increased NCC-dependent Na(+) transport in a WNK4-dependent manner. Substitution of the leucine with phenylalanine at residue 322 of WNK4, homologous to the chloride-binding pocket in L-WNK1, converted WNK4 into a constitutively autophosphorylated kinase that activated NCC, even without chloride depletion. Elimination of the catalytic activity (D321A or D321K-K186D) or the autophosphorylation site (S335A) in mutant WNK4-L322F abrogated the positive effect on NCC. These observations suggest that WNK4 can exert differential effects on NCC, depending on the intracellular chloride concentration. Copyright © 2015 by the American Society of Nephrology.

  14. Characteristics and functions of Na-K-Cl cotransport in epithelial tissues

    International Nuclear Information System (INIS)

    O'Grady, S.M.; Palfrey, H.C.; Field, M.

    1987-01-01

    This review summarizes our present understanding of Na-K-Cl cotransport and its physiological role in absorption and secretion of electrolytes and water in epithelial tissues. In the past several years an extensive literature about this cotransporter has developed due to its widespread distribution in a variety of cell types and its essential role in fluid and electrolyte transport in several epithelial tissues. We summarize this literature and speculate on the future characterization of this transport system. Although this review focuses on cotransport as it relates to absorptive and secretory processes in epithelia, important information concerning the pharmacology, stoichiometry, and regulation of Na-K-Cl cotransport in nonepithelial systems (i.e., erythrocytes, fibroblasts, squid axon, etc.) has been included to supplement areas that are less well established in the epithelial literature. 114 references

  15. Cotransport of H+, lactate, and H2O in porcine retinal pigment epithelial cells

    DEFF Research Database (Denmark)

    Hamann, Steffen; Kiilgaard, Jens Folke; la Cour, Morten

    2003-01-01

    ) for the H(+) and lactate fluxes. The data suggest that H(2)O is cotransported along with H(+) and lactate ions in MCT1 localized to the retinal membrane. The study emphasizes the importance of this cotransporter in the maintenance of water homeostasis and pH in the subretinal space of a mammalian tissue...... and supports our previous study performed by an invasive technique in an amphibian tissue....

  16. Tofogliflozin, a potent and highly specific sodium/glucose cotransporter 2 inhibitor, improves glycemic control in diabetic rats and mice.

    Science.gov (United States)

    Suzuki, Masayuki; Honda, Kiyofumi; Fukazawa, Masanori; Ozawa, Kazuharu; Hagita, Hitoshi; Kawai, Takahiro; Takeda, Minako; Yata, Tatsuo; Kawai, Mio; Fukuzawa, Taku; Kobayashi, Takamitsu; Sato, Tsutomu; Kawabe, Yoshiki; Ikeda, Sachiya

    2012-06-01

    Sodium/glucose cotransporter 2 (SGLT2) is the predominant mediator of renal glucose reabsorption and is an emerging molecular target for the treatment of diabetes. We identified a novel potent and selective SGLT2 inhibitor, tofogliflozin (CSG452), and examined its efficacy and pharmacological properties as an antidiabetic drug. Tofogliflozin competitively inhibited SGLT2 in cells overexpressing SGLT2, and K(i) values for human, rat, and mouse SGLT2 inhibition were 2.9, 14.9, and 6.4 nM, respectively. The selectivity of tofogliflozin toward human SGLT2 versus human SGLT1, SGLT6, and sodium/myo-inositol transporter 1 was the highest among the tested SGLT2 inhibitors under clinical development. Furthermore, no interaction with tofogliflozin was observed in any of a battery of tests examining glucose-related physiological processes, such as glucose uptake, glucose oxidation, glycogen synthesis, hepatic glucose production, glucose-stimulated insulin secretion, and glucosidase reactions. A single oral gavage of tofogliflozin increased renal glucose clearance and lowered the blood glucose level in Zucker diabetic fatty rats. Tofogliflozin also improved postprandial glucose excursion in a meal tolerance test with GK rats. In db/db mice, 4-week tofogliflozin treatment reduced glycated hemoglobin and improved glucose tolerance in the oral glucose tolerance test 4 days after the final administration. No blood glucose reduction was observed in normoglycemic SD rats treated with tofogliflozin. These findings demonstrate that tofogliflozin inhibits SGLT2 in a specific manner, lowers blood glucose levels by increasing renal glucose clearance, and improves pathological conditions of type 2 diabetes with a low hypoglycemic potential.

  17. 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.

  18. Renal venogram

    Science.gov (United States)

    ... be black. Other structures will be shades of gray. Veins are not normally seen in an x- ... Venogram - kidney; Renal vein thrombosis - venogram Images Kidney anatomy Kidney - blood and urine flow Renal veins References ...

  19. Pharmacodynamics, efficacy and safety of sodium-glucose co-transporter type 2 (SGLT2) inhibitors for the treatment of type 2 diabetes mellitus.

    Science.gov (United States)

    Scheen, André J

    2015-01-01

    Inhibitors of sodium-glucose co-transporter type 2 (SGLT2) are proposed as a novel approach for the management of type 2 diabetes mellitus (T2DM). Several compounds are already available in many countries (dapagliflozin, canagliflozin, empagliflozin and ipragliflozin) and some others are in a late phase of development. The available SGLT2 inhibitors share similar pharmacokinetic characteristics, with a rapid oral absorption, a long elimination half-life allowing once-daily administration, an extensive hepatic metabolism mainly via glucuronidation to inactive metabolites, the absence of clinically relevant drug-drug interactions and a low renal elimination as parent drug. SGLT2 co-transporters are responsible for reabsorption of most (90 %) of the glucose filtered by the kidneys. The pharmacological inhibition of SGLT2 co-transporters reduces hyperglycaemia by decreasing renal glucose threshold and thereby increasing urinary glucose excretion. The amount of glucose excreted in the urine depends on both the level of hyperglycaemia and the glomerular filtration rate. Results of numerous placebo-controlled randomised clinical trials of 12-104 weeks duration have shown significant reductions in glycated haemoglobin (HbA1c), resulting in a significant increase in the proportion of patients reaching HbA1c targets, and a significant lowering of fasting plasma glucose when SGLT2 inhibitors were administered as monotherapy or in addition to other glucose-lowering therapies including insulin in patients with T2DM. In head-to-head trials of up to 2 years, SGLT2 inhibitors exerted similar glucose-lowering activity to metformin, sulphonylureas or sitagliptin. The durability of the glucose-lowering effect of SGLT2 inhibitors appears to be better; however, this remains to be more extensively investigated. The risk of hypoglycaemia was much lower with SGLT2 inhibitors than with sulphonylureas and was similarly low as that reported with metformin, pioglitazone or sitagliptin

  20. Hepatocyte cotransport of taurocholate and bilirubin glucuronides: Role of microtubules

    International Nuclear Information System (INIS)

    Crawford, J.M.; Gollan, J.L.

    1988-01-01

    Modulation of bile pigment excretion by bile salts has been attributed to modification of canalicular membrane transport or a physical interaction in bile. Based on the observation that a microtubule-dependent pathway is involved in the hepatocellular transport of bile salts, the authors investigated the possibility that bilirubin glucuronides are associated with bile salts during intracellular transport. Experiments were conducted in intact rats (basal) or after overnight biliary diversion and intravenous reinfusion of taurocholate (depleted/reinfused). All rats were pretreated with intravenous low-dose colchicine or its inactive isomer lumicolchicine. Biliary excretion of radiolabeled bilirubin glucuronides derived from tracer [ 14 C]bilirubin-[ 3 H]bilirubin monoglucuronide (coinjected iv) was unchanged in basal rats but was consistently delayed in depleted/reinfused rats. This was accompanied by a significant shift toward bilirubin diglucuronide formation from both substrates. In basal Gunn rats, with deficient bilirubin glucuronidation, biliary excretion of intravenous [ 14 C]bilirubin monoglucuronide-[ 3 H]bilirubin diglucuronide was unaffected by colchicine but was retarded in depleted/reinfused Gunn rats. Colchicine had no effect on the rate of bilirubin glucuronidation in vitro in rat liver microsomes. They conclude that a portion of the bilirubin glucuronides generated endogenously in hepatocytes or taken up directly from plasma may be cotransported with bile salts to the bile canalicular membrane via a microtubule-dependent mechanism

  1. Water permeation through the sodium-dependent galactose cotransporter vSGLT.

    Science.gov (United States)

    Choe, Seungho; Rosenberg, John M; Abramson, Jeff; Wright, Ernest M; Grabe, Michael

    2010-10-06

    It is well accepted that cotransporters facilitate water movement by two independent mechanisms: osmotic flow through a water channel in the protein and flow driven by ion/substrate cotransport. However, the molecular mechanism of transport-linked water flow is controversial. Some researchers believe that it occurs via cotransport, in which water is pumped along with the transported cargo, while others believe that flow is osmotic in response to an increase in intracellular osmolarity. In this letter, we report the results of a 200-ns molecular dynamics simulation of the sodium-dependent galactose cotransporter vSGLT. Our simulation shows that a significant number of water molecules cross the protein through the sugar-binding site in the presence as well as the absence of galactose, and 70-80 water molecules accompany galactose as it moves from the binding site into the intracellular space. During this event, the majority of water molecules in the pathway are unable to diffuse around the galactose, resulting in water in the inner half of the transporter being pushed into the intracellular space and replaced by extracellular water. Thus, our simulation supports the notion that cotransporters act as both passive water channels and active water pumps with the transported substrate acting as a piston to rectify the motion of water. Copyright © 2010 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  2. Renal perfusion scintiscan

    Science.gov (United States)

    ... Radionuclide renal perfusion scan; Perfusion scintiscan - renal; Scintiscan - renal perfusion Images Kidney anatomy Kidney - blood and urine flow Intravenous pyelogram References Rottenberg G, Andi AC. Renal ...

  3. Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors from Natural Products: Discovery of Next-Generation Antihyperglycemic Agents.

    Science.gov (United States)

    Choi, Chang-Ik

    2016-08-27

    Diabetes mellitus is a chronic condition associated with the metabolic impairment of insulin actions, leading to the development of life-threatening complications. Although many kinds of oral antihyperglycemic agents with different therapeutic mechanisms have been marketed, their undesirable adverse effects, such as hypoglycemia, weight gain, and hepato-renal toxicity, have increased demand for the discovery of novel, safer antidiabetic drugs. Since the important roles of the sodium-glucose cotransporter 2 (SGLT2) for glucose homeostasis in the kidney were recently elucidated, pharmacological inhibition of SGLT2 has been considered a promising therapeutic target for the treatment of type 2 diabetes. Since the discovery of the first natural SGLT2 inhibitor, phlorizin, several synthetic glucoside analogs have been developed and introduced into the market. Furthermore, many efforts to find new active constituents with SGLT2 inhibition from natural products are still ongoing. This review introduces the history of research on the development of early-generation SGLT2 inhibitors, and recent progress on the discovery of novel candidates for SGLT2 inhibitor from several natural products that are widely used in traditional herbal medicine.

  4. Sodium-Glucose Cotransporter 2 (SGLT2 Inhibitors from Natural Products: Discovery of Next-Generation Antihyperglycemic Agents

    Directory of Open Access Journals (Sweden)

    Chang-Ik Choi

    2016-08-01

    Full Text Available Diabetes mellitus is a chronic condition associated with the metabolic impairment of insulin actions, leading to the development of life-threatening complications. Although many kinds of oral antihyperglycemic agents with different therapeutic mechanisms have been marketed, their undesirable adverse effects, such as hypoglycemia, weight gain, and hepato-renal toxicity, have increased demand for the discovery of novel, safer antidiabetic drugs. Since the important roles of the sodium-glucose cotransporter 2 (SGLT2 for glucose homeostasis in the kidney were recently elucidated, pharmacological inhibition of SGLT2 has been considered a promising therapeutic target for the treatment of type 2 diabetes. Since the discovery of the first natural SGLT2 inhibitor, phlorizin, several synthetic glucoside analogs have been developed and introduced into the market. Furthermore, many efforts to find new active constituents with SGLT2 inhibition from natural products are still ongoing. This review introduces the history of research on the development of early-generation SGLT2 inhibitors, and recent progress on the discovery of novel candidates for SGLT2 inhibitor from several natural products that are widely used in traditional herbal medicine.

  5. Clinical risk factors predicting genital fungal infections with sodium-glucose cotransporter 2 inhibitor treatment: The ABCD nationwide dapagliflozin audit.

    Science.gov (United States)

    Thong, Ken Yan; Yadagiri, Mahender; Barnes, Dennis Joseph; Morris, David Stuart; Chowdhury, Tahseen Ahmad; Chuah, Ling Ling; Robinson, Anthony Michael; Bain, Stephen Charles; Adamson, Karen Ann; Ryder, Robert Elford John

    2018-02-01

    Treatment of type 2 diabetes with sodium-glucose cotransporter 2 (SGLT2) inhibitors may result in genital fungal infections. We investigated possible risk factors for developing such infections among patients treated with the SGLT2 inhibitor dapagliflozin. The Association of British Clinical Diabetologists (ABCD) collected data on patients treated with dapagliflozin in routine clinical practice from 59 diabetes centres. We assessed possible associations of patient's age, diabetes duration, body mass index, glycated haemoglobin, renal function, patient sex, ethnicity and prior genital fungal infection, urinary tract infection, urinary incontinence or nocturia, with the occurrence of ≥1 genital fungal infection within 26 weeks of treatment. 1049 out of 1116 patients (476 women, 573 men) were analysed. Baseline characteristics were, mean±SD, age 56.7±10.2years, BMI 35.5±6.9kg/m 2 and HbA 1c 9.4±1.5%. Only patient sex (13.2% women vs 3.3% men) and prior history of genital fungal infection (21.6% vs 7.3%) were found to be associated with occurrence of genital fungal infections after dapagliflozin treatment, adjusted OR 4.22 [95%CI 2.48,7.19], Prisks of developing genital fungal infections with dapagliflozin treatment. Copyright © 2017 Primary Care Diabetes Europe. All rights reserved.

  6. Do sodium-glucose co-transporter-2 inhibitors prevent heart failure with a preserved ejection fraction by counterbalancing the effects of leptin? A novel hypothesis.

    Science.gov (United States)

    Packer, Milton

    2018-06-01

    Sodium-glucose co-transporter-2 (SGLT2) inhibitors reduce the risk of serious heart failure events in patients with type 2 diabetes, but little is known about mechanisms that might mediate this benefit. The most common heart failure phenotype in type 2 diabetes is obesity-related heart failure with a preserved ejection fraction (HFpEF). It has been hypothesized that the synthesis of leptin in this disorder leads to sodium retention and plasma volume expansion as well as to cardiac and renal inflammation and fibrosis. Interestingly, leptin-mediated neurohormonal activation appears to enhance the expression of SGLT2 in the renal tubules, and SGLT2 inhibitors exert natriuretic actions at multiple renal tubular sites in a manner that can oppose the sodium retention produced by leptin. In addition, SGLT2 inhibitors reduce the accumulation and inflammation of perivisceral adipose tissue, thus minimizing the secretion of leptin and its paracrine actions on the heart and kidneys to promote fibrosis. Such fibrosis probably contributes to the impairment of cardiac distensibility and glomerular function that characterizes obesity-related HFpEF. Ongoing clinical trials with SGLT2 inhibitors in heart failure are positioned to confirm or refute the hypothesis that these drugs may favourably influence the course of obesity-related HFpEF by their ability to attenuate the secretion and actions of leptin. © 2018 John Wiley & Sons Ltd.

  7. Euglycemic Diabetic Ketoacidosis with Elevated Acetone in a Patient Taking a Sodium-Glucose Cotransporter-2 (SGLT2) Inhibitor.

    Science.gov (United States)

    Andrews, Tory J; Cox, Robert D; Parker, Christina; Kolb, James

    2017-02-01

    Sodium-glucose cotransporter-2 (SGLT2) inhibitor medications are a class of antihyperglycemic agents that increase urinary glucose excretion by interfering with the reabsorption of glucose in the proximal renal tubules. In May of 2015, the U.S. Food and Drug Administration released a warning concerning a potential increased risk of ketoacidosis and ketosis in patients taking these medications. We present a case of a 57-year-old woman with type 2 diabetes mellitus taking a combination of canagliflozin and metformin who presented with progressive altered mental status over the previous 2 days. Her work-up demonstrated a metabolic acidosis with an anion gap of 38 and a venous serum pH of 7.08. The serum glucose was 168 mg/dL. The urinalysis showed glucose > 500 mg/dL and ketones of 80 mg/dL. Further evaluation demonstrated an elevated serum osmolality of 319 mOsm/kg and an acetone concentration of 93 mg/dL. She was treated with intravenous insulin and fluids, and the metabolic abnormalities and her altered mental status resolved within 36 h. This was the first episode of diabetic ketoacidosis (DKA) for this patient. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Diabetic patients on SGLT2 inhibitor medications are at risk for ketoacidosis. Due to the renal glucose-wasting properties of these drugs, they may present with ketoacidosis with only mild elevations in serum glucose, potentially complicating the diagnosis. Acetone is one of the three main ketone bodies formed during DKA and it may be present at considerable concentrations, contributing to the serum osmolality. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Regulation of K-Cl cotransport: from function to genes.

    Science.gov (United States)

    Adragna, N C; Di Fulvio, M; Lauf, P K

    2004-10-01

    This review intends to summarize the vast literature on K-Cl cotransport (COT) regulation from a functional and genetic viewpoint. Special attention has been given to the signaling pathways involved in the transporter's regulation found in several tissues and cell types, and more specifically, in vascular smooth muscle cells (VSMCs). The number of publications on K-Cl COT has been steadily increasing since its discovery at the beginning of the 1980s, with red blood cells (RBCs) from different species (human, sheep, dog, rabbit, guinea pig, turkey, duck, frog, rat, mouse, fish, and lamprey) being the most studied model. Other tissues/cell types under study are brain, kidney, epithelia, muscle/smooth muscle, tumor cells, heart, liver, insect cells, endothelial cells, bone, platelets, thymocytes and Leishmania donovani. One of the salient properties of K-Cl-COT is its activation by cell swelling and its participation in the recovery of cell volume, a process known as regulatory volume decrease (RVD). Activation by thiol modification with N-ethylmaleimide (NEM) has spawned investigations on the redox dependence of K-Cl COT, and is used as a positive control for the operation of the system in many tissues and cells. The most accepted model of K-Cl COT regulation proposes protein kinases and phosphatases linked in a chain of phosphorylation/dephosphorylation events. More recent studies include regulatory pathways involving the phosphatidyl inositol/protein kinase C (PKC)-mediated pathway for regulation by lithium (Li) in low-K sheep red blood cells (LK SRBCs), and the nitric oxide (NO)/cGMP/protein kinase G (PKG) pathway as well as the platelet-derived growth factor (PDGF)-mediated mechanism in VSMCs. Studies on VSM transfected cells containing the PKG catalytic domain demonstrated the participation of this enzyme in K-Cl COT regulation. Commonly used vasodilators activate K-Cl COT in a dose-dependent manner through the NO/cGMP/PKG pathway. Interaction between the

  9. SODIUM-POTASSIUM-CHLORIDE COTRANSPORT IN THE REGULATION OF VASCULAR MYOGENIC TONE

    Directory of Open Access Journals (Sweden)

    S. N. Orlov

    2014-01-01

    Full Text Available The article discusses the data on the functioning of Na+,K+,2Cl– cotransport – the carrier providing electroneutral symport of sodium, potassium and chloride, as well as molecular mechanisms of the regulation and physiological significance of this carrier. We analyzed the novel data on involvement of ubiquitous isoform of Na+,K+,2Cl–cotransporter (NKCC1 in regulation of vascular smooth muscle contraction, and role of this carrier in the regulation of cell volume and intracellular chloride concentration.

  10. 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.

  11. Renal Dysfunction Induced by Kidney-Specific Gene Deletion of Hsd11b2 as a Primary Cause of Salt-Dependent Hypertension.

    Science.gov (United States)

    Ueda, Kohei; Nishimoto, Mitsuhiro; Hirohama, Daigoro; Ayuzawa, Nobuhiro; Kawarazaki, Wakako; Watanabe, Atsushi; Shimosawa, Tatsuo; Loffing, Johannes; Zhang, Ming-Zhi; Marumo, Takeshi; Fujita, Toshiro

    2017-07-01

    Genome-wide analysis of renal sodium-transporting system has identified specific variations of Mendelian hypertensive disorders, including HSD11B2 gene variants in apparent mineralocorticoid excess. However, these genetic variations in extrarenal tissue can be involved in developing hypertension, as demonstrated in former studies using global and brain-specific Hsd11b2 knockout rodents. To re-examine the importance of renal dysfunction on developing hypertension, we generated kidney-specific Hsd11b2 knockout mice. The knockout mice exhibited systemic hypertension, which was abolished by reducing salt intake, suggesting its salt-dependency. In addition, we detected an increase in renal membrane expressions of cleaved epithelial sodium channel-α and T53-phosphorylated Na + -Cl - cotransporter in the knockout mice. Acute intraperitoneal administration of amiloride-induced natriuresis and increased urinary sodium/potassium ratio more in the knockout mice compared with those in the wild-type control mice. Chronic administration of amiloride and high-KCl diet significantly decreased mean blood pressure in the knockout mice, which was accompanied with the correction of hypokalemia and the resultant decrease in Na + -Cl - cotransporter phosphorylation. Accordingly, a Na + -Cl - cotransporter blocker hydrochlorothiazide significantly decreased mean blood pressure in the knockout mice. Chronic administration of mineralocorticoid receptor antagonist spironolactone significantly decreased mean blood pressure of the knockout mice along with downregulation of cleaved epithelial sodium channel-α and phosphorylated Na + -Cl - cotransporter expression in the knockout kidney. Our data suggest that kidney-specific deficiency of 11β-HSD2 leads to salt-dependent hypertension, which is attributed to mineralocorticoid receptor-epithelial sodium channel-Na + -Cl - cotransporter activation in the kidney, and provides evidence that renal dysfunction is essential for developing the

  12. 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

  13. 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

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

    Directory of Open Access Journals (Sweden)

    Nobuhiko Satoh

    2015-01-01

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

  15. Regulation of the sodium/potassium/chloride cotransporter by calcium and cyclic AMP in cultured vascular smooth muscle cells

    International Nuclear Information System (INIS)

    Higgins, B.L.; Smith, L.; Smith, J.B.

    1987-01-01

    The activity of the Na/K/Cl cotransporter in smooth muscle cells cultured from rat aorta was assayed by measuring the initial rate of furosemide-inhibitable 86 Rb influx or efflux. Five uM furosemide or 0.2 uM bumetanide inhibited influx by 50%. Furosemide-inhibitable 86 Rb influx depended on the presence of all 3 ions in the external medium. The dependence on Na and K was hyperbolic with apparent Km values of 45 and 5 mM, respectively. The dependence on Cl was sigmoidal. Assuming a stoichiometry of 1:1:2 for Na:K:Cl, a Km for Cl of 60 mM was obtained from a Hofstee plot of the data. Rapidly growing cells had 3 fold higher cotransport activity than quiescent cells. Angiotensin II (ANG) stimulated furosemide-inhibitable 86 Rb efflux by 2 fold. An ANG receptor antagonist prevented ANG from increasing cotransport activity. Two calcium ionophores, A23187 and ionomycin, increased cotransport activity by 2 fold. Phorbol myristate acetate had no effect on cotransport activity. Isoproterenol, dibutyryl cyclic AMP, cholera toxin, or methylisobutylxanthine inhibited furosemide-sensitive 86 Rb influx by 35 to 50%. From these findings they conclude that increasing cytoplasmic free calcium stimulates cotransport activity, whereas increasing cellular cyclic AMP inhibits the cotransporter

  16. Isotonic transport by the Na+-glucose cotransporter SGLT1 from humans and rabbit

    DEFF Research Database (Denmark)

    Zeuthen, T; Meinild, A K; Loo, D D

    2001-01-01

    water transport was divided about equally between cotransport, osmosis across the SGLT1 and osmosis across the native oocyte membrane. 6. Coexpression of AQP1 with the SGLT1 increased the water permeability more than 10-fold and steady state isotonic transport was achieved after less than 2 s of sugar......1. In order to study its role in steady state water transport, the Na+-glucose cotransporter (SGLT1) was expressed in Xenopus laevis oocytes; both the human and the rabbit clones were tested. The transport activity was monitored as a clamp current and the flux of water followed optically...... as the change in oocyte volume. 2. SGLT1 has two modes of water transport. First, it acts as a molecular water pump: for each 2 Na+ and 1 sugar molecule 264 water molecules were cotransported in the human SGLT1 (hSGLT1), 424 for the rabbit SGLT1 (rSGLT1). Second, it acts as a water channel. 3. The cotransport...

  17. Water permeability of Na+-K+-2Cl- cotransporters in mammalian epithelial cells

    DEFF Research Database (Denmark)

    Hamann, Steffen; Herrera-Perez, José Jaime; Bundgaard, Magnus

    2005-01-01

    Water transport properties of the Na+-K+-2Cl- cotransporter (NKCC) were studied in cultures of pigmented epithelial cells (PE) from the ciliary body of the eye. Here, the membrane that faces upwards contains NKCCs and can be subjected to rapid changes in bathing solution composition and osmolarity...

  18. Functional assessment of sodium chloride cotransporter NCC mutants in polarized mammalian epithelial cells

    DEFF Research Database (Denmark)

    Rosenbaek, Lena L; Rizzo, Federica; MacAulay, Nanna

    2017-01-01

    The thiazide-sensitive sodium chloride cotransporter NCC is important for maintaining serum sodium (Na(+)) and, indirectly, serum potassium (K(+)) levels. Functional studies on NCC have used cell lines with native NCC expression, transiently transfected nonpolarized cell lines, or Xenopus laevis...

  19. K-Cl cotransport function and its potential contribution to cardiovascular disease.

    Science.gov (United States)

    Adragna, Norma C; Lauf, Peter K

    2007-12-01

    K-Cl cotransport is the coupled electroneutral movement of K and Cl ions carried out by at least four protein isoforms, KCC1-4. These transporters belong to the SLC12A family of coupled cotransporters and, due to their multiple functions, play an important role in the maintenance of cellular homeostasis. Significant information exists on the overall function of these transporters, but less is known about the role of the specific isoforms. Most functional studies were done on K-Cl cotransport fluxes without knowing the molecular details, and only recently attention has been paid to the isoforms and their individual contribution to the fluxes. This review summarizes briefly and updates the information on the overall functions of this transporter, and offers some ideas on its potential contribution to the pathophysiological basis of cardiovascular disease. By virtue of its properties and the cellular ionic distribution, K-Cl cotransport participates in volume regulation of the nucleated and some enucleated cells studied thus far. One of the hallmarks in cardiovascular disease is the inability of the organism to maintain water and electrolyte balance in effectors and/or target tissues. Oxidative stress is another compounding factor in cardiovascular disease and of great significance in our modern life styles. Several functions of the transporter are modulated by oxidative stress, which in turn may cause the transporter to operate in either "overdrive" with the purpose to counteract homeostatic changes, or not to respond at all, again setting the stage for pathological changes leading to cardiovascular disease. Intracellular Mg, a second messenger, acts as an inhibitor of K-Cl cotransport and plays a crucial role in regulating the activity of protein kinases and phosphatases, which, in turn, regulate a myriad of cellular functions. Although the role of Mg in cardiovascular disease has been dealt with for several decades, this chapter is evolving nowadays at a faster

  20. Diabetes and kidney disease: the role of sodium-glucose cotransporter-2 (SGLT-2) and SGLT-2 inhibitors in modifying disease outcomes.

    Science.gov (United States)

    Mende, Christian W

    2017-03-01

    Patients with type 2 diabetes (T2D) often have coexisting chronic kidney disease (CKD). However, healthy renal function is crucial in maintaining glucose homeostasis, assuring that almost all of the filtered glucose is reabsorbed by the sodium glucose cotransporters (SGLTs) SGLT-1 and SGLT-2. In diabetes, an increased amount of glucose is filtered by the kidneys and SGLT-2 is upregulated, leading to increased glucose absorption and worsening hyperglycemia. Prolonged hyperglycemia contributes to the development of CKD by inducing metabolic and hemodynamic changes in the kidneys. Due to the importance of SGLT-2 in regulating glucose levels, investigation into SGLT-2 inhibitors was initiated as a glucose-dependent mechanism to control hyperglycemia, and there are three agents currently approved for use in the United States: dapagliflozin, canagliflozin, and empagliflozin. SGLT-2 inhibitors have been shown to reduce glycated hemoglobin (A1C), weight, and blood pressure, which not only affects glycemic control, but may also help slow the progression of renal disease by impacting the underlying mechanisms of kidney injury. In addition, SGLT-2 inhibitors have shown reductions in albuminuria, uric acid, and an increase in magnesium. Caution is advised when prescribing SGLT-2 inhibitors to patients with moderately impaired renal function and those at risk for volume depletion and hypotension. Published data on slowing of the development, as well as progression of CKD, is a hopeful indicator for the possible renal protection potential of this drug class. This narrative review provides an in-depth discussion of the interplay between diabetes, SGLT-2 inhibitors, and factors that affect kidney function.

  1. Renal scan

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003790.htm Renal scan To use the sharing features on this ... anaphylaxis . Alternative Names Renogram; Kidney scan Images Kidney anatomy Kidney - blood and urine flow References Chernecky CC, ...

  2. Renal Hemangiopericytoma

    Directory of Open Access Journals (Sweden)

    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.

  3. Empagliflozin: a new sodium-glucose co-transporter 2 (SGLT2 inhibitor for the treatment of type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Joshua J Neumiller

    2014-06-01

    Full Text Available Type 2 diabetes is increasing in prevalence worldwide, and hyperglycemia is often poorly controlled despite a number of therapeutic options. Unlike previously available agents, sodium-glucose co-transporter 2 (SGLT2 inhibitors offer an insulin-independent mechanism for improving blood glucose levels, since they promote urinary glucose excretion (UGE by inhibiting glucose reabsorption in the kidney. In addition to glucose control, SGLT2 inhibitors are associated with weight loss and blood pressure reductions, and do not increase the risk of hypoglycemia. Empagliflozin is a selective inhibitor of SGLT2, providing dose-dependent UGE increases in healthy volunteers, with up to 90 g of glucose excreted per day. It can be administered orally, and studies of people with renal or hepatic impairment indicated empagliflozin needed no dose adjustment based on pharmacokinetics. In Phase II trials in patients with type 2 diabetes, empagliflozin provided improvements in glycosylated hemoglobin (HbA1c and other measures of glycemic control when given as monotherapy or add-on to metformin, as well as reductions in weight and systolic blood pressure. As add-on to basal insulin, empagliflozin not only improved HbA1c levels but also reduced insulin doses. Across studies, empagliflozin was generally well tolerated with a similar rate of hypoglycemia to placebo; however, patients had a slightly increased frequency of genital infections, but not urinary tract infections, versus placebo. Phase III studies have also reported a good safety profile along with significant improvements in HbA1c, weight and blood pressure, with no increased risk of hypoglycemia versus placebo. Based on available data, it appears that empagliflozin may be a useful option in a range of patients; however, clinical decisions will be better informed by the results of ongoing studies, in particular, a large cardiovascular outcome study (EMPA-REG OUTCOME™.

  4. Sodium Glucose Cotransporter 2 (SGLT2 Plays as a Physiological Glucose Sensor and Regulates Cellular Contractility in Rat Mesangial Cells.

    Directory of Open Access Journals (Sweden)

    Masanori Wakisaka

    Full Text Available Mesangial cells play an important role in regulating glomerular filtration by altering their cellular tone. We report the presence of a sodium glucose cotransporter (SGLT in rat mesangial cells. This study in rat mesangial cells aimed to evaluate the expression and role of SGLT2.The SGLT2 expression in rat mesangial cells was assessed by Western blotting and reverse transcription-polymerase chain reaction (RT-PCR. Changes in the mesangial cell surface area at different glucose concentrations and the effects of extracellular Na+ and Ca2+ and of SGLT and Na+/Ca2+ exchanger (NCX inhibitors on cellular size were determined. The cellular sizes and the contractile response were examined during a 6-day incubation with high glucose with or without phlorizin, an SGLT inhibitor.Western blotting revealed an SGLT2 band, and RT-PCR analysis of SGLT2 revealed the predicted 422-bp band in both rat mesangial and renal proximal tubular epithelial cells. The cell surface area changed according to the extracellular glucose concentration. The glucose-induced contraction was abolished by the absence of either extracellular Na+ or Ca2+ and by SGLT and NCX inhibitors. Under the high glucose condition, the cell size decreased for 2 days and increased afterwards; these cells did not contract in response to angiotensin II, and the SGLT inhibitor restored the abolished contraction.These data suggest that SGLT2 is expressed in rat mesangial cells, acts as a normal physiological glucose sensor and regulates cellular contractility in rat mesangial cells.

  5. Expression of three isoforms of Na-K-2Cl cotransporter (NKCC2) in the kidney and regulation by dehydration.

    Science.gov (United States)

    Itoh, Kazuko; Izumi, Yuichiro; Inoue, Takeaki; Inoue, Hideki; Nakayama, Yushi; Uematsu, Takayuki; Fukuyama, Takashi; Yamazaki, Taiga; Yasuoka, Yukiko; Makino, Takeshi; Nagaba, Yasushi; Tomita, Kimio; Kobayashi, Noritada; Kawahara, Katsumasa; Mukoyama, Masashi; Nonoguchi, Hiroshi

    2014-10-24

    Sodium reabsorption via Na-K-2Cl cotransporter 2 (NKCC2) in the thick ascending limbs has a major role for medullary osmotic gradient and subsequent water reabsorption in the collecting ducts. We investigated intrarenal localization of three isoforms of NKCC2 mRNA expressions and the effects of dehydration on them in rats. To further examine the mechanisms of dehydration, the effects of hyperosmolality on NKCC2 mRNA expression in microdissected renal tubules was studied. RT-PCR and RT-competitive PCR were employed. The expressions of NKCC2a and b mRNA were observed in the cortical thick ascending limbs (CAL) and the distal convoluted tubules (DCT) but not in the medullary thick ascending limbs (MAL), whereas NKCC2f mRNA expression was seen in MAL and CAL. Two-day dehydration did not affect these mRNA expressions. In contrast, hyperosmolality increased NKCC2 mRNA expression in MAL in vitro. Bradykinin dose-dependently decreased NKCC2 mRNA expression in MAL. However, dehydration did not change NKCC2 protein expression in membrane fraction from cortex and outer medulla and in microdissected MAL. These data show that NKCC2a/b and f types are mainly present in CAL and MAL, respectively. Although NKCC2 mRNA expression was stimulated by hyperosmolality in vitro, NKCC2 mRNA and protein expressions were not stimulated by dehydration in vivo. These data suggest the presence of the inhibitory factors for NKCC2 expression in dehydration. Considering the role of NKCC2 for the countercurrent multiplier system, NKCC2f expressed in MAL might be more important than NKCC2a/b. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Sodium Glucose Cotransporter 2 Inhibitors in the Treatment of Diabetes Mellitus : Cardiovascular and Kidney Effects, Potential Mechanisms, and Clinical Applications

    NARCIS (Netherlands)

    Heerspink, Hiddo J. L.; Perkins, Bruce A.; Fitchett, David H.; Husain, Mansoor; Cherney, David Z. I.

    2016-01-01

    Sodium-glucose cotransporter-2 (SGLT2) inhibitors, including empagliflozin, dapagliflozin, and canagliflozin, are now widely approved antihyperglycemic therapies. Because of their unique glycosuric mechanism, SGLT2 inhibitors also reduce weight. Perhaps more important are the osmotic diuretic and

  7. The human Na+-glucose cotransporter is a molecular water pump

    DEFF Research Database (Denmark)

    Meinild, A; Klaerke, D A; Loo, D D

    1998-01-01

    1. The human Na+-glucose cotransporter (hSGLT1) was expressed in Xenopus laevis oocytes. The transport activity, given by the Na+ current, was monitored as a clamp current and the concomitant flux of water followed optically as the change in oocyte volume. 2. When glucose was added to the bathing...... solution there was an abrupt increase in clamp current and an immediate swelling of the oocyte. The transmembrane transport of two Na+ ions and one sugar molecule was coupled, within the protein itself, to the influx of 210 water molecules. 3. This stoichiometry was constant and independent of the external...... parameters: Na+ concentrations, sugar concentrations, transmembrane voltages, temperature and osmotic gradients. 4. The cotransport of water occurred in the presence of adverse osmotic gradients. In accordance with the Gibbs equation, energy was transferred within the protein from the downhill fluxes of Na...

  8. Na+ -K+ -2Cl- Cotransporter (NKCC) Physiological Function in Nonpolarized Cells and Transporting Epithelia.

    Science.gov (United States)

    Delpire, Eric; Gagnon, Kenneth B

    2018-03-25

    Two genes encode the Na + -K + -2Cl - cotransporters, NKCC1 and NKCC2, that mediate the tightly coupled movement of 1Na + , 1K + , and 2Cl - across the plasma membrane of cells. Na + -K + -2Cl - cotransport is driven by the chemical gradient of the three ionic species across the membrane, two of them maintained by the action of the Na + /K + pump. In many cells, NKCC1 accumulates Cl - above its electrochemical potential equilibrium, thereby facilitating Cl - channel-mediated membrane depolarization. In smooth muscle cells, this depolarization facilitates the opening of voltage-sensitive Ca 2+ channels, leading to Ca 2+ influx, and cell contraction. In immature neurons, the depolarization due to a GABA-mediated Cl - conductance produces an excitatory rather than inhibitory response. In many cell types that have lost water, NKCC is activated to help the cells recover their volume. This is specially the case if the cells have also lost Cl - . In combination with the Na + /K + pump, the NKCC's move ions across various specialized epithelia. NKCC1 is involved in Cl - -driven fluid secretion in many exocrine glands, such as sweat, lacrimal, salivary, stomach, pancreas, and intestine. NKCC1 is also involved in K + -driven fluid secretion in inner ear, and possibly in Na + -driven fluid secretion in choroid plexus. In the thick ascending limb of Henle, NKCC2 activity in combination with the Na + /K + pump participates in reabsorbing 30% of the glomerular-filtered Na + . Overall, many critical physiological functions are maintained by the activity of the two Na + -K + -2Cl - cotransporters. In this overview article, we focus on the functional roles of the cotransporters in nonpolarized cells and in epithelia. © 2018 American Physiological Society. Compr Physiol 8:871-901, 2018. Copyright © 2018 American Physiological Society. All rights reserved.

  9. Cotransport of sodium and chloride by the adult mammalian choroid plexus

    Energy Technology Data Exchange (ETDEWEB)

    Johanson, C.E.; Sweeney, S.M.; Parmelee, J.T.; Epstein, M.H. (Brown Univ./Rhode Island Hospital, Providence (USA))

    1990-02-01

    Cerebrospinal fluid formation stems primarily from the transport of Na and Cl in choroid plexus (CP). To characterize properties and modulation of choroidal transporters, we tested diuretics and other agents for ability to alter ion transport in vitro. Adult Sprague-Dawley rats were the source of CPs preincubated with drug for 20 min and then transferred to cerebrospinal fluid (CSF) medium containing 22Na or 36Cl with (3H)mannitol (extracellular correction). Complete base-line curves were established for cellular uptake of Na and Cl at 37 degrees C. The half-maximal uptake occurred at 12 s, so it was used to assess drug effects on rate of transport (nmol Na or Cl/mg CP). Bumetanide (10(-5) and 10(-4) M) decreased uptake of Na and Cl with maximal inhibition (up to 45%) at 10(-5) M. Another cotransport inhibitor, furosemide (10(-4) M), reduced transport of Na by 25% and Cl by 33%. However, acetazolamide (10(-4) M) and atriopeptin III (10(-7) M) significantly lowered uptake of Na (but not Cl), suggesting effect(s) other than on cotransport. The disulfonic stilbene 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS; 10(-4) M), known to inhibit Cl-HCO3 exchange, substantially reduced the transport of 36Cl. Bumetanide plus DIDS (both 10(-4) M) caused additive inhibition of 90% of Cl uptake, which provides strong evidence for the existence of both cotransport and antiport Cl carriers. Overall, this in vitro analysis, uncomplicated by variables of blood flow and neural tone, indicates the presence in rat CP of the cotransport of Na and Cl in addition to the established Na-H and Cl-HCO3 exchangers.

  10. Cotransport of water and solutes in plant membranes: The molecular basis, and physiological functions

    Directory of Open Access Journals (Sweden)

    Lars H. Wegner

    2017-03-01

    Full Text Available Current concepts of plant membrane transport are based on the assumption that water and solutes move across membranes via separate pathways. According to this view, coupling between the fluxes is more or less exclusively constituted via the osmotic force that solutes exert on water transport. This view is questioned here, and experimental evidence for a cotransport of water and solutes is reviewed. The overview starts with ion channels that provide pathways for both ion and water transport, as exemplified for maxi K+ channels from cytoplasmic droplets of Chara corallina. Aquaporins are usually considered to be selective for water (just allowing for slippage of some other small, neutral molecules. Recently, however, a “dual function” aquaporin has been characterized from Arabidopsis thaliana (AtPIP2.1 that translocates water and at the same time conducts cations, preferentially Na+. By analogy with mammalian physiology, other candidates for solute-water flux coupling are cation-chloride cotransporters of the CCC type, and transporters of sugars and amino acids. The last part is dedicated to possible physiological functions that could rely on solute-water cotransport. Among these are the generation of root pressure, refilling of embolized xylem vessels, fast turgor-driven movements of leaves, cell elongation (growth, osmoregulation and adjustment of buoyancy in marine algae. This review will hopefully initiate further research in the field.

  11. Tyrosine transport in winter flounder intestine: Interaction with Na+-K+-2Cl- cotransport

    International Nuclear Information System (INIS)

    Musch, M.W.; McConnell, F.M.; Goldstein, L.; Field, M.

    1987-01-01

    Tyrosine absorption across the brush border of the intestinal epithelium of the winter flounder Pseudopleuronectes americanus was studied in Ussing chambers modified to determine early rates of uptake. At 0.1 mM tyrosine, the 4-min rate of uptake (influx) of tyrosine across the brush border averaged 37.5 nmol·cm -2 ·h -1 . Omission of Na decreased influx by 60%, indicting that tyrosine influx occurs, at least in part, by a Na-coupled process. Ouabain inhibited influx by 80%. Inhibition of brush border Na + -K + -2Cl - cotransport by bumetanide, 8-bromo-cyclic GMP, or Cl replacement stimulated tyrosine influx 2.5- to 4-fold. However, atriopeptin III, which also inhibits Na + -K + -2Cl - cotransport, did not stimulate tyrosine influx. Cyclic AMP, which does not appear to inhibit ion cotransport, did not stimulate tyrosine influx. Both cyclic GMP and bumetanide also stimulated the net mucosa-to-serosa tyrosine flux (43 and 29%, respectively) and increased the cellular concentration of tyrosine by 50%. Thus tyrosine's influx is increased to a greater extent than is its transmural flux or its cellular concentration, suggesting that the main change occurs at the brush border and represents large increases in both influx and efflux of tyrosine across this membrane

  12. Modeling glial contributions to seizures and epileptogenesis: cation-chloride cotransporters in Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Zeid M Rusan

    Full Text Available Flies carrying a kcc loss-of-function mutation are more seizure-susceptible than wild-type flies. The kcc gene is the highly conserved Drosophila melanogaster ortholog of K+/Cl- cotransporter genes thought to be expressed in all animal cell types. Here, we examined the spatial and temporal requirements for kcc loss-of-function to modify seizure-susceptibility in flies. Targeted RNA interference (RNAi of kcc in various sets of neurons was sufficient to induce severe seizure-sensitivity. Interestingly, kcc RNAi in glia was particularly effective in causing seizure-sensitivity. Knockdown of kcc in glia or neurons during development caused a reduction in seizure induction threshold, cell swelling, and brain volume increase in 24-48 hour old adult flies. Third instar larval peripheral nerves were enlarged when kcc RNAi was expressed in neurons or glia. Results suggest that a threshold of K+/Cl- cotransport dysfunction in the nervous system during development is an important determinant of seizure-susceptibility in Drosophila. The findings presented are the first attributing a causative role for glial cation-chloride cotransporters in seizures and epileptogenesis. The importance of elucidating glial cell contributions to seizure disorders and the utility of Drosophila models is discussed.

  13. Sodium-glucose co-transporter type 2 inhibitors reduce evening home blood pressure in type 2 diabetes with nephropathy.

    Science.gov (United States)

    Takenaka, Tsuneo; Kishimoto, Miyako; Ohta, Mari; Tomonaga, Osamu; Suzuki, Hiromichi

    2017-05-01

    The effects of sodium-glucose co-transporter type 2 inhibitors on home blood pressure were examined in type 2 diabetes with nephropathy. The patients with diabetic nephropathy were screened from medical records in our hospitals. Among them, 52 patients who measured home blood pressure and started to take sodium-glucose co-transporter type 2 inhibitors were selected. Clinical parameters including estimated glomerular filtration rate, albuminuria and home blood pressure for 6 months were analysed. Sodium-glucose co-transporter type 2 inhibitors (luseogliflozin 5 mg/day or canagliflozin 100 mg/day) reduced body weight, HbA1c, albuminuria, estimated glomerular filtration rate and office blood pressure. Although sodium-glucose co-transporter type 2 inhibitors did not alter morning blood pressure, it reduced evening systolic blood pressure. Regression analyses revealed that decreases in evening blood pressure predicted decrements in albuminuria. The present data suggest that sodium-glucose co-transporter type 2 inhibitors suppress sodium overload during daytime to reduce evening blood pressure and albuminuria.

  14. Human NKCC2 cation–Cl– co-transporter complements lack of Vhc1 transporter in yeast vacuolar membranes.

    Science.gov (United States)

    Petrezselyova, Silvia; Dominguez, Angel; Herynkova, Pavla; Macias, Juan F; Sychrova, Hana

    2013-10-01

    Cation–chloride co-transporters serve to transport Cl– and alkali metal cations. Whereas a large family of these exists in higher eukaryotes, yeasts only possess one cation–chloride co-transporter, Vhc1, localized to the vacuolar membrane. In this study, the human cation–chloride co-transporter NKCC2 complemented the phenotype of VHC1 deletion in Saccharomyces cerevisiae and its activity controlled the growth of salt-sensitive yeast cells in the presence of high KCl, NaCl and LiCl. A S. cerevisiae mutant lacking plasma-membrane alkali–metal cation exporters Nha1 and Ena1-5 and the vacuolar cation–chloride co-transporter Vhc1 is highly sensitive to increased concentrations of alkali–metal cations, and it proved to be a suitable model for characterizing the substrate specificity and transport activity of human wild-type and mutated cation–chloride co-transporters. Copyright © 2013 John Wiley & Sons, Ltd.

  15. Ipragliflozin and other sodium-glucose cotransporter-2 (SGLT2) inhibitors in the treatment of type 2 diabetes: preclinical and clinical data.

    Science.gov (United States)

    Kurosaki, Eiji; Ogasawara, Hideaki

    2013-07-01

    Sodium-glucose cotransporter-2 (SGLT2) is expressed in the proximal tubules of the kidneys and plays a key role in renal glucose reabsorption. A novel class of antidiabetic medications, SGLT2-selective inhibitors attempt to improve glycemic control in diabetics by preventing glucose from being reabsorbed through SGLT2 and re-entering circulation. Ipragliflozin is an SGLT2 inhibitor in Phase 3 clinical development for the treatment of type 2 diabetes mellitus (T2DM). In this review, we summarize recent animal and human studies on ipragliflozin and other SGLT2 inhibitors including dapagliflozin, canagliflozin, empagliflozin, tofogliflozin, and luseogliflozin. These agents all show potent and selective SGLT2 inhibition in vitro and reduce blood glucose levels and HbA1c in both diabetic animal models and patients with T2DM. SGLT2 inhibitors offer several advantages over other classes of hypoglycemic agents. Due to their insulin-independent mode of action, SGLT2 inhibitors provide steady glucose control without major risk for hypoglycemia and may also reverse β-cell dysfunction and insulin resistance. Other favorable effects of SGLT2 inhibitors include a reduction in both body weight and blood pressure. SGLT2 inhibitors are safe and well tolerated and can easily be combined with other classes of antidiabetic medications to achieve tighter glycemic control. The long-term safety and efficacy of these agents are under evaluation. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. The role of disease-linked residue glutamine-913 in support of the structure and function of the human electrogenic sodium/bicarbonate cotransporter NBCe1-A.

    Science.gov (United States)

    Myers, Evan J; Marshall, Aniko; Parker, Mark D

    2018-02-15

    Mutations in the sodium bicarbonate cotransporter NBCe1 (SLC4A4) cause proximal renal tubular acidosis (pRTA). We recently described a novel pRTA mutation p.Gln913Arg (Q913R), inherited in compound heterozygous form with p.Arg510His (R510H). Q913R causes intracellular retention of NBCe1 and a 'gain of function' Cl - leak. To learn more about the importance of glutamine at position 913, we substituted a variety of alternative amino-acid residues (Cys, Glu, Lys, Leu, Ser) at position 913. Studying cRNA-injected Xenopus oocytes by voltage clamp, we find that most de novo mutants exhibit close-to-normal NBCe1 activity; only Q913K expresses a Cl - leak. Studying transiently-transfected, polarised kidney cells by fluorescence microscopy we find that most de novo mutants (except Q913E) are intracellularly retained. A 3D homology model predicts that Gln913 is located in the gating domain of NBCe1 and neighbours the 3D space occupied by another pRTA-associated residue (Arg881), highlighting an important and conformationally-sensitive region of NBCe1. We conclude that the intracellular retention of Q913R is caused by the loss of Gln at position 913, but that the manifestation of the Cl - leak is related to the introduction of Arg at position 913. Our findings will inform future studies to elucidate the nature and the consequences of the leak.

  17. Renal candidiasis

    International Nuclear Information System (INIS)

    Khanna, S.; Malik, N.; Khandelwal, N.

    1990-01-01

    Most fungal infections of the urinary tract are caused by Candida albicans, a yeast-like saprophytic fungus which may become apathogen under various conditions which lower the host resistance. The use of computed tomography in the diagnosis of renal fungus balls is the subject of this communication with emphasis on the radiologists role in the recognition of this entity. (H.W.). 6 refs.; 2 figs

  18. Renal hemangioma

    Directory of Open Access Journals (Sweden)

    Theodorico F. da Costa Neto

    2004-06-01

    Full Text Available INTRODUCTION: Renal hemangioma is a relatively rare benign tumor, seldom diagnosed as a cause of hematuria. CASE REPORT: A female 40-year old patient presented with continuous gross hematuria, anemia and episodic right lumbar pain, with onset about 3 months previously. The patient underwent multiple blood transfusions during her hospital stay and extensive imaging propedeutics was performed. Semi-rigid ureterorenoscopy evidenced a bleeding focus in the upper calix of the right kidney, with endoscopic treatment being unfeasible. The patient underwent right upper pole nephrectomy and presented a favorable outcome. Histopathological analysis of the surgical specimen showed that it was a renal hemangioma. COMMENTS: Imaging methods usually employed for diagnostic investigation of hematuria do not have good sensitivity for renal hemangioma. However, they are important to exclude the most frequent differential diagnoses. The ureterorenoscopy is the diagnostic method of choice and endoscopic treatment can be feasible when the lesion is accessible and electrocautery or laser are available. We emphasize the open surgical treatment as a therapeutic option upon failure of less invasive methods.

  19. 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

  20. Radiopharmaceuticals for renal studies

    International Nuclear Information System (INIS)

    Verdera, Silvia

    1994-01-01

    Between the diagnostic techniques using radiopharmaceuticals in nuclear medicine it find renal studies.A brief description about renal glomerular filtration(GFR) and reliability renal plasma flux (ERPF),renal blood flux measurement agents (RBF),renal scintillation agents and radiation dose estimates by organ physiology was given in this study.tabs

  1. Comparison of colon-cleansing methods in preparation for colonoscopy - Comparative efficacy of solutions of mannitol, sodium picosulfate and monobasic and dibasic sodium phosphates Estudo comparativo entre as soluções de manitol, picossulfato de sódio e fosfato monobásico e dibásico de sódio no preparo de cólon para colonoscopia

    Directory of Open Access Journals (Sweden)

    Paulo Miki Jr

    2008-01-01

    Full Text Available PURPOSE: Colonoscopy plays an essential role in the therapeutic and diagnostic approach in various colonic pathologies, the aim of the present study was to compare three solutions and their efficacy for the bowel preparation in adult patients submitted to elective colonoscopy. METHODS: Sixty patients were randomly divided into three groups of 20 each. Each group was submitted to a bowel preparation with one of the following solutions: 10% manitol, sodium picosulphate or sodium phosphate. The parameters evaluated were: taste, tolerance, associated side effects and quality of cleansing. Postural blood pressure and pulse rate as well as serum sodium, potassium, calcium and phosphate were compared. RESULTS: Sodium phosphate and 10% manitol solutions provided superior results in terms of colon cleansing compared to sodium picosulphate solution. All serum electrolytes evaluated were significantly altered in the three groups, without important clinical signs. DISCUSSION: High levels of serum phosphate were the most striking alteration in patients prepared with sodium phosphate solution, again with no clinical signs. Variations related to blood pressure and pulse rate suggested contraction of intravascular volume, with no clinical effects. CONCLUSION: Sodium phosphate and 10% manitol solutions are equivalent in providing good quality colon cleansing, with no significant side effects that could compromise the procedure.INTRODUÇÃO: A colonoscopia é exame fundamental na avaliação das doenças do cólon e na abordagem terapêutica de determinado grupo de patologias. O preparo intestinal é obrigatório para a realização das colonoscopias eletivas, e a qualidade encontra-se relacionada ao sucesso do procedimento. Comparou-se três soluções para limpeza anterógrada do cólon em pacientes adultos, submetidos à colonoscopia. METODOS: Sessenta pacientes foram distribuídos em três grupos de vinte. Cada grupo realizou o preparo do cólon com uma das

  2. Drug-drug interactions with sodium-glucose cotransporters type 2 (SGLT2) inhibitors, new oral glucose-lowering agents for the management of type 2 diabetes mellitus.

    Science.gov (United States)

    Scheen, André J

    2014-04-01

    Inhibitors of sodium-glucose cotransporters type 2 (SGLT2) reduce hyperglycaemia by decreasing renal glucose threshold and thereby increasing urinary glucose excretion. They are proposed as a novel approach for the management of type 2 diabetes mellitus. They have proven their efficacy in reducing glycated haemoglobin, without inducing hypoglycaemia, as monotherapy or in combination with various other glucose-lowering agents, with the add-on value of promoting some weight loss and lowering arterial blood pressure. As they may be used concomitantly with many other drugs, we review the potential drug-drug interactions (DDIs) regarding the three leaders in the class (dapagliglozin, canagliflozin and empagliflozin). Most of the available studies were performed in healthy volunteers and have assessed the pharmacokinetic interferences with a single administration of the SGLT2 inhibitor. The exposure [assessed by peak plasma concentrations (Cmax) and area under the concentration-time curve (AUC)] to each SGLT2 inhibitor tested was not significantly influenced by the concomitant administration of other glucose-lowering agents or cardiovascular agents commonly used in patients with type 2 diabetes. Reciprocally, these medications did not influence the pharmacokinetic parameters of dapagliflozin, canagliflozin or empagliflozin. Some modest changes were not considered as clinically relevant. However, drugs that could specifically interfere with the metabolic pathways of SGLT2 inhibitors [rifampicin, inhibitors or inducers of uridine diphosphate-glucuronosyltransferase (UGT)] may result in significant changes in the exposure of SGLT2 inhibitors, as shown for dapagliflozin and canagliflozin. Potential DDIs in patients with type 2 diabetes receiving chronic treatment with an SGLT2 inhibitor deserve further attention, especially in individuals treated with several medications or in more fragile patients with hepatic and/or renal impairment.

  3. LX4211 increases serum glucagon-like peptide 1 and peptide YY levels by reducing sodium/glucose cotransporter 1 (SGLT1)-mediated absorption of intestinal glucose.

    Science.gov (United States)

    Powell, David R; Smith, Melinda; Greer, Jennifer; Harris, Angela; Zhao, Sharon; DaCosta, Christopher; Mseeh, Faika; Shadoan, Melanie K; Sands, Arthur; Zambrowicz, Brian; Ding, Zhi-Ming

    2013-05-01

    LX4211 [(2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(methylthio)tetrahydro-2H-pyran-3,4,5-triol], a dual sodium/glucose cotransporter 1 (SGLT1) and SGLT2 inhibitor, is thought to decrease both renal glucose reabsorption by inhibiting SGLT2 and intestinal glucose absorption by inhibiting SGLT1. In clinical trials in patients with type 2 diabetes mellitus (T2DM), LX4211 treatment improved glycemic control while increasing circulating levels of glucagon-like peptide 1 (GLP-1) and peptide YY (PYY). To better understand how LX4211 increases GLP-1 and PYY levels, we challenged SGLT1 knockout (-/-) mice, SGLT2-/- mice, and LX4211-treated mice with oral glucose. LX4211-treated mice and SGLT1-/- mice had increased levels of plasma GLP-1, plasma PYY, and intestinal glucose during the 6 hours after a glucose-containing meal, as reflected by area under the curve (AUC) values, whereas SGLT2-/- mice showed no response. LX4211-treated mice and SGLT1-/- mice also had increased GLP-1 AUC values, decreased glucose-dependent insulinotropic polypeptide (GIP) AUC values, and decreased blood glucose excursions during the 6 hours after a challenge with oral glucose alone. However, GLP-1 and GIP levels were not increased in LX4211-treated mice and were decreased in SGLT1-/- mice, 5 minutes after oral glucose, consistent with studies linking decreased intestinal SGLT1 activity with reduced GLP-1 and GIP levels 5 minutes after oral glucose. These data suggest that LX4211 reduces intestinal glucose absorption by inhibiting SGLT1, resulting in net increases in GLP-1 and PYY release and decreases in GIP release and blood glucose excursions. The ability to inhibit both intestinal SGLT1 and renal SGLT2 provides LX4211 with a novel dual mechanism of action for improving glycemic control in patients with T2DM.

  4. Why Do SGLT2 inhibitors inhibit only 30-50% of renal glucose reabsorption in humans?

    Science.gov (United States)

    Liu, Jiwen Jim; Lee, TaeWeon; DeFronzo, Ralph A

    2012-09-01

    Sodium glucose cotransporter 2 (SGLT2) inhibition is a novel and promising treatment for diabetes under late-stage clinical development. It generally is accepted that SGLT2 mediates 90% of renal glucose reabsorption. However, SGLT2 inhibitors in clinical development inhibit only 30-50% of the filtered glucose load. Why are they unable to inhibit 90% of glucose reabsorption in humans? We will try to provide an explanation to this puzzle in this perspective analysis of the unique pharmacokinetic and pharmacodynamic profiles of SGLT2 inhibitors in clinical trials and examine possible mechanisms and molecular properties that may be responsible.

  5. Why Do SGLT2 Inhibitors Inhibit Only 30–50% of Renal Glucose Reabsorption in Humans?

    Science.gov (United States)

    Liu, Jiwen (Jim); Lee, TaeWeon; DeFronzo, Ralph A.

    2012-01-01

    Sodium glucose cotransporter 2 (SGLT2) inhibition is a novel and promising treatment for diabetes under late-stage clinical development. It generally is accepted that SGLT2 mediates 90% of renal glucose reabsorption. However, SGLT2 inhibitors in clinical development inhibit only 30–50% of the filtered glucose load. Why are they unable to inhibit 90% of glucose reabsorption in humans? We will try to provide an explanation to this puzzle in this perspective analysis of the unique pharmacokinetic and pharmacodynamic profiles of SGLT2 inhibitors in clinical trials and examine possible mechanisms and molecular properties that may be responsible. PMID:22923645

  6. Sodium-glucose cotransporter 2 inhibition and health benefits: The Robin Hood effect.

    Science.gov (United States)

    Kalra, Sanjay; Jain, Arpit; Ved, Jignesh; Unnikrishnan, A G

    2016-01-01

    This review discusses two distinct, yet related, mechanisms of sodium-glucose cotransporter 2 (SGLT2) inhibition: Calorie restriction mimicry (CRM) and pro-ketogenic effect, which may explain their cardiovascular benefits. We term these adaptive CRM and pro-ketogenic effects of SGLT2 inhibition, the Robin Hood hypothesis. In English history, Robin Hood was a "good person," who stole from the rich and helped the poor. He supported redistribution of resources as he deemed fit for the common good. In a similar fashion, SGLT2 inhibition provides respite to the overloaded glucose metabolism while utilizing lipid stores for energy production.

  7. Sodium-glucose cotransporter 2 inhibition and health benefits: The Robin Hood effect

    Directory of Open Access Journals (Sweden)

    Sanjay Kalra

    2016-01-01

    Full Text Available This review discusses two distinct, yet related, mechanisms of sodium-glucose cotransporter 2 (SGLT2 inhibition: Calorie restriction mimicry (CRM and pro-ketogenic effect, which may explain their cardiovascular benefits. We term these adaptive CRM and pro-ketogenic effects of SGLT2 inhibition, the Robin Hood hypothesis. In English history, Robin Hood was a "good person," who stole from the rich and helped the poor. He supported redistribution of resources as he deemed fit for the common good. In a similar fashion, SGLT2 inhibition provides respite to the overloaded glucose metabolism while utilizing lipid stores for energy production.

  8. Sodium-glucose cotransporter 2 inhibitor use: A pharmaco-ergonomic qualification tool

    Directory of Open Access Journals (Sweden)

    Sanjay Kalra

    2017-01-01

    Full Text Available Pharmaco-ergonomics implies tailoring the drug therapy to an individual patient's requirement(s. The development of sodium-glucose cotransporter 2 inhibitor (SGLT2-i agents has impelled multiple clinical considerations, in the management of type-2 diabetes. This paper attempts to summarize the pharmaco-ergonomic considerations for these agents, in the form of an SGLT2-i qualification tool, based on a clinical score. This tool may serve as a simple and inexpensive practical guide, to optimize the risk-benefit considerations for SGLT2-i agents.

  9. Bilateral renal artery variation

    OpenAIRE

    Üçerler, Hülya; Üzüm, Yusuf; İkiz, Z. Aslı Aktan

    2014-01-01

    Each kidney is supplied by a single renal artery, although renal artery variations are common. Variations of the renal arteryhave become important with the increasing number of renal transplantations. Numerous studies describe variations in renalartery anatomy. Especially the left renal artery is among the most critical arterial variations, because it is the referred side forresecting the donor kidney. During routine dissection in a formalin fixed male cadaver, we have found a bilateral renal...

  10. Contribution of the basolateral isoform of the Na-K-2Cl- cotransporter (NKCC1/BSC2) to renin secretion

    DEFF Research Database (Denmark)

    Castrop, Hayo; Lorenz, John N; Hansen, Pernille B

    2005-01-01

    Acute administration of loop diuretics like furosemide leads to a stimulation of renin secretion, an effect thought to result from inhibition of Na-K-2Cl cotransporter (NKCC2)-mediated salt transport at the luminal surface of the macula densa (MD). However, loop diuretics also inhibit NKCC1......, the second isoform of the Na-K-2Cl cotransporter, with similar potency. In the present study, we examined the influence of furosemide on renin secretion in NKCC1-deficient mice to distinguish between effects of the loop diuretic involving NKCC2 and, by implication, the MD pathway, and effects that might...

  11. 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

  12. Renal denervation

    DEFF Research Database (Denmark)

    Olsen, Lene Kjær; Kamper, Anne-Lise; Svendsen, Jesper Hastrup

    2015-01-01

    PURPOSE OF REVIEW: Renal denervation (RDN) has, within recent years, been suggested as a novel treatment option for patients with resistant hypertension. This review summarizes the current knowledge on this procedure as well as limitations and questions that remain to be answered. RECENT FINDINGS...... selection, anatomical and physiological effects of RDN as well as possible beneficial effects on other diseases with increased sympathetic activity. The long awaited Symplicity HTN-3 (2014) results illustrated that the RDN group and the sham-group had similar reductions in BP. SUMMARY: Initial studies...

  13. Renal papillary necrosis

    Science.gov (United States)

    ... asking your provider. Alternative Names Necrosis - renal papillae; Renal medullary necrosis Images Kidney anatomy Kidney - blood and urine flow References Bushinsky DA, Monk RD. Nephrolithiasis and nephrocalcinosis. ...

  14. Renal calculus

    CERN Document Server

    Pyrah, Leslie N

    1979-01-01

    Stone in the urinary tract has fascinated the medical profession from the earliest times and has played an important part in the development of surgery. The earliest major planned operations were for the removal of vesical calculus; renal and ureteric calculi provided the first stimulus for the radiological investigation of the viscera, and the biochemical investigation of the causes of calculus formation has been the training ground for surgeons interested in metabolic disorders. It is therefore no surprise that stone has been the subject of a number of monographs by eminent urologists, but the rapid development of knowledge has made it possible for each one of these authors to produce something new. There is still a technical challenge to the surgeon in the removal of renal calculi, and on this topic we are always glad to have the advice of a master craftsman; but inevitably much of the interest centres on the elucidation of the causes of stone formation and its prevention. Professor Pyrah has had a long an...

  15. Inhibition of Na+-P/sub i/ cotransporter in small gut brush border by phosphonocarboxylic acids

    International Nuclear Information System (INIS)

    Loghman-Adham, M.; Szczepsanska-Konkel, M.; Yusufi, A.N.K.; Van Scoy, M.; Dousa, T.P.

    1987-01-01

    The authors examined the effect of phosphonoformic acid (PFA) and phosphonoacetic acid (PAA) upon Na + -P/sub i/ cotransport in brush-border membrane (BBM) from small gut of rat. Both PFA and PAA inhibited the Na + gradient-dependent uptake of 32 P/sub i/ by BBM vesicles (BBMV) prepared from intestinal mucosa but had no effect on Na + -dependent uptakes of D-[ 3 H]glucose, L-[ 3 H]proline, or [ 14 C]succinate. The uptake in the absence of Na + gradient, or uptake at equilibrium period (180 min), was not affected by PFA or by PAA. A chemical analogue of PFA and PAA, phosphonopropionic acid, had only a minor inhibitory effect and phenylphosphonic acid was inactive. Neither PFA nor PAA influenced the activity of rat intestinal BBM alkaline phosphatase. The BBMV from rat jejunum had a much higher capacity for Na + gradient-dependent uptake of 32 P/sub i/ than BBMV from duodenum or ileum. The inhibition of BBMV 32 P/sub i/ transport across rat jejunum by PFA is competitive. They suggest that PFA and PAA are specific inhibitors of Na + gradient-dependent uptake of P/sub i/ by BBMV from small intestinal mucosa and that they could serve as useful experimental tools for the studies of intestinal Na + -P/sub i/ cotransport

  16. NONOates regulate KCl cotransporter-1 and -3 mRNA expression in vascular smooth muscle cells.

    Science.gov (United States)

    Di Fulvio, Mauricio; Lauf, Peter K; Shah, Shalin; Adragna, Norma C

    2003-05-01

    Nitric oxide (NO) donors regulate KCl cotransport (KCC) activity and cotransporter-1 and -3 (KCC1 and KCC3) mRNA expression in sheep erythrocytes and in primary cultures of rat vascular smooth muscle cells (VSMCs), respectively. In this study, we used NONOates as rapid and slow NO releasers to provide direct evidence implicating NO as a regulator of KCC3 gene expression at the mRNA level. In addition, we used the expression of KCC3 mRNA to further investigate the mechanism of action of these NO donors at the cellular level. Treatment of VSMCs with rapid NO releasers, like NOC-5 and NOC-9, as well as with the direct NO-independent soluble guanylyl cyclase (sGC) stimulator YC-1, acutely increased KCC3 mRNA expression in a concentration- and time-dependent manner. The slow NO releaser NOC-18 had no effect on KCC3 gene expression. A specific NO scavenger completely prevented the NONOate-induced KCC3 mRNA expression. Inhibition of sGC with LY-83583 blocked the NONOate- and YC-1-induced KCC3 mRNA expression. This study shows that in primary cultures of rat VSMCs, the fast NO releasers NOC-9 and NOC-5, but not the slow NO releaser NOC-18, acutely upregulate KCC3 mRNA expression in a NO/sGC-dependent manner.

  17. Metal Oxide Decomposition In Hydrothermal Alkaline Sodium Phosphate Solutions

    Energy Technology Data Exchange (ETDEWEB)

    S.E. Ziemniak

    2003-09-24

    Alkaline hydrothermal solutions of sodium orthophosphate (2.15 < Na/P < 2.75) are shown to decompose transition metal oxides into two families of sodium-metal ion-(hydroxy)phosphate compounds. Equilibria for these reactions are quantified by determining phosphate concentration-temperature thresholds for decomposition of five oxides in the series: Ti(IV), Cr(III), Fe(III, II), Ni(II) and Zn(II). By application of a computational chemistry method General Utility Lattice Program (GULP), it is demonstrated that the unique non-whole-number Na/P molar ratio of sodium ferric hydroxyphosphate is a consequence of its open-cage structure in which the H{sup +} and excess Na{sup +} ions are located.

  18. TRANSPLANTE RENAL

    Directory of Open Access Journals (Sweden)

    Soraia Geraldo Rozza Lopes

    2014-01-01

    Full Text Available El objetivo del estudio fue comprender el significado de espera del trasplante renal para las mujeres en hemodiálisis. Se trata de un estudio cualitativo-interpretativo, realizado con 12 mujeres en hemodiálisis en Florianópolis. Los datos fueron recolectados a través de entrevistas en profundidad en el domicilio. Fue utilizado el software Etnografh 6.0 para la pre-codificación y posterior al análisis interpretativo emergieron dos categorías: “las sombras del momento actual”, que mostró que las dificultades iniciales de la enfermedad están presentes, pero las mujeres pueden hacer frente mejor a la enfermedad y el tratamiento. La segunda categoría, “la luz del trasplante renal”, muestra la esperanza impulsada por la entrada en la lista de espera para un trasplante.

  19. Transport of proteolipid protein to the plasma membrane does not depend on glycosphingolipid cotransport in oligodendrocyte cultures

    NARCIS (Netherlands)

    van der Haar, ME; Visser, HW; de Vries, H; Hoekstra, D

    1998-01-01

    The possibility that transport of proteolipid protein (PLP) from its site of synthesis to the plasma membrane is dependent on cotransport with (sulfo)galactocerebrosides was investigated in primary cultured oligodendrocytes and Chinese hamster ovary (CHO) cells expressing PLP. Sulfation was

  20. New aspects of cellular thallium uptake: Tl+-Na+-2Cl--cotransport is the central mechanism of ion uptake

    International Nuclear Information System (INIS)

    Sessler, M.J.; Maul, F.D.; Hoer, G.; Munz, D.L.; Geck, P.

    1986-01-01

    Cellular uptake mechanisms of 201 Tl + were studied in Ehrlich mouse ascites tumor cells. 201 Tl + phases the cell membrane of tumor cells using three transport systems: the ATPase, the Tl + -Na + -2Cl - -cotransport, and the Ca ++ -dependent ion channel. In the case of 201 Tl + the main route for entering the cells was the cotransport, its importance increasing with the age of the cells; in parallel, the ATPase activity was reduced. In contrast, the transport capacities of the ATPase and the cotransport were of the same magnitude in the case of 42 K + and 86 Rb + . This change in ion distribution was not brought about by varying velocity relations but by changing the number of transport systems in the cell membrane. There was no relationship between transport rates and diameters of the ions. 201 Tl + distribution is proportional to that of K + with a higher intracellular concentration of about 30%. Under physiological conditions the cotransport was reversible suggesting the ability to regulate steady state during varying extracellular ion concentrations. Cells and medium were two compartments, kinetically seen. Due to the significant difference of transport capacities between the three systems with the respective ions the term ''potassium-thallium-analogy'' may be misleading as it erroneously assumes identical uptake conditions. (orig.) [de

  1. Potassium co-transport and antiport during the uptake of sucrose and glutamic acid from the xylem vessels

    NARCIS (Netherlands)

    Bel, A.J.E. van; Erven, A.J. van

    Perfusion experiments with excised internodes of tomato (Lycopersicon esculentum cv Moneymaker) showed that the uptake of glutamic acid and sucrose from the xylem vessels is accompanied with coupled proton co-transport and potassium antiport at low pH (<5.5). At high pH (5.5) both proton and

  2. BILATERAL DUPLICATION OF RENAL ARTERIES

    OpenAIRE

    Prajkta A Thete; Mehera Bhoir; M.V.Ambiye

    2014-01-01

    Routine dissection of a male cadaver revealed the presence of bilateral double renal arteries. On the right side the accessory renal artery originated from the abdominal aorta just above the main renal artery. On the left side the accessory renal artery originated from the abdominal aorta about 1 cm above the main renal artery. Knowledge of the variations of renal vascular anatomy has importance in exploration and treatment of renal trauma, renal transplantation, renal artery embolization, su...

  3. Lithium fluxes indicate presence of Na-Cl cotransport (NCC) in human lens epithelial cells.

    Science.gov (United States)

    Lauf, Peter K; Chimote, Ameet A; Adragna, Norma C

    2008-01-01

    During regulatory volume decrease (RVD) of human lens epithelial cells (hLECs) by clotrimazole (CTZ)-sensitive K fluxes, Na-K-2Cl cotransport (NKCC) remains active and K-Cl cotransport (KCC) inactive. To determine whether such an abnormal behavior was caused by RVD-induced cell shrinkage, NKCC was measured in the presence of either CTZ or in high K media to prevent RVD. NKCC transports RbCl + NaCl, and LiCl + KCl; thus ouabain-insensitive, bumetanide-sensitive (BS) or Cl-dependent (ClD) Rb and Li fluxes were determined in hyposmotic high NaCl media with CTZ, or in high KCl media alone, or with sulfamate (Sf) or nitrate as Cl replacement at varying Rb, Li or Cl mol fractions (MF). Unexpectedly, NKCC was inhibited by 80% with CTZ (IC(50) = 31 microM). In isosmotic (300 mOsM) K, Li influx was approximately 1/3 of Rb influx in Na, 50% lower in Sf, and bumetanide-insensitive (BI). In hypotonic (200 mOsM) K, only the ClD but not BS Li fluxes were detected. At Li MFs from 0.1-1, Li fluxes fitted a bell-shaped curve maxing at approximately 0.6 Li MF, with the BS fluxes equaling approximately 1/4 of the ClD-Li influx. The difference, i.e. the BI/ClD Li influx, saturated with increasing Li and Cl MFs, with K(ms) for Li of 11 with, and 7 mM without K, and of approximately 46 mM for Cl. Inhibition of this K-independent Li influx by thiazides was weak whilst furosemide (<100 microM) was ineffective. Reverse transcription polymerase chain reaction and Western blots verified presence of both NKCC1 and Na-Cl cotransport (NCC). In conclusion, in hyposmotic high K media, which prevents CTZ-sensitive K flux-mediated RVD in hLECs, NKCC1, though molecularly expressed, was functionally silent. However, a K-independent and moderately thiazide-sensitive ClD-Li flux, i.e. LiCC, likely occurring through NCC was detected operationally and molecularly. (c) 2008 S. Karger AG, Basel.

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

    Directory of Open Access Journals (Sweden)

    Shoko Horita

    2015-01-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

  6. ACE and SGLT2 inhibitors: the future for non-diabetic and diabetic proteinuric renal disease.

    Science.gov (United States)

    Perico, Norberto; Ruggenenti, Piero; Remuzzi, Giuseppe

    2017-04-01

    Most chronic nephropathies progress relentlessly to end-stage kidney disease. Research in animals and humans has helped our understanding of the mechanisms of chronic kidney disease progression. Current therapeutic strategies to prevent or revert renal disease progression focus on reduction of urinary protein excretion and blood pressure control. Blockade of the renin-angiotensin system (RAS) with angiotensin-converting enzyme inhibitors and/or angiotensin II type 1 receptor blockers is the most effective treatment to achieve these purposes in non-diabetic and diabetic proteinuric renal diseases. For those individuals in which nephroprotection by RAS blockade is only partial, sodium-glucose linked cotransporter-2 (SGLT2) inhibitors could be a promising new class of drugs to provide further renoprotective benefit when added on to RAS blockers. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

    Weiner, I David; Verlander, Jill W

    2011-01-01

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

  8. [Sodium Glucose Co-transporter Type 2 (SGLT2) Inhibitors in CKD].

    Science.gov (United States)

    Insalaco, Monica; Zanoli, Luca; Rastelli, Stefania; Lentini, Paolo; Rapisarda, Francesco; Fatuzzo, Pasquale; Castellino, Pietro; Granata, Antonio

    2015-01-01

    Among the new drugs used for the treatment of Diabetes Mellitus type 2, sodium-glucose cotransporter 2 (SGLT2) inhibitors represent a promising therapeutic option. Since their ability to lower glucose is proportional to GFR, their effect is reduced in patients with chronic kidney disease (CKD). The antidiabetic mechanism of these drugs is insulin-independent and, therefore, complimentary to that of others antihyperglicaemic agents. Moreover, SGLT2 inhibitors are able to reduce glomerular hyperfiltration, systemic and intraglomerular pressure and uric acid levels, with consequent beneficial effects on the progression of kidney disease in non diabetic patients as well. Only few studies have been performed to evaluate the effects of SGLT2 inhibitors in patients with CKD. Therefore, safety and efficacy of SGLT2 inhibitors should be better clarified in the setting of CKD. In this paper, we will review the use of SGLT2 inhibitors in diabetic patients, including those with CKD.

  9. Sodium-glucose cotransporter 2 (SGLT-2) inhibitors for patients with Type 2 diabetes

    DEFF Research Database (Denmark)

    Røder, Michael Einar; Storgaard, Heidi; Rungby, Jørgen

    2016-01-01

    The sodium-glucose cotransporter 2 inhibitor (SGLT-2i)-class is efficacious as monotherapy and as add-on therapy with an expected lowering of the glycated haemoglobin (HbA1c) concentration of approximately 7 mmol/mol. Side effects relate to the mode of action, genital infections are the main...... problem. Extremely rare cases of ketoacidosis are reported, mostly in patients with Type 1 diabetes. One SGLT-2i, empagliflozin, has been shown to reduce cardiovascular mortality and progression of kidney disease in patients with Type 2 diabetes and cardiovascular disease. Outcome trials for other SGLT-2i...... are pending. SGLT-2i are now in guidelines as a possible second-line therapy or in case of metformin intolerance....

  10. Sodium-glucose cotransporter (SGLT)-2-inhibitorer til patienter med type 2-diabetes

    DEFF Research Database (Denmark)

    Røder, Michael Einar; Storgaard, Heidi; Rungby, Jørgen

    2016-01-01

    The sodium-glucose cotransporter 2 inhibitor (SGLT-2i)-class is efficacious as monotherapy and as add-on therapy with an expected lowering of the glycated haemoglobin (HbA1c) concentration of approximately 7 mmol/mol. Side effects relate to the mode of action, genital infections are the main...... problem. Extremely rare cases of ketoacidosis are reported, mostly in patients with Type 1 diabetes. One SGLT-2i, empagliflozin, has been shown to reduce cardiovascular mortality and progression of kidney disease in patients with Type 2 diabetes and cardiovascular disease. Outcome trials for other SGLT-2i...... are pending. SGLT-2i are now in guidelines as a possible second-line therapy or in case of metformin intolerance....

  11. A mathematical model of rat ascending Henle limb. I. Cotransporter function.

    Science.gov (United States)

    Weinstein, Alan M

    2010-03-01

    Kinetic models of Na+-K+-2Cl- costransporter (NKCC2) and K+-Cl- cotransporter (KCC4), two of the key cotransporters of the Henle limb, are fashioned with inclusion of terms representing binding and transport of NH4+. The models are simplified using assumptions of equilibrium ion binding, binding symmetry, and identity of Cl- binding sites. Model parameters are selected to be consistent with flux data from expression of these transporters in oocytes, specifically inwardly directed coupled transport of rubidium. In the analysis of these models, it is found that despite the simplifying assumptions to reduce the number of model parameters, neither model is uniquely determined by the data. For NKCC or KCC there are two- or three-parameter families of "optimal" solutions. As a consequence, one may specify several carrier translocation rates and/or ion affinities before fitting the remaining coefficients to the data, with no loss of fidelity in simulating the experiments. Model calculations suggest that with respect to NKCC2 near its operating point, the curve of ion flux as a function of cell Cl- is steep, and with respect to KCC4, its curve of ion flux as a function of peritubular K+ is also steep. The implication is that the kinetics are suitable for these two transporters in series to act as a sensor for peritubular K+, to modulate AHL Na+ reabsorption, with cytosolic Cl- as the intermediate variable. The models also reveal the potential for luminal NH4+ to be a potent catalyst for NKCC2 Na+ reabsorption, provided suitable exit mechanisms for NH4+ (from cell-to-lumen) are operative. It is found that KCC4 is likely to augment the secretory NH4+ flux, with peritubular NH4+ uptake driven by the cell-to-blood K+ gradient.

  12. Current view on the functional regulation of the neuronal K+-Cl- cotransporter KCC2

    Directory of Open Access Journals (Sweden)

    Igor eMedina

    2014-02-01

    Full Text Available In the mammalian central nervous system, the inhibitory strength of chloride (Cl--permeable GABAA and glycine receptors (GABAAR and GlyR depends on the intracellular Cl- concentration ([Cl-]i. Lowering [Cl-]i enhances inhibition, whereas raising [Cl-]i facilitates neuronal activity. A neuron’s basal level of [Cl-]i, as well as its Cl- extrusion capacity, is critically dependent on the activity of the electroneutral K+-Cl- cotransporter KCC2, a member of the SLC12 cation-Cl- cotransporter (CCC family. KCC2 deficiency compromises neuronal migration, formation and the maturation of GABAergic and glutamatergic synaptic connections, and results in network hyperexcitability and seizure activity. Several neurological disorders including multiple epilepsy subtypes, neuropathic pain, and schizophrenia, as well as various insults such as trauma and ischemia, are associated with significant decreases in the Cl- extrusion capacity of KCC2 that result in increases of [Cl-]i and the subsequent hyperexcitability of neuronal networks. Accordingly, identifying the key upstream molecular mediators governing the functional regulation of KCC2, and modifying these signalling pathways with small molecules, might constitute a novel neurotherapeutic strategy for multiple diseases. Here, we discuss recent advances in the understanding of the mechanisms regulating KCC2 activity, and of the role these mechanisms play in neuronal Cl- homeostasis and GABAergic neurotransmission. As KCC2 mediates electroneutral transport, the experimental recording of its activity constitutes an important research challenge; we therefore also, provide an overview of the different methodological approaches utilized to monitor function of KCC2 in both physiological and pathological conditions.

  13. Characterization of an extracellular epitope antibody to the neuronal K-Cl cotransporter, KCC2.

    Science.gov (United States)

    Gagnon, Kenneth Be; Fyffe, Robert Ew; Adragna, Norma C; Lauf, Peter K

    2007-07-01

    1. Ion gradients across the cell membrane are important for proper cellular communication and homeostasis. With the exception of erythrocytes, chloride (Cl), one of the most important free anions in animal cells, is not distributed at thermodynamic equilibrium across the plasma membrane. The K-Cl cotransporter (COT), consisting of at least four isoforms, utilizes the larger outwardly directed chemical driving force of K to expel Cl from the cell against its inwardly directed chemical gradient and has been implicated recently as one of the main Cl extruders in developing neurons. 2. Previous in situ hybridization studies have indicated widespread mRNA distribution of the neuronal-specific K-Cl COT isoform (KCC2) throughout the rat central nervous system (CNS). However, immunohistochemical studies have been limited owing to the availability of a more selective antibody to KCC2. The goal of the present study was to develop a new molecular tool for the immunohistochemical identification and neuronal distribution of KCC2. 3. Herein, we present evidence of immunohistochemical corroboration of the widespread KCC2 mRNA expression using a novel extracellular anti-peptide antibody directed against the second extracellular loop (ECL2) of KCC2. Immunoperoxidase and immunofluorescent labelling revealed widespread post-synaptic somatic and dendritic localization of KCC2 in multiple neuronal populations in the cerebral cortex, hippocampus, brainstem, lumbar spinal cord and cerebellum. We also demonstrate that binding of the antibody to an extracellular epitope within ECL2 does not alter cotransporter function. In essence, the present study reports on a new molecular tool for structural and functional studies of KCC2.

  14. Safety of Sodium-Glucose Cotransporter 2 Inhibitors (SGLT2-I During the Month of Ramadan in Muslim Patients with Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Alaaeldin Bashier

    2018-03-01

    Full Text Available Objectives: Sodium-glucose cotransporter 2 inhibitors (SGLT2-I are a new class of antidiabetic drugs that might increase the risk of dehydration and hypoglycemia, particularly during the month of Ramadan in which Muslims abstain from eating and drinking for 14–16 hours daily. We aimed to provide real-life evidence about the safety of SGLT2-I during Ramadan. Methods: All patients over the age of 18 years on SGLT2-I before Ramadan 2016 who would be fasting during Ramadan were included. Demographic data, detailed medical history including comorbidities and medication profile, and laboratory results were collected before and after Ramadan. We also conducted a phone interview to evaluate the frequency and severity of hypoglycemia and dehydration. Results: Of the total of 417 patients, 113 (27.0% experienced hypoglycemic events, and 93 of these (82.3% checked their blood glucose using a glucometer. Confirmed hypoglycemia (< 70 mg/dL was observed in 78 (83.8%. The hypoglycemic events were significantly more frequent in the SGLT2-I plus insulin-treated group than in those treated with SGLT2-I plus oral hypoglycemic agents group (p < 0.001. Confirmed hypoglycemic events were more frequent in those using SGLT2-I plus intensive insulin compared to those using SGLT2-I plus basal insulin (p = 0.020. Symptoms of dehydration were seen in 9.3% (n = 39 of the total population. We observed statistically significant reductions in glycated hemoglobin and weight by the end of Ramadan (p < 0.001. There were no significant changes in lipid profile and creatinine levels by the end of the study. Conclusions: The use of insulin in combination with SGLT2-I increases the risk of hypoglycemia during Ramadan. Hypoglycemic events were mild and did not require hospital admission. However, careful monitoring during prolonged fasting is warranted. No significant harmful effects on renal function result from treatment with SGLT2-I during Ramadan.

  15. Functional expression of the Na-K-2Cl cotransporter NKCC2 in mammalian cells fails to confirm the dominant-negative effect of the AF splice variant.

    Science.gov (United States)

    Hannemann, Anke; Christie, Jenny K; Flatman, Peter W

    2009-12-18

    The renal bumetanide-sensitive Na-K-2Cl cotransporter (NKCC2) is the major salt transport pathway in the apical membrane of the mammalian thick ascending limb. It is differentially spliced and the three major variants (A, B, and F) differ in their localization and transport characteristics. Most knowledge about its regulation comes from experiments in Xenopus oocytes as NKCC2 proved difficult to functionally express in a mammalian system. Here we report the cloning and functional expression of untagged and unmodified versions of the major splice variants from ferret kidney (fNKCC2A, -B, and -F) in human embryonic kidney (HEK) 293 cells. Many NKCC2 antibodies used in this study detected high molecular weight forms of the transfected proteins, probably NKCC2 dimers, but not the monomers. Interestingly, monomers were strongly detected by phosphospecific antibodies directed against phosphopeptides in the regulatory N terminus. Bumetanide-sensitive (86)Rb uptake was significantly higher in transfected HEK-293 cells and could be stimulated by incubating cells in a medium containing a low chloride concentration prior the uptake measurements. fNKCC2 was less sensitive to the reduction in chloride concentration than NKCC1. Using HEK-293 cells stably expressing fNKCC2A we also show that co-expression of variant NKCC2AF does not have the dominant-negative effect on NKCC2A activity that was seen in Xenopus oocytes, nor is it trafficked to the cell surface. In addition, fNKCC2AF is neither complex glycosylated nor phosphorylated in its N terminus regulatory region like other variants.

  16. Oral peptide specific egg antibody to intestinal sodium-dependent phosphate co-transporter-2b is effective at altering phosphate transport in vitro and in vivo.

    Science.gov (United States)

    Bobeck, Elizabeth A; Hellestad, Erica M; Sand, Jordan M; Piccione, Michelle L; Bishop, Jeff W; Helvig, Christian; Petkovich, Martin; Cook, Mark E

    2015-06-01

    Hyperimmunized hens are an effective means of generating large quantities of antigen specific egg antibodies that have use as oral supplements. In this study, we attempted to create a peptide specific antibody that produced outcomes similar to those of the human pharmaceutical, sevelamer HCl, used in the treatment of hyperphosphatemia (a sequela of chronic renal disease). Egg antibodies were generated against 8 different human intestinal sodium-dependent phosphate cotransporter 2b (NaPi2b) peptides, and hNaPi2b peptide egg antibodies were screened for their ability to inhibit phosphate transport in human intestinal Caco-2 cell line. Antibody produced against human peptide sequence TSPSLCWT (anti-h16) was specific for its peptide sequence, and significantly reduced phosphate transport in human Caco-2 cells to 25.3±11.5% of control nonspecific antibody, when compared to nicotinamide, a known inhibitor of phosphate transport (P≤0.05). Antibody was then produced against the mouse-specific peptide h16 counterpart (mouse sequence TSPSYCWT, anti-m16) for further analysis in a murine model. When anti-m16 was fed to mice (1% of diet as dried egg yolk powder), egg yolk immunoglobulin (IgY) was detected using immunohistochemical staining in mouse ileum, and egg anti-m16 IgY colocalized with a commercial goat anti-NaPi2b antibody. The effectiveness of anti-m16 egg antibody in reducing serum phosphate, when compared to sevelamer HCl, was determined in a mouse feeding study. Serum phosphate was reduced 18% (Pegg yolk powder) and 30% (Pegg immunoglobulin. The methods described and the findings reported show that oral egg antibodies are useful and easy to prepare reagents for the study and possible treatment of select diseases. © 2015 Poultry Science Association Inc.

  17. Water transport by Na+-coupled cotransporters of glucose (SGLT1) and of iodide (NIS). The dependence of substrate size studied at high resolution

    DEFF Research Database (Denmark)

    Zeuthen, Thomas; Belhage, Bo; Zeuthen, Emil

    2005-01-01

    and osmosis at the membrane with diffusion in the cytoplasm. The combination of high resolution measurements and precise modelling showed that water transport across the membrane can be explained by cotransport of water in the membrane proteins and that intracellular unstirred layers effects are minute.......The relation between substrate and water transport was studied in Na+-coupled cotransporters of glucose (SGLT1) and of iodide (NIS) expressed in Xenopus oocytes. The water transport was monitored from changes in oocyte volume at a resolution of 20 pl, more than one order of magnitude better than...... previous investigations. The rate of cotransport was monitored as the clamp current obtained from two-electrode voltage clamp. The high resolution data demonstrated a fixed ratio between the turn-over of the cotransporter and the rate of water transport. This applied to experiments in which the rate...

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

    International Nuclear Information System (INIS)

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

    2005-01-01

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

  19. Radionuclide evaluation of renal transplants

    International Nuclear Information System (INIS)

    Yang Hong; Zhao Deshan

    2000-01-01

    Radionuclide renal imaging and plasma clearance methods can quickly quantitate renal blood flow and function in renal transplants. They can diagnose acute tubular necrosis and rejection, renal scar, surgical complications such as urine leaks, obstruction and renal artery stenosis after renal transplants. At the same time they can assess the therapy effect of renal transplant complications and can also predict renal transplant survival from early post-operative function studies

  20. Distal renal tubular acidosis

    Science.gov (United States)

    ... this disorder. Alternative Names Renal tubular acidosis - distal; Renal tubular acidosis type I; Type I RTA; RTA - distal; Classical RTA Images Kidney anatomy Kidney - blood and urine flow References Bose A, Monk RD, Bushinsky DA. Kidney ...

  1. SGLT2 inhibitors and renal outcomes in type 2 diabetes with or without renal impairment: A systematic review and meta-analysis.

    Science.gov (United States)

    Seidu, Samuel; Kunutsor, Setor K; Cos, Xavier; Gillani, Syed; Khunti, Kamlesh

    2018-06-01

    Sodium-glucose co-transporter 2 (SGLT2) inhibitors may have renal protective effects in people with impaired kidney function. We assessed the use of SGLT2 inhibitors in people with type 2 diabetes with or without renal impairment [defined as estimated glomerular filtration rate (eGFR) of ≥30 and 300 and ≤5000mg/g] by conducting a systematic review and meta-analysis of available studies. Randomised controlled trials (RCTs) were identified from MEDLINE, EMABASE, Web of Science, the Cochrane Library, and search of bibliographies to March 2017. No relevant observational study was identified. Summary measures were presented as mean differences and narrative synthesis performed for studies that could not be pooled. 42 articles which included 40 RCTs comprising 29,954 patients were included. In populations with renal impairment, SGLT2 inhibition compared with placebo was consistently associated with an initial decrease in eGFR followed by an increase and return to baseline levels. In pooled analysis of 17 studies in populations without renal impairment, there was no significant change in eGFR comparing SGLT2 inhibitors with placebo (mean difference, 0.51ml/min/1.73m 2 ; 95% CI: -0.69, 1.72; p=403). SGLT2 inhibition relative to placebo was associated with preservation in serum creatinine levels or initial increases followed by return to baseline levels in patients with renal impairment, but levels were preserved in patients without renal impairment. In populations with or without renal impairment, SGLT2 inhibitors (particularly canagliflozin and empagliflozin) compared with placebo were associated with decreased urine albumin, improved albuminiuria, slowed progression to macroalbuminuria, and reduced the risk of worsening renal impairment, the initiation of kidney transplant, and death from renal disease. Emerging data suggests that with SGLT2 inhibition, renal function seems to be preserved in people with diabetes with or without renal impairment. Furthermore, SGLT2

  2. Cardio-renal syndrome

    OpenAIRE

    Gnanaraj, Joseph; Radhakrishnan, Jai

    2016-01-01

    Cardio-renal syndrome is a commonly encountered problem in clinical practice. Its pathogenesis is not fully understood. The purpose of this article is to highlight the interaction between the cardiovascular system and the renal system and how their interaction results in the complex syndrome of cardio-renal dysfunction. Additionally, we outline the available therapeutic strategies to manage this complex syndrome.

  3. Renal inflammatory myofibroblastic tumor

    DEFF Research Database (Denmark)

    Heerwagen, S T; Jensen, C; Bagi, P

    2007-01-01

    Renal inflammatory myofibroblastic tumor (IMT) is a rare soft-tissue tumor of controversial etiology with a potential for local recurrence after incomplete surgical resection. The radiological findings in renal IMT are not well described. We report two cases in adults with a renal mass treated...

  4. Use of 86Rb and 22Na in assaying active and cotransport activities in hum erythrocytes in a biracial population

    International Nuclear Information System (INIS)

    Sharma, C.; Dalferes, E.R. Jr; Freedman, D.S.; Asamoah, A.; Berenson, G.S.

    1988-01-01

    A defect in Na/sup +/-K/sup +/ transport across the red cell membrane has been shown to be associated with essential hypertension. A sensitive assay system to measure active, co- and countertransport systems in erythrocytes from normotensive adults was developed. Active, co- and countertransport systems in the erythrocytes were assayed by measuring the influx of radioactive /sup 22/Na/sup +/ and /sup 86/Rb/ sup +/. In the biracial (black-white) population group studied, analysis of variance of the active transport showed a significant race effect. Cotransport activity showed age by race interaction and age by sex. Cotransport activity was significantly higher in whites than blacks. The results suggest a subtle difference in Na/sup +/-K/sup +/ transport systems between blacks and whites, and these variations may be related to differences for susceptibility to essential hypertension

  5. Traumatic renal infarction

    International Nuclear Information System (INIS)

    Yashiro, Naobumi; Ohtomo, Kuni; Kokubo, Takashi; Itai, Yuji; Iio, Masahiro

    1986-01-01

    Four cases of traumatic renal artery occlusion were described and illustrated. In two cases, direct blows to the abdomen compressed the renal artery against the vertebral column. Clinically, they were severely injured with macroscopic hematuria. Aortograms showed abrupt truncation of renal arteries. In the other two, rapid deceleration caused sudden displacement of the kidney producing an intimal tear with resultant thrombosis. Although they showed little injury without macrohematuria, aortograms revealed tapered occlusion of renal arteries. One of them developed hypertension. ''Rim sign'' of post-contrast CT and hypertension resulted from traumatic renal artery occlusion were reviewed. (author)

  6. Potassium channel and NKCC cotransporter involvement in ocular refractive control mechanisms.

    Directory of Open Access Journals (Sweden)

    Sheila G Crewther

    Full Text Available Myopia affects well over 30% of adult humans globally. However, the underlying physiological mechanism is little understood. This study tested the hypothesis that ocular growth and refractive compensation to optical defocus can be controlled by manipulation of potassium and chloride ion-driven transretinal fluid movements to the choroid. Chicks were raised with +/-10D or zero power optical defocus rendering the focal plane of the eye in front of, behind, or at the level of the retinal photoreceptors respectively. Intravitreal injections of barium chloride, a non-specific inhibitor of potassium channels in the retina and RPE or bumetanide, a selective inhibitor of the sodium-potassium-chloride cotransporter were made, targeting fluid control mechanisms. Comparison of refractive compensation to 5 mM Ba(2+ and 10(-5 M bumetanide compared with control saline injected eyes shows significant change for both positive and negative lens defocus for Ba(2+ but significant change only for negative lens defocus with bumetanide (Rx(SAL(-10D = -8.6 +/- .9 D; Rx(Ba2+(-10D = -2.9 +/- .9 D; Rx(Bum(-10D = -2.9 +/- .9 D; Rx(SAL(+10D = +8.2 +/- .9 D; Rx(Ba2+(+10D = +2.8 +/- 1.3 D; Rx(Bum(+10D = +8.0 +/- .7 D. Vitreous chamber depths showed a main effect for drug conditions with less depth change in response to defocus shown for Ba(2+ relative to Saline, while bumetanide injected eyes showed a trend to increased depth without a significant interaction with applied defocus. The results indicate that both K channels and the NKCC cotransporter play a role in refractive compensation with NKCC blockade showing far more specificity for negative, compared with positive, lens defocus. Probable sites of action relevant to refractive control include the apical retinal pigment epithelium membrane and the photoreceptor/ON bipolar synapse. The similarities between the biometric effects of NKCC inhibition and biometric reports of the blockade of the retinal ON response, suggest a

  7. Sodium-glucose cotransporter 2 inhibitors with insulin in type 2 diabetes: Clinical perspectives

    Directory of Open Access Journals (Sweden)

    Mathew John

    2016-01-01

    Full Text Available The treatment of type 2 diabetes is a challenging problem. Most subjects with type 2 diabetes have progression of beta cell failure necessitating the addition of multiple antidiabetic agents and eventually use of insulin. Intensification of insulin leads to weight gain and increased risk of hypoglycemia. Sodium-glucose cotransporter 2 (SGLT2 inhibitors are a class of antihyperglycemic agents which act by blocking the SGLT2 in the proximal tubule of the kidney. They have potential benefits in terms of weight loss and reduction of blood pressure in addition to improvements in glycemic control. Further, one of the SGLT2 inhibitors, empagliflozin has proven benefits in reducing adverse cardiovascular (CV outcomes in a CV outcome trial. Adding SGLT2 inhibitors to insulin in subjects with type 2 diabetes produced favorable effects on glycemic control without the weight gain and hypoglycemic risks associated with insulin therapy. The general risks of increased genital mycotic infections, urinary tract infections, volume, and osmosis-related adverse effects in these subjects were similar to the pooled data of individual SGLT2 inhibitors. There are subsets of subjects with type 2 diabetes who may have insulin deficiency, beta cell autoimmunity, or is prone to diabetic ketoacidosis. In these subjects, SGLT2 inhibitors should be used with caution to prevent the rare risks of ketoacidosis.

  8. Differential cardiovascular profiles of sodium-glucose cotransporter 2 inhibitors: critical evaluation of empagliflozin

    Directory of Open Access Journals (Sweden)

    Sanon VP

    2017-05-01

    Full Text Available Vani P Sanon,1 Shalin Patel,1 Saurabh Sanon,2 Ruben Rodriguez,1 Son V Pham,1 Robert Chilton1 1Division of Cardiology, University of Texas Health Science Center at San Antonio, Audie L Murphy VA Hospital, San Antonio, TX, 2Interventional Cardiology-Structural Heart Disease, Cardiology Consultants at Baptist Heart and Vascular Institute, Pensacola, FL, USA Abstract: One of the most feared repercussions of type 2 diabetes mellitus is the risk of adverse cardiovascular outcomes. The current antidiabetic agents on the market have had difficulty in showing cardiovascular outcome improvement. The EMPA-REG OUTCOME trial studied the sodium-glucose cotransporter 2 inhibitor empagliflozin in type 2 diabetic patients at high risk of cardiovascular events. The trial results revealed a decrease in the composite primary end points of death from cardiovascular causes, nonfatal myocardial infarction, and nonfatal stroke in those taking empagliflozin vs placebo. Those taking the medication also had a significant decrease in death from any cause, death from cardiovascular cause, and hospitalization for heart failure. The EMPA-REG trial is paradigm shifting because it demonstrates a clear mortality benefit to cardiovascular outcomes with a low side-effect profile, in contrast to prior outcome studies of hypoglycemic agents. Further studies are required to better clarify the long-term safety and efficacy of this promising class of diabetic drugs. Keywords: SGLT2 inhibitors, diabetes, cardiovascular mortality, heart failure, hypertension

  9. A specific pharmacophore model of sodium-dependent glucose co-transporter 2 (SGLT2) inhibitors.

    Science.gov (United States)

    Tang, Chunlei; Zhu, Xiaoyun; Huang, Dandan; Zan, Xin; Yang, Baowei; Li, Ying; Du, Xiaoyong; Qian, Hai; Huang, Wenlong

    2012-06-01

    Sodium-dependent glucose co-transporter 2 (SGLT2) plays a pivotal role in maintaining glucose equilibrium in the human body, emerging as one of the most promising targets for the treatment of diabetes mellitus type 2. Pharmacophore models of SGLT2 inhibitors have been generated with a training set of 25 SGLT2 inhibitors using Discovery Studio V2.1. The best hypothesis (Hypo1(SGLT2)) contains one hydrogen bond donor, five excluded volumes, one ring aromatic and three hydrophobic features, and has a correlation coefficient of 0.955, cost difference of 68.76, RMSD of 0.85. This model was validated by test set, Fischer randomization test and decoy set methods. The specificity of Hypo1(SGLT2) was evaluated. The pharmacophore features of Hypo1(SGLT2) were different from the best pharmacophore model (Hypo1(SGLT1)) of SGLT1 inhibitors we developed. Moreover, Hypo1(SGLT2) could effectively distinguish selective inhibitors of SGLT2 from those of SGLT1. These results indicate that a highly predictive and specific pharmacophore model of SGLT2 inhibitors has been successfully obtained. Then Hypo1(SGLT2) was used as a 3D query to screen databases including NCI and Maybridge for identifying new inhibitors of SGLT2. The hit compounds were subsequently subjected to filtering by Lipinski's rule of five. And several compounds selected from the top ranked hits have been suggested for further experimental assay studies.

  10. Characterization and comparison of sodium-glucose cotransporter 2 inhibitors in pharmacokinetics, pharmacodynamics, and pharmacologic effects

    Directory of Open Access Journals (Sweden)

    Atsuo Tahara

    2016-03-01

    Full Text Available The sodium-glucose cotransporter (SGLT 2 offer a novel approach to treating type 2 diabetes by reducing hyperglycaemia via increased urinary glucose excretion. In the present study, the pharmacokinetic, pharmacodynamic, and pharmacologic properties of all six SGLT2 inhibitors commercially available in Japan were investigated and compared. Based on findings in normal and diabetic mice, the six drugs were classified into two categories, long-acting: ipragliflozin and dapagliflozin, and intermediate-acting: tofogliflozin, canagliflozin, empagliflozin, and luseogliflozin. Long-acting SGLT2 inhibitors exerted an antihyperglycemic effect with lower variability of blood glucose level via a long-lasting increase in urinary glucose excretion. In addition, ipragliflozin and luseogliflozin exhibited superiority over the others with respect to fast onset of pharmacological effect. Duration and onset of the pharmacologic effects seemed to be closely correlated with the pharmacokinetic properties of each SGLT2 inhibitor, particularly with respect to high distribution and long retention in the target organ, the kidney. While all six SGLT2 inhibitors were significantly effective in increasing urinary glucose excretion and reducing hyperglycemia, our findings suggest that variation in the quality of daily blood glucose control associated with duration and onset of pharmacologic effects of each SGLT2 inhibitor might cause slight differences in rates of improvement in type 2 diabetes.

  11. Sodium glucose CoTransporter 2 (SGLT2) inhibitors: Current status and future perspective.

    Science.gov (United States)

    Madaan, Tushar; Akhtar, Mohd; Najmi, Abul Kalam

    2016-10-10

    Diabetes mellitus is a disease that affects millions of people worldwide and its prevalence is estimated to rise in the future. Billions of dollars are spent each year around the world in health expenditure related to diabetes. There are several anti-diabetic drugs in the market for the treatment of non-insulin dependent diabetes mellitus. In this article, we will be talking about a relatively new class of anti-diabetic drugs called sodium glucose co-transporter 2 (SGLT2) inhibitors. This class of drugs has a unique mechanism of action focusing on inhibition of glucose reabsorption that separates it from other classes. This article covers the mechanism of glucose reabsorption in the kidneys, the mechanism of action of SGLT2 inhibitors, several SGLT2 inhibitors currently available in the market as well as those in various phases of development, their individual pharmacokinetics as well as the discussion about the future role of SGLT2 inhibitors, not only for the treatment of diabetes, but also for various other diseases like obesity, hepatic steatosis, and cardiovascular disorders. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Relevance of sodium/glucose cotransporter-1 (SGLT1) to diabetes mellitus and obesity in dogs.

    Science.gov (United States)

    Batchelor, D J; German, A J; Shirazi-Beechey, S P

    2013-04-01

    Glucose transport across the enterocyte brush border membrane by sodium/glucose cotransporter-1 (SGLT1, coded by Slc5a1) is the rate-limiting step for intestinal glucose transport. The relevance of SGLT1 expression in predisposition to diabetes mellitus and to obesity was investigated in dogs. Cultured Caco-2/TC7 cells were shown to express SGLT1 in vitro. A 2-kbp fragment of the Slc5a1 5' flanking region was cloned from canine genomic DNA, ligated into reporter gene plasmids, and shown to drive reporter gene expression in these cells above control (P obesity (Labrador retriever and cocker spaniel). The Slc5a1 5' flanking region was amplified from 10 healthy individuals of each of these breeds by high-fidelity PCR with the use of breed-labeled primers and sequenced by pyrosequencing. The sequence of the Slc5a1 5' flanking region in all individuals of all breeds tested was identical. On this evidence, variations in Slc5a1 promoter sequence between dogs do not influence the pathogenesis of diabetes mellitus or obesity in these breeds. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. Sodium-glucose co-transporter-2 inhibitors and euglycemic ketoacidosis: Wisdom of hindsight

    Directory of Open Access Journals (Sweden)

    Awadhesh Kumar Singh

    2015-01-01

    Full Text Available Sodium-glucose co-transporter-2 inhibitors (SGLT-2i are newly approved class of oral anti-diabetic drugs, in the treatment of type 2 diabetes, which reduces blood glucose through glucouresis via the kidney, independent, and irrespective of available pancreatic beta-cells. Studies conducted across their clinical development program found, a modest reduction in glycated hemoglobin ranging from −0.5 to −0.8%, without any significant hypoglycemia. Moreover, head-to-head studies versus active comparators yielded comparable efficacy. Interestingly, weight and blood pressure reduction were additionally observed, which was not only consistent but significantly superior to active comparators, including metformin, sulfonylureas, and dipeptydylpeptide-4 inhibitors. Indeed, these additional properties makes this class a promising oral anti-diabetic drug. Surprisingly, a potentially fatal unwanted side effect of diabetic ketoacidosis has been noted with its widespread use, albeit rarely. Nevertheless, this has created a passé among the clinicians. This review is an attempt to pool those ketosis data emerging with SGLT-2i, and put a perspective on its implicated mechanism.

  14. Evidence for a specific glutamate/H+ cotransport in isolated mesophyll cells

    International Nuclear Information System (INIS)

    McCutcheon, S.L.; Bown, A.W.

    1987-01-01

    Mechanically isolated Asparagus sprengeri Regel mesophyll cells were suspended in 1 millimolar CaSO 4 . Immediate alkalinization of the medium occurred on the addition of 1 millimolar concentrations of L-glutamate (Glu) and its analog L-methionine-D,L-sulfoximine (L-MSO). D-Glu and the L isomers of the protein amino acids did not elicit alkalinization. L-Glu dependent alkalinization was transient and acidification resumed after approximately 30 to 45 minutes. At pH 6.0, 5 millimolar L-Glu stimulated initial rates of alkalinization that varied between 1.3 to 4.1 nmol H + /10 6 cells minute. L-Glu dependent alkalinization was saturable, increased with decreasing pH, was inhibited by carbonyl cyanide-p-trichloromethoxyphenyl hydrazone (CCCP), and was not stimulated by light. Uptake of L-[U- 14 C]glutamate increased as the pH decreased from 6.5 to 5.5, and was inhibited by L-MSO. L-Glu had no influence on K + efflux. Although evidence for multiple amino acid/proton cotransport systems has been found in other tissues, the present report indicates that a highly specific L-Glu/proton uptake process is present in Asparagus mesophyll cells

  15. Abnormal expression of cerebrospinal fluid cation chloride cotransporters in patients with Rett syndrome.

    Directory of Open Access Journals (Sweden)

    Sofia Temudo Duarte

    Full Text Available OBJECTIVE: Rett Syndrome is a progressive neurodevelopmental disorder caused mainly by mutations in the gene encoding methyl-CpG-binding protein 2. The relevance of MeCP2 for GABAergic function was previously documented in animal models. In these models, animals show deficits in brain-derived neurotrophic factor, which is thought to contribute to the pathogenesis of this disease. Neuronal Cation Chloride Cotransporters (CCCs play a key role in GABAergic neuronal maturation, and brain-derived neurotrophic factor is implicated in the regulation of CCCs expression during development. Our aim was to analyse the expression of two relevant CCCs, NKCC1 and KCC2, in the cerebrospinal fluid of Rett syndrome patients and compare it with a normal control group. METHODS: The presence of bumetanide sensitive NKCC1 and KCC2 was analysed in cerebrospinal fluid samples from a control pediatric population (1 day to 14 years of life and from Rett syndrome patients (2 to 19 years of life, by immunoblot analysis. RESULTS: Both proteins were detected in the cerebrospinal fluid and their levels are higher in the early postnatal period. However, Rett syndrome patients showed significantly reduced levels of KCC2 and KCC2/NKCC1 ratio when compared to the control group. CONCLUSIONS: Reduced KCC2/NKCC1 ratio in the cerebrospinal fluid of Rett Syndrome patients suggests a disturbed process of GABAergic neuronal maturation and open up a new therapeutic perspective.

  16. The plant homolog to the human sodium/dicarboxylic cotransporter is the vacuolar malate carrier.

    Science.gov (United States)

    Emmerlich, Vera; Linka, Nicole; Reinhold, Thomas; Hurth, Marco A; Traub, Michaela; Martinoia, Enrico; Neuhaus, H Ekkehard

    2003-09-16

    Malate plays a central role in plant metabolism. It is an intermediate in the Krebs and glyoxylate cycles, it is the store for CO2 in C4 and crassulacean acid metabolism plants, it protects plants from aluminum toxicity, it is essential for maintaining the osmotic pressure and charge balance, and it is therefore involved in regulation of stomatal aperture. To fulfil many of these roles, malate has to be accumulated within the large central vacuole. Many unsuccessful efforts have been made in the past to identify the vacuolar malate transporter; here, we describe the identification of the vacuolar malate transporter [A. thaliana tonoplast dicarboxylate transporter (AttDT)]. This transporter exhibits highest sequence similarity to the human sodium/dicarboxylate cotransporter. Independent T-DNA [portion of the Ti (tumor-inducing) plasmid that is transferred to plant cells] Arabidopsis mutants exhibit substantially reduced levels of leaf malate, but respire exogenously applied [14C]malate faster than the WT. An AttDT-GFP fusion protein was localized to vacuole. Vacuoles isolated from Arabidopsis WT leaves exhibited carbonylcyanide m-chlorophenylhydrazone and citrate inhibitable malate transport, which was not stimulated by sodium. Vacuoles isolated from mutant plants import [14C]-malate at strongly reduced rates, confirming that this protein is the vacuolar malate transporter.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1979-08-01

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

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

    International Nuclear Information System (INIS)

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

    1979-01-01

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

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

    Science.gov (United States)

    Andrianesis, Vasileios; Glykofridi, Spyridoula; Doupis, John

    2016-12-01

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

  20. Vasopressin alters the mechanism of apical Cl- entry from Na+:Cl- to Na+:K+:2Cl- cotransport in mouse medullary thick ascending limb

    Energy Technology Data Exchange (ETDEWEB)

    Sun, A.; Grossman, E.B.; Lombardi, M.; Hebert, S.C. (Brigham and Women' s Hospital, Boston, MA (USA))

    1991-02-01

    Experiments were performed using in vitro perfused medullary thick ascending limbs of Henle (MTAL) and in suspensions of MTAL tubules isolated from mouse kidney to evaluate the effects of arginine vasopressin (AVP) on the K+ dependence of the apical, furosemide-sensitive Na{sup +}:Cl{sup {minus}} cotransporter and on transport-related oxygen consumption (QO{sub 2}). In isolated perfused MTAL segments, the rate of cell swelling induced by removing K+ from, and adding one mM ouabain to, the basolateral solution (ouabain(zero-K+)) provided an index to apical cotransporter activity and was used to evaluate the ionic requirements of the apical cotransporter in the presence and absence of AVP. In the absence of AVP cotransporter activity required Na{sup +} and Cl{sup {minus}}, but not K{sup +}, while the presence of AVP the apical cotransporter required all three ions. {sup 86}Rb{sup +} uptake into MTAL tubules in suspension was significant only after exposure of tubules to AVP. Moreover, {sup 22}Na{sup +} uptake was unaffected by extracellular K+ in the absence of AVP while after AVP exposure {sup 22}Na{sup +} uptake was strictly K{sup +}-dependent. The AVP-induced coupling of K{sup +} to the Na{sup +}:Cl{sup {minus}} cotransporter resulted in a doubling in the rate of NaCl absorption without a parallel increase in the rate of cellular {sup 22}Na{sup +} uptake or transport-related oxygen consumption. These results indicate that arginine vasopressin alters the mode of a loop diuretic-sensitive transporter from Na{sup +}:Cl{sup {minus}} cotransport to Na{sup +}:K{sup +}:2Cl{sup {minus}} cotransport in the mouse MTAL with the latter providing a distinct metabolic advantage for sodium transport. A model for AVP action on NaCl absorption by the MTAL is presented and the physiological significance of the coupling of K{sup +} to the apical Na{sup +}:Cl{sup {minus}} cotransporter in the MTAL and of the enhanced metabolic efficiency are discussed.

  1. Imaging of renal osteodystrophy

    Energy Technology Data Exchange (ETDEWEB)

    Jevtic, V. E-mail: vladimir.jevtic@mf.uni-lj.si

    2003-05-01

    Chronic renal insufficiency, hemodialysis, peritoneal dialysis, renal transplantation and administration of different medications provoke complex biochemical disturbances of the calcium-phosphate metabolism with wide spectrum of bone and soft tissue abnormalities termed renal osteodystrophy. Clinically most important manifestation of renal bone disease includes secondary hyperparathyroidism, osteomalacia/rickets, osteoporosis, adynamic bone disease and soft tissue calcification. As a complication of long-term hemodialysis and renal transplantation amyloid deposition, destructive spondyloarthropathy, osteonecrosis, and musculoskeletal infections may occur. Due to more sophisticated diagnostic methods and more efficient treatment classical radiographic features of secondary hyperparathyroidism and osteomalacia/rickets are now less frequently seen. Radiological investigations play an important role in early diagnosis and follow-up of the renal bone disease. Although numerous new imaging modalities have been introduced in clinical practice (scintigraphy, CT, MRI, quantitative imaging), plain film radiography, especially fine quality hand radiograph, still represents most widely used examination.

  2. Imaging of renal osteodystrophy

    International Nuclear Information System (INIS)

    Jevtic, V.

    2003-01-01

    Chronic renal insufficiency, hemodialysis, peritoneal dialysis, renal transplantation and administration of different medications provoke complex biochemical disturbances of the calcium-phosphate metabolism with wide spectrum of bone and soft tissue abnormalities termed renal osteodystrophy. Clinically most important manifestation of renal bone disease includes secondary hyperparathyroidism, osteomalacia/rickets, osteoporosis, adynamic bone disease and soft tissue calcification. As a complication of long-term hemodialysis and renal transplantation amyloid deposition, destructive spondyloarthropathy, osteonecrosis, and musculoskeletal infections may occur. Due to more sophisticated diagnostic methods and more efficient treatment classical radiographic features of secondary hyperparathyroidism and osteomalacia/rickets are now less frequently seen. Radiological investigations play an important role in early diagnosis and follow-up of the renal bone disease. Although numerous new imaging modalities have been introduced in clinical practice (scintigraphy, CT, MRI, quantitative imaging), plain film radiography, especially fine quality hand radiograph, still represents most widely used examination

  3. Approaching to DM2 through sodium-glucose cotransporter-2: does it make sense?

    Science.gov (United States)

    Segura, Julián

    2016-11-01

    The kidney is involved in glucose homeostasis through three main mechanisms: renal gluconeogenesis, renal glucose consumption and glucose reabsorption in the proximal tubule. Glucose reabsorption is one of the most relevant physiological functions of the kidney, through which filtered glucose is fully recovered, urine is free of glucose, and calorie loss is prevented. Approximately 90% of the glucose is reabsorbed in the S1 segment of the proximal tubule, where GLUT2 and SGLT2 transporters are located, while the remaining 10% is reabsorbed in the S3 segment by SGLT1 and GLUT1 transporters. In patients with hyperglycaemia, the kidney continues reabsorbing glucose, and hyperglycaemia is maintained. Most renal glucose reabsorption is mediated by the SGLT2 transporter. Several experimental and clinical studies suggest that pharmacological blockade of this transporter might be beneficial in the management of hyperglycemia in patients with type 2 diabetes. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  4. Altered Regulation of type 3 Na+/H+ exchanger, type 1 Na+/HCO3- cotransporter, and Na+,K+-ATPase in the Kidney of Rats with Experimental Rhabdomyolysis

    Science.gov (United States)

    Ma, Seong Kwon; Bae, Eun Hui; Lee, JongUn; Kim, Sun Young; Kim, Sung Zoo; Choi, Ki Chul

    2007-01-01

    Metabolic acidosis was shown to correlate with deterioration of renal function in patients with rhabdomyolysis. The present study was aimed to investigate whether the changes of type 3 Na+/H+ exchanger (NHE3), type 1 Na+/HCO3- cotransporter (NBC1), and Na+,K+-ATPase α1 subunit may play a role in the pathogenesis of metabolic acidosis in glycerol-induced experimental rhabdomyolysis. Male Sprague-Dawley rats were deprived of fluid intake for 24 hours, and then were injected with 50% glycerol in normal saline (10 mL/kg, intramuscularly). At 24 hours after the glycerol injection, rats were sacrificed by decapitation. Control rats were injected with normal saline. The protein expression of NHE3, NBC1 and Na+,K+-ATPase α1 subunit was determined in the cortex of the kidney by immunoblotting and immunohistochemistry. Following the treatment of glycerol, creatinine clearance was significantly decreased, and high anion gap metabolic acidosis developed. In the experimental group, the expression of Na+,K+-ATPase α1 subunit was significantly decreased in the cortex of the kidney. On the contrary, the expression of NHE3 and NBC1 was significantly increased. Immunohistochemical analyses confirmed the immunoblotting data. In conclusion, the coordinate up-regulation of NHE3 and NBC1 may play an adaptive role against the metabolic acidosis in glycerol-induced rhabdomyolysis. PMID:24459502

  5. Renal artery stenosis

    International Nuclear Information System (INIS)

    Desberg, A.; Paushter, D.M.; Lammert, G.K.; Hale, J.; Troy, R.; Novic, A.; Nally, J. Jr.

    1989-01-01

    Renal artery disease is a potentially correctable cause of hypertension. Previous studies have suggested the utility of duplex sonography in accurately detecting and grading the severity of renal artery stenosis. The purpose of this paper is to evaluate color flow Doppler for this use. Forty-three kidneys were examined by color-flow Doppler and conventional duplex sampling in patients with suspected renovascular hypertension or those undergoing aortography for unrelated reasons. Doppler tracings were obtained from the renal arteries and aorta with calculation of the renal aortic ratio (RAR) and resistive index (RI). Results of Doppler sampling with color flow guidance were compared with aortograms in a blinded fashion

  6. Incidental renal neoplasms

    DEFF Research Database (Denmark)

    Rabjerg, Maj; Mikkelsen, Minne Nedergaard; Walter, Steen

    2014-01-01

    On the basis of associations between tumor size, pathological stage, histological subtype and tumor grade in incidentally detected renal cell carcinoma vs symptomatic renal cell carcinoma, we discussed the need for a screening program of renal cell carcinoma in Denmark. We analyzed a consecutive...... series of 204 patients with renal tumors in 2011 and 2012. The tumors were classified according to detection mode: symptomatic and incidental and compared to pathological parameters. Eighty-nine patients (44%) were symptomatic, 113 (55%) were incidental. Information was not available in two patients...

  7. Renal cell carcinoma in patient with crossed fused renal ectopia

    Directory of Open Access Journals (Sweden)

    Ozgur Cakmak

    2016-01-01

    Full Text Available Primary renal cell carcinomas have rarely been reported in patients with crossed fused renal ectopia. We presented a patient with right to left crossed fused kidney harbouring renal tumor. The most frequent tumor encountered in crossed fused renal ectopia is renal cell carcinoma. In this case, partial nephrectomy was performed which pave way to preservation of the uninvolved both renal units. Due to unpredictable anatomy, careful preoperative planning and meticulous delineation of renal vasculature is essential for preservation of the uninvolved renal units.

  8. Stages of Renal Cell Cancer

    Science.gov (United States)

    ... Tumors Treatment Genetics of Kidney Cancer Research Renal Cell Cancer Treatment (PDQ®)–Patient Version General Information About Renal Cell Cancer Go to Health Professional Version Key Points Renal ...

  9. Bilateral papillary renal cell carcinoma

    International Nuclear Information System (INIS)

    Gossios, K.; Vazakas, P.; Argyropoulou, M.; Stefanaki, S.; Stavropoulos, N.E.

    2001-01-01

    Papillary renal cell carcinoma is a subgroup of malignant renal epithelial neoplasms. We report the clinical and imaging findings of a case with multifocal and bilateral renal cell carcinoma which are nonspecific. (orig.)

  10. Blood pressure effects of sodium-glucose co-transport 2 (SGLT2) inhibitors.

    Science.gov (United States)

    Oliva, Raymond V; Bakris, George L

    2014-05-01

    Management of hypertension in diabetes is critical for reduction of cardiovascular mortality and morbidity. While blood pressure (BP) control has improved over the past two decades, the control rate is still well below 50% in the general population of patients with type 2 diabetes mellitus (T2DM). A new class of oral glucose-lowering agents has recently been approved; the sodium-glucose co-transporter 2 (SGLT2) inhibitors, which act by eliminating large amounts of glucose in the urine. Two agents, dapagliflozin and canagliflozin, are currently approved in the United States and Europe, and empagliflozin and ipragliflozin have reported Phase 3 trials. In addition to glucose lowering, SGLT2 inhibitors are associated with weight loss and act as osmotic diuretics, resulting in a lowering of BP. While not approved for BP-lowering, they may potentially aid BP goal achievement in people within 7-10 mm Hg of goal. It should be noted that the currently approved agents have side effects that include an increased incidence of genital infections, predominantly in women. The approved SGLT2 inhibitors have limited use based on kidney function and should be used only in those with an estimated glomerular filtration rate (eGFR) > 60 mL/min/1.73 m2 for dapagliflozin and ≥45 mL/min/1.73 m2 for canagliflozin. Cardiovascular outcome trials are ongoing with these agents and will be completed within the next 4-5 years. Copyright © 2014 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

  11. Natural Products as Lead Compounds for Sodium Glucose Cotransporter (SGLT) Inhibitors.

    Science.gov (United States)

    Blaschek, Wolfgang

    2017-08-01

    Glucose homeostasis is maintained by antagonistic hormones such as insulin and glucagon as well as by regulation of glucose absorption, gluconeogenesis, biosynthesis and mobilization of glycogen, glucose consumption in all tissues and glomerular filtration, and reabsorption of glucose in the kidneys. Glucose enters or leaves cells mainly with the help of two membrane integrated transporters belonging either to the family of facilitative glucose transporters (GLUTs) or to the family of sodium glucose cotransporters (SGLTs). The intestinal glucose absorption by endothelial cells is managed by SGLT1, the transfer from them to the blood by GLUT2. In the kidney SGLT2 and SGLT1 are responsible for reabsorption of filtered glucose from the primary urine, and GLUT2 and GLUT1 enable the transport of glucose from epithelial cells back into the blood stream.The flavonoid phlorizin was isolated from the bark of apple trees and shown to cause glucosuria. Phlorizin is an inhibitor of SGLT1 and SGLT2. With phlorizin as lead compound, specific inhibitors of SGLT2 were developed in the last decade and some of them have been approved for treatment mainly of type 2 diabetes. Inhibition of SGLT2 eliminates excess glucose via the urine. In recent times, the dual SGLT1/SGLT2 inhibitory activity of phlorizin has served as a model for the development and testing of new drugs exhibiting both activities.Besides phlorizin, also some other flavonoids and especially flavonoid enriched plant extracts have been investigated for their potency to reduce postprandial blood glucose levels which can be helpful in the prevention and supplementary treatment especially of type 2 diabetes. Georg Thieme Verlag KG Stuttgart · New York.

  12. Experimental investigation of virus and clay particles cotransport in partially saturated columns packed with glass beads.

    Science.gov (United States)

    Syngouna, Vasiliki I; Chrysikopoulos, Constantinos V

    2015-02-15

    Suspended clay particles in groundwater can play a significant role as carriers of viruses, because, depending on the physicochemical conditions, clay particles may facilitate or hinder the mobility of viruses. This experimental study examines the effects of clay colloids on the transport of viruses in variably saturated porous media. All cotransport experiments were conducted in both saturated and partially saturated columns packed with glass beads, using bacteriophages MS2 and ΦX174 as model viruses, and kaolinite (KGa-1b) and montmorillonite (STx-1b) as model clay colloids. The various experimental collision efficiencies were determined using the classical colloid filtration theory. The experimental data indicated that the mass recovery of viruses and clay colloids decreased as the water saturation decreased. Temporal moments of the various breakthrough concentrations collected, suggested that the presence of clays significantly influenced virus transport and irreversible deposition onto glass beads. The mass recovery of both viruses, based on total effluent virus concentrations, was shown to reduce in the presence of suspended clay particles. Furthermore, the transport of suspended virus and clay-virus particles was retarded, compared to the conservative tracer. Under unsaturated conditions both clay particles facilitated the transport of ΦX174, while hindered the transport of MS2. Moreover, the surface properties of viruses, clays and glass beads were employed for the construction of classical DLVO and capillary potential energy profiles, and the results suggested that capillary forces play a significant role on colloid retention. It was estimated that the capillary potential energy of MS2 is lower than that of ΦX174, and the capillary potential energy of KGa-1b is lower than that of STx-1b, assuming that the protrusion distance through the water film is the same for each pair of particles. Moreover, the capillary potential energy is several orders of

  13. Modulation of the cardiac sodium/bicarbonate cotransporter by the renin angiotensin aldosterone system: pathophysiological consequences.

    Science.gov (United States)

    De Giusti, Verónica C; Ciancio, María C; Orlowski, Alejandro; Aiello, Ernesto A

    2013-01-01

    The sodium/bicarbonate cotransporter (NBC) is one of the major alkalinizing mechanisms in the cardiomyocytes. It has been demonstrated the existence of at least two functional isoforms, one that promotes the co-influx of 1 molecule of Na(+) per 1 molecule of HCO(-) 3 (electroneutral isoform; NBCn1) and the other one that generates the co-influx of 1 molecule of Na(+) per 2 molecules of HCO(-) 3 (electrogenic isoform; NBCe1). Both isoforms are important to maintain intracellular pH (pH i ) and sodium concentration ([Na(+)] i ). In addition, NBCe1 generates an anionic repolarizing current that modulates the action potential duration (APD). The renin-angiotensin-aldosterone system (RAAS) is implicated in the modulation of almost all physiological cardiac functions and is also involved in the development and progression of cardiac diseases. It was reported that angiotensin II (Ang II) exhibits an opposite effect on NBC isoforms: it activates NBCn1 and inhibits NBCe1. The activation of NBCn1 leads to an increase in pH i and [Na(+)] i , which indirectly, due to the stimulation of reverse mode of the Na(+)/Ca(2+) exchanger (NCX), conduces to an increase in the intracellular Ca(2+) concentration. On the other hand, the inhibition of NBCe1 generates an APD prolongation, potentially representing a risk of arrhythmias. In the last years, the potentially altered NBC function in pathological scenarios, as cardiac hypertrophy and ischemia-reperfusion, has raised increasing interest among investigators. This review attempts to draw the attention on the relevant regulation of NBC activity by RAAS, since it modulates pH i and [Na(+)] i , which are involved in the development of cardiac hypertrophy, the damage produced by ischemia-reperfusion and the generation of arrhythmic events, suggesting a potential role of NBC in cardiac diseases.

  14. Salt sensitivity of blood pressure is associated with polymorphisms in the sodium-bicarbonate cotransporter.

    Science.gov (United States)

    Carey, Robert M; Schoeffel, Cynthia D; Gildea, John J; Jones, John E; McGrath, Helen E; Gordon, Lindsay N; Park, Min Jeong; Sobota, Rafal S; Underwood, Patricia C; Williams, Jonathan; Sun, Bei; Raby, Benjamin; Lasky-Su, Jessica; Hopkins, Paul N; Adler, Gail K; Williams, Scott M; Jose, Pedro A; Felder, Robin A

    2012-11-01

    Previous studies have demonstrated that single nucleotide polymorphisms (SNPs) of the sodium-bicarbonate co-transporter gene (SLC4A5) are associated with hypertension. We tested the hypothesis that SNPs in SLC4A5 are associated with salt sensitivity of blood pressure in 185 whites consuming an isocaloric constant diet with a randomized order of 7 days of low Na(+) (10 mmol/d) and 7 days of high Na(+) (300 mmol/d) intake. Salt sensitivity was defined as a ≥ 7-mm Hg increase in mean arterial pressure during a randomized transition between high and low Na(+) diet. A total of 35 polymorphisms in 17 candidate genes were assayed, 25 of which were tested for association. Association analyses with salt sensitivity revealed 3 variants that associated with salt sensitivity, 2 in SLC4A5 (P<0.001) and 1 in GRK4 (P=0.020). Of these, 2 SNPs in SLC4A5 (rs7571842 and rs10177833) demonstrated highly significant results and large effects sizes, using logistic regression. These 2 SNPs had P values of 1.0 × 10(-4) and 3.1 × 10(-4) with odds ratios of 0.221 and 0.221 in unadjusted regression models, respectively, with the G allele at both sites conferring protection. These SNPs remained significant after adjusting for body mass index and age (P=8.9 × 10(-5) and 2.6 × 10(-4) and odds ratios 0.210 and 0.286, respectively). Furthermore, the association of these SNPs with salt sensitivity was replicated in a second hypertensive population. Meta-analysis demonstrated significant associations of both SNPs with salt sensitivity (rs7571842 [P=1.2 × 10(-5)]; rs1017783 [P=1.1 × 10(-4)]). In conclusion, SLC4A5 variants are strongly associated with salt sensitivity of blood pressure in 2 separate white populations.

  15. Impact of sodium–glucose cotransporter 2 inhibitors on blood pressure

    Directory of Open Access Journals (Sweden)

    Reed JW

    2016-10-01

    control. Keywords: blood pressure, canagliflozin, dapagliflozin, empagliflozin, sodium–glucose cotransporter 2 inhibitors, type 2 diabetes

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

    Science.gov (United States)

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

    2006-04-01

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

  17. Role of sodium glucose cotransporter-2 inhibitors in type I diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Ahmadieh H

    2017-05-01

    Full Text Available Hala Ahmadieh,1 Nisrine Ghazal,2 Sami T Azar3 1Faculty of Medicine, Clinical Sciences Department, Beirut Arab University, 2Department of Endocrinology and Metabolism, American University of Beirut, Beirut, Lebanon; 3Department of Internal Medicine, Division of Endocrinology, American University of Beirut, New York, NY, USA Abstract: The burden of diabetes mellitus (DM in general has been extensively increasing over the past few years. Selective sodium glucose cotransporter-2 (SGLT2 inhibitors were extensively studied in type 2 DM and found to have sustained urinary glucose loss, improvement of glycemic control, in addition to their proven metabolic effects on weight, blood pressure, and cardiovascular benefits. Type 1 DM (T1D patients clearly depend on insulin therapy, which till today fails to achieve the optimal glycemic control and metabolic targets that are needed to prevent risk of complications. New therapies are obviously needed as an adjunct to insulin therapy in order to try to achieve optimal control in T1D. Many oral diabetic medications have been tried in T1D patients as an adjunct to insulin treatment and have shown conflicting results. Adjunctive use of SGLT2 inhibitors in addition to insulin therapies in T1D was found to have the potential to improve glycemic control along with decrease in the insulin doses, as has been shown in certain animal and short-term human studies. Furthermore, larger well-randomized studies are needed to better evaluate their efficacy and safety in patients with T1D. Euglycemic diabetic ketoacidosis incidences were found to be increased among users of SGLT2 inhibitors, although the incidence remains very low. Recent beneficial effects of ketone body production and this shift in fuel energetics have been suggested based on the findings of protective cardiovascular benefits associated with one of the SGLT2 inhibitors. Keywords: glycemic control, glycosylated hemoglobin, euglucemic diabetic ketoacidosis

  18. Functional assessment of sodium chloride cotransporter NCC mutants in polarized mammalian epithelial cells.

    Science.gov (United States)

    Rosenbaek, Lena L; Rizzo, Federica; MacAulay, Nanna; Staub, Olivier; Fenton, Robert A

    2017-08-01

    The thiazide-sensitive sodium chloride cotransporter NCC is important for maintaining serum sodium (Na + ) and, indirectly, serum potassium (K + ) levels. Functional studies on NCC have used cell lines with native NCC expression, transiently transfected nonpolarized cell lines, or Xenopus laevis oocytes. Here, we developed the use of polarized Madin-Darby canine kidney type I (MDCKI) mammalian epithelial cell lines with tetracycline-inducible human NCC expression to study NCC activity and membrane abundance in the same system. In radiotracer assays, induced cells grown on filters had robust thiazide-sensitive and chloride dependent sodium-22 ( 22 Na) uptake from the apical side. To minimize cost and maximize throughput, assays were modified to use cells grown on plastic. On plastic, cells had similar thiazide-sensitive 22 Na uptakes that increased following preincubation of cells in chloride-free solutions. NCC was detected in the plasma membrane, and both membrane abundance and phosphorylation of NCC were increased by incubation in chloride-free solutions. Furthermore, in cells exposed for 15 min to low or high extracellular K + , the levels of phosphorylated NCC increased and decreased, respectively. To demonstrate that the system allows rapid and systematic assessment of mutated NCC, three phosphorylation sites in NCC were mutated, and NCC activity was examined. 22 Na fluxes in phosphorylation-deficient mutants were reduced to baseline levels, whereas phosphorylation-mimicking mutants were constitutively active, even without chloride-free stimulation. In conclusion, this system allows the activity, cellular localization, and abundance of wild-type or mutant NCC to be examined in the same polarized mammalian expression system in a rapid, easy, and low-cost fashion. Copyright © 2017 the American Physiological Society.

  19. Age-dependent susceptibility to phenobarbital-resistant neonatal seizures: role of chloride co-transporters

    Directory of Open Access Journals (Sweden)

    Seok Kyu eKang

    2015-05-01

    Full Text Available Ischemia in the immature brain is an important cause of neonatal seizures. Temporal evolution of acquired neonatal seizures and their response to anticonvulsants are of great interest, given the unreliability of the clinical correlates and poor efficacy of first-line anti-seizure drugs. The expression and function of the electroneutral chloride co-transporters KCC2 and NKCC1 influence the anti-seizure efficacy of GABAA-agonists. To investigate ischemia-induced seizure susceptibility and efficacy of the GABAA-agonist phenobarbital (PB, with NKCC1 antagonist bumetanide (BTN as an adjunct treatment, we utilized permanent unilateral carotid-ligation to produce acute ischemic-seizures in postnatal day 7, 10 and 12 CD1 mice. Immediate post-ligation video-electroencephalograms (EEGs quantitatively evaluated baseline and post-treatment seizure burdens. Brains were examined for stroke-injury and western blot analyses to evaluate the expression of KCC2 and NKCC1. Severity of acute ischemic seizures post-ligation was highest at P7. PB was an efficacious anti-seizure agent at P10 and P12, but not at P7. BTN failed as an adjunct, at all ages tested and significantly blunted PB-efficacy at P10. Significant acute post-ischemic downregulation of KCC2 was detected at all ages. At P7, males displayed higher age-dependent seizure susceptibility, associated with a significant developmental lag in their KCC2 expression. This study established a novel neonatal mouse model of PB-resistant seizures that demonstrates age/sex-dependent susceptibility. The age-dependent profile of KCC2 expression and its post-insult downregulation may underlie the PB-resistance reported in this model. Blocking NKCC1 with low-dose BTN following PB treatment failed to improve PB-efficacy.

  20. The Sodium Glucose Cotransporter SGLT1 Is an Extremely Efficient Facilitator of Passive Water Transport.

    Science.gov (United States)

    Erokhova, Liudmila; Horner, Andreas; Ollinger, Nicole; Siligan, Christine; Pohl, Peter

    2016-04-29

    The small intestine is void of aquaporins adept at facilitating vectorial water transport, and yet it reabsorbs ∼8 liters of fluid daily. Implications of the sodium glucose cotransporter SGLT1 in either pumping water or passively channeling water contrast with its reported water transporting capacity, which lags behind that of aquaporin-1 by 3 orders of magnitude. Here we overexpressed SGLT1 in MDCK cell monolayers and reconstituted the purified transporter into proteoliposomes. We observed the rate of osmotic proteoliposome deflation by light scattering. Fluorescence correlation spectroscopy served to assess (i) SGLT1 abundance in both vesicles and plasma membranes and (ii) flow-mediated dilution of an aqueous dye adjacent to the cell monolayer. Calculation of the unitary water channel permeability, pf, yielded similar values for cell and proteoliposome experiments. Neither the absence of glucose or Na(+), nor the lack of membrane voltage in vesicles, nor the directionality of water flow grossly altered pf Such weak dependence on protein conformation indicates that a water-impermeable occluded state (glucose and Na(+) in their binding pockets) lasts for only a minor fraction of the transport cycle or, alternatively, that occlusion of the substrate does not render the transporter water-impermeable as was suggested by computational studies of the bacterial homologue vSGLT. Although the similarity between the pf values of SGLT1 and aquaporin-1 makes a transcellular pathway plausible, it renders water pumping physiologically negligible because the passive flux would be orders of magnitude larger. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  1. MODULATION OF THE CARDIAC SODIUM/BICARBONATE COTRANSPORTER BY THE RENIN ANGIOTENSIN ALDOSTERONE SYSTEM: PATHOPHYSIOLOGICAL CONSEQUENCES.

    Directory of Open Access Journals (Sweden)

    Verónica Celeste De Giusti

    2014-01-01

    Full Text Available The sodium/bicarbonate cotransporter (NBC is one of the major alkalinizing mechanisms in the cardiomyocytes. It has been demonstrated the existence of at least two functional isoforms, one that promotes the co-influx of 1 molecule of Na+ per 1 molecule of HCO3- (electroneutral isoform; NBCn1 and the other one that generates the co-influx of 1 molecule of Na+ per 2 molecules of HCO3- (electrogenic isoform; NBCe1. Both isoforms are important to maintain intracellular pH (pHi and sodium concentration ([Na+]i. In addition, NBCe1 generates an anionic repolarizing current that modulates the action potential duration (APD. The renin-angiotensin-aldosterone system (RAAS is implicated in the modulation of almost all physiological cardiac functions and is also involved in the development and progression of cardiac diseases. It was reported that angiotensin II (Ang II exhibits an opposite effect on NBC isoforms: it activates NBCn1 and inhibits NBCe1. The activation of NBCn1 leads to an increase in pHi and [Na+]i, which indirectly, due to the stimulation of reverse mode of the Na+/Ca2+ exchanger (NCX, conduces to an increase in the intracellular Ca2+ concentration. On the other hand, the inhibition of NBCe1 generates an APD prolongation, potentially representing a risk of arrhythmias. In the last years, the potentially altered NBC function in pathological scenarios, as cardiac hypertrophy and ischemia-reperfusion, has raised increasing interest among investigators. This review attempts to draw the attention on the relevant regulation of NBC activity by RAAS, since it modulates pHi and [Na+]i, which are involved in the development of cardiac hypertrophy, the damage produced by ischemia-reperfusion and the generation of arrhythmic events, suggesting a potential role of NBC in cardiac diseases.

  2. Platelet-derived growth factor regulates K-Cl cotransport in vascular smooth muscle cells.

    Science.gov (United States)

    Zhang, Jing; Lauf, Peter K; Adragna, Norma C

    2003-03-01

    Platelet-derived growth factor (PDGF), a potent serum mitogen for vascular smooth muscle cells (VSMCs), plays an important role in membrane transport regulation and in atherosclerosis. K-Cl cotransport (K-Cl COT/KCC), the coupled-movement of K and Cl, is involved in ion homeostasis. VSMCs possess K-Cl COT activity and the KCC1 and KCC3 isoforms. Here, we report on the effect of PDGF on K-Cl COT activity and mRNA expression in primary cultures of rat VSMCs. K-Cl COT was determined as the Cl-dependent Rb influx and mRNA expression by semiquantitative RT-PCR. Twenty four-hour serum deprivation inhibited basal K-Cl COT activity. Addition of PDGF increased total protein content and K-Cl COT activity in a time-dependent manner. PDGF activated K-Cl COT in a dose-dependent manner, both acutely (10 min) and chronically (12 h). AG-1296, a selective inhibitor of the PDGF receptor tyrosine kinase, abolished these effects. Actinomycin D and cycloheximide had no effect on the acute PDGF activation of K-Cl COT, suggesting posttranslational regulation by the drug. Furthermore, PDGF increased KCC1 and decreased KCC3 mRNA expression in a time-dependent manner. These results indicate that chronic activation of K-Cl COT activity by PDGF may involve regulation of the two KCC mRNA isoforms, with KCC1 playing a dominant role in the mechanism of PDGF-mediated activation.

  3. Signal transduction mechanisms of K+-Cl- cotransport regulation and relationship to disease.

    Science.gov (United States)

    Adragna, N C; Ferrell, C M; Zhang, J; Di Fulvio, M; Temprana, C F; Sharma, A; Fyffe, R E W; Cool, D R; Lauf, P K

    2006-01-01

    The K+-Cl- cotransport (COT) regulatory pathways recently uncovered in our laboratory and their implication in disease state are reviewed. Three mechanisms of K+-Cl- COT regulation can be identified in vascular cells: (1) the Li+-sensitive pathway, (2) the platelet-derived growth factor (PDGF)-sensitive pathway and (3) the nitric oxide (NO)-dependent pathway. Ion fluxes, Western blotting, semi-quantitative RT-PCR, immunofluorescence and confocal microscopy were used. Li+, used in the treatment of manic depression, stimulates volume-sensitive K+-Cl- COT of low K+ sheep red blood cells at cellular concentrations 3 mM, causes cell swelling, and appears to regulate K+-Cl- COT through a protein kinase C-dependent pathway. PDGF, a potent serum mitogen for vascular smooth muscle cells (VSMCs), regulates membrane transport and is involved in atherosclerosis. PDGF stimulates VSM K+-Cl- COT in a time- and concentration-dependent manner, both acutely and chronically, through the PDGF receptor. The acute effect occurs at the post-translational level whereas the chronic effect may involve regulation through gene expression. Regulation by PDGF involves the signalling molecules phosphoinositides 3-kinase and protein phosphatase-1. Finally, the NO/cGMP/protein kinase G pathway, involved in vasodilation and hence cardiovascular disease, regulates K+-Cl- COT in VSMCs at the mRNA expression and transport levels. A complex and diverse array of mechanisms and effectors regulate K+-Cl- COT and thus cell volume homeostasis, setting the stage for abnormalities at the genetic and/or regulatory level thus effecting or being affected by various pathological conditions.

  4. Internal magnesium, 2,3-diphosphoglycerate, and the regulation of the steady-state volume of human red blood cells by the Na/K/2Cl cotransport system

    Science.gov (United States)

    1992-01-01

    This study is concerned with the relationship between the Na/K/Cl cotransport system and the steady-state volume (MCV) of red blood cells. Cotransport rate was determined in unfractionated and density- separated red cells of different MCV from different donors to see whether cotransport differences contribute to the difference in the distribution of MCVs. Cotransport, studied in cells at their original MCVs, was determined as the bumetanide (10 microM)-sensitive 22Na efflux in the presence of ouabain (50 microM) after adjusting cellular Na (Nai) and Ki to achieve near maximal transport rates. This condition was chosen to rule out MCV-related differences in Nai and Ki that might contribute to differences in the net chemical driving force for cotransport. We found that in both unfractionated and density-separated red cells the cotransport rate was inversely correlated with MCV. MCV was correlated directly with red cell 2,3-diphosphoglycerate (DPG), whereas total red cell Mg was only slightly elevated in cells with high MCV. Thus intracellular free Mg (Mgifree) is evidently lower in red cells with high 2,3-DPG (i.e., high MCV) and vice versa. Results from flux measurements at their original MCVs, after altering Mgifree with the ionophore A23187, indicated a high Mgi sensitivity of cotransport: depletion of Mgifree inhibited and an elevation of Mgifree increased the cotransport rate. The apparent K0.5 for Mgifree was approximately 0.4 mM. Maximizing Mgifree at optimum Nai and Ki minimized the differences in cotransport rates among the different donors. It is concluded that the relative cotransport rate is regulated for cells in the steady state at their original cell volume, not by the number of copies of the cotransporter but by differences in Mgifree. The interindividual differences in Mgifree, determined primarily by differences in the 2,3-DPG content, are responsible for the differences in the relative cotransport activity that results in an inverse relationship

  5. Deficiency of electroneutral K+-Cl- cotransporter 3 causes a disruption in impulse propagation along peripheral nerves.

    Science.gov (United States)

    Sun, Yuan-Ting; Lin, Thy-Sheng; Tzeng, Shun-Fen; Delpire, Eric; Shen, Meng-Ru

    2010-10-01

    Nerve conduction requires the fine tuning of ionic currents through delicate interactions between axons and Schwann cells. The K(+)-Cl(-) cotransporter (KCC) family includes four isoforms (KCC1-4) that play an important role in the maintenance of cellular osmotic homeostasis via the coupled electroneutral movement of K(+) and Cl(-) with concurrent water flux. Mutation in SLC12A6 gene encoding KCC3 results in an autosomal recessive disease, known as agenesis of the corpus callosum associated with peripheral neuropathy. Nevertheless, the role of KCC3 in nerve function remains a puzzle. In this study, the microscopic examination of KCC isoforms expressed in peripheral nerves showed high expression of KCC2-4 in nodal segments of the axons and in the perinucleus and microvilli of Schwann cells. The KCC inhibitor [[(dihydroindenyl)oxy]alkanoic acid] but not the Na(+)-K(+)-2Cl(-)-cotransport inhibitor (bumetanide) dose-dependently suppressed the amplitude and area of compound muscle action potential, indicating the involvement of KCC activity in peripheral nerve conduction. Furthermore, the amplitude and area under the curve were smaller, and the nerve conduction velocity was slower in nerves from KCC3(-/-) mice than in nerves from wild-type mice, while the expression pattern of KCC2 and KCC4 was similar in KCC3 kockout and wild-type strains. KCC3(-/-) mice also manifested a prominent motor deficit in the beam-walking test. This is the first study to demonstrate that the K(+)-Cl(-) cotransporter activity of KCC3 contributes to the propagation of action potentials along peripheral nerves. (c) 2010 Wiley-Liss, Inc.

  6. Potassium-chloride cotransporter 3 interacts with Vav2 to synchronize the cell volume decrease response with cell protrusion dynamics.

    Directory of Open Access Journals (Sweden)

    Adèle Salin-Cantegrel

    Full Text Available Loss-of-function of the potassium-chloride cotransporter 3 (KCC3 causes hereditary motor and sensory neuropathy with agenesis of the corpus callosum (HMSN/ACC, a severe neurodegenerative disease associated with defective midline crossing of commissural axons in the brain. Conversely, KCC3 over-expression in breast, ovarian and cervical cancer is associated with enhanced tumor cell malignancy and invasiveness. We identified a highly conserved proline-rich sequence within the C-terminus of the cotransporter which when mutated leads to loss of the KCC3-dependent regulatory volume decrease (RVD response in Xenopus Laevis oocytes. Using SH3 domain arrays, we found that this poly-proline motif is a binding site for SH3-domain containing proteins in vitro. This approach identified the guanine nucleotide exchange factor (GEF Vav2 as a candidate partner for KCC3. KCC3/Vav2 physical interaction was confirmed using GST-pull down assays and immuno-based experiments. In cultured cervical cancer cells, KCC3 co-localized with the active form of Vav2 in swelling-induced actin-rich protruding sites and within lamellipodia of spreading and migrating cells. These data provide evidence of a molecular and functional link between the potassium-chloride co-transporters and the Rho GTPase-dependent actin remodeling machinery in RVD, cell spreading and cell protrusion dynamics, thus providing new insights into KCC3's involvement in cancer cell malignancy and in corpus callosum agenesis in HMSN/ACC.

  7. Integrated responses of Na+/HCO3- cotransporters and V-type H+-ATPases in the fish gill and kidney during respiratory acidosis.

    Science.gov (United States)

    Perry, S F; Furimsky, M; Bayaa, M; Georgalis, T; Shahsavarani, A; Nickerson, J G; Moon, T W

    2003-12-30

    Using degenerate primers, followed by 3' and 5' RACE and "long" PCR, a continuous 4050-bp cDNA was obtained and sequenced from rainbow trout (Oncorhynchus mykiss) gill. The cDNA included an open reading frame encoding a deduced protein of 1088 amino acids. A BLAST search of the GenBank protein database demonstrated that the trout gene shared high sequence similarity with several vertebrate Na(+)/HCO(3)(-) cotransporters (NBCs) and in particular, NBC1. Protein alignment revealed that the trout NBC is >80% identical to vertebrate NBC1s and phylogenetic analysis provided additional evidence that the trout NBC is indeed a homolog of NBC1. Using the same degenerate primers, a partial cDNA (404 bp) for NBC was obtained from eel (Anguilla rostrata) kidney. Analysis of the tissue distribution of trout NBC, as determined by Northern blot analysis and real-time PCR, indicated high transcript levels in several absorptive/secretory epithelia including gill, kidney and intestine and significant levels in liver. NBC mRNA was undetectable in eel gill by real-time PCR. In trout, the levels of gill NBC1 mRNA were increased markedly during respiratory acidosis induced by exposure to hypercarbia; this response was accompanied by a transient increase in branchial V-type H(+)-ATPase mRNA levels. Assuming that the branchial NBC1 is localised to basolateral membranes of gill cells and operates in the influx mode (HCO(3)(-) and Na(+) entry into the cell), it would appear that in trout, the expression of branchial NBC1 is transcriptionally regulated to match the requirements of gill pHi regulation rather than to match trans-epithelial HCO(3)(-) efflux requirements for systemic acid-base balance. By analogy with mammalian systems, NBC1 in the kidney probably plays a role in the tubular reabsorption of both Na(+) and HCO(3)(-). During periods of respiratory acidosis, levels of renal NBC1 mRNA increased (after a transient reduction) in both trout and eel, presumably to increase HCO(3

  8. Renal Function in Hypothyroidism

    International Nuclear Information System (INIS)

    Khalid, S.; Khalid, M; Elfaki, M.; Hassan, N.; Suliman, S.M.

    2007-01-01

    Background Hypothyroidism induces significant changes in the function of organ systems such as the heart, muscles and brain. Renal function is also influenced by thyroid status. Physiological effects include changes in water and electrolyte metabolism, notably hyponatremia, and reliable alterations of renal hemodynamics, including decrements in renal blood flow, renal plasma flow, glomerular filtration rate (GFR). Objective Renal function is profoundly influenced by thyroid status; the purpose of the present study was to determine the relationship between renal function and thyroid status of patients with hypothyroidism. Design and Patients In 5 patients with primary hypothyroidism and control group renal functions are measured by serum creatinine and glomerular filtration rate (GFR) using modified in diet renal disease (MDRD) formula. Result In hypothyroidism, mean serum creatinine increased and mean estimated GFR decreased, compared to the control group mean serum creatinine decreased and mean estimated GFR Increased. The hypothyroid patients showed elevated serum creatinine levels (> 1.1mg/dl) compared to control group (p value .000). In patients mean estimated GFR decreased, compared to mean estimated GFR increased in the control group (p value= .002).

  9. Renal Function in Hypothyroidism

    International Nuclear Information System (INIS)

    Khalid, A. S; Ahmed, M.I; Elfaki, H.M; Hassan, N.; Suliman, S. M.

    2006-12-01

    Background hypothyroidism induces significant changes in the function of organ systems such as the heart, muscles and brain. Renal function is also influenced by thyroid status. Physiological effects include changes in water and electrolyte metabolism, notably hyponatraemia, and reliable alterations of renal hemodynamics, including decrements in renal blood flow, renal plasma flow, glomerular filtration rate (GFR). Objective renal function is profoundly influenced by thyroid status, the purpose of the present study was to determine the relationship between renal function and thyroid status of patients with hypothyroidism. Design and patients in 5 patients with primary hypothyroidism and control group renal functions are measured by serum creatinine and glomerular filtration rate(GFR) using modified in diet renal disease (MDRD) formula. Result in hypothyroidism, mean serum creatinine increased and mean estimated GFR decreased, compared to the control group mean serum creatinine decreased and mean estimated GFR increased. The hypothyroid patients showed elevated serum creatinine levels(>1.1 mg/d1) compared to control group (p value= 000). In patients mean estimated GFR increased in the control group (p value=.002).Conclusion thus the kidney, in addition to the brain, heart and muscle, is an important target of the action of thyroid hormones.(Author)

  10. Disappearing renal calculus.

    Science.gov (United States)

    Cui, Helen; Thomas, Johanna; Kumar, Sunil

    2013-04-10

    We present a case of a renal calculus treated solely with antibiotics which has not been previously reported in the literature. A man with a 17 mm lower pole renal calculus and concurrent Escherichia coli urine infection was being worked up to undergo percutaneous nephrolithotomy. However, after a course of preoperative antibiotics the stone was no longer seen on retrograde pyelography or CT imaging.

  11. Bilateral triple renal arteries

    International Nuclear Information System (INIS)

    Pestemalci, Turan; Yildiz, Yusuf Zeki; Yildirim, Mehmet; Mavi, Ayfer; Gumusburun, Erdem

    2009-01-01

    Knowledge of the variations of the renal artery has grown in importance with increasing numbers of renal transplants, vascular reconstructions and various surgical and radio logic techniques being performed in recent years. We report the presence of bilateral triple renal arteries, discovered on routine dissection of a male cadaver. On the right side, one additional renal artery originated from the abdominal aorta (distributed to superior pole of the kidney) and one other originated from the right common iliac artery (distributed to lower pole of the kidney). On the left side, both additional renal arteries originated from the abdominal aorta. Our observation has been compared with variations described in the literature and their clinical importance has been emphasized. (author)

  12. Radiology of renal failure

    International Nuclear Information System (INIS)

    Griffiths, H.J.

    1990-01-01

    This book covers most aspects of imaging studies in patients with renal failure. The initial chapter provides basic information on contrast agents, intravenous urography, and imaging findings in the urinary tract disorders responsible for renal failure and in patients who have undergone transplantation. It illustrates common gastro-intestinal abnormalities seen on barium studies in patients with renal failure. It illustrates the cardiopulmonary complications of renal failure and offers advice for radiologic differentiation. It details different aspects of skeletal changes in renal failure, including a basic description of the pathophysiology of the changes; many excellent illustrations of classic bone changes, arthritis, avascular necrosis, and soft-tissue calcifications; and details of bone mineral analysis

  13. [Hypertension and renal disease

    DEFF Research Database (Denmark)

    Kamper, A.L.; Pedersen, E.B.; Strandgaard, S.

    2009-01-01

    Renal mechanisms, in particular the renin-angiotensin system and renal salt handling, are of major importance in blood pressure regulation. Co-existence of hypertension and decreased renal function may be due to nephrosclerosis secondary to hypertension, or primary renal disease with secondary...... hypertension. Mild degrees of chronic kidney disease (CKD) can be detected in around 10% of the population, and detection is important as CKD is an important risk factor for atherosclerotic cardiovascular disease. Conversely, heart failure may cause an impairment of renal function. In chronic progressive...... nephropathy, effective blood pressure lowering is of paramount importance, and angiotensin converting enzyme inhibitors and angiotensin receptor blockers are agents of choice Udgivelsesdato: 2009/6/15...

  14. Benefits of SGLT2 Inhibitors beyond glycemic control - A focus on metabolic, cardiovascular, and renal outcomes.

    Science.gov (United States)

    Minze, Molly G; Will, Kayley; Terrell, Brian T; Black, Robin L; Irons, Brian K

    2017-08-16

    Sodium-glucose co-transporter 2 (SGLT2) inhibitors are a new pharmacotherapeutic class for the treatment of type 2 diabetes mellitus (T2DM). To evaluate beneficial effects of the SGLT2 inhibitors on metabolic, cardiovascular, and renal outcomes. A Pub-Med search (1966 to July 2017) was performed of published English articles using keywords sodium-glucose co-transporter 2 inhibitors, canagliflozin, dapagliflozin, and empagliflozin. A review of literature citations provided further references. The search identified 17clinical trials and 2 meta-analysis with outcomes of weight loss and blood pressure reduction with dapagliflozin, canagliflozin, or empagliflozin. Three randomized trials focused on either empagliflozin or canagliflozin and reduction of cardiovascular disease and progression of renal disease. SGLT2 inhibitors have a beneficial profile in the treatment of T2DM. They have evidence of reducing weight between 2.9 kilograms when used as monotherapy to 4.7 kilograms when used in combination with metformin, and reduce systolic blood pressure between 3 to 5 mmHg and reduce diastolic blood pressure approximately 2 mmHg. To date, reduction of cardiovascular events was seen specifically with empagliflozin in patients with T2DM and a history of cardiovascular disease. In the same population, empagliflozin was associated with slowing the progression of kidney disease. Moreover, patients with increased risk of cardiovascular disease treated with canagliflozin has decreased risk of death from cardiovascular causes, nonfatal MI, or nonfatal stroke. Data regarding these outcomes with dapagliflozin are underway. SGLT2 inhibitors demonstrate some positive metabolic effects. In addition, empagliflozin specifically has demonstrated reduction in cardiovascular events and delay in the progression of kidney disease in patients with T2DM and a history of cardiovascular disease. Further data is needed to assess if this is a class effect. Copyright© Bentham Science Publishers

  15. Altered regulation of renal sodium transporters in salt-sensitive hypertensive rats induced by uninephrectomy.

    Science.gov (United States)

    Jung, Ji Yong; Lee, Jay Wook; Kim, Sejoong; Jung, Eun Sook; Jang, Hye Ryoun; Han, Jin Suk; Joo, Kwon Wook

    2009-12-01

    Uninephrectomy (uNx) in young rats causes salt-sensitive hypertension (SSH). Alterations of sodium handling in residual nephrons may play a role in the pathogenesis. Therefore, we evaluated the adaptive alterations of renal sodium transporters according to salt intake in uNx-SSH rats. uNx or sham operations were performed in male Sprague-Dawley rats, and normal-salt diet was fed for 4 weeks. Four experimental groups were used: sham-operated rats raised on a high-salt diet for 2 weeks (CHH) or on a low-salt diet for 1 week after 1 week's high-salt diet (CHL) and uNx rats fed on the same diet (NHH, NHL) as the sham-operated rats were fed. Expression of major renal sodium transporters were determined by semiquantitative immunoblotting. Systolic blood pressure was increased in NHH and NHL groups, compared with CHH and CHL, respectively. Protein abundances of Na(+)/K(+)/2Cl(-) cotransporter (NKCC2) and Na(+)/Cl(-) cotransporter (NCC) in the CHH group were lower than the CHL group. Expression of epithelial sodium channel (ENaC)-γ increased in the CHH group. In contrast, expressions of NKCC2 and NCC in the NHH group didn't show any significant alterations, compared to the NHL group. Expressions of ENaC-α and ENaC-β in the NHH group were higher than the CHH group. Adaptive alterations of NKCC2 and NCC to changes of salt intake were different in the uNx group, and changes in ENaC-α and ENaC-β were also different. These altered regulations of sodium transporters may be involved in the pathogenesis of SSH in the uNx rat model.

  16. Co-transport of chlordecone and sulfadiazine in the presence of functionalized multi-walled carbon nanotubes in soils.

    Science.gov (United States)

    Zhang, Miaoyue; Engelhardt, Irina; Šimůnek, Jirka; Bradford, Scott A; Kasel, Daniela; Berns, Anne E; Vereecken, Harry; Klumpp, Erwin

    2017-02-01

    Batch and saturated soil column experiments were conducted to investigate sorption and mobility of two 14 C-labeled contaminants, the hydrophobic chlordecone (CLD) and the sulfadiazine (SDZ), in the absence or presence of functionalized multi-walled carbon nanotubes (MWCNTs). The transport behaviors of CLD, SDZ, and MWCNTs were studied at environmentally relevant concentrations (0.1-10 mg L -1 ) and they were applied in the column studies at different times. The breakthrough curves and retention profiles were simulated using a numerical model that accounted for the advective-dispersive transport of all compounds, attachment/detachment of MWCNTs, equilibrium and kinetic sorption of contaminants, and co-transport of contaminants with MWCNTs. The experimental results indicated that the presence of mobile MWCNTs facilitated remobilization of previously deposited CLD and its co-transport into deeper soil layers, while retained MWCNTs enhanced SDZ deposition in the topsoil layers due to the increased adsorption capacity of the soil. The modeling results then demonstrated that the mobility of engineered nanoparticles (ENPs) in the environment and the high affinity and entrapment of contaminants to ENPs were the main reasons for ENP-facilitated contaminant transport. On the other hand, immobile MWCNTs had a less significant impact on the contaminant transport, even though they were still able to enhance the adsorption capacity of the soil. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Membrane potential and proton cotransport of alanine and phosphate as affected by permeant weak acids in Lemna gibba

    International Nuclear Information System (INIS)

    Basso, B.; Ullrich-Eberius, C.I.

    1987-01-01

    The treatment of Lemna gibba plants with the weak acids (trimethylacetic acid and butyric acid), used as tools to decrease intracellular pH, induced a hyperpolarization of membrane potential, dependent on the concentration of the undissociated permeant form of the weak acid and on the value of the resting potential. Measurements were carried out both with high potential and low potential plants and the maximum values of acid induced hyperpolarization were about 35 and 71 millivolts, respectively. Weak acids influenced also the transient light-dark membrane potential changes, typical for photosynthesizing material, suggesting a dependence of these changes on an acidification of cytoplasm. In the presence of the weak acids, the membrane depolarization induced by the cotransport of alanine and phosphate with protons was reduced; the maximum reduction (about 90%) was obtained with alanine during 2 millimolar trimethylacetic acid perfusion at pH 5. A strong inhibition of the uptake rates (up to 48% for [ 14 C]alanine and 68% for 32 P-phosphate) was obtained in the presence of the weak acids, both by decreasing the pH of the medium and by increasing the concentration of the acid. In these experimental conditions, the ATP level and O 2 uptake rates did not change significantly. These results constitute good evidence that H + /solute cotransport in Lemna, already known to be dependent on the electrochemical potential difference for protons, is also strongly regulated by the cytoplasmic pH value

  18. Renal imaging in paediatrics

    International Nuclear Information System (INIS)

    Porn, U.; Hahn, K.; Fischer, S.

    2003-01-01

    The most frequent renal diseases in paediatrics include urinary tract infections, hydronephrosis, kidney anomalies and reflux. The main reason for performing DMSA scintigraphy in paediatrics is the detection of cortical abnormalities related to urinary tract infection. Because the amount of tracer retained in the tubular cells is associated with the distribution of functioning renal parenchyma in the kidney, it is possible, to evaluate the split renal function. In comparison to ultrasound and intravenous urography the sensitivity in the detection of acute as well as chronic inflammatory changes is very high, however less specific. An indication for a renography in neonates and children is beside an estimation of the total renal function and the calculation of the split renal function, the assessment of renal drainage in patients with unclear dilatation of the collecting system in ultrasound. The analysis of the time activity curve provides, especially for follow-up studies, a reproducible method to assess the urinary outflow. The diuretic scintigraphy allows the detection of urinary obstruction. Subsequently it is possible to image the micturition phase to detect vesico-ureteric reflux (indirect MCU) after drainage of tracer from the renal pelvis. An reflux in the ureters or the pelvicalyceal system is visible on the scintigraphic images and can be confirmed by time activity curves. A more invasive technique is the direct isotope cystography with bladder catheterization. The present paper should give an overview about the role of nuclear medicine in paediatric urology. (orig.) [de

  19. Perioperative acute renal failure.

    LENUS (Irish Health Repository)

    Mahon, Padraig

    2012-02-03

    PURPOSE OF REVIEW: Recent biochemical evidence increasingly implicates inflammatory mechanisms as precipitants of acute renal failure. In this review, we detail some of these pathways together with potential new therapeutic targets. RECENT FINDINGS: Neutrophil gelatinase-associated lipocalin appears to be a sensitive, specific and reliable biomarker of renal injury, which may be predictive of renal outcome in the perioperative setting. For estimation of glomerular filtration rate, cystatin C is superior to creatinine. No drug is definitively effective at preventing postoperative renal failure. Clinical trials of fenoldopam and atrial natriuretic peptide are, at best, equivocal. As with pharmacological preconditioning of the heart, volatile anaesthetic agents appear to offer a protective effect to the subsequently ischaemic kidney. SUMMARY: Although a greatly improved understanding of the pathophysiology of acute renal failure has offered even more therapeutic targets, the maintenance of intravascular euvolaemia and perfusion pressure is most effective at preventing new postoperative acute renal failure. In the future, strategies targeting renal regeneration after injury will use bone marrow-derived stem cells and growth factors such as insulin-like growth factor-1.

  20. Cadmium and renal cancer

    International Nuclear Information System (INIS)

    Il'yasova, Dora; Schwartz, Gary G.

    2005-01-01

    Background: Rates of renal cancer have increased steadily during the past two decades, and these increases are not explicable solely by advances in imaging modalities. Cadmium, a widespread environmental pollutant, is a carcinogen that accumulates in the kidney cortex and is a cause of end-stage renal disease. Several observations suggest that cadmium may be a cause of renal cancer. Methods: We performed a systematic review of the literature on cadmium and renal cancer using MEDLINE for the years 1966-2003. We reviewed seven epidemiological and eleven clinical studies. Results: Despite different methodologies, three large epidemiologic studies indicate that occupational exposure to cadmium is associated with increased risk renal cancer, with odds ratios varying from 1.2 to 5.0. Six of seven studies that compared the cadmium content of kidneys from patients with kidney cancer to that of patients without kidney cancer found lower concentrations of cadmium in renal cancer tissues. Conclusions: Exposure to cadmium appears to be associated with renal cancer, although this conclusion is tempered by the inability of studies to assess cumulative cadmium exposure from all sources including smoking and diet. The paradoxical findings of lower cadmium content in kidney tissues from patients with renal cancer may be caused by dilution of cadmium in rapidly dividing cells. This and other methodological problems limit the interpretation of studies of cadmium in clinical samples. Whether cadmium is a cause of renal cancer may be answered more definitively by future studies that employ biomarkers of cadmium exposure, such as cadmium levels in blood and urine

  1. Renal Branch Artery Stenosis

    DEFF Research Database (Denmark)

    Andersson, Zarah; Thisted, Ebbe; Andersen, Ulrik Bjørn

    2017-01-01

    Renovascular hypertension is a common cause of pediatric hypertension. In the fraction of cases that are unrelated to syndromes such as neurofibromatosis, patients with a solitary stenosis on a branch of the renal artery are common and can be diagnostically challenging. Imaging techniques...... that perform well in the diagnosis of main renal artery stenosis may fall short when it comes to branch artery stenosis. We report 2 cases that illustrate these difficulties and show that a branch artery stenosis may be overlooked even by the gold standard method, renal angiography....

  2. Renal artery stenosis.

    Science.gov (United States)

    Tafur-Soto, Jose David; White, Christopher J

    2015-02-01

    Atherosclerotic renal artery stenosis (RAS) is the single largest cause of secondary hypertension; it is associated with progressive renal insufficiency and causes cardiovascular complications such as refractory heart failure and flash pulmonary edema. Medical therapy, including risk factor modification, renin-angiotensin-aldosterone system antagonists, lipid-lowering agents, and antiplatelet therapy, is advised in all patients. Patients with uncontrolled renovascular hypertension despite optimal medical therapy, ischemic nephropathy, and cardiac destabilization syndromes who have severe RAS are likely to benefit from renal artery revascularization. Screening for RAS can be done with Doppler ultrasonography, CT angiography, and magnetic resonance angiography. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Cryoablation of Renal Angiomyolipoma

    DEFF Research Database (Denmark)

    Makki, Ahmad; Graumann, Ole; Hoyer, Soren

    2017-01-01

    BACKGROUND: Small series have reported that cryoablation (CA) is a safe and feasible minimally invasive nephron-sparing alternative for the treatment of renal angiomyolipomas (renal AMLs). The aim of the present study was to investigate the safety and efficacy of CA in patients with renal AML......-guided CA. The mean patient age was 46 years [interquartile range (IQR) 30] and the mean tumor volume was 50.1 cm(3) (IQR 53.3). In all cases, the procedure was effectively conducted with no conversion to open surgery, and no major complications were experienced. The mean follow-up time was 25 months (IQR...

  4. Acute renal failure in children

    International Nuclear Information System (INIS)

    Vergesslich, K.A.; Balzar, E.; Weninger, M.; Ponhold, W.; Sommer, G.; Wittich, G.R.; Vienna Univ.

    1987-01-01

    Acute renal failure (ARF) may be due to obstructive uropathy or renal parenchymal disease. Twenty-five children with acute renal failure secondary to renal parenchymal disease underwent ultrasonographic examination of the kidneys. Changes of renal size and cortical echogenicity were correlated with renal function. All patients presented with bilaterally enlarged kidneys with the exception in renal function resulted in normalization of renal size. With regard to cortical echogenicity two groups were formed. Group A comprised 11 patients whose kidneys had the same echogenicity as the liver, while in group B the kidneys were more echogenic (14 patients). Cortical echogenicity was always increased. Determination of creatinine levels showed a statistically significant difference between group A (3.32 mg% ± 1.40 S.D.) and group B (5.95 mg% ± 1.96 S.D.), p < 0.001. Changes in renal function were paralleled by rapid changes in renal size and cortical echogenicity. (orig.)

  5. Dynamics of Na+,K+,2Cl- cotransporter and Na+,K+-ATPase expression in the branchial epithelium of brown trout (Salmo trutta) and Atlantic salmon (Salmo salar)

    DEFF Research Database (Denmark)

    Tipsmark, Christian Kølbæk; Madsen, Steffen; Seidelin, Michel

    2002-01-01

    The dynamics of branchial Na+,K+,2Cl- cotransporter (NKCC) and Na+,K+-ATPase (NKA) expression were investigated in brown trout and Atlantic salmon during salinity shifts and the parr-smolt transformation, respectively. In the brown trout, Western blotting revealed that NKCC and NKA abundance...

  6. Contribution of Na+,HCO3--cotransport to cellular pH control in human breast cancer

    DEFF Research Database (Denmark)

    Bødtkjer, Ebbe; Moreira, José; Mele, Marco

    2013-01-01

    Genome-wide association studies recently linked the locus for Na(+) ,HCO(3) (-) -cotransporter NBCn1 (SLC4A7) to breast cancer susceptibility, yet functional insights have been lacking. To determine whether NBCn1, by transporting HCO(3) (-) into cells, may dispose of acid produced during high met...

  7. Renal tumors in infancy

    International Nuclear Information System (INIS)

    Lucaya, J.; Garcia, P.

    1997-01-01

    The classification of childhood renal masses in updated, including the clinical signs and imaging techniques currently employed to confirm their presence and type them. Several bening and malignant childhood tumors are described in substantial detail. (Author) 24 refs

  8. Renal cell carcinoma

    Science.gov (United States)

    ... kidney Patient Instructions Kidney removal - discharge Images Kidney anatomy Kidney tumor - CT scan Kidney metastases, CT scan Kidney - blood and urine flow References Campbell SC, Lane BR. Malignant renal tumors. In: Wein AJ, Kavoussi LR, Partin AW, ...

  9. Primary renal synovial sarcoma

    Directory of Open Access Journals (Sweden)

    Girish D. Bakhshi

    2012-03-01

    Full Text Available Primary Renal Sarcoma is rare tumor comprising only 1% of all renal tumours. Synovial sarcomas are generally deep-seated tumors arising in the proximity of large joints of adolescents and young adults and account for 5-10% of all soft tissue tumours. Primary synovial sarcoma of kidney is rare and has poor prognosis. It can only be diagnosed by immunohistochemistry. It should be considered as a differential in sarcomatoid and spindle cell tumours. We present a case of 33-year-old female, who underwent left sided radical nephrectomy for renal tumour. Histopathology and genetic analysis diagnosed it to be primary renal synovial sarcoma. Patient underwent radiation therapy and 2 years follow up is uneventful. A brief case report with review of literature is presented.

  10. [Small renal mass].

    Science.gov (United States)

    Prokofiev, D; Kreutzer, N; Kress, A; Wissing, F; Pfeifer, H; Stolzenburg, J-U; Dietel, A; Schwalenberg, T; Do, M; Truß, M C

    2012-10-01

    The frequent application of ultrasound and radiological imaging for non-urological indications in recent years has resulted in an increase in the diagnosis of small renal masses. The treatment options for patients with a small renal mass include active surveillance, surgery (both open and minimally invasive) as well as ablative techniques. As there is a risk for metastatic spread even in small renal masses surgical extirpation remains the treatment of choice in most patients. Ablative procedures, such as cryoablation and radiofrequency ablation are appropriate for old and multi-morbid patients who require active treatment of a small renal mass. Active surveillance is an alternative for high-risk patients. Meticulous patient selection by the urologist and patient preference will determine the choice of treatment option in the future.

  11. Common paediatric renal conditions

    African Journals Online (AJOL)

    Few children in South Africa have access to dialysis or renal transplantation, so it is important to .... the chronic administration of antibiotics increases the risk of a UTI with a resistant .... factors for recurrent urinary tract infection in young women.

  12. Renal and perirenal abscesses

    International Nuclear Information System (INIS)

    Patterson, J.E.; Andriole, V.T.

    1987-01-01

    Our knowledge of the spectrum of renal abscesses has increased as a result of more sensitive radiologic techniques. The classification of intrarenal abscess now includes acute focal bacterial nephritis and acute multifocal bacterial nephritis, as well as the previously recognized renal cortical abscess, renal corticomedullary abscess, and xanthogranulomatous pyelonephritis. In general, the clinical presentation of these entities does not differentiate them; various radiographic studies can distinguish them, however. The intrarenal abscess is usually treated successfully with antibiotic therapy alone. Antistaphylococcal therapy is indicated for the renal cortical abscess, whereas therapy directed against the common gram-negative uropathogens is indicated for most of the other entities. The perinephric abscess is often an elusive diagnosis, has a more serious prognosis, and is more difficult to treat. Drainage of the abscess and sometimes partial or complete nephrectomy are required for resolution. 73 references

  13. Lithium and Renal Impairment

    DEFF Research Database (Denmark)

    Nielsen, René Ernst; Kessing, Lars Vedel; Nolen, Willem A

    2018-01-01

    INTRODUCTION: Lithium is established as an effective treatment of mania, of depression in bipolar and unipolar disorder, and in maintenance treatment of these disorders. However, due to the necessity of monitoring and concerns about irreversible adverse effects, in particular renal impairment......, after long-term use, lithium might be underutilized. METHODS: This study reviewed 6 large observational studies addressing the risk of impaired renal function associated with lithium treatment and methodological issues impacting interpretation of results. RESULTS: An increased risk of renal impairment...... associated with lithium treatment is suggested. This increased risk may, at least partly, be a result of surveillance bias. Additionally, the earliest studies pointed toward an increased risk of end-stage renal disease associated with lithium treatment, whereas the later and methodologically most sound...

  14. Renal dynamic scintigraphy in renal graft evaluation; Cintilografia renal dinamica na avaliacao do transplante renal

    Energy Technology Data Exchange (ETDEWEB)

    Cervo, Marco Antonio Cadorna; Amarante Junior, Jose Luiz de Medeiros; Souza, Ricardo Alberto Manhaes de; Evangelista, Maria Gardenia; Cavalcante, Carlos Alberto Provasi; Neder, Jacqueline de Roure e; Espinola, Ircania Jorge [Hospital Naval Marcilio Dias, Rio de Janeiro, RJ (Brazil). Servico de Medicina Nuclear

    1996-12-31

    The goal of this was to describe the use of the dynamic renal scintigraphy in patients grafted. The authors described the scintigraphy method utilised and results were discussed 8 refs., 9 figs., 1 tab.

  15. OBSTETRIC RENAL FAILURE

    Directory of Open Access Journals (Sweden)

    Rajeshwari

    2015-11-01

    Full Text Available Renal failure in obstetrics is rare but important complication, associated with significant mortality and long term morbidity.1,2 It includes acute renal failure due to obstetrical complications or due to deterioration of existing renal disease. AIMS AND OBJECTIVES: To evaluate the etiology and outcome of renal failure in obstetric patients. METHODS: We prospectively analyzed 30 pregnant and puerperal women with acute renal failure or pre-existing renal disease developing renal failure during pregnancy between November 2007 to sep-2009. Patients who presented/developed ARF during the hospital stay were included in this study. RESULTS: Among 30 patients, mean age was 23 years and 33 years age group. 12 cases (40% patients were primigravidae and 9(30% patients were multigravidae and 9 cases (30% presented in post-partum period. Eighteen cases (60% with ARF were seen in third trimester, followed by in postpartum period 9 cases (30%. Most common contributing factors to ARF were Pre-eclampsia, eclampsia and HELLP syndrome 60%, sepsis 56.6%, post abortal ARF 10%. DIC 40%. Haemorrhage as the aetiology for ARF was present 46%, APH in 20% and PPH in 26.6%. The type of ARF was renal in (63% and prerenal (36%; Oliguric seen in 10 patients (33% and high mortality (30%. Among the 20 pregnant patients with ARF, The average period of gestation was 33±2 weeks (30 -36 weeks, 5 cases (25% presented with intrauterine fetal demise and 18 cases (66% had preterm vaginal delivery and 2 cases (10% had induced abortion. And the average birth weight was 2±0.5 kg (1.5 kg. Eight cases (26% required dialysis. 80% of patients recovered completely of renal functions. 63% patients recovered without renal replacement therapy whereas 17% required dialysis. the maternal mortality was 20%, the main reason for mortality was septic shock and multi organ dysfunction (66%. CONCLUSION: ARF related pregnancy was seen commonly in the primigravidae and in the third trimester, the most

  16. 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...

  17. Renal artery pseudoaneurysm

    Directory of Open Access Journals (Sweden)

    Luiz Inácio Roman

    Full Text Available Abstract The renal artery pseudoaneurysm embody a rare vascular complication coming of percutaneous procedures, renal biopsy, nephrectomy, penetrating traumas and more rarely blunt traumas. The clinical can be vary according the patient, the haematuria is the symptom more commom. Is necessary a high level of clinical suspicion for your diagnosis, this can be elucidated by through complementary exams as the eco-color Doppler and the computed tomography scan (CT. This report is a case of a patient submitted a right percutaneous renal biopsy and that, after the procedure started with macroscopic haematuria, urinary tenesmus and hypogastric pain. The diagnosis of pseudoaneurysm was given after one week of evolution when the patient was hospitalized because gross haematuria, tachycardia, hypotension and hypochondrium pain. In the angiotomography revealed a focal dilation of the accessory right renal inferior polar artery, dilation of renal pelvis and all the ureteral course with presence hyperdenso material (clots inside the middle third of the ureter. The treatment for the majority of this cases are conservative, through arterial embolization, indicated for thouse of smaller dimensions in patients who are hemodynamically stable. However, it was decided by clinical treatment with aminocaproic acid 1 g, according to previous studies for therapy of haematuria. The patient received discharge without evidence of macroscopic haematuria and with normal renal ultrasound, following ambulatory care.

  18. RENAL MALIGNANT NEOPLASMS: RENAL CELL CARCINOMA

    Directory of Open Access Journals (Sweden)

    Elisangela Giachini

    2017-06-01

    Full Text Available The aim of this study is to evaluate the incidence and prevalence of malignant kidney tumors, to contribute to identifying factors which the diagnosis of renal cell carcinomas. Through this study, we understand that kidney disease over the years had higher incidence rates, especially in adults in the sixth decade of life. The renal cell carcinoma (RCC is the third most common malignancy of the genitourinary tract, affecting 2% to 3% of the population. There are numerous ways of diagnosis; however, the most important are ultrasonography, magnetic resonance imaging and computed tomography. In general most of the patients affected by the CCR, have a good prognosis when diagnosed early and subjected to an effective treatment. This study conducted a literature review about the CCR, through this it was possible to understand the development needs of the imaging methods used for precise diagnosis and classification of RCC through the TNM system.

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

    Science.gov (United States)

    Robson, L; Hunter, M

    1999-01-01

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

  20. Regulation of the Na+2Cl–K+ cotransporter in in vitro perfused rectal gland tubules of Squalus acanthias.

    Science.gov (United States)

    Warth, R; Bleich, M; Thiele, I; Lang, F; Greger, R

    1998-07-01

    Previously it has been shown that the Na+2Cl–K+ cotransporter accepts NH4 + at its K+ binding site. This property can be used to estimate its transport rates by adding NH4 + to the bath and measuring the initial furosemide-dependent rates of change in BCECF fluorescence. We have utilized this technique to determine the regulation of the furosemide-inhibitable Na+2Cl–K+ cotransporter in in vitroperfused rectal gland tubules (RGT) of Squalus acanthias. Addition of NH4 + to the bath (20 mmol/l) led to an initial alkalinization, corresponding to NH3 uptake. This was followed by an acidification, corresponding to NH4 + uptake. The rate of this uptake was quantified by exponential curve fitting and is given in arbitrary units (Δfluorescence/time). This acidification could be completely inhibited by furosemide. In the absence of any secretagogue preincubation of RGT in a low Cl– solution (6 mmol/l, low Cl–) for 10 min enhanced the uptake rate significantly from 4.04±0.51 to 12.7±1.30 (n=5). The addition of urea (200 mmol/l) was without effect, but the addition of 300 mmol/l mannitol (+300 mannitol) enhanced the rate significantly from 7.24±1.33 to 14.7±4.6 (n=6). Stimulation of NaCl secretion by a solution maximizing the cytosolic cAMP concentration (Stim) led to a significant increase in NH4 + uptake rate from 5.00±1.33 to 13.3±1.54 (n=6). Similar results were obtained in the additional presence of Ba2+ (1 mmol/l): the uptake rate was increased significantly from 4.23±0.34 to 15.1±1.86 (n=16). In the presence of Stim low Cl– had no additional effect on the uptake rate: 15.1±3.1 versus 15.2±2.8 in high Cl– (n=6). The uptake rate in Stim containing additional +300 mannitol (22.3±4.0, n=5) was not significantly different from that obtained with Stim or +300 mannitol alone. By whatever mechanism the NH4 + uptake rate was increased furosemide (500 µmol/l) always reduced this rate to control values. Hence three manoeuvres enhanced furosemide

  1. Renal PTA stenting

    International Nuclear Information System (INIS)

    Tsetis, D.

    2012-01-01

    Full text: Renal artery stenosis (RAS) is a common condition that may lead to hypertension, progressive renal dysfunction and cardiovascular morbidity. Catheter-based therapy for symptomatic, haemodynamically significant, RAS has become the preferred method of revascularization. Balloon angioplasty has been the traditional treatment of choice for fibromuscular dysplasia, however stents are increasingly used for the treatment of atheromatous lesions; in many cases-such as in ostial lesions-, direct stenting is strongly indicated. Despite the increased use of endovascular therapy for renal artery stenosis, there is still controversy regarding the optimal management and the net benefit of this treatment. Several randomized trials of balloon angioplasty or stenting for renal artery stenosis compared with medical therapy alone have been conducted, however these could not show definite advantage of endovascular therapy. Problems encountered with those trials include enrollment of small number of patients, frequent crossover from medical to interventional therapy compromising the intention-to-treat results, or selection of patients that are not expected to show clear benefit. The Angioplasty and Stenting for Renal Artery Lesions (ASTRAL) is the most important of these trials; however, it,s study design was faulty and therefore did not provide conclusive evidence to answer the question of whether angioplasty and stenting or medical therapy is the best treatment for haemodynamically significant RAS. All expectations are now focused on the Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) trial which was designed to answer the same question, and its methodologies took into consideration the weaknesses of the ASTRAL trial. Regarding stent device itself, it seems that the optimal design is probably a stainless steel, laser cut, open-cells stent mounted on a rapid exchange delivery balloon catheter compatible with 0.014-in and 0.018-in guidewire. As a future

  2. Evidence for the involvement of Ala 166 in coupling Na(+) to sugar transport through the human Na(+)/glucose cotransporter

    DEFF Research Database (Denmark)

    Meinild, A K; Loo, D D; Hirayama, B A

    2001-01-01

    . The affinity for Na(+) was unchanged compared to that of hSGLT1, whereas the sugar affinity was reduced and sugar specificity was altered. There was a reduction in the turnover rate of the transporter, and in contrast to that of hSGLT1, the turnover rate depended on the sugar molecule. Exposure of A166C......We mutated residue 166, located in the putative Na(+) transport pathway between transmembrane segments 4 and 5 of human Na(+)/glucose cotransporter (hSGLT1), from alanine to cysteine (A166C). A166C was expressed in Xenopus laevis oocytes, and electrophysiological methods were used to assay function...... to MTSEA and MTSET, but not MTSES, abolished sugar transport. Accessibility of A166C to alkylating reagents was independent of protein conformation, indicating that the residue is always accessible from the extracellular surface. Sugar and phlorizin did not protect the residue from being alkylated...

  3. Cotransport of Herbaspirillum chlorophenolicum FA1 and heavy metals in saturated porous media: column studies and modeling approaches

    Science.gov (United States)

    Li, X.; Xu, H.; Wu, J.

    2017-12-01

    For in situ biodegradation of organic contaminants in soil and groundwater, precise prediction and monitoring of the movement of the bio-agent is vital for the effectiveness of the subsurface bioremediation technologies. Therefore, the fate and transport of functional microorganisms in porous media has been extensively investigated in the literature, and the effects of a number of physical and chemical factors have been explored. During the bioremediation of contaminated sites, it is highly likely that functional bacteria and heavy metals would be simultaneously present for heavy metals often co-exist with organic contaminants like polycyclic aromatic hydrocarbons (PAHs) in polluted environment. To date, relevant studies on the interactions between heavy metals and functional agents such as PAHs-degrading bacteria are lacking and thus require investigation. In this study, the cotransport of bioremediation agents and heavy metals were evaluated through batch and column experiments. Herbaspirillum chlorophenolicum FA1, a pure bacterial strain capable of absorbing heavy metals and degrading polycyclic aromatic hydrocarbons (PAHs), was used as the model remediation agent, and metal ions of Pb(Ⅱ) and Cd(Ⅱ) were used as the representative heavy metals. Effects of metal species, the concentration of heavy metals, the sequence of entering the media, and the activity of biomass were investigated in detail. In addition, numerical simulations of breakthrough curves (BTC) data were also performed for information gathering. Results of this study could advance our understanding of interactions between functional bacteria and heavy metals during bioremediation process and help to develop successful bioremediation strategies.This work was financially supported by the National Natural Science Foundation of China -Xinjiang Project (U1503282), the National Natural Science Foundation of China (41030746, 41102148), and the Natural Science Foundation of Jiangsu Province (BK20151385

  4. Cotransport of clay colloids and viruses through water-saturated vertically oriented columns packed with glass beads: Gravity effects.

    Science.gov (United States)

    Syngouna, Vasiliki I; Chrysikopoulos, Constantinos V

    2016-03-01

    The cotransport of clay colloids and viruses in vertically oriented laboratory columns packed with glass beads was investigated. Bacteriophages MS2 and ΦX174 were used as model viruses, and kaolinite (ΚGa-1b) and montmorillonite (STx-1b) as model clay colloids. A steady flow rate of Q=1.5 mL/min was applied in both vertical up (VU) and vertical down (VD) flow directions. In the presence of KGa-1b, estimated mass recovery values for both viruses were higher for VD than VU flow direction, while in the presence of STx-1b the opposite was observed. However, for all cases examined, the produced mass of viruses attached onto suspended clay particles were higher for VD than VU flow direction, suggesting that the flow direction significantly influences virus attachment onto clays, as well as packed column retention of viruses attached onto suspended clays. KGa-1b hindered the transport of ΦX174 under VD flow, while STx-1b facilitated the transport of ΦX174 under both VU and VD flow directions. Moreover, KGa-1b and STx-1b facilitated the transport of MS2 in most of the cases examined except of the case where KGa-1b was present under VD flow. Also, the experimental data were used for the estimation of virus surface-coverages and virus surface concentrations generated by virus diffusion-limited attachment, as well as virus attachment due to sedimentation. Both sedimentation and diffusion limited virus attachment were higher for VD than VU flow, except the case of MS2 and STx-1b cotransport. The diffusion-limited attachment was higher for MS2 than ΦΧ174 for all cases examined. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Distal renal tubular acidosis in recurrent renal stone formers

    DEFF Research Database (Denmark)

    Osther, P J; Hansen, A B; Røhl, H F

    1989-01-01

    Renal acidification ability was examined in 90 recurrent renal stone formers, using fasting morning urinary pH levels followed by a short ammonium chloride loading test in subjects with pH levels above 6.0. Fifteen patients (16.6%) revealed a distal renal tubular acidification defect: one patient......, this has important therapeutic implications. The pathological sequence in renal stone formers with dRTA is discussed....

  6. Effects of reducing blood pressure on renal outcomes in patients with type 2 diabetes: Focus on SGLT2 inhibitors and EMPA-REG OUTCOME.

    Science.gov (United States)

    Scheen, A J; Delanaye, P

    2017-04-01

    Empagliflozin, a sodium-glucose cotransporter type 2 (SGLT2) inhibitor, has enabled remarkable reductions in cardiovascular and all-cause mortality as well as in renal outcomes in patients with type 2 diabetes (T2D) and a history of cardiovascular disease in the EMPA-REG OUTCOME. These results have been attributed to haemodynamic rather than metabolic effects, in part due to the osmotic/diuretic action of empagliflozin and the reduction in arterial blood pressure (BP). The present narrative review includes the results of meta-analyses of trials evaluating the effects on renal outcomes of lowering BP in patients with T2D, with a special focus on the influence of baseline and achieved systolic BP, and compares the renal outcome results of the EMPA-REG OUTCOME with those of other major trials with inhibitors of the renin-angiotensin system in patients with T2D and the preliminary findings with other SGLT2 inhibitors, and also evaluates post hoc analyses from the EMPA-REG OUTCOME of special interest as regards the BP-lowering hypothesis and renal function. While systemic BP reduction associated to empagliflozin therapy may have contributed to the renal benefits reported in EMPA-REG OUTCOME, other local mechanisms related to kidney homoeostasis most probably also played a role in the overall protection observed in the trial. Copyright © 2017. Published by Elsevier Masson SAS.

  7. Renal sympathetic denervation: MDCT evaluation of the renal arteries.

    LENUS (Irish Health Repository)

    Hutchinson, Barry D

    2013-08-01

    Percutaneous transluminal renal sympathetic denervation is a new treatment of refractory systemic hypertension. The purpose of this study was to assess the clinical utility of MDCT to evaluate the anatomic configuration of the renal arteries in the context of renal sympathetic denervation.

  8. Imaging chronic renal disease and renal transplant in children

    International Nuclear Information System (INIS)

    Carmichael, Jim; Easty, Marina

    2010-01-01

    At Great Ormond Street Hospital we have the highest number of paediatric renal transplant patients in Europe, taking cases from across the United Kingdom and abroad. Our caseload includes many children with rare complicating medical problems and chronic renal failure related morbidity. This review aims to provide an overview of our experience of imaging children with chronic renal failure and transplants. (orig.)

  9. Eligibility for renal denervation

    DEFF Research Database (Denmark)

    Persu, Alexandre; Jin, Yu; Baelen, Marie

    2014-01-01

    -resistant hypertension (ENCOReD). The analysis included 731 patients. Age averaged 61.6 years, office blood pressure at screening was 177/96 mm Hg, and the number of blood pressure-lowering drugs taken was 4.1. Specialists referred 75.6% of patients. The proportion of patients eligible for renal denervation according...... undetected secondary causes of hypertension (11.1%). In conclusion, after careful screening and treatment adjustment at hypertension expert centers, only ≈40% of patients referred for renal denervation, mostly by specialists, were eligible for the procedure. The most frequent cause of ineligibility...... (approximately half of cases) was blood pressure normalization after treatment adjustment by a hypertension specialist. Our findings highlight that hypertension centers with a record in clinical experience and research should remain the gatekeepers before renal denervation is considered....

  10. [Renal colic in pregnancy].

    Science.gov (United States)

    Negru, Irina; Pricop, C; Costăchescu, Gh

    2010-01-01

    Renal colic in pregnant women is a serious condition, mainly when is associated with fever. Our retro-prospective study analyzes 111 cases managed conservatively or with endourological procedures for renal colic--insertion of JJ stents and percutaneous nephrostomy. Clinical evolution determined the insertion of JJ stents in 60 cases and the failure of this procedure imposed percutaneous nephrostomy in 5 cases. In 56 cases urinary tract infection was associated and in 2 cases, despite all efforts, the patients deceased due to sever sepsis. The immediate drainage of the upper urinary tract for renal colic in pregnancy is the recommended treatment, especially when the pain is associated with fever. JJ stens were well tolerated, even when they were replaced after 3 months. Pregnant women with a history of UTI or stone disease should be carefully followed-up.

  11. Renal cell karcinoma trial

    International Nuclear Information System (INIS)

    Werf-Messing, B. van der; Heul, R.O. van der; Ledeboer, R.C.

    1981-01-01

    A total of 174 patients underwent simple nephrectomy in case of clinically operable kidney cancer without demonstrable metastases. Of these 85 received preoperative irradiation to the kidney and the regional lymph nodes (3000-4000 rad in 3-4 weeks). Prognosis was not influenced by preoperative irradiation. The preoperatively assessable prognostic criteria were sex and sedimentation rate: ESR >= 30 and being male worsened prognosis. The clinical T-categories of the UICC were not related to prognosis. Of the microscopic examination of the nephrectomy specimen, renal vein invasion and to a lesser extent a low degree of differentiation appeared to worsen prognosis. The prognostic influence of the P-categories was caused by a higher incidence of renal vein involvement in case of higher P-category. The most important prognostic factors - ESR, renal vein involvement, and sex - were not interrelated. Elective chemotherapy, radiation therapy, and hormone therapy could be considered in certain high-risk groups. (orig.)

  12. Scintigraphy of renal transplant

    International Nuclear Information System (INIS)

    Ramackers, J.M.; Marrast, A.C.; Touraine, J.L.; Peyrin, J.O.

    1995-01-01

    Scintigraphy is useful for monitoring perfusion and function of renal transplant, as well as for diagnosing miscellaneous surgical. This non-invasive imaging technique, which uses no deleterious products, is an attractive alternative for patients. This is especially true for those patients in early post-transplant course, with immunity depression and often impairment of renal function. Otherwise, multiple indices with a large range of inter-patient values has not favoured a methodological and interpretative consensus. Furthermore, the poor specificity of renogram patterns does not allow for discrimination of all etiologies with only one scintigraphy. Nevertheless, follow-up with iterative scintigraphy may be helpful due to the high intra-patient reproducibility and to the early appreciate change of parameters, according to clinical and histological renal post-transplant outcome. (authors). 43 refs., 8 figs

  13. Drug-induced renal injury

    African Journals Online (AJOL)

    The kidney receives a rich blood flow of 25% of resting cardiac output ... Drugs can cause acute renal failure by causing pre-renal, intrinsic or .... tubular epithelial cells causing cell swelling ... the dose as required or prescribe alternative drugs.

  14. Leiomyosarcoma of the renal pelvis

    Directory of Open Access Journals (Sweden)

    Dhamne Sagar

    2009-10-01

    Full Text Available Leiomyosarcomas are rare malignant tumors of the kidney. They may arise from the renal capsule, renal vein, renal pelvic musculature or renal parenchyma. Renal pelvis is an uncommon site of occurrence, with around 10 cases reported in the literature so far. Here we present a 60-year-old male who presented with increased urinary frequency, lower limb weakness, anorexia and weight loss. Imaging showed a right renal mass. A renal cell carcinoma was suspected clinically. A right nephrectomy was performed, which showed a large circumscribed mass in the hilar region. Histology revealed a tumor mass arising from the renal pelvis. The tumor was composed of spindle cells arranged in fascicles. Immunohistochemistry showed tumor cells to be positive for smooth muscle actin (SMA and desmin (Des and negative for cytokeratin (CK, HMB 45, CD117 (C-kit, and CD34. That confirmed the diagnosis of leiomyosarcoma.

  15. Renal denervation and hypertension.

    Science.gov (United States)

    Schlaich, Markus P; Krum, Henry; Sobotka, Paul A; Esler, Murray D

    2011-06-01

    Essential hypertension remains one of the biggest challenges in medicine with an enormous impact on both individual and society levels. With the exception of relatively rare monogenetic forms of hypertension, there is now general agreement that the condition is multifactorial in nature and hence requires therapeutic approaches targeting several aspects of the underlying pathophysiology. Accordingly, all major guidelines promote a combination of lifestyle interventions and combination pharmacotherapy to reach target blood pressure (BP) levels in order to reduce overall cardiovascular risk in affected patients. Although this approach works for many, it fails in a considerable number of patients for various reasons including drug-intolerance, noncompliance, physician inertia, and others, leaving them at unacceptably high cardiovascular risk. The quest for additional therapeutic approaches to safely and effectively manage hypertension continues and expands to the reappraisal of older concepts such as renal denervation. Based on the robust preclinical and clinical data surrounding the role of renal sympathetic nerves in various aspects of BP control very recent efforts have led to the development of a novel catheter-based approach using radiofrequency (RF) energy to selectively target and disrupt the renal nerves. The available evidence from the limited number of uncontrolled hypertensive patients in whom renal denervation has been performed are auspicious and indicate that the procedure has a favorable safety profile and is associated with a substantial and presumably sustained BP reduction. Although promising, a myriad of questions are far from being conclusively answered and require our concerted research efforts to explore the full potential and possible risks of this approach. Here we briefly review the science surrounding renal denervation, summarize the current data on safety and efficacy of renal nerve ablation, and discuss some of the open questions that need

  16. Imaging of Renal Leiomyomas

    Energy Technology Data Exchange (ETDEWEB)

    Derchi, L. E.; Grenier, N.; Heinz-Peer, G.; Dogra, V.; Franco, F.; Rollandi, G. A.; Deminiere, C. (Radiologia - DICMI, Univ. di Genova, Genova (Italy))

    2008-09-15

    Background: Renal leiomyomas are rare benign tumors of the kidney which can be found at autopsy as small capsular nodules in about 5% of cases. The clinical incidence of such lesions is much smaller, and only case reports or small series have been reported in the imaging literature. Purpose: To describe the imaging characteristics observed in a series of eight patients with pathology-proven asymptomatic leiomyomas of the kidney. Material and Methods: We reviewed the imaging findings observed in eight patients with pathologically proven asymptomatic renal leiomyomas discovered during studies performed for reasons unrelated to the kidney. All patients had undergone computed tomography (CT), two ultrasonography, and one magnetic resonance imaging (MRI). Results: Lesions ranged in size from 1.2 to 13 cm. Six were at the periphery of the kidney, compressed its outer surface, but did not cause disruption of the cortex; two involved the renal cortex. All had regular outer margins. A cleavage plane between the tumor and the kidney was revealed at CT and/or ultrasonography in three of the cases located at the periphery. At ultrasonography, leiomyomas appeared hypoechogenic. At CT, they were slightly hyperdense before contrast medium injection; all were hypodense to the renal cortex after contrast medium. Four were homogeneous, two were slightly heterogeneous, and the remaining two were frankly heterogeneous. The lesion studied by MRI, which was homogeneous at the postcontrast CT study, had a heterogeneous structure on both T1- and T2-weighted images, with internal areas of hypointensity on T1. Conclusion: There are some imaging findings that can help to suggest the diagnosis of renal leiomyomas. First, their density: all tumors examined before contrast were hyperdense to the kidney, with density similar to that of muscles, and all had lower enhancement than the adjacent renal parenchyma. Second, the location and margins of the tumors: most were peripheral, without

  17. Renal lithiasis and nutrition

    Directory of Open Access Journals (Sweden)

    Prieto Rafel M

    2006-09-01

    Full Text Available Abstract Renal lithiasis is a multifactorial disease. An important number of etiologic factors can be adequately modified trough diet, since it must be considered that the urine composition is directly related to diet. In fact, the change of inappropriate habitual diet patterns should be the main measure to prevent kidney stones. In this paper, the relation between different dietary factors (liquid intake, pH, calcium, phosphate, oxalate, citrate, phytate, urate and vitamins and each type of renal stone (calcium oxalate monohydrate papillary, calcium oxalate monohydrate unattached, calcium oxalate dihydrate, calcium oxalate dihydrate/hydroxyapatite, hydroxyapatite, struvite infectious, brushite, uric acid, calcium oxalate/uric acid and cystine is discussed.

  18. Management of chronic renal failure.

    NARCIS (Netherlands)

    de Zeeuw, D.; Apperloo, AJ; de Jong, P.

    1992-01-01

    There is growing evidence that treatment of patients with renal function impairment will undergo a major shift within the next few years. Along with more or less successful attempts to alleviate the signs and symptoms of reduced renal function, new insights into renal pathophysiology as well as new

  19. Screening renal stone formers for distal renal tubular acidosis

    DEFF Research Database (Denmark)

    Osther, P J; Hansen, A B; Røhl, H F

    1989-01-01

    A group of 110 consecutive renal stone formers were screened for distal renal tubular acidosis (RTA) using morning fasting urinary pH (mfUpH) levels followed by a short ammonium chloride loading test in patients with levels above 6.0. In 14 patients (12.7%) a renal acidification defect was noted...... RTA in renal stone formers. Regardless of whether the acidification defect is primary or secondary to stone formation, however, all renal stone formers with distal RTA can expect to benefit from prophylactic alkaline therapy and it is recommended that the screening procedure, which is easy to use...

  20. Dapagliflozin Aggravates Renal Injury via Promoting Gluconeogenesis in db/db Mice.

    Science.gov (United States)

    Jia, Yingli; He, Jinzhao; Wang, Liang; Su, Limin; Lei, Lei; Huang, Wei; Geng, Xiaoqiang; Zhang, Shun; Meng, Xiaolu; Zhou, Hong; Yang, Baoxue

    2018-01-01

    A sodium-glucose co-transporter-2 inhibitor dapagliflozin is widely used for lowering blood glucose and its usage is limited in type 2 diabetes mellitus patients with moderate renal impairment. As its effect on kidney function is discrepant and complicated, the aim of this study is to determine the effect of dapagliflozin on the progression of diabetic nephropathy and related mechanisms. Twelve-week-old male C57BL/6 wild-type and db/db mice were treated with vehicle or 1 mg/kg dapagliflozin for 12 weeks. Body weight, blood glucose, insulin tolerance, glucose tolerance, pyruvate tolerance and 24-hour urine were measured every 4 weeks. At 24 weeks of age, renal function was evaluated by blood urea nitrogen level, creatinine clearance, urine output, urinary albumin excretion, Periodic Acid-Schiff staining, Masson's trichrome staining and electron microscopy. Changes in insulin signaling and gluconeogenic key regulatory enzymes were detected using Western blot analysis. Dapagliflozin did not alleviate but instead aggravated diabetic nephropathy manifesting as increased levels of microalbuminuria, blood urea nitrogen, and glomerular and tubular damage in db/db mice. Despite adequate glycemic control by dapagliflozin, urinary glucose excretion increased after administration before 24 weeks of age and was likely associated with renal impairment. Increased urinary glucose excretion was mainly derived from the disturbance of glucose homeostasis with elevated hepatic and renal gluconeogenesis induced by dapagliflozin. Although it had no effect on insulin sensitivity and glucose tolerance, dapagliflozin further induced the expression of gluconeogenic key rate-limiting enzymes through increasing the expression levels of FoxO1 in the kidney and liver. These experimental results indicate that dapagliflozin aggravates diabetes mellitus-induced kidney injury, mostly through increasing gluconeogenesis. © 2018 The Author(s). Published by S. Karger AG, Basel.

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

    Science.gov (United States)

    Alexander, R Todd; Dimke, Henrik

    2017-06-01

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

  2. Mobilization and removing of cadmium from kidney by GMDTC utilizing renal glucose reabsorption pathway

    International Nuclear Information System (INIS)

    Tang, Xiaojiang; Zhu, Jinqiu; Zhong, Zhiyong; Luo, Minhui; Li, Guangxian; Gong, Zhihong; Zhang, Chenzi; Fei, Fan; Ruan, Xiaolin; Zhou, Jinlin; Liu, Gaofeng; Li, Guoding; Olson, James; Ren, Xuefeng

    2016-01-01

    Chronic exposure to cadmium compounds (Cd 2+ ) is one of the major public health problems facing humans in the 21st century. Cd 2+ in the human body accumulates primarily in the kidneys which leads to renal dysfunction and other adverse health effects. Efforts to find a safe and effective drug for removing Cd 2+ from the kidneys have largely failed. We developed and synthesized a new chemical, sodium (S)-2-(dithiocarboxylato((2S,3R,4R,5R)-2,3,4,5,6 pentahydroxyhexyl)amino)-4-(methylthio) butanoate (GMDTC). Here we report that GMDTC has a very low toxicity with an acute lethal dose (LD50) of more than 10,000 mg/kg or 5000 mg/kg body weight, respectively, via oral or intraperitoneal injection in mice and rats. In in vivo settings, up to 94% of Cd 2+ deposited in the kidneys of Cd 2+ -laden rabbits was removed and excreted via urine following a safe dose of GMDTC treatment for four weeks, and renal Cd 2+ level was reduced from 12.9 μg/g to 1.3 μg/g kidney weight. We observed similar results in the mouse and rat studies. Further, we demonstrated both in in vitro and in animal studies that the mechanism of transporting GMDTC and GMDTC-Cd complex into and out of renal tubular cells is likely assisted by two glucose transporters, sodium glucose cotransporter 2 (SGLT2) and glucose transporter 2 (GLUT2). Collectively, our study reports that GMDTC is safe and highly efficient in removing deposited Cd 2+ from kidneys assisted by renal glucose reabsorption system, suggesting that GMDTC may be the long-pursued agent used for preventive and therapeutic purposes for both acute and chronic Cd 2+ exposure.

  3. Mobilization and removing of cadmium from kidney by GMDTC utilizing renal glucose reabsorption pathway

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Xiaojiang, E-mail: river-t@126.com [Guangdong Medical Laboratory Animal Center (China); Zhu, Jinqiu [Department of Epidemiology and Environmental Health, The State University of New York, Buffalo, NY (United States); Zhong, Zhiyong; Luo, Minhui; Li, Guangxian [Guangdong Medical Laboratory Animal Center (China); Gong, Zhihong [Department of Epidemiology and Environmental Health, The State University of New York, Buffalo, NY (United States); Zhang, Chenzi; Fei, Fan [Guangdong Medical Laboratory Animal Center (China); Ruan, Xiaolin [Guangdong Poison Control Center (China); Zhou, Jinlin [Golden Health (Foshan) Technology Co., Ltd (China); Liu, Gaofeng [School of Chemistry and Chemical Engineering, Sun Yat-Sen University (China); Li, Guoding [Guangdong Medical Laboratory Animal Center (China); Olson, James [Department of Epidemiology and Environmental Health, The State University of New York, Buffalo, NY (United States); Department of Pharmacology and Toxicology, The State University of New York, Buffalo, NY (United States); Ren, Xuefeng, E-mail: xuefengr@buffalo.edu [Guangdong Medical Laboratory Animal Center (China); Department of Epidemiology and Environmental Health, The State University of New York, Buffalo, NY (United States); Department of Pharmacology and Toxicology, The State University of New York, Buffalo, NY (United States)

    2016-08-15

    Chronic exposure to cadmium compounds (Cd{sup 2+}) is one of the major public health problems facing humans in the 21st century. Cd{sup 2+} in the human body accumulates primarily in the kidneys which leads to renal dysfunction and other adverse health effects. Efforts to find a safe and effective drug for removing Cd{sup 2+} from the kidneys have largely failed. We developed and synthesized a new chemical, sodium (S)-2-(dithiocarboxylato((2S,3R,4R,5R)-2,3,4,5,6 pentahydroxyhexyl)amino)-4-(methylthio) butanoate (GMDTC). Here we report that GMDTC has a very low toxicity with an acute lethal dose (LD50) of more than 10,000 mg/kg or 5000 mg/kg body weight, respectively, via oral or intraperitoneal injection in mice and rats. In in vivo settings, up to 94% of Cd{sup 2+} deposited in the kidneys of Cd{sup 2+}-laden rabbits was removed and excreted via urine following a safe dose of GMDTC treatment for four weeks, and renal Cd{sup 2+} level was reduced from 12.9 μg/g to 1.3 μg/g kidney weight. We observed similar results in the mouse and rat studies. Further, we demonstrated both in in vitro and in animal studies that the mechanism of transporting GMDTC and GMDTC-Cd complex into and out of renal tubular cells is likely assisted by two glucose transporters, sodium glucose cotransporter 2 (SGLT2) and glucose transporter 2 (GLUT2). Collectively, our study reports that GMDTC is safe and highly efficient in removing deposited Cd{sup 2+} from kidneys assisted by renal glucose reabsorption system, suggesting that GMDTC may be the long-pursued agent used for preventive and therapeutic purposes for both acute and chronic Cd{sup 2+} exposure.

  4. Angiography for renal hypertension

    International Nuclear Information System (INIS)

    Chuang, V.P.; Ernst, C.B.

    1985-01-01

    As angioplasty and operative techniques have become more precise and successful, so have evaluation techniques. Preoperative arteriography is indispensible for deciding on the appropriate treatment modality and the specifics of the procedure. Arteriography, therefore, remains the cornerstone in managing renovascular hypertension and renal arterial disease

  5. Dopamins renale virkninger

    DEFF Research Database (Denmark)

    Olsen, Niels Vidiendal

    1990-01-01

    is frequently employed in cases of acute oliguric renal failure but the results available concerning the therapeutic effect are frequently retrospective and uncontrolled. The results suggest that early treatment with 1-3 micrograms/kg/min dopamine combined with furosemide can postpone or possibly render...

  6. Primary renal graft thrombosis

    NARCIS (Netherlands)

    Bakir, N; Sluiter, WJ; Ploeg, RJ; van Son, WJ; Tegzess, Adam

    Background. Renal allograft thrombosis is a serious complication of kidney transplantation that ultimately leads to graft loss. Its association with acute and hyperacute rejection is well documented; however, in a large proportion of patients the precise cause remains obscure. The exact incidence

  7. Expression of Na+/HCO3- co-transporter proteins (NBCs) in rat and human skeletal muscle

    DEFF Research Database (Denmark)

    Kristensen, Jonas Møller; Kristensen, Michael; Juel, Carsten

    2004-01-01

    AIM: Sodium/bicarbonate co-transport (NBC) has been suggested to have a role in muscle pH regulation. We investigated the presence of NBC proteins in rat and human muscle samples and the fibre type distribution of the identified NBCs. METHODS AND RESULTS: Western blotting of muscle homogenates...... the T-tubules. The two NBCs localized in muscle have distinct fibre type distributions. CONCLUSIONS: Skeletal muscle possesses two variants of the sodium/bicarbonate co-transporter (NBC) isoforms, which have been called NBCe1 and NBCe2....... and sarcolemmal membranes (sarcolemmal giant vesicles) were used to screen for the presence of NBCs. Immunohistochemistry was used for the subcellular localization. The functional test revealed that approximately half of the pH recovery in sarcolemmal vesicles produced from rat muscle is mediated by bicarbonate...

  8. Increased renal alpha-epithelial sodium channel (ENAC) protein and increased ENAC activity in normal pregnancy.

    Science.gov (United States)

    West, Crystal; Zhang, Zheng; Ecker, Geoffrey; Masilamani, Shyama M E

    2010-11-01

    Pregnancy-mediated sodium (Na) retention is required to provide an increase in plasma volume for the growing fetus. The mechanisms responsible for this Na retention are not clear. We first used a targeted proteomics approach and found that there were no changes in the protein abundance compared with virgin rats of the β or γ ENaC, type 3 Na(+)/H(+) exchanger (NHE3), bumetanide-sensitive cotransporter (NKCC2), or NaCl cotransporter (NCC) in mid- or late pregnancy. In contrast, we observed marked increases in the abundance of the α-ENaC subunit. The plasma volume increased progressively during pregnancy with the greatest plasma volume being evident in late pregnancy. ENaC inhibition abolished the difference in plasma volume status between virgin and pregnant rats. To determine the in vivo activity of ENaC, we conducted in vivo studies of rats in late pregnancy (days 18-20) and virgin rats to measure the natriuretic response to ENaC blockade (with benzamil). The in vivo activity of ENaC (U(Na)V postbenzamil-U(Na)V postvehicle) was markedly increased in late pregnancy, and this difference was abolished by pretreatment with the mineralocorticoid receptor antagonist, eplerenone. These findings demonstrate that the increased α-ENaC subunit of pregnancy is associated with an mineralocorticoid-dependent increase in ENaC activity. Further, we show that ENaC activity is a major contributor of plasma volume status in late pregnancy. These changes are likely to contribute to the renal sodium retention and plasma volume expansion required for an optimal pregnancy.

  9. Vasoconstriction triggered by hydrogen sulfide: Evidence for Na+,K+,2Cl-cotransport and L-type Ca2+ channel-mediated pathway.

    Science.gov (United States)

    Orlov, Sergei N; Gusakova, Svetlana V; Smaglii, Liudmila V; Koltsova, Svetlana V; Sidorenko, Svetalana V

    2017-12-01

    This study examined the dose-dependent actions of hydrogen sulfide donor sodium hydrosulphide (NaHS) on isometric contractions and ion transport in rat aorta smooth muscle cells (SMC). Isometric contraction was measured in ring aortas segments from male Wistar rats. Activity of Na + /K + -pump and Na + ,K + ,2Cl - cotransport was measured in cultured endothelial and smooth muscle cells from the rat aorta as ouabain-sensitive and ouabain-resistant, bumetanide-sensitive components of the 86 Rb influx, respectively. NaHS exhibited the bimodal action on contractions triggered by modest depolarization ([K + ] o =30 mM). At 10 -4 M, NaHS augmented contractions of intact and endothelium-denuded strips by ~ 15% and 25%, respectively, whereas at concentration of 10 -3  M it decreased contractile responses by more than two-fold. Contractions evoked by 10 -4  M NaHS were completely abolished by bumetanide, a potent inhibitor of Na + ,K + ,2Cl - cotransport, whereas the inhibition seen at 10 -3  M NaHS was suppressed in the presence of K + channel blocker TEA. In cultured SMC, 5×10 -5  M NaHS increased Na + ,K + ,2Cl - - cotransport without any effect on the activity of this carrier in endothelial cells. In depolarized SMC, 45 Ca influx was enhanced in the presence of 10 -4  M NaHS and suppressed under elevation of [NaHS] up to 10 -3  M. 45 Ca influx triggered by 10 -4  M NaHS was abolished by bumetanide and L-type Ca 2+ channel blocker nicardipine. Our results strongly suggest that contractions of rat aortic rings triggered by low doses of NaHS are mediated by activation of Na + ,K + ,2Cl - cotransport and Ca 2+ influx via L-type channels.

  10. SGLT2 Inhibitors: Glucotoxicity and Tumorigenesis Downstream the Renal Proximal Tubule?

    Science.gov (United States)

    Bertinat, Romina; Nualart, Francisco; Yáñez, Alejandro J

    2016-08-01

    At present, diabetes mellitus is the main cause of end-stage renal disease. Effective glycaemic management is the most powerful tool to delay the establishment of diabetic complications, such as diabetic kidney disease. Together with reducing blood glucose levels, new anti-diabetic agents are expected not only to control the progression but also to restore known defects of the diabetic kidney. Sodium-glucose co-transporter 2 (SGLT2) inhibitors are promising anti-diabetic agents that reduce hyperglycaemia by impairing glucose reabsorption in proximal tubule of the kidney and increasing glucosuria. SGLT2 inhibitors have shown to reduce glucotoxicity in isolated proximal tubule cells and also to attenuate expression of markers of overall kidney damage in experimental animal models of diabetes, but the actual renoprotective effect for downstream nephron segments is still unknown and deserves further attention. Here, we briefly discuss possible undesired effects of enhanced glucosuria and albuminuria in nephron segments beyond the proximal tubule after SGLT2 inhibitor treatment, offering new lines of research to further understand the renoprotective action of these anti-diabetic agents. Strategies blocking glucose reabsorption by renal proximal tubule epithelial cells (RPTEC) may be protective for RPTEC, but downstream nephron segments will still be exposed to high glucose and albumin levels through the luminal face. The actual effect of constant enhanced glucosuria over distal nephron segments remains to be established. J. Cell. Physiol. 231: 1635-1637, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  11. Acute renal dysfunction in liver diseases

    OpenAIRE

    Betrosian, Alex P; Agarwal, Banwari; Douzinas, Emmanuel E

    2007-01-01

    Renal dysfunction is common in liver diseases, either as part of multiorgan involvement in acute illness or secondary to advanced liver disease. The presence of renal impairment in both groups is a poor prognostic indicator. Renal failure is often multifactorial and can present as pre-renal or intrinsic renal dysfunction. Obstructive or post renal dysfunction only rarely complicates liver disease. Hepatorenal syndrome (HRS) is a unique form of renal failure associated with advanced liver dise...

  12. Chronic renal failure due to unilateral renal agenesis and total renal dysplasia (=aplasia)

    International Nuclear Information System (INIS)

    Kroepelin, T.; Ziupa, J.; Wimmer, B.

    1983-01-01

    Three adult patients with unilateral renal agenesis/total dysplasia (= aplasia) and with an early chronic renal failure are presented. One patient had renal agenesis without ureter bud and ureteric ostium on one side, and reflux pyelonephritis on the other; one had small compact total renal dysplasia (= aplasia) on one side, while chronic uric acid nephropathy (chronic renal disease as a cause of gout) was diagnosed on the other; the third patient had a total large multicystic dysplasia on one side, and on the other a segmental large multicystic dysplasia. Radiological steps and radiodiagnostic criteria are discussed and the combination of urogenital and extraurogenital anomalies is referred to. (orig.)

  13. Compensatory role of the NBCn1 sodium/bicarbonate cotransporter on Ca2+-induced mitochondrial swelling in hypertrophic hearts.

    Science.gov (United States)

    Vargas, Lorena A; Velasquez, Fernanda Carrizo; Alvarez, Bernardo V

    2017-03-01

    NBC Na + /HCO 3 - cotransporter (NBCn1) and NHE1 Na + /H + exchanger have been associated with cardiac disorders and recently located in coronary endothelial cells (CEC) and cardiomyocytes mitochondria, respectively. Mitochondrial NHE1 blockade delays permeability transition pore (MPTP) opening and reduces superoxide levels, two critical events exacerbated in cells of diseased hearts. Conversely, activation of NBCn1 prevented apoptosis in CEC subjected to ischemic stress. We characterized the role of the NHE1 and NBCn1 transporters in heart mitochondria from hypertrophic (SHR) and control (Wistar) rats. Expression of NHE1 was analyzed in left ventricular mitochondrial lysates (LVML), by immunoblots. NHE1 expression increased by ~40% in SHR compared to control (P < 0.05, n = 4). To examine NHE1-mediated Na + /H + exchange activity in cardiac hypertrophy, mitochondria were loaded with BCECF-AM dye and the maximal rate of pHm change measured after the addition of 50 mM NaCl. SHR mitochondria had greater changes in pHm compared to Wistar, 0.10 ± 0.01 vs. 0.06 ± 0.01, respectively (P < 0.05, n = 5). In addition, mitochondrial suspensions from SHR and control myocardium were exposed to 200 μM CaCl 2 to induce MPTP opening (light-scattering decrease, LSD) and swelling. Surprisingly, SHR rats showed smaller LSD and a reduction in mitochondrial swelling, 67 ± 10% (n = 15), compared to control, 100 ± 8% (n = 13). NBC inhibition with S0859 (1 μM) significantly increased swelling in both control 139 ± 10% (n = 8) and SHR 115 ± 10% (n = 4). Finally, NBCn1 Na + /HCO 3 - cotransporter increased by twofold its expression in SHR LVML, compared to normal (P < 0.05, n = 5). We conclude that increased NBCn1 activity may play a compensatory role in hypertrophic hearts, protecting mitochondria from Ca 2+ -induced MPTP opening and swelling.

  14. CT findings of renal abscess

    International Nuclear Information System (INIS)

    Lee, Myung Jun; Kim, Mi Young; Woo, Jung Ju; Kim, Ho Kyun; Kim, Won Hong; Jeon, Jeong Dong; Jeon, Woo Ki; Han, Chang Yul

    1996-01-01

    The purpose of this study is to determine characteristic CT findings in renal abscess. Twenty cases of renal abscess were retrospectively analyzed for CT findings relating to the shape and extent of the abscess, change of nephrogram, peripheral rim enhancement, wedge-shaped enhancement on delayed scans, enlargement of the kidney involved and associated findings. Seven patients had a renal abscess at the right kidney, nine at the lift kidney and two bilaterally. The abscesses were round in 18 cases and finger-like in two. Rim enhancement around renal abscess was seen in four cases (20%). Changes in the nephrogram around the abscess were seen in 12 cases (60%). In all six patients who had undergone delayed postcontrast scans, wedge-shaped enhancement was shown around the abscess (100%). In the observation of the extent of renal abscesses, 14 cases were within the kidney, six cases extended the beyond renal capsule, and two were loculated in the renal fascia itself. Renal enlargement was seen in nine cases (45%). These results suggest that CT findings such as delayed wedge-shaped enhancement, change of nephrogram, peripheral rim enhancement, renal enlargement, and associated findings are valuable for diagnosis, and that CT also gives information concerning the extent, evolution and complication of a renal abscess

  15. Bilateral renal calculi

    Science.gov (United States)

    Sreenevasan, G

    1974-01-01

    Bilateral renal calculi were present in 114 (10.7%) of 1,070 cases of proved urinary calculus admitted to the Urological Department of the General Hospital, Kuala Lumpur, during the period November 1968—May 1973. The management of bilateral renal calculi is discussed with reference to the first 100 cases in this series. The introduction of renography has greatly facilitated the decision as to which kidney should be operated on first. The management of patients with and without uraemia is discussed and the use of the modified V and V—Y incisions for the removal of staghorn calculi is described. Complications and results are briefly reviewed. ImagesFig. 1Fig. 4Fig. 6Fig. 7 PMID:4845653

  16. Renal protection in diabetes

    DEFF Research Database (Denmark)

    Parving, H H; Tarnow, L; Rossing, P

    1996-01-01

    BACKGROUND: The combination of diabetes and hypertension increases the chances of progressive renal disorder and, ultimately, renal failure. Roughly 40% of all diabetics, whether insulin-dependent or not, develop diabetic nephropathy. Diabetic nephropathy is the single most important cause of end...... function in diabetic patients with incipient diabetic nephropathy. There are still no long-term trials using the new long-acting dihydropyridine calcium antagonists to treat patients with incipient nephropathy. A recent, 1-year, randomized, double-blind study in hypertensive insulin-dependent diabetic...... identical in both treatment groups, at 103 (SD 9) and 101 (SD 11) mmHg, respectively. Furthermore, a recent 5-year randomized open study in hypertensive non-insulin-dependent patients with diabetic nephropathy has revealed the same beneficial effect of a calcium antagonist and of ACE inhibition...

  17. Renal computed angiography. Part I: Renal CT arteriography in hypertension

    International Nuclear Information System (INIS)

    Al-Amin, M.; Hadjidekov, V.

    2012-01-01

    Visualization of renal vasculature is needed in several clinical condition among which hypertension is dominant. CT angiography now day replaces catheter angiography as non-invasive method. The goal of this study is to present initial authors experience in visualization of renal arteries using 64 MDCT and to evaluated the utility in hypertensive patients. MDCT assures excellent assessment of renal arteries conditions. Multiplanar reconstruction and allow better delineation in tortuous vessels course and anatomic variants. (authors)

  18. Renal phosphate handling: Physiology

    Directory of Open Access Journals (Sweden)

    Narayan Prasad

    2013-01-01

    Full Text Available Phosphorus is a common anion. It plays an important role in energy generation. Renal phosphate handling is regulated by three organs parathyroid, kidney and bone through feedback loops. These counter regulatory loops also regulate intestinal absorption and thus maintain serum phosphorus concentration in physiologic range. The parathyroid hormone, vitamin D, Fibrogenic growth factor 23 (FGF23 and klotho coreceptor are the key regulators of phosphorus balance in body.

  19. Quality of methodological reporting of randomized clinical trials of sodium-glucose cotransporter-2 (sglt2 inhibitors

    Directory of Open Access Journals (Sweden)

    Hadeel Alfahmi

    2017-01-01

    Full Text Available Sodium-glucose cotransporter-2 (SGLT2 inhibitors are a new class of medicines approved recently for the treatment of type 2 diabetes. To improve the quality of randomized clinical trial (RCT reports, the Consolidated Standards of Reporting Trials (CONSORT statement for methodological features was created. For achieving our objective in this study, we assessed the quality of methodological reporting of RCTs of SGLT2 inhibitors according to the 2010 CONSORT statement. We reviewed and analyzed the methodology of SGLT2 inhibitors RCTs that were approved by the Food & Drug Administration (FDA. Of the 27 trials, participants, eligibility criteria, and additional analyses were reported in 100% of the trials. In addition, trial design, interventions, and statistical methods were reported in 96.3% of the trials. Outcomes were reported in 93.6% of the trials. Settings were reported in 85.2% of the trials. Blinding and sample size were reported in 66.7 and 59.3% of the trials, respectively. Sequence allocation and the type of randomization were reported in 63 and 74.1% of the trials, respectively. Besides those, a few methodological items were inadequate in the trials. Allocation concealment was inadequate in most of the trials. It was reported only in 11.1% of the trials. The majority of RCTs have high percentage adherence for more than half of the methodological items of the 2010 CONSORT statement.

  20. Characterization and comparison of sodium-glucose cotransporter 2 inhibitors: Part 2. Antidiabetic effects in type 2 diabetic mice

    Directory of Open Access Journals (Sweden)

    Atsuo Tahara

    2016-07-01

    Full Text Available Previously we investigated the pharmacokinetic, pharmacodynamic, and pharmacologic properties of all six sodium-glucose cotransporter (SGLT 2 inhibitors commercially available in Japan using normal and diabetic mice. We classified the SGLT2 inhibitors with respect to duration of action as either long-acting (ipragliflozin and dapagliflozin or intermediate-acting (tofogliflozin, canagliflozin, empagliflozin, and luseogliflozin. In the present study, antidiabetic effects of repeated administration of these SGLT2 inhibitors in type 2 diabetic mice were investigated. When repeatedly administered for 4 weeks, all SGLT2 inhibitors significantly exhibited antihyperglycemic, antihyperinsulinemic, and pancreas-protective effects, as well as insulin resistance-improving effects. When compared at doses producing comparable reduction in hyperglycemia across all drugs, the antidiabetic effects of ipragliflozin and dapagliflozin were more potent than those of the other four drugs, but these differences among the six drugs were not statistically significant. Further, an oral glucose tolerance test performed after repeated administration demonstrated significant improvement in glucose tolerance only with ipragliflozin and dapagliflozin, implying improved insulin resistance and secretion. Taken together, these findings demonstrate that, although all SGLT2 inhibitors exert antidiabetic effects in type 2 diabetic mice, these pharmacologic effects might be slightly superior with the long-acting drugs, which are able to provide favorable blood glucose control throughout the day.

  1. Benefits and Harms of Sodium-Glucose Co-Transporter 2 Inhibitors in Patients with Type 2 Diabetes

    DEFF Research Database (Denmark)

    Storgaard, Heidi; Gluud, Lise L; Bennett, Cathy

    2016-01-01

    OBJECTIVE: Sodium-glucose co-transporter 2 inhibitors (SGLT2-i) are a novel drug class for the treatment of diabetes. We aimed at describing the maximal benefits and risks associated with SGLT2-i for patients with type 2 diabetes. DESIGN: Systematic review and meta-analysis. DATA SOURCES AND STUDY......, ketoacidosis and CVD. Secondary outcomes were fasting plasma glucose, body weight, blood pressure, heart rate, lipids, liver function tests, creatinine and adverse events including infections. The quality of the evidence was assessed using GRADE. RESULTS: Meta-analysis of 34 RCTs with 9,154 patients showed...... to low quality evidence). Analysis of 12 RCTs found a beneficial effect of SGLT2-i on HbA1c compared with OAD (-0.20%, -0.28 to -0.13%; moderate quality evidence). CONCLUSION: This review includes a large number of patients with type 2 diabetes and found that SGLT2-i reduces HbA1c with a notable...

  2. Sodium-glucose co-transporter (SGLT) and glucose transporter (GLUT) expression in the kidney of type 2 diabetic subjects.

    Science.gov (United States)

    Norton, Luke; Shannon, Christopher E; Fourcaudot, Marcel; Hu, Cheng; Wang, Niansong; Ren, Wei; Song, Jun; Abdul-Ghani, Muhammad; DeFronzo, Ralph A; Ren, Jimmy; Jia, Weiping

    2017-09-01

    The sodium-glucose co-transporters (SGLTs) are responsible for the tubular reabsorption of filtered glucose from the kidney into the bloodstream. The inhibition of SGLT2-mediated glucose reabsorption is a novel and highly effective strategy to alleviate hyperglycaemia in patients with type 2 diabetes mellitus (T2DM). However, the effectiveness of SGLT2 inhibitor therapy is diminished due, in part, to a compensatory increase in the maximum reabsorptive capacity (Tm) for glucose in patients with T2DM. We hypothesized that this increase in Tm could be explained by an increase in the tubular expression of SGLT and glucose transporters (GLUT) in these patients. To examine this, we obtained human kidney biopsy specimens from patients with or without T2DM and examined the mRNA expression of SGLTs and GLUTs. The expression of SGLT1 is markedly increased in the kidney of patients with T2DM, and SGLT1 mRNA is highly and significantly correlated with fasting and postprandial plasma glucose and HbA1c. In contrast, our data demonstrate that the levels of SGLT2 and GLUT2 mRNA are downregulated in diabetic patients, but not to a statistically significant level. These important findings are clinically significant and may have implications for the treatment of T2DM using strategies that target SGLT transporters in the kidney. © 2017 John Wiley & Sons Ltd.

  3. Transport activity of the sodium bicarbonate cotransporter NBCe1 is enhanced by different isoforms of carbonic anhydrase.

    Directory of Open Access Journals (Sweden)

    Christina Schueler

    Full Text Available Transport metabolons have been discussed between carbonic anhydrase II (CAII and several membrane transporters. We have now studied different CA isoforms, expressed in Xenopus oocytes alone and together with the electrogenic sodium bicarbonate cotransporter 1 (NBCe1, to determine their catalytic activity and their ability to enhance NBCe1 transport activity. pH measurements in intact oocytes indicated similar activity of CAI, CAII and CAIII, while in vitro CAIII had no measurable activity and CAI only 30% of the activity of CAII. All three CA isoforms increased transport activity of NBCe1, as measured by the transport current and the rate of intracellular sodium rise in oocytes. Two CAII mutants, altered in their intramolecular proton pathway, CAII-H64A and CAII-Y7F, showed significant catalytic activity and also enhanced NBCe1 transport activity. The effect of CAI, CAII, and CAII mutants on NBCe1 activity could be reversed by blocking CA activity with ethoxyzolamide (EZA, 10 µM, while the effect of the less EZA-sensitive CAIII was not reversed. Our results indicate that different CA isoforms and mutants, even if they show little enzymatic activity in vitro, may display significant catalytic activity in intact cells, and that the ability of CA to enhance NBCe1 transport appears to depend primarily on its catalytic activity.

  4. Nitric oxide signaling pathway regulates potassium chloride cotransporter-1 mRNA expression in vascular smooth muscle cells.

    Science.gov (United States)

    Di Fulvio, M; Lauf, P K; Adragna, N C

    2001-11-30

    Rat vascular smooth muscle cells (VSMCs) express at least two mRNAs for K-Cl cotransporters (KCC): KCC1 and KCC3. cGMP-dependent protein kinase I regulates KCC3 mRNA expression in these cells. Here, we show evidence implicating the nitric oxide (NO)/cGMP signaling pathway in the expression of KCC1 mRNA, considered to be the major cell volume regulator. VSMCs, expressing soluble guanylyl cyclase (sGC) and PKG-I isoforms showed a time- and concentration-dependent increase in KCC1 mRNA levels after treatment with sodium nitroprusside as demonstrated by semiquantitative RT-PCR. sGC-dependent regulation of KCC1 mRNA expression was confirmed using YC-1, a NO-independent sGC stimulator. The sGC inhibitor LY83583 blocked the effects of sodium nitroprusside and YC-1. Moreover, 8-Br-cGMP increased KCC1 mRNA expression in a concentration- and time-dependent fashion. The 8-Br-cGMP effect was partially blocked by KT5823 but not by actinomycin D. However, actinomycin D and cycloheximide increased basal KCC1 mRNA in an additive manner, suggesting different mechanisms of action for both drugs. These findings suggest that in VSMCs, the NO/cGMP-signaling pathway participates in KCC1 mRNA regulation at the post-transcriptional level.

  5. Efficacy of ultrasonography-guided renal biopsy for the evaluation of renal dysfunction following renal transplantation

    International Nuclear Information System (INIS)

    Kim, Young Jae; Choi, Chul Soon; Min, Seon Jeong; Lee, Gyung Kyu; Lee, Eil Seong; Kang, Ik Won; Bae, Sang Hoon

    2003-01-01

    To evaluate the usefulness and complications of renal biopsy under ultrasonography-guidance in renal dysfunction after renal transplantation. Ultrasonography-guided renal biopsy was done in 47 patients with the transplanted kidney. The subjects consisted of 30 males and 17 females, age ranged from 16 to 66 years (average age=38 years). Biopsies were done once in 27 patients, twice in 17 patients, three times in 3 patients, a total of 70 biopsies. The success rate of renal biopsy for the accurate pathologic diagnosis and the incidence and types of complications following biopsy were evaluated. The success rate of renal biopsy for the accurate pathologic diagnosis was 96%(67/70). Pathologic diagnosis included 27 cases of acute rejection (39%), 8 cases of acute tubular necrosis (11%), 4 cases of acute rejection and acute tubular necrosis (6%), 4 cases of cyclosporin toxicity (6%), 4 cases of primary disease recurrence (6%), 4 cases of infection (6%) and others. Complications after renal biopsy included 15 cases of microscopic hematuria (21%), 1 case of gross hematuria with spontaneous cessation and 1 case of life threatening hemorrhage. Ultrasonography-guided renal biopsy is a safe and effective diagnostic method for the evaluation of renal dysfunction following renal transplantation.

  6. Renal angiomyoadenomatous tumour: Imaging features

    Science.gov (United States)

    Sahni, V. Anik; Hirsch, Michelle S.; Silverman, Stuart G.

    2012-01-01

    Renal angiomyoadenomatous tumour is a rare, recently described neoplasm with a distinctive histological appearance. Although reported in the pathology literature, to our knowledge, no prior reports have described its imaging appearance. We describe the computed tomography and magnetic resonance imaging features of an incidentally detected renal angiomyoadenomatous tumour that appeared as a well-marginated, solid T2-hypointense enhancing mass, in a 50-year-old woman. It is indistinguishable from a variety of benign and malignant renal neoplasms. PMID:23093565

  7. Multiple oncocytomas and renal carcinoma

    International Nuclear Information System (INIS)

    Velasquez, G.; Glass, T.A.; D'Souza, V.J.; Formanek, A.G.

    1984-01-01

    Renal oncocytoma, although rare, is being diagnosed more frequently, and criteria to differentiate it from other tumors have been described. Multiple oncocytomas have been reported, but an association between multiple oncocytomas and renal carcinoma in the same kidney has not been described. The authors report a case with two oncocytomas and a renal carcinoma in the right kidney as well as a right adrenal adenoma

  8. CT features of renal infarction

    International Nuclear Information System (INIS)

    Suzer, Okan; Shirkhoda, Ali; Jafri, S. Zafar; Madrazo, Beatrice L.; Bis, Kostaki G.; Mastromatteo, James F.

    2002-01-01

    Purpose: To demonstrate the different patterns of renal infarction to avoid pitfalls. To present 'flip-flop enhancement' pattern in renal infarction. Materials and methods: Retrospective review of a total of 41 renal infarction in 37 patients were done. These patients underwent initial CT and the diagnosis of renal infarction was confirmed with either follow up CT or at surgery. Results: Twenty-three patients had wedge-shaped focal infarcts, nine patients had global and five patients had multifocal infarcts of the kidneys. Cortical rim sign was seen predominantly with global infarcts. In five patients, a 'flip-flop enhancement' pattern was observed. In two patients, planned renal biopsies due to tumefactive renal lesions were cancelled because of 'flip-flop enhancement' pattern on follow up CTs. Conclusion: Although most of our cases were straightforward for the diagnosis of renal infarction, cases with tumefactive lesions and global infarctions without the well-known cortical rim sign were particularly challenging. We describe a new sign, flip-flop enhancement pattern, which we believe solidified the diagnosis of renal infarction in five of our cases. The authors recommend further investigations for association of flip-flop enhancement and renal infarction

  9. Sporotrichosis in Renal Transplant Patients

    Directory of Open Access Journals (Sweden)

    Paulo Gewehr

    2013-01-01

    Full Text Available The current report describes two renal transplant recipients who presented with sporotrichosis. In addition, the authors review the general aspects of sporotrichosis in renal transplant recipients reported in the literature. Sporotrichosis is a rare fungal infection in transplant patients and has been reported primarily in renal transplant recipients not treated with antifungal prophylaxis. Extracutaneous forms of sporotrichosis without skin manifestations and no previous history of traumatic injuries have been described in such patients and are difficult to diagnose. Renal transplant recipients with sporotrichosis described in the present report were successfully treated with antifungal therapy including amphotericin B deoxycholate, lipid amphotericin B formulations, fluconazole and itraconazole.

  10. Renal myxoma: a case report

    Directory of Open Access Journals (Sweden)

    Carlos Henrique C Souza

    2015-04-01

    Full Text Available Myxomas are rare tumors that can appear in many anatomical locations. There are only 14 cases of renal involvement documented in the literature. This article reports a case of renal myxoma in an elderly woman with recurrent cystitis. After five years of follow-up, the computed tomography (CT revealed a large solid tumor mass in the left kidney. Tumor resection was performed preserving the affected kidney with histopathological diagnosis of renal myxoma. The objective of this study is to report a rare case of renal myxoma, emphasizing the importance of the differential diagnosis from other benign and malignant mesenchymal tumors.

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

    International Nuclear Information System (INIS)

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

    2012-01-01

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

  12. General Information about Renal Cell Cancer

    Science.gov (United States)

    ... Tumors Treatment Genetics of Kidney Cancer Research Renal Cell Cancer Treatment (PDQ®)–Patient Version General Information About Renal Cell Cancer Go to Health Professional Version Key Points Renal ...

  13. Treatment Option Overview (Renal Cell Cancer)

    Science.gov (United States)

    ... Tumors Treatment Genetics of Kidney Cancer Research Renal Cell Cancer Treatment (PDQ®)–Patient Version General Information About Renal Cell Cancer Go to Health Professional Version Key Points Renal ...

  14. Inhibition of renal glucose reabsorption as a novel treatment for diabetes patients

    Directory of Open Access Journals (Sweden)

    Eugenio Cersosimo

    2014-03-01

    Full Text Available The importance of the kidney in glucose homeostasis has been recognized for many years. Recent observations indicating a greater role of renal glucose metabolism in various physiologic and pathologic conditions have rekindled the interest in renal glucose handling as a potential target for the treatment of diabetes. The enormous capacity of the proximal tubular cells to reabsorb the filtered glucose load entirely, utilizing the sodium-glucose co-transporter system (primarily SGLT-2, became the focus of attention. Original studies conducted in experimental animals with the nonspecific SGLT inhibitor phlorizin showed that hyperglycemia after pancreatectomy decreased as a result of forced glycosuria. Subsequently, several compounds with more selective SGLT-2 inhibition properties (“second-generation” were developed. Some agents made it into pre-clinical and clinical trials and a few have already been approved for commercial use in the treatment of type 2 diabetes. In general, a 6-month period of therapy with SGLT-2 inhibitors is followed by a mean urinary glucose excretion rate of ~80 g/day accompanied by a decline in fasting and postprandial glucose with average decreases in HgA1C ~1.0%. Concomitant body weight loss and a mild but consistent drop in blood pressure also have been reported. In contrast, transient polyuria, thirst with dehydration and occasional hypotension have been described early in the treatment. In addition, a significant increase in the occurrence of uro-genital infections, particularly in women has been documented with the use of SGLT-2 inhibitors. Conclusion: Although long-term cardiovascular, renal and bone/mineral effects are unknown SGLT-2 inhibitors, if used with caution and in the proper patient provide a unique insulin-independent therapeutic option in the management of obese type 2 diabetes patients.

  15. The renal scan in pregnant renal transplant patients

    International Nuclear Information System (INIS)

    Goldstein, H.A.; Ziessman, H.A.; Fahey, F.H.; Collea, J.V.; Alijani, M.R.; Helfrich, G.B.

    1985-01-01

    With the greater frequency of renal transplant surgery, more female pts are becoming pregnant and carrying to term. In the renal allograft blood vessels and ureter may be compressed resulting in impaired renal function and/or, hypertension. Toxemia of pregnancy is seen more frequently than normal. Radionuclide renal scan monitoring may be of significant value in this high risk obstetrical pt. After being maintained during the pregnancy, renal function may also deteriorate in the post partum period. 5 pregnant renal transplant pts who delivered live babies had renal studies with Tc-99m DTPA to assess allograft perfusion and function. No transplanted kidney was lost during or after pregnancy as a result of pregnancy. No congenital anomalies were associated with transplant management. 7 studies were performed on these 5 pts. The 7 scans all showed the uterus/placenta. The bladder was always distorted. The transplanted kidney was rotated to a more vertical position in 3 pts. The radiation dose to the fetus is calculated at 0.024 rad/mCi administered. This study demonstrates the anatomic and physiologic alterations expected in the transplanted kidney during pregnancy when evaluated by renal scan and that the radiation burden may be acceptable in management of these pts

  16. Renal posttransplant's vascular complications

    Directory of Open Access Journals (Sweden)

    Bašić Dragoslav

    2003-01-01

    Full Text Available INTRODUCTION Despite high graft and recipient survival figures worldwide today, a variety of technical complications can threaten the transplant in the postoperative period. Vascular complications are commonly related to technical problems in establishing vascular continuity or to damage that occurs during donor nephrectomy or preservation [13]. AIM The aim of the presenting study is to evaluate counts and rates of vascular complications after renal transplantation and to compare the outcome by donor type. MATERIAL AND METHODS A total of 463 kidneys (319 from living related donor LD and 144 from cadaveric donor - CD were transplanted during the period between June 1975 and December 1998 at the Urology & Nephrology Institute of Clinical Centre of Serbia in Belgrade. Average recipients' age was 33.7 years (15-54 in LD group and 39.8 (19-62 in CD group. Retrospectively, we analyzed medical records of all recipients. Statistical analysis is estimated using Hi-squared test and Fischer's test of exact probability. RESULTS Major vascular complications including vascular anastomosis thrombosis, internal iliac artery stenosis, internal iliac artery rupture obliterant vasculitis and external iliac vein rupture were analyzed. In 25 recipients (5.4% some of major vascular complications were detected. Among these cases, 22 of them were from CD group vs. three from LD group. Relative rate of these complications was higher in CD group vs. LD group (p<0.0001. Among these complications dominant one was vascular anastomosis thrombosis which occurred in 18 recipients (17 from CD vs. one from LD. Of these recipients 16 from CD lost the graft, while the rest of two (one from each group had lethal outcome. DISCUSSION Thrombosis of renal allograft vascular anastomosis site is the most severe complication following renal transplantation. In the literature, renal allograft thrombosis is reported with different incidence rates, from 0.5-4% [14, 15, 16]. Data from the

  17. Citrato y litiasis renal

    Directory of Open Access Journals (Sweden)

    Elisa E. Del Valle

    2013-08-01

    Full Text Available El citrato es un potente inhibidor de la cristalización de sales de calcio. La hipocitraturia es una alteración bioquímica frecuente en la formación de cálculos de calcio en adultos y especialmente en niños. El pH ácido (sistémico, tubular e intracelular es el principal determinante de la excreción de citrato en la orina. Si bien la mayoría de los pacientes con litiasis renal presentan hipocitraturia idiopática, hay un número de causas para esta anormalidad que incluyen acidosis tubular renal distal, hipokalemia, dietas ricas en proteínas de origen animal y/o dietas bajas en álcalis y ciertas drogas, como la acetazolamida, topiramato, IECA y tiazidas. Las modificaciones dietéticas que benefician a estos pacientes incluyen: alta ingesta de líquidos y frutas, especialmente cítricos, restricción de sodio y proteínas, con consumo normal de calcio. El tratamiento con citrato de potasio es efectivo en pacientes con hipocitraturia primaria o secundaria y en aquellos desordenes en la acidificación, que provocan un pH urinario persistentemente ácido. Los efectos adversos son bajos y están referidos al tracto gastrointestinal. Si bien hay diferentes preparaciones de citrato (citrato de potasio, citrato de sodio, citrato de potasio-magnesio en nuestro país solo está disponible el citrato de potasio en polvo que es muy útil para corregir la hipocitraturia y el pH urinario bajo, y reducir marcadamente la recurrencia de la litiasis renal.

  18. Automatic quantitative renal scintigraphy

    International Nuclear Information System (INIS)

    Valeyre, J.; Deltour, G.; Delisle, M.J.; Bouchard, A.

    1976-01-01

    Renal scintigraphy data may be analyzed automatically by the use of a processing system coupled to an Anger camera (TRIDAC-MULTI 8 or CINE 200). The computing sequence is as follows: normalization of the images; background noise subtraction on both images; evaluation of mercury 197 uptake by the liver and spleen; calculation of the activity fractions on each kidney with respect to the injected dose, taking into account the kidney depth and the results referred to normal values; edition of the results. Automation minimizes the scattering parameters and by its simplification is a great asset in routine work [fr

  19. Imaging of renal metastases

    International Nuclear Information System (INIS)

    Bruneton, J.N.; Normand, F.; Balu-Maestro, C.; Rogopoulos, A.; Drouillard, J.; Laurent, F.

    1988-01-01

    Metastases are the most frequent malignant tumors of the kidney, but these lesions are of late onset in neoplastic disease. The 19 cases reported here were all investigated with various imaging techniques (CT 12 cases, ultrasonography 12 cases, urography 8 cases, angiography 2 cases, MRI 1 case). The most common primary malignancies were lung cancer, melanoma and cancer of the controlateral kidney. In this series, 8 of the lesions were solitary, and 9 were unilateral. Tumor vascularity was evaluated in 15 cases: 14 of these lesions were hypovascular. The differential diagnosis includes small cysts, lymphoma, bilateral renal cancer, multiple small abscesses and multiple small infarcts [fr

  20. Renal involvement in behcet's disease

    International Nuclear Information System (INIS)

    Ardalan, Mohammad Reza; Noshad, Hamid; Sadreddini, Shahram; Ebrahimi, Aliasghar; Molaeefard, Mahsheed; Somi, Mohammad Hossein; Shoja, Mohammadali Mohajel

    2009-01-01

    There are conflicting reports about the renal involvement in Behcet's disease (BD). In this study we aimed to study the frequency and type of renal involvement in a group of patients with BD in Azerbaijan province that is one of the prevalent areas of BD in Iran. All cases of BD were prospectively followed between June 2004 and January 2007, and evaluated for renal dys-function (serum creatinine > 1.7 mg/dL), glomerular hematuria and proteinuria. Those patients with proteinuria > 500 mg/day and serum creatinine level > 2 mg/dL, underwent renal biopsy. From a total number of 100 patients, six patients (6%) had obvious renal involvements. Four patients had glomerular hematuria and proteinuria. Renal biopsy in two of them revealed measangial proliferative glumerulonephritis with IgA deposit in one of them and membranoproliferative glumerolonephritis in another one. Two remaining patients had serum creatinine > 2 mg/dL without any hematuria or proteinuria. Serologic study for viral agents and collagen vascular disease were negative in all patients with renal involvements. In conclusion, renal involvement in BD is not infrequent, although in most cases it is mild in nature and may be missed. (author)

  1. Leiomyosarcoma of the renal vein

    Directory of Open Access Journals (Sweden)

    Lemos Gustavo C.

    2003-01-01

    Full Text Available Leiomyosarcoma of the renal vein is a rare tumor of complex diagnosis. We presented a case of renal vein leiomyosarcoma detected in a routine study. The primary treatment was complete surgical removal of the mass. In cases where surgical removal is not possible the prognosis is poor, with high rates of local recurrence and distant spread.

  2. Ultrasonography in chronic renal failure

    International Nuclear Information System (INIS)

    Buturovic-Ponikvar, Jadranka; Visnar-Perovic, Alenka

    2003-01-01

    Many chronic renal diseases lead to the final common state of decrease in renal size, parenchymal atrophy, sclerosis and fibrosis. The ultrasound image show a smaller kidney, thinning of the parenchyma and its hyperechogenicity (reflecting sclerosis and fibrosis). The frequency of renal cysts increases with the progression of the disease. Ultrasound generally does not allow for the exact diagnosis of an underlying chronic disease (renal biopsy is usually required), but it can help to determine an irreversible disease, assess prognosis and avoid unnecessary diagnostic or therapeutic procedures. The main exception in which the ultrasound image does not show a smaller kidney with parenchymal atrophy is diabetic nephropathy, the leading cause of chronic and end-stage renal failure in developed countries in recent years. In this case, both renal size and parenchymal thickness are preserved until end-stage renal failure. Doppler study of intrarenal vessels can provide additional information about microvascular and parenchymal lesions, which is helpful in deciding for or against therapeutic intervention and timely planning for optimal renal replacement therapy option

  3. Acute renal failure after rifampicin

    Directory of Open Access Journals (Sweden)

    Adriana Weinberg

    1984-12-01

    Full Text Available A patient with miliary tuberculosis and a chronic urogenital focus is described, who had a borderline renal function at diagnosis and developed overt renal failure upon daily treatment with rifampin (RMP, isoniazid (INH and ethambutol (EMB. This is the first Brazilian report of BMP induced renal damage. A renal biopsy taken on the third day of oliguria showed recent tubular necrosis with acute interstitial inflammation and granuloma formation. The aspect of the granulomatous lesion hightly suggested drug etiology because of the lack of palisading, high incidence of neutrophils and absence of facid-fast bacilli. This is the first presentation of an acute granulomatous interstitial nephritis probably due to RMP. Furthermore the pathogenesis of the renal damage caused by tuberculosis and RMP are discussed.

  4. Fetal programming of renal function.

    Science.gov (United States)

    Dötsch, Jörg; Plank, Christian; Amann, Kerstin

    2012-04-01

    Results from large epidemiological studies suggest a clear relation between low birth weight and adverse renal outcome evident as early as during childhood. Such adverse outcomes may include glomerular disease, hypertension, and renal failure and contribute to a phenomenon called fetal programming. Other factors potentially leading to an adverse renal outcome following fetal programming are maternal diabetes mellitus, smoking, salt overload, and use of glucocorticoids during pregnancy. However, clinical data on the latter are scarce. Here, we discuss potential underlying mechanisms of fetal programming, including reduced nephron number via diminished nephrogenesis and other renal (e.g., via the intrarenal renin-angiotensin-aldosterone system) and non-renal (e.g., changes in endothelial function) alterations. It appears likely that the outcomes of fetal programming may be influenced or modified postnatally, for example, by the amount of nutrients given at critical times.

  5. Renal manifestations of primary hyperparathyroidism

    Directory of Open Access Journals (Sweden)

    Anurag Ranjan Lila

    2012-01-01

    Full Text Available Primary hyperparathyroidism (PHPT is associated with nephrolithiasis and nephrocalcinosis. Hypercalciuria is one of the multiple factors that is implicated in the complex pathophysiology of stone formation. The presence of a renal stone (symptomatic or asymptomatic categorizes PHPT as symptomatic and is an indication for parathyroid adenomectomy. Progression of nephrocalcinosis is largely reversible after successful surgery, but the residual risk persists. PHPT is also associated with declining renal function. In case of asymptomatic mild PHPT, annual renal functional assessment is advised. Guidelines suggest that an estimated glomerular filtration rate (eGFR < 60 ml / minute / 1.73 m 2 is an indication for parathyroid adenomectomy. This article discusses how to monitor and manage renal stones and other related renal parameters in case of PHPT.

  6. Renal replacement therapy in Europe

    DEFF Research Database (Denmark)

    Pippias, Maria; Stel, Vianda S; Abad Diez, José Maria

    2015-01-01

    BACKGROUND: This article summarizes the 2012 European Renal Association-European Dialysis and Transplant Association Registry Annual Report (available at www.era-edta-reg.org) with a specific focus on older patients (defined as ≥65 years). METHODS: Data provided by 45 national or regional renal...... disease (ESRD) receiving renal replacement therapy (RRT) and renal transplantation rates for 2012 are presented. RESULTS: In 2012, the overall unadjusted incidence rate of patients with ESRD receiving RRT was 109.6 per million population (pmp) (n = 69 035), ranging from 219.9 pmp in Portugal to 24.2 pmp...... to 32% between countries. The overall renal transplantation rate in 2012 was 28.3 pmp (n = 15 673), with the highest rate seen in the Spanish region of Catalonia. The proportion of patients ≥65 years receiving a transplant ranged from 0 to 35%. Five-year adjusted survival for all RRT patients was 59...

  7. Magnification renal arteriography

    International Nuclear Information System (INIS)

    Carr, D.; Davidson, J.K.; McMillan, M.; Davison, M.

    1979-01-01

    Magnification selective renal arteriograms were performed on 24 patients, 12 of whom were hypertensive, and compared with non-magnification arteriograms by two observers independently. The magnification angiograms were performed on a Siemens Microfocus Bi 125/3/50 RG tube with a 0.1 mm focal spot. Of the 24 patients examined, information crucial to the diagnosis was found only on the magnification films in three patients (12.5%). Extra information compared with the non-magnification films was found in the magnification films in 12 patients (50%). No additional information was discovered in the remaining nine patients (37.5%). The magnification angiograms enabled the interlobular vessels to be visualised - this was not possible on the non-magnification films. Against the additional information gained must be weighed the disadvantages of magnification arteriography which include increased radiation dose and lengthening of procedure time plus additional injections of contrast. In conclusion, there is a place for magnification renal arteriography and the advantages seem to outweigh the disadvantages. (author)

  8. Renal complications of anaesthesia.

    Science.gov (United States)

    McKinlay, J; Tyson, E; Forni, L G

    2018-01-01

    Peri-operative acute kidney injury is common, accounting for 30-40% of all in-hospital cases of acute kidney injury. It is associated with clinically significant morbidity and mortality even with what was hitherto regarded as relatively trivial increases in serum creatinine, and carries over a 12-fold relative risk of death following major abdominal surgery. Comorbid conditions such as diabetes, hypertension, liver disease and particularly pre-existing chronic kidney disease, as well as the type and urgency of surgery, are major risk factors for the development of postoperative acute kidney injury. As yet, there are no specific treatment options for the injured kidney, although there are several modifiable risk factors of which the anaesthetist should be aware. As well as the avoidance of potential nephrotoxins and appropriate volume balance, optimal anaesthetic management should aim to reduce the risk of postoperative renal complications. This may include careful ventilatory management and blood pressure control, as well as appropriate analgesic strategies. The choice of anaesthetic agent may also influence renal outcomes. Rather than concentrate on the classical management of acute kidney injury, this review focuses on the potential development of acute kidney injury peri-operatively, and the means by which this may be ameliorated. © 2018 The Association of Anaesthetists of Great Britain and Ireland.

  9. Angiography in renal tuberculosis

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Doo Suk [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    1974-10-15

    Angiographies on forty cases of renal tuberculosis performed at the National Medical Center during a period 1960 through 1970 were reviewed. Abdominal angiography was performed via the femoral route. Some were followed by selective nephroangiography. All patients were subjected to urographyior to angiography. The results of X-ray findings in the forty cases with renal tuberculosis were follows. 1. The age varied 18 to 57 years, average 30.5 years. Twenty one patients were male, and nineteen were female. 2. The right kidney was involved in 17 cases and the left in 15 cases. Both kidneys were involved in 8 cases. 3. Urographic examination revealed pathologic changes in all patients. 4. Focal destruction in the collecting system was the most common finding in the urography of 16 patients. 5. A varying degree of hydronephrosis was present in 15 patients, of whom nine had complained of palpable mass due to hydronephrosis. 6. In the 7 patients with extensive destruction there was no observable excretion contrast medium from the diseased kidney. 7. Angiographic examination was normal in 6 of the 40 patients. 8. Decreased vascularity in the subsegmental or smaller arteries of the affected kidney was the most frequent finding, being found in 34 patients. 9. Occlusion or abrupt termination of the subsegmental arteries was present in 4 patients. 10. Eighteen of the patients had signs of an expansive process within the cavity, the vessels being displaced and stretched around the lesions.

  10. Safety of Sodium-Glucose Co-Transporter 2 Inhibitors during Ramadan Fasting: Evidence, Perceptions and Guidelines

    Directory of Open Access Journals (Sweden)

    Salem A. Beshyah

    2016-06-01

    Full Text Available Sodium-glucose co-transporter 2 (SGLT2 inhibitors are a new glucose-lowering therapy for T2DM with documented benefits on blood glucose, hypertension, weight reduction and long term cardiovascular benefit. They have an inherent osmotic diuretic effect and lead to some volume loss and possible dehydration. There is some concern about the safety of using SGLT2 inhibitors in Muslim type 2 diabetes mellitus (T2DM patients during the fast during Ramadan. Currently, there is a dearth of research data to help guide physicians and reassure patients.  One study confirmed good glycemic control with less risk of hypoglycemia and no marked volume depletion. Data in the elderly and in combination with diuretics are reassuring of their safe to use in Ramadan in general. SGLT2 inhibitor-related diabetic ketoacidosis has not been reported during Ramadan and is unlikely to be relevant. Survey of physicians revealed that the majority felt that SGLT2 inhibitors are generally safe in T2DM patients during Ramadan fasting but should be discontinued in certain high risk patients. Some professional groups with interest in diabetes and Ramadan fasting included SGLT2 inhibitors in their guidelines on management of diabetes during Ramadan. They acknowledged the lack of trial data, recommended caution in high risk groups, advised regular monitoring and emphasized pre-Ramadan patients’ education. In conclusion, currently, knowledge, data and experience with SGLT2 inhibitors in Ramadan are limited. Nonetheless, stable patients with normal kidney function and low risk of dehydration may safely use the SGLT2 inhibitors therapy. Higher risk patients should be observed carefully and managed on individual basis.

  11. Sodium-glucose cotransporter-2 inhibitors and cardiovascular outcomes in type 2 diabetes mellitus: A systematic review

    Directory of Open Access Journals (Sweden)

    Ziad G Nasr

    2017-01-01

    Full Text Available Sodium-glucose cotransporter - 2 (SGLT2 inhibitors are a novel class of anti-diabetics proven to reduce blood pressure, blood glucose and body weight. However, the long-term cardiovascular (CV safety implications of these agents remain unclear. This systematic review aimed to evaluate the available clinical trial evidence pertaining to long-term cardiovascular safety of SGLT2 inhibitors. The databases EMBASE and MEDLINE were searched. Randomized controlled trials assessing CV safety of SGLT2 inhibitors compared with placebo or anti-diabetic medications were included. Two investigators independently extracted study data and completed risk of bias assessments (sequence generation, allocation concealment, blinding, incomplete outcome data, or selective outcome reporting and other biases. Outcomes included CV death, myocardial infarction, and stroke. A total of 464 studies were identified in the electronic search and 14 from other sources. Sixteen randomized clinical trials were included after full-text review. All studies reported at least one of the pre-defined outcomes (CV death, myocardial infarction, and stroke. Nineteen CV deaths were reported in SGLT2 inhibitors groups versus 10 CV deaths in placebo or other comparator arms; numerically higher in the dapagliflozin arms. The number of CV events was numerically higher in SGLT2 inhibitor groups than in other arms. Risk of bias assessment showed mixed results, with overall quality assessments deemed unclear for 6 of 16 studies (37.5%. Findings showed CV outcomes do occur in patients taking SGLT2 inhibitors yet the clinical significance remains unclear. These results can be considered hypothesis generating, as studies were limited by inadequate power and/or follow-up time. Future longitudinal studies are needed to further assess the efficacy and safety profiles of these new agents before they become widely adopted in clinical practice.

  12. Evidence for the role of a Na(+)/HCO(3)(-) cotransporter in trout hepatocyte pHi regulation.

    Science.gov (United States)

    Furimsky, M; Moon, T W; Perry, S F

    2000-07-01

    The mechanisms of intracellular pH (pHi) regulation were examined in hepatocytes of the rainbow trout Oncorhynchus mykiss. pHi was monitored using the pH-sensitive fluorescent dye BCECF, and the effects of various media and pharmacological agents were examined for their influence on baseline pHi and recovery rates from acid and base loading. Rates of Na(+) uptake were measured using (22)Na, and changes in membrane potential were examined using the potentiometric fluorescent dye Oxonol VI. The rate of proton extrusion following acid loading was diminished by the blockade of either Na(+)/H(+) exchange (using amiloride) or anion transport (using DIDS). The removal of external HCO(3)(-) and the abolition of outward K(+) diffusion by the channel blocker Ba(2+) also decreased the rate of proton extrusion following acid load. Depolarization of the cell membrane with 50 mmol l(-)(1) K(+), however, did not affect pHi. The rate of recovery from base loading was significantly diminished by the blockade of anion transport, removal of external HCO(3)(-) and, to a lesser extent, by blocking Na(+)/H(+) exchange. The blockade of K(+) conductance had no effect. The decrease in Na(+) uptake rate observed in the presence of the anion transport blocker DIDS and the DIDS-sensitive hyperpolarization of membrane potential during recovery from acid loading suggest that a Na(+)-dependent electrogenic transport system is involved in the restoration of pHi after intracellular acidification. The effects on baseline pHi indicate that the different membrane exchangers are tonically active in the maintenance of steady-state pHi. This study confirms the roles of a Na(+)/H(+) exchanger and a Cl(-)/HCO(3)(-) exchanger in the regulation of trout hepatocyte pHi and provides new evidence that a Na(+)/HCO(3)(-) cotransporter contributes to pHi regulation.

  13. Role of Sodium Bicarbonate Cotransporters in Intracellular pH Regulation and Their Regulatory Mechanisms in Human Submandibular Glands.

    Science.gov (United States)

    Namkoong, Eun; Shin, Yong-Hwan; Bae, Jun-Seok; Choi, Seulki; Kim, Minkyoung; Kim, Nahyun; Hwang, Sung-Min; Park, Kyungpyo

    2015-01-01

    Sodium bicarbonate cotransporters (NBCs) are involved in the pH regulation of salivary glands. However, the roles and regulatory mechanisms among different NBC isotypes have not been rigorously evaluated. We investigated the roles of two different types of NBCs, electroneutral (NBCn1) and electrogenic NBC (NBCe1), with respect to pH regulation and regulatory mechanisms using human submandibular glands (hSMGs) and HSG cells. Intracellular pH (pHi) was measured and the pHi recovery rate from cell acidification induced by an NH4Cl pulse was recorded. Subcellular localization and protein phosphorylation were determined using immunohistochemistry and co-immunoprecipitation techniques. We determined that NBCn1 is expressed on the basolateral side of acinar cells and the apical side of duct cells, while NBCe1 is exclusively expressed on the apical membrane of duct cells. The pHi recovery rate in hSMG acinar cells, which only express NBCn1, was not affected by pre-incubation with 5 μM PP2, an Src tyrosine kinase inhibitor. However, in HSG cells, which express both NBCe1 and NBCn1, the pHi recovery rate was inhibited by PP2. The apparent difference in regulatory mechanisms for NBCn1 and NBCe1 was evaluated by artificial overexpression of NBCn1 or NBCe1 in HSG cells, which revealed that the pHi recovery rate was only inhibited by PP2 in cells overexpressing NBCe1. Furthermore, only NBCe1 was significantly phosphorylated and translocated by NH4Cl, which was inhibited by PP2. Our results suggest that both NBCn1 and NBCe1 play a role in pHi regulation in hSMG acinar cells, and also that Src kinase does not regulate the activity of NBCn1.

  14. K-Cl Cotransporter 2-mediated Cl- Extrusion Determines Developmental Stage-dependent Impact of Propofol Anesthesia on Dendritic Spines.

    Science.gov (United States)

    Puskarjov, Martin; Fiumelli, Hubert; Briner, Adrian; Bodogan, Timea; Demeter, Kornel; Lacoh, Claudia-Marvine; Mavrovic, Martina; Blaesse, Peter; Kaila, Kai; Vutskits, Laszlo

    2017-05-01

    General anesthetics potentiating γ-aminobutyric acid (GABA)-mediated signaling are known to induce a persistent decrement in excitatory synapse number in the cerebral cortex when applied during early postnatal development, while an opposite action is produced at later stages. Here, the authors test the hypothesis that the effect of general anesthetics on synaptogenesis depends upon the efficacy of GABA receptor type A (GABAA)-mediated inhibition controlled by the developmental up-regulation of the potassium-chloride (K-Cl) cotransporter 2 (KCC2). In utero electroporation of KCC2 was used to prematurely increase the efficacy of (GABAA)-mediated inhibition in layer 2/3 pyramidal neurons in the immature rat somatosensory cortex. Parallel experiments with expression of the inward-rectifier potassium channel Kir2.1 were done to reduce intrinsic neuronal excitability. The effects of these genetic manipulations (n = 3 to 4 animals per experimental group) were evaluated using iontophoretic injection of Lucifer Yellow (n = 8 to 12 cells per animal). The total number of spines analyzed per group ranged between 907 and 3,371. The authors found a robust effect of the developmental up-regulation of KCC2-mediated Cl transport on the age-dependent action of propofol on dendritic spines. Premature expression of KCC2, unlike expression of a transport-inactive KCC2 variant, prevented a propofol-induced decrease in spine density. In line with a reduction in neuronal excitability, the above result was qualitatively replicated by overexpression of Kir2.1. The KCC2-dependent developmental increase in the efficacy of GABAA-mediated inhibition is a major determinant of the age-dependent actions of propofol on dendritic spinogenesis.

  15. Age- and sex-dependent susceptibility to phenobarbital-resistant neonatal seizures: role of chloride co-transporters.

    Science.gov (United States)

    Kang, Seok Kyu; Markowitz, Geoffrey J; Kim, Shin Tae; Johnston, Michael V; Kadam, Shilpa D

    2015-01-01

    Ischemia in the immature brain is an important cause of neonatal seizures. Temporal evolution of acquired neonatal seizures and their response to anticonvulsants are of great interest, given the unreliability of the clinical correlates and poor efficacy of first-line anti-seizure drugs. The expression and function of the electroneutral chloride co-transporters KCC2 and NKCC1 influence the anti-seizure efficacy of GABAA-agonists. To investigate ischemia-induced seizure susceptibility and efficacy of the GABAA-agonist phenobarbital (PB), with NKCC1 antagonist bumetanide (BTN) as an adjunct treatment, we utilized permanent unilateral carotid-ligation to produce acute ischemic-seizures in post-natal day 7, 10, and 12 CD1 mice. Immediate post-ligation video-electroencephalograms (EEGs) quantitatively evaluated baseline and post-treatment seizure burdens. Brains were examined for stroke-injury and western blot analyses to evaluate the expression of KCC2 and NKCC1. Severity of acute ischemic seizures post-ligation was highest at P7. PB was an efficacious anti-seizure agent at P10 and P12, but not at P7. BTN failed as an adjunct, at all ages tested and significantly blunted PB-efficacy at P10. Significant acute post-ischemic downregulation of KCC2 was detected at all ages. At P7, males displayed higher age-dependent seizure susceptibility, associated with a significant developmental lag in their KCC2 expression. This study established a novel neonatal mouse model of PB-resistant seizures that demonstrates age/sex-dependent susceptibility. The age-dependent profile of KCC2 expression and its post-insult downregulation may underlie the PB-resistance reported in this model. Blocking NKCC1 with low-dose BTN following PB treatment failed to improve PB-efficacy.

  16. Role of an extracellular loop in determining the stoichiometry of Na+–HCO3− cotransporters

    Science.gov (United States)

    Chen, Li-Ming; Liu, Ying; Boron, Walter F

    2011-01-01

    The Na+–HCO3− cotransporters (NBCs) of the solute carrier 4 family (SLC4) are critical for regulating pH in cells as well as in fluids such as blood and cerebrospinal fluid. Moreover, mutations and gene disruptions in NBC are linked to a wide range of pathologies. NBCe1 (SLC4A4) is electrogenic because it has an apparent Na+:HCO3− stoichiometry of 1:2 or 1:3, whereas NBCn1 (SLC4A7) is electroneutral because it has an apparent stoichiometry of 1:1. Because stoichiometry influences the effect of transport on membrane potential and vice versa, a central question is what structural features underlie electrogenicity versus electroneutrality. A previous study on rat NBCe1/n1 chimeras demonstrated that the structural elements determining the electrogenicity of NBCe1-A are located within the transmembrane domain, excluding the large third extracellular loop. In the present study we generated a series of chimeras of human NBCe1-A and human NBCn1-A. We found that replacing merely the predicted fourth extracellular loop (EL4) – containing 32 amino acid residues that include 7 prolines – of human NBCe1-A with EL4 of NBCn1-A creates an electroneutral NBC. The opposite switch converts an electroneutral construct to one with electrogenic properties. The introduction of an N-glycosylation site into EL4 confirms that at least a part of it is exposed to the extracellular fluid. We hypothesize that putative EL4 either contributes to the substrate-binding vestibule or indirectly influences substrate binding by interacting with one or more transmembrane segments, thereby controlling the nature of transport. PMID:21224233

  17. Role of Sodium Bicarbonate Cotransporters in Intracellular pH Regulation and Their Regulatory Mechanisms in Human Submandibular Glands.

    Directory of Open Access Journals (Sweden)

    Eun Namkoong

    Full Text Available Sodium bicarbonate cotransporters (NBCs are involved in the pH regulation of salivary glands. However, the roles and regulatory mechanisms among different NBC isotypes have not been rigorously evaluated. We investigated the roles of two different types of NBCs, electroneutral (NBCn1 and electrogenic NBC (NBCe1, with respect to pH regulation and regulatory mechanisms using human submandibular glands (hSMGs and HSG cells. Intracellular pH (pHi was measured and the pHi recovery rate from cell acidification induced by an NH4Cl pulse was recorded. Subcellular localization and protein phosphorylation were determined using immunohistochemistry and co-immunoprecipitation techniques. We determined that NBCn1 is expressed on the basolateral side of acinar cells and the apical side of duct cells, while NBCe1 is exclusively expressed on the apical membrane of duct cells. The pHi recovery rate in hSMG acinar cells, which only express NBCn1, was not affected by pre-incubation with 5 μM PP2, an Src tyrosine kinase inhibitor. However, in HSG cells, which express both NBCe1 and NBCn1, the pHi recovery rate was inhibited by PP2. The apparent difference in regulatory mechanisms for NBCn1 and NBCe1 was evaluated by artificial overexpression of NBCn1 or NBCe1 in HSG cells, which revealed that the pHi recovery rate was only inhibited by PP2 in cells overexpressing NBCe1. Furthermore, only NBCe1 was significantly phosphorylated and translocated by NH4Cl, which was inhibited by PP2. Our results suggest that both NBCn1 and NBCe1 play a role in pHi regulation in hSMG acinar cells, and also that Src kinase does not regulate the activity of NBCn1.

  18. Increased NBCn1 expression, Na+/ HCO 3 ? co-transport and intracellular pH in human vascular smooth muscle cells with a risk allele for hypertension

    OpenAIRE

    Ng, Fu Liang; Boedtkjer, Ebbe; Witkowska, Kate; Ren, Meixia; Zhang, Ruoxin; Tucker, Arthur; Aalkj?r, Christian; Caulfield, Mark J.; Ye, Shu

    2017-01-01

    Abstract Genome-wide association studies have revealed an association between variation at the SLC4A7 locus and blood pressure. SLC4A7 encodes the electroneutral Na+/ HCO 3 ? co-transporter NBCn1 which regulates intracellular pH (pH i ). We conducted a functional study of variants at this locus in primary cultures of vascular smooth muscle and endothelial cells. In both cell types, we found genotype-dependent differences for rs13082711 in DNA-nuclear protein interactions, where the risk allel...

  19. Vhc1, a novel transporter belonging to the family of electroneutral cation–Cl− cotransporters, participates in the regulation of cation content and morphology of Saccharomyces cerevisiae vacuoles

    Czech Academy of Sciences Publication Activity Database

    Petrezsélyová, Silvia; Kinclová-Zimmermannová, Olga; Sychrová, Hana

    2013-01-01

    Roč. 1828, č. 2 (2013), s. 623-631 ISSN 0005-2736 R&D Projects: GA AV ČR(CZ) IAA500110801; GA MŠk(CZ) LC531; GA MŠk(CZ) OC10012 Grant - others:Rada Programu interní podpory projektů mezinárodní spolupráce AV ČR(CZ) M200110901 Institutional research plan: CEZ:AV0Z50110509 Institutional support: RVO:67985823 Keywords : salt tolerance * yeast vacuole * potassium homeostasis * cation- chloride cotransport Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.431, year: 2013

  20. Synergy between scientific advancement and technological innovation, illustrated by a mechanism-based model characterizing sodium-glucose cotransporter-2 inhibition.

    Science.gov (United States)

    Zhang, Liping; Ng, Chee M; List, James F; Pfister, Marc

    2010-09-01

    Advances in experimental medicine and technological innovation during the past century have brought tremendous progress in modern medicine and generated an ever-increasing amount of data from bench and bedside. The desire to extend scientific knowledge motivates effective data integration. Technological innovation makes this possible, which in turn accelerates the advancement in science. This mutually beneficial interaction is illustrated by the development of an expanded mechanism-based model for understanding a novel mechanism, sodium-glucose cotransporter-2 SGLT2 inhibition for potential treatment of type 2 diabetes mellitus.

  1. The treatment of type 2 diabetes in the presence of renal impairment: what we should know about newer therapies

    Directory of Open Access Journals (Sweden)

    Davies M

    2016-06-01

    Full Text Available Melanie Davies,1,2 Sudesna Chatterjee,1,2 Kamlesh Khunti1,2 1Diabetes Research Centre, University of Leicester, 2Leicester Diabetes Centre, University Hospitals of Leicester NHS Trust, Leicester, UK Abstract: Worldwide, an estimated 200 million people have chronic kidney disease (CKD, the most common causes of which include hypertension, arteriosclerosis, and diabetes. Importantly, ~40% of patients with diabetes develop CKD, yet evidence from major multicenter randomized controlled trials shows that intensive blood glucose control through pharmacological intervention can reduce the incidence and progression of CKD. Standard therapies for the treatment of type 2 diabetes include metformin, sulfonylureas, meglitinides, thiazolidinediones, and insulin. While these drugs have an important role in the management of type 2 diabetes, only the thiazolidinedione pioglitazone can be used across the spectrum of CKD (stages 2–5 and without dose adjustment; there are contraindications and dose adjustments required for the remaining standard therapies. Newer therapies, particularly dipeptidyl peptidase-IV inhibitors, glucagon-like peptide-1 receptor agonists, and sodium-glucose cotransporter-2 inhibitors, are increasingly being used in the treatment of type 2 diabetes; however, a major consideration is whether these newer therapies can also be used safely and effectively across the spectrum of renal impairment. Notably, reductions in albuminuria, a marker of CKD, are observed with many of the drug classes. Dipeptidyl peptidase-IV inhibitors can be used in all stages of renal impairment, with appropriate dose reduction, with the exception of linagliptin, which can be used without dose adjustment. No dose adjustment is required for liraglutide, albiglutide, and dulaglutide in CKD stages 2 and 3, although all glucagon-like peptide-1 receptor agonists are currently contraindicated in stages 4 and 5 CKD. At stage 3 CKD or greater, the sodium

  2. RENAL DAMAGE WITH MALIGNANT NEOPLASMS

    Directory of Open Access Journals (Sweden)

    I. B. Kolina

    2015-01-01

    Full Text Available The relationship between renal damage and malignant neoplasms is one of the most actual problems of the medicine of internal diseases. Very often, exactly availability of renal damage determines the forecast of cancer patients. The range of renal pathologies associated with tumors is unusually wide: from the mechanical effect of the tumor or metastases on the kidneys and/or the urinary tract and paraneoplastic manifestations in the form of nephritis or amyloidosis to nephropathies induced with drugs or tumor lysis, etc. Thrombotic complications that develop as a result of exposure to tumor effects, side effects of certain drugs or irradiation also play an important role in the development of the kidney damage. The most frequent variants of renal damage observed in the practice of medical internists (therapists, urologists, surgeons, etc., as well as methods of diagnosis and treatment approaches are described in the article. Timely and successful prevention and treatment of tumor-associated nephropathies give hope for retaining renal functions, therefore, a higher life standard after completion of anti-tumor therapy. Even a shortterm episode of acute renal damage suffered by a cancer patient must be accompanied with relevant examination and treatment. In the caseof transformation of acute renal damage into the chronic kidney disease, such patients need systematic and weighted renoprotective therapy and correct dosing of nephrotoxic drugs.

  3. Renal acidification defects in medullary sponge kidney

    DEFF Research Database (Denmark)

    Osther, P J; Hansen, A B; Røhl, H F

    1988-01-01

    Thirteen patients with medullary sponge kidney underwent a short ammonium chloride loading test to investigate their renal acidification capacity. All but 1 presented with a history of recurrent renal calculi and showed bilateral widespread renal medullary calcification on X-ray examination. Nine...... of renal calculi in medullary sponge kidney, have considerable therapeutic implications....

  4. Cólica renal

    OpenAIRE

    Pinheiro, JC

    1999-01-01

    Os aspectos práticos de actuação na cólica renal são abordados nesta apresentação, que o médico de família, a quem os doentes primeiro recorrem, deve conhecer em pormenor.É referida a incidência da afecção num serviço de urgência dum grande hospital e descreve-se, ainda que sumariamente, a fisiopatologia da dor, o quadro clínico mais frequente e a conveniente actuação terapêutica para o imediato alívio da dor intensa que estes doentes apresentam. Nas conclusões sublinha-se que a cólica ...

  5. Mature Cystic Renal Teratoma

    International Nuclear Information System (INIS)

    Yavuz, Alpaslan; Ceken, Kagan; Alimoglu, Emel; Akkaya, Bahar

    2014-01-01

    Teratomas are rare germline tumors that originate from one or more embryonic germ cell layers. Teratoma of the kidney is extremely rare, and less than 30 cases of primary intrarenal teratomas have been published to date. We report the main radiologic features of an unusual case of mature cystic teratoma arising from the left kidney in a two-year-old boy. A left-sided abdominal mass was detected on physical examination and B-Mod Ultrasound (US) examination revealed a heterogeneous mass with central cystic component. Computed tomography (CT) demonstrated a lobulated, heterogeneous, hypodense mass extending craniocaudally from the splenic hilum to the level of the left iliac fossa. Nephrectomy was performed and a large, fatty mass arising from the left kidney was excised. The final pathologic diagnosis was confirmed as cystic renal teratoma

  6. Hyperparathyroidism of Renal Disease.

    Science.gov (United States)

    Yuen, Noah K; Ananthakrishnan, Shubha; Campbell, Michael J

    2016-01-01

    Renal hyperparathyroidism (rHPT) is a common complication of chronic kidney disease characterized by elevated parathyroid hormone levels secondary to derangements in the homeostasis of calcium, phosphate, and vitamin D. Patients with rHPT experience increased rates of cardiovascular problems and bone disease. The Kidney Disease: Improving Global Outcomes guidelines recommend that screening and management of rHPT be initiated for all patients with chronic kidney disease stage 3 (estimated glomerular filtration rate, < 60 mL/min/1.73 m(2)). Since the 1990s, improving medical management with vitamin D analogs, phosphate binders, and calcimimetic drugs has expanded the treatment options for patients with rHPT, but some patients still require a parathyroidectomy to mitigate the sequelae of this challenging disease.

  7. The effects of GLP-1 analogues, DPP-4 inhibitors and SGLT2 inhibitors on the renal system.

    Science.gov (United States)

    Schernthaner, Guntram; Mogensen, Carl Erik; Schernthaner, Gerit-Holger

    2014-09-01

    Diabetic nephropathy (DN) affects an estimated 20%-40% of patients with type 2 diabetes mellitus (T2DM). Key modifiable risk factors for DN are albuminuria, anaemia, dyslipidaemia, hyperglycaemia and hypertension, together with lifestyle factors, such as smoking and obesity. Early detection and treatment of these risk factors can prevent DN or slow its progression, and may even induce remission in some patients. DN is generally preceded by albuminuria, which frequently remains elevated despite treatment in patients with T2DM. Optimal treatment and prevention of DN may require an early, intensive, multifactorial approach, tailored to simultaneously target all modifiable risk factors. Regular monitoring of renal function, including urinary albumin excretion, creatinine clearance and glomerular filtration rate, is critical for following any disease progression and making treatment adjustments. Dipeptidyl peptidase (DPP)-4 inhibitors and sodium-glucose cotransporter 2 (SGLT2) inhibitors lower blood glucose levels without additional risk of hypoglycaemia, and may also reduce albuminuria. Further investigation of the potential renal benefits of DPP-4 and SGLT2 inhibitors is underway. © The Author(s) 2014.

  8. Lung and renal transplantation

    Directory of Open Access Journals (Sweden)

    Patrícia Caetano Mota

    2009-11-01

    Full Text Available Renal transplantation is the most common type of solid organ transplantation and kidney transplant recipients are susceptible to pulmonary complications of immunosuppressive therapy, which are a diagnostic and therapeutic challenge. Aim: To evaluate patients admitted to the Renal Transplant Unit (RTU of Hospital de S. João with respiratory disease. Subject and methods: We performed a retrospective study of all patients admitted to RTU with respiratory disease during a period of 12 months. Results: Thirty-six patients were included. Mean age 55.2 ( ± 13.4 years; 61.1% male. Immunosuppressive agents most frequently used were prednisolone and mycophenolate mofetil associated with ciclosporin (38.9% or tacrolimus (22.2% or rapamycin (13.9%. Thirty-one patients (86.1% presented infectious respiratory disease. In this group the main diagnoses were 23 (74.2% pneumonias, 5 (16.1% opportunistic infections, 2 (6.5% tracheobronchitis, and 1 case (3.2% of lung abscesses. Microbiological agent was identified in 7 cases (22.6%. Five patients (13.9% presented rapamycin-induced lung disease. Fibreoptic bronchoscopy was performed in 15 patients (41.7%, diagnostic in 10 cases (66.7%. Mean hospital stay was 17.1 ( ± 18.5 days and no related death was observed. Conclusion: Respiratory infections were the main complications in these patients. Drug-induced lung disease implies recognition of its features and a rigorous monitoring of drug serum levels. A more invasive diagnostic approach was determinant in the choice of an early and more specific therapy. Resumo: O transplante renal é o transplante de órgãos sólidos mais frequente, sendo os transplantados renais alvo de complicações pulmonares inerentes à própria terapêutica imunossupressora, as quais constituem, por vezes, um desafio diagnóstico e terapêutico. Objectivo: Avaliar os doentes admitidos na Unidade de Transplante Renal (UTR do Hospital de S. João com o diagnóstico de patologia respirat

  9. Characterization of complex renal cysts

    DEFF Research Database (Denmark)

    Graumann, Ole; Osther, Susanne Sloth; Osther, Palle Jörn Sloth

    2010-01-01

    Abstract Objective. Complex renal cysts represent a major clinical problem, since it is often difficult to exclude malignancy. The Bosniak classification system, based on computed tomography (CT), is widely used to categorize cystic renal lesions. The aim of this study was to evaluate critically...... available data on the Bosniak classification. Material and methods. All publications from an Entrez Pubmed search were reviewed, focusing on clinical applicability and the use of imaging modalities other than CT to categorize complex renal cysts. Results. Fifteen retrospective studies were found. Most...

  10. Renal rickets-practical approach

    Science.gov (United States)

    Sahay, Manisha; Sahay, Rakesh

    2013-01-01

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

  11. Renal epithelioid angiomyolipoma presenting clinically as renal cell ...

    African Journals Online (AJOL)

    M.S. Johnson

    a Detroit Medical Center, Michigan State University School of Osteopathic Medicine, Detroit, MI, USA .... Immunohistochemically, the tumor cells stained strongly positive .... [10] Cao Q, Liu F, Xiao P, Tian X, Li B, Li Z. Coexistence of renal.

  12. Diagnosis of renal disease in rabbits.

    Science.gov (United States)

    Harcourt-Brown, Frances Margaret

    2013-01-01

    There are differences in renal anatomy and physiology between rabbits and other domestic species. Neurogenic renal ischemia occurs readily. Reversible prerenal azotemia may be seen in conjunction with gut stasis. Potentially fatal acute renal failure may be due to structural kidney damage or post-renal disease. Chronic renal failure is often associated with encephalitozoonosis. Affected rabbits cannot vomit and often eat well. Weight loss, lethargy, and cachexia are common clinical signs. Polydypsia/polyuria may be present. Derangements in calcium and phosphorus metabolism are features of renal disease. Radiography is always indicated. Urolithiasis, osteosclerosis, aortic and renal calcification are easily seen on radiographs. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. Renal vein oxygen saturation in renal artery stenosis

    DEFF Research Database (Denmark)

    Nielsen, K; Rehling, M; Henriksen, Jens Henrik Sahl

    1992-01-01

    Renal vein oxygen-saturation was measured in 56 patients with arterial hypertension and unilateral stenosis or occlusion of the renal artery. Oxygen-saturation in blood from the ischaemic kidney (84.4%, range 73-93%) was significantly higher than that from the 'normal' contralateral kidney (81...... than its blood flow. This is probably due to decreased filtration fraction and filtered sodium with subsequent reduction in absolute tubular re-absorption of sodium ions....

  14. CUTANEOUS MANIFESTATIONS OF CHRONIC RENAL FAILURE AND RENAL TRANSPLANTATION

    OpenAIRE

    R. Suganya Gnanadeepam; S. Kayalvizhi Money

    2017-01-01

    BACKGROUND The kidney and the skin are the two large networks of the body with abundant blood supply associated with various cutaneous manifestations. This study aims to detect the various cutaneous manifestations and its incidence in patients with chronic renal failure and renal transplantation. MATERIALS AND METHODS This study was done for a period of 1 year from January 2016 to December 2016 at Nephrology OPD ward and Medicine wards, Government KAPV Medical College Hos...

  15. An Inverse Relationship Links Temperature and Substrate Apparent Affinity in the Ion-Coupled Cotransporters rGAT1 and KAAT1

    Directory of Open Access Journals (Sweden)

    Antonio Peres

    2012-11-01

    Full Text Available The effects of temperature on the operation of two ion-coupled cotransporters of the SLC6A family, namely rat GAT1 (SLC6A1 and KAAT1 (SLC6A19 from Manduca sexta, have been studied by electrophysiological means in Xenopus laevis oocytes expressing these proteins. The maximal transport-associated current (Imax and the apparent substrate affinity (K05 were measured. In addition to the expected increase in transport rate (Q10 = 3–6, both transporters showed greater K05 values (i.e., a decrease in apparent affinity at higher temperatures. The transport efficiency, estimated as Imax/K05, increased at negative potentials in both transporters, but did not show statistically significant differences with temperature. The observation that the apparent substrate affinity is inversely related to the transport rate suggests a kinetic regulation of this parameter. Furthermore, the present results indicate that the affinities estimated at room temperature for mammalian cotransporters may not be simply extrapolated to their physiological operating conditions.

  16. General anaesthetics do not impair developmental expression of the KCC2 potassium-chloride cotransporter in neonatal rats during the brain growth spurt

    KAUST Repository

    Lacoh, Claudia Marvine

    2013-03-26

    BackgroundThe developmental transition from depolarizing to hyperpolarizing γ-aminobutyric acid-mediated neurotransmission is primarily mediated by an increase in the amount of the potassium-chloride cotransporter KCC2 during early postnatal life. However, it is not known whether early neuronal activity plays a modulatory role in the expression of total KCC2 mRNA and protein in the immature brain. As general anaesthetics are powerful modulators of neuronal activity, the purpose of this study was to explore how these drugs affect KCC2 expression during the brain growth spurt.MethodsWistar rat pups were exposed to either a single dose or 6 h of midazolam, propofol, or ketamine anaesthesia at postnatal days 0, 5, 10, or 15. KCC2 expression was assessed using immunoblotting, immunohistochemistry, or quantitative polymerase chain reaction analysis up to 3 days post-exposure in the medial prefrontal cortex.ResultsThere was a progressive and steep increase in the expression of KCC2 between birth and 2 weeks of age. Exposure to midazolam, propofol, or ketamine up to 6 h at any investigated stages of the brain growth spurt did not influence the expression of this cotransporter protein.ConclusionI.V. general anaesthetics do not seem to influence developmental expression of KCC2 during the brain growth spurt. © 2013 © The Author [2013].

  17. Sodium-glucose cotransporter 2 inhibitors combined with dipeptidyl peptidase-4 inhibitors in the management of type 2 diabetes: a review of current clinical evidence and rationale

    Directory of Open Access Journals (Sweden)

    Yassin SA

    2017-03-01

    Full Text Available Sayf A Yassin,1 Vanita R Aroda2 1MedStar Union Memorial Hospital, Baltimore, 2MedStar Health Research Institute, Hyattsville, MD, USA Abstract: Type 2 diabetes mellitus (T2DM is a progressive and multifactorial cardiometabolic disorder. Almost half of adults with diabetes fail to achieve their recommended glucose control target. This has prompted some clinicians to advocate the use of more intensive initial therapy, including the use of combination therapy to target multiple physiologic defects in diabetes with the goal of achieving and sustaining glucose control. Numerous options exist for combining the various classes of glucose-lowering agents in the treatment of T2DM. This report reviews the mechanism, rationale, and evidence from clinical trials for combining two of the newer drug classes, namely, dipeptidyl peptidase-4 inhibitors and sodium-glucose cotransporter 2 inhibitors, and considers the possible role of such dual therapy in the management of T2DM. Keywords: sodium-glucose cotransporter 2 inhibitors, dipeptidyl peptidase-4 inhibitors, type 2 diabetes mellitus, combination therapy

  18. Regulated phosphorylation of the K-Cl cotransporter KCC3 at dual C-terminal threonines is a potent switch of intracellular potassium content and cell volume homeostasis

    Directory of Open Access Journals (Sweden)

    Norma C. Adragna

    2015-07-01

    Full Text Available The defense of cell volume against excessive shrinkage or swelling is a requirement for cell function and organismal survival. Cell swelling triggers a coordinated homeostatic response termed regulatory volume decrease (RVD, resulting in K+ and Cl– efflux via the activation of K+ channels, volume-regulated anion channels (VRACs, and the K+-Cl– cotransporters, including KCC3. Here, we show genetic alanine (Ala substitution at threonines (Thr 991 and 1048 in the KCC3a isoform carboxyl-terminus, preventing inhibitory phosphorylation at these sites, not only significantly up-regulates KCC3a activity up to 25-fold in normally inhibitory isotonic conditions, but is also accompanied by reversal of activity of the related bumetanide-sensitive Na+-K+-2Cl– cotransporter isoform 1 (NKCC1. This results in a rapid (90 % reduction in intracellular K+ content (Ki via both Cl-dependent (KCC3a + NKCC1 and Cl-independent (DCPIB [VRAC inhibitor]-sensitive pathways, which collectively renders cells less prone to acute swelling in hypotonic osmotic stress. Together, these data demonstrate the phosphorylation state of Thr991/Thr1048 in the KCC3a encodes a potent switch of transporter activity, Ki homeostasis, and cell volume regulation, and reveal novel observations into the functional interaction among ion transport molecules involved in RVD.

  19. Regulated phosphorylation of the K-Cl cotransporter KCC3 is a molecular switch of intracellular potassium content and cell volume homeostasis.

    Science.gov (United States)

    Adragna, Norma C; Ravilla, Nagendra B; Lauf, Peter K; Begum, Gulnaz; Khanna, Arjun R; Sun, Dandan; Kahle, Kristopher T

    2015-01-01

    The defense of cell volume against excessive shrinkage or swelling is a requirement for cell function and organismal survival. Cell swelling triggers a coordinated homeostatic response termed regulatory volume decrease (RVD), resulting in K(+) and Cl(-) efflux via activation of K(+) channels, volume-regulated anion channels (VRACs), and the K(+)-Cl(-) cotransporters, including KCC3. Here, we show genetic alanine (Ala) substitution at threonines (Thr) 991 and 1048 in the KCC3a isoform carboxyl-terminus, preventing inhibitory phosphorylation at these sites, not only significantly up-regulates KCC3a activity up to 25-fold in normally inhibitory isotonic conditions, but is also accompanied by reversal of activity of the related bumetanide-sensitive Na(+)-K(+)-2Cl(-) cotransporter isoform 1 (NKCC1). This results in a rapid (90%) reduction in intracellular K(+) content (Ki) via both Cl-dependent (KCC3a + NKCC1) and Cl-independent [DCPIB (VRAC inhibitor)-sensitive] pathways, which collectively renders cells less prone to acute swelling in hypotonic osmotic stress. Together, these data demonstrate the phosphorylation state of Thr991/Thr1048 in KCC3a encodes a potent switch of transporter activity, Ki homeostasis, and cell volume regulation, and reveal novel observations into the functional interaction among ion transport molecules involved in RVD.

  20. Relationship between renal cortex and parenchyma thickness and renal function: study with CT measurement

    International Nuclear Information System (INIS)

    Xu Yufeng; Tang Guangjian; Jiang Xuexiang

    2006-01-01

    Objective: To study the relationship between renal morphology and renal function, and to assess the value of CT as a criterion to grade renal function. Methods: Enhancement CT were performed in 89 patients with no local renal disease whose split renal glomerular filtration rates (GFR) were measured by renal dynamic imaging with 99 Tc m -DTPA. The 178 kidneys were divided into normal renal function, mild and severe renal impairment groups according to renal function. Differences between three groups respect to the mean thickness of renal cortex and parenchyma were assessed by ANOVA. Using Pearson's correlation test, the correlation between the renal cortex, parenchyma thicknesses and renal GFR were examined. The value of CT in predicting renal function was assessed by using ROC analysis. Results: The renal cortex thicknesses of normal renal function, mild and severe renal impairment groups were (5.9±1.1), (4.6± 1.1), and (3.3±1.0) mm respectively, and the renal parenchyma thicknesses were (26.3±4.2), (21.3±4.6), (16.2±4.6) mm. There were significant differences of renal cortex, parenchyma thicknesses between 3 groups (cortex F=54.78, P<0.01; parenehyma F=43.90, P<0.01). The thicknesses of renal cortex (r=0.752, P<0.01), parenchyma (r=0.738, P<0.01) had positive linear correlation with renal function. ROC analysis of the renal cortex thicknesses measured by CT in predicting mild and severe renal impairment showed that the Az was 0.860 and 0.905 respectively, whereas that of parenchyma was 0.868 and 0.884. Conclusion: The thicknesses of renal cortex, parenchyma measured by CT can reflect renal function. CT was a supplementary method to assess renal function. (authors)

  1. The Effects of Renal Denervation on Renal Hemodynamics and Renal Vasculature in a Porcine Model.

    Directory of Open Access Journals (Sweden)

    Willemien L Verloop

    Full Text Available Recently, the efficacy of renal denervation (RDN has been debated. It is discussed whether RDN is able to adequately target the renal nerves.We aimed to investigate how effective RDN was by means of functional hemodynamic measurements and nerve damage on histology.We performed hemodynamic measurements in both renal arteries of healthy pigs using a Doppler flow and pressure wire. Subsequently unilateral denervation was performed, followed by repeated bilateral hemodynamic measurements. Pigs were terminated directly after RDN or were followed for 3 weeks or 3 months after the procedure. After termination, both treated and control arteries were prepared for histology to evaluate vascular damage and nerve damage. Directly after RDN, resting renal blood flow tended to increase by 29±67% (P = 0.01. In contrast, renal resistance reserve increased from 1.74 (1.28 to 1.88 (1.17 (P = 0.02 during follow-up. Vascular histopathology showed that most nerves around the treated arteries were located outside the lesion areas (8±7 out of 55±25 (14% nerves per pig were observed within a lesion area. Subsequently, a correlation was noted between a more impaired adventitia and a reduction in renal resistance reserve (β: -0.33; P = 0.05 at three weeks of follow-up.Only a small minority of renal nerves was targeted after RDN. Furthermore, more severe adventitial damage was related to a reduction in renal resistance in the treated arteries at follow-up. These hemodynamic and histological observations may indicate that RDN did not sufficiently target the renal nerves. Potentially, this may explain the significant spread in the response after RDN.

  2. The Effects of Renal Denervation on Renal Hemodynamics and Renal Vasculature in a Porcine Model

    Science.gov (United States)

    Verloop, Willemien L.; Hubens, Lisette E. G.; Spiering, Wilko; Doevendans, Pieter A.; Goldschmeding, Roel; Bleys, Ronald L. A. W.; Voskuil, Michiel

    2015-01-01

    Rationale Recently, the efficacy of renal denervation (RDN) has been debated. It is discussed whether RDN is able to adequately target the renal nerves. Objective We aimed to investigate how effective RDN was by means of functional hemodynamic measurements and nerve damage on histology. Methods and Results We performed hemodynamic measurements in both renal arteries of healthy pigs using a Doppler flow and pressure wire. Subsequently unilateral denervation was performed, followed by repeated bilateral hemodynamic measurements. Pigs were terminated directly after RDN or were followed for 3 weeks or 3 months after the procedure. After termination, both treated and control arteries were prepared for histology to evaluate vascular damage and nerve damage. Directly after RDN, resting renal blood flow tended to increase by 29±67% (P = 0.01). In contrast, renal resistance reserve increased from 1.74 (1.28) to 1.88 (1.17) (P = 0.02) during follow-up. Vascular histopathology showed that most nerves around the treated arteries were located outside the lesion areas (8±7 out of 55±25 (14%) nerves per pig were observed within a lesion area). Subsequently, a correlation was noted between a more impaired adventitia and a reduction in renal resistance reserve (β: -0.33; P = 0.05) at three weeks of follow-up. Conclusion Only a small minority of renal nerves was targeted after RDN. Furthermore, more severe adventitial damage was related to a reduction in renal resistance in the treated arteries at follow-up. These hemodynamic and histological observations may indicate that RDN did not sufficiently target the renal nerves. Potentially, this may explain the significant spread in the response after RDN. PMID:26587981

  3. Transcatheter embolisation of renal angiomyolipoma.

    LENUS (Irish Health Repository)

    Leong, S

    2010-06-01

    Angiomyolipomas (AML) are rare benign renal tumours which are associated with aneurysms that can cause haemorrhage. Embolisation of AML greater than 4 cm with a variety of embolic agents is now the first-line treatment in these cases.

  4. Renal cell carcinoma in childhood

    International Nuclear Information System (INIS)

    Zanier, J.F.C.; Ramos, C.O.P.; Pereira, A.A.

    1990-01-01

    The authors present five cases of renal cell carcinoma in children, describing its aspects on excretory urography, ultra-sonography and computerized tomography. The clinical, pathological and radiological features are compared with those of the literature. (author)

  5. Antibiotic managment in renal failure.

    Science.gov (United States)

    Winter, R E

    1976-06-01

    This is a brief compilation of the work of many investigators. It includes facts about toxicity and recommendations about antibiotic management in patients with renal failure. As new data are accrued, changes in these recommendations will be necessary.

  6. Bone scintigraphy in renal osteodystrophy

    International Nuclear Information System (INIS)

    de Graaf, P.; Schicht, I.M.; Pauwels, E.K.J.; te Velde, J.; de Graeff, J.

    1978-01-01

    Bone scintigraphy with Tc-99m HEDP was performed in 30 patients on maintenance hemodialysis, and the results of quantitative analysis were compared wth those of a normal group. To permit this comparison, elevated background activity due to the absence of renal radiotracer excretion was reduced by hemodialysis to levels found in the normals. Histologic proof of renal osteodystrophy had been obtained in all patients. the incidence of radiographic abnormalities was 46%, whereas abnormal scans were found in 25 patients (83%); skeletal lesions were also more pronounced and detected earlier. However, even when the scans appeared normal, the quantitative analysis showed increased skeletal activity in all patients. The total skeletal activity proved to be a good index of the severity of renal osteodystrophy and appeared dependent on both osteomalacia and hyperparathyroidism. These findings show that bone scintigraphy is a sensitive method to detect skeletal involvement in renal osteodystrophy

  7. Prolonged Intermittent Renal Replacement Therapy.

    Science.gov (United States)

    Edrees, Fahad; Li, Tingting; Vijayan, Anitha

    2016-05-01

    Prolonged intermittent renal replacement therapy (PIRRT) is becoming an increasingly popular alternative to continuous renal replacement therapy in critically ill patients with acute kidney injury. There are significant practice variations in the provision of PIRRT across institutions, with respect to prescription, technology, and delivery of therapy. Clinical trials have generally demonstrated that PIRRT is non-inferior to continuous renal replacement therapy regarding patient outcomes. PIRRT offers cost-effective renal replacement therapy along with other advantages such as early patient mobilization and decreased nursing time. However, due to lack of standardization of the procedure, PIRRT still poses significant challenges, especially pertaining to appropriate drug dosing. Future guidelines and clinical trials should work toward developing consensus definitions for PIRRT and ensure optimal delivery of therapy. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  8. Mucormycosis (zygomycosis) of renal allograft

    Science.gov (United States)

    Gupta, Krishan L.; Joshi, Kusum; Kohli, Harbir S.; Jha, Vivekanand; Sakhuja, Vinay

    2012-01-01

    Fungal infection is relatively common among renal transplant recipients from developing countries. Mucormycosis, also known as zygomycosis, is one of the most serious fungal infections in these patients. The most common of presentation is rhino-cerebral. Isolated involvement of a renal allograft is very rare. A thorough search of literature and our medical records yielded a total of 24 cases with mucormycosis of the transplanted kidney. There was an association with cytomegalovirus (CMV) infection and anti-rejection treatment in these patients and most of these transplants were performed in the developing countries from unrelated donors. The outcome was very poor with an early mortality in 13 (54.5%) patients. Renal allograft mucormycosis is a relatively rare and potentially fatal complication following renal transplantation. Early diagnosis, graft nephrectomy and appropriate antifungal therapy may result in an improved prognosis for these patients. PMID:26069793

  9. Fibromuscular dysplasia of renal arteries

    International Nuclear Information System (INIS)

    Akhtar, N.; Ahmed, T.M.

    2007-01-01

    This case reports a young child having uncontrolled hypertension, resulting from bilateral renal artery stenosis due to fibromuscular dysplasia presenting with abdominal pain, headache and visual disturbance. Diagnostic features and management is discussed. (author)

  10. Cancer - renal pelvis or ureter

    Science.gov (United States)

    ... ureter; Kidney cancer - renal pelvis; Ureter cancer Images Kidney anatomy References National Cancer Institute website. Transitional cell cancer (kidney/ureter) treatment (PDQ) - health professional version. www.cancer. ...

  11. Radiological evaluation of renal transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Dorph, S [Herlev University Hospital, Copenhagen (Denmark). Dept. of Radiology

    1996-12-31

    Briefly discussed the nephrologic complications, episodes of rejection, acute tubular necrosis, cyclosporine, urologic complications, perirenal fluid collections, small asymptomatic hematomas, urinomas, abscesses, lymphocele, ureteral obstruction, cascular complications, imaging of the renal allograft, radionuclide imaging, ultrasonography, conventional radiography, cystograhy (8 refs.).

  12. Radiological evaluation of renal transplantation

    International Nuclear Information System (INIS)

    Dorph, S.

    1995-01-01

    Briefly discussed the nephrologic complications, episodes of rejection, acute tubular necrosis, cyclosporine, urologic complications, perirenal fluid collections, small asymptomatic hematomas, urinomas, abscesses, lymphocele, ureteral obstruction, cascular complications, imaging of the renal allograft, radionuclide imaging, ultrasonography, conventional radiography, cystograhy (8 refs.)

  13. Inflammation in renal atherosclerotic disease.

    Science.gov (United States)

    Udani, Suneel M; Dieter, Robert S

    2008-07-01

    The study of renal atherosclerotic disease has conventionally focused on the diagnosis and management of renal artery stenosis. With the increased understanding of atherosclerosis as a systemic inflammatory process, there has been increased interest in vascular biology at the microvasculature level. While different organ beds share some features, the inflammation and injury in the microvasculature of the kidney has unique elements as well. Understanding of the pathogenesis yields a better understanding of the clinical manifestations of renal atherosclerotic disease, which can be very subtle. Furthermore, identifying the molecular mechanisms responsible for the progression of kidney damage can also direct clinicians and scientists toward targeted therapies. Existing therapies used to treat atherosclerotic disease in other vascular beds may also play a role in the treatment of renal atherosclerotic disease.

  14. Epigenetic suppression of potassium-chloride co-transporter 2 expression in inflammatory pain induced by complete Freund's adjuvant (CFA).

    Science.gov (United States)

    Lin, C-R; Cheng, J-K; Wu, C-H; Chen, K-H; Liu, C-K

    2017-02-01

    Multiple mechanisms contribute to the stimulus-evoked pain hypersensitivity that may be experienced after peripheral inflammation. Persistent pathological stimuli in many pain conditions affect the expression of certain genes through epigenetic alternations. The main purpose of our study was to investigate the role of epigenetic modification on potassium-chloride co-transporter 2 (KCC2) gene expression in the persistence of inflammatory pain. Persistent inflammatory pain was induced through the injection of complete Freund's adjuvant (CFA) in the left hind paw of rats. Acetyl-histone H3 and H4 level was determined by chromatin immunoprecipitation in the spinal dorsal horn. Pain behaviour and inhibitory synaptic function of spinal cord were determined before and after CFA injection. KCC2 expression was determined by real time RT-PCR and Western blot. Intrathecal KCC2 siRNA (2 μg per 10 μL per rat) or HDAC inhibitor (10 μg per 10 μL per rat) was injected once daily for 3 days before CFA injection. Persistent inflammatory pain epigenetically suppressed KCC2 expression through histone deacetylase (HDAC)-mediated histone hypoacetylation, resulting in decreased inhibitory signalling efficacy. KCC2 knock-down caused by intrathecal administration of KCC2 siRNA in naïve rats reduced KCC2 expression in the spinal cord, leading to sensitized pain behaviours and impaired inhibitory synaptic transmission in their spinal cords. Moreover, intrathecal HDAC inhibitor injection in CFA rats increased KCC2 expression, partially restoring the spinal inhibitory synaptic transmission and relieving the sensitized pain behaviour. These findings suggest that the transcription of spinal KCC2 is regulated by histone acetylation epigenetically following CFA. Persistent pain suppresses KCC2 expression through HDAC-mediated histone hypoacetylation and consequently impairs the inhibitory function of inhibitory interneurons. Drugs such as HDAC inhibitors that suppress the influences of

  15. Volume regulation in mammalian skeletal muscle: the role of sodium-potassium-chloride cotransporters during exposure to hypertonic solutions.

    Science.gov (United States)

    Lindinger, Michael I; Leung, Matthew; Trajcevski, Karin E; Hawke, Thomas J

    2011-06-01

    Controversy exists as to whether mammalian skeletal muscle is capable of volume regulation in response to changes in extracellular osmolarity despite evidence that muscle fibres have the required ion transport mechanisms to transport solute and water in situ. We addressed this issue by studying the ability of skeletal muscle to regulate volume during periods of induced hyperosmotic stress using single, mouse extensor digitorum longus (EDL) muscle fibres and intact muscle (soleus and EDL). Fibres and intact muscles were loaded with the fluorophore, calcein, and the change in muscle fluorescence and width (single fibres only) used as a metric of volume change. We hypothesized that skeletal muscle exposed to increased extracellular osmolarity would elicit initial cellular shrinkage followed by a regulatory volume increase (RVI) with the RVI dependent on the sodium–potassium–chloride cotransporter (NKCC). We found that single fibres exposed to a 35% increase in extracellular osmolarity demonstrated a rapid, initial 27–32% decrease in cell volume followed by a RVI which took 10-20 min and returned cell volume to 90–110% of pre-stimulus values. Within intact muscle, exposure to increased extracellular osmolarity of varying degrees also induced a rapid, initial shrinkage followed by a gradual RVI, with a greater rate of initial cell shrinkage and a longer time for RVI to occur with increasing extracellular tonicities. Furthermore, RVI was significantly faster in slow-twitch soleus than fast-twitch EDL. Pre-treatment of muscle with bumetanide (NKCC inhibitor) or ouabain (Na+,K+-ATPase inhibitor), increased the initial volume loss and impaired the RVI response to increased extracellular osmolarity indicating that the NKCC is a primary contributor to volume regulation in skeletal muscle. It is concluded that mouse skeletal muscle initially loses volume then exhibits a RVI when exposed to increases in extracellular osmolarity. The rate of RVI is dependent on the

  16. Renal Ammonia Metabolism and Transport

    Science.gov (United States)

    Weiner, I. David; Verlander, Jill W.

    2015-01-01

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

  17. Novel genes in renal aging

    OpenAIRE

    Noordmans, Gerda Anke

    2015-01-01

    Renal aging is characterized by structural changes and functional decline. These changes make the elderly more vulnerable to chronic kidney disease, hypertension, and cardiovascular disease. Furthermore, they also make it more difficult to cope with stress factors, such as dehydration, toxicity, and obstruction. These stress factors can lead to acute kidney injury and reduced recovery from acute kidney injury and may result in chronic kidney disease or even end-stage renal disease. The rate o...

  18. Parasites and chronic renal failure

    OpenAIRE

    Mohammadi Manesh, Reza; Hosseini Safa, Ahmad; Sharafi, Seyedeh Maryam; Jafari, Rasool; Bahadoran, Mehran; Yousefi, Morteza; Nasri, Hamid; Yousofi Darani, Hossein

    2014-01-01

    Suppression of the human immune system results in an increase in susceptibility to infection by various infectious agents. Conditions such as AIDS, organ transplantation and chronic renal insufficiency (CRI) are the most important cause of insufficient immune response against infections. Long term renal disorders result in uremia, which can suppress human immune system. Parasitic infections are one of the most important factors indicating the public health problems of the societies. These inf...

  19. MR Imaging of renal transplants

    International Nuclear Information System (INIS)

    Gremo, L.; Avataneo, T.; Potenzoni, F.; Colla, L.; Segoloni, G.

    1988-01-01

    The authors report their experience in the study of renal transplant recipients by MR, in order to determine its clinical potentials. The main purpose of this work is to focus on MR patterns in relation to clinical findings of rejector or normally fuctioning kidney. Twenty-four patients were examined with a 0.5 T superconductive magnete, body coil, spin-echo pulse sequence (SE) and inversion-recovery (IR). MRI patterns could be seen in normally functioning kidneys and transplant rejections, while variable MRI findings were observed in transplants with acute tubular necrosis (ATN). In the normally functioning transplanted kidney there is a clear corticomedullary differentiation (CMD), and the extent of vascular penetration into the renal parenchyma is clearly seen. In transplant rejection, CMD is either diminished or absent, and there is no vascular penetration into the parenchyma; to differentiate acute from chronic rejections, the increase/decrease in renal size and the change in renal shape (spherical shape in acute transplant rejection) respectively must be observed. MRI proves thus to be useful in the study of renal transplants, even in case of questionable clinical findings, and in patients in whom renal biopsy is contraindicated

  20. Renal transplant scintigraphy (Part 1)

    International Nuclear Information System (INIS)

    Chew, Ghee

    2005-01-01

    Renal transplantation is the most effective mode of renal replacement therapy for correction of renal failure. Renal donors can either be: a. a deceased person - the kidneys being removed when brain death or absence of cerebral cortical function / perfusion is confirmed - the cadaveric kidney is packed in ice and nutrient solution and transplanted within 24 hours of removal ('cold ischemia') ob. a living donor - the donor may or may not be related to the recipient. Due to the limited length of the renal vessels and ureter of the donor kidney, it is implanted close to the bladder of the recipient. The donor vessels are anastomosed to the iliac artery and vein of the recipient. Transplant variants: a. 2 kidneys maybe transplanted because: - an old donor with less kidney reserve from atrophy due to age or disease (e.g. hypertension) - an infant donor when both kidneys are removed en bloc, b. Donor kidneys with more than 1 artery, vein or ureter. c. Donor horse shoe kidney d. Combined renal and pancreas transplant for type I diabetics -a short segment of duodenum transplanted with the pancreas maybe implanted into the bladder. Copyright (2005) The Australian and New Zealand Society of Nuclear Medicine

  1. 21 CFR 522.163 - Betamethasone dipropionate and betamethasone sodium phosphate aqueous suspension.

    Science.gov (United States)

    2010-04-01

    ...) Conditions of use—(1) Dogs. (i) It is used as an aid in the control of pruritus associated with dermatoses... may induce the first stage of parturition when administered during the last trimester of pregnancy and may precipitate premature parturition followed by dystocia, fetal death, retained placenta, and...

  2. Technical aspects of renal denervation in end-stage renal disease patients with challenging anatomy.

    Science.gov (United States)

    Spinelli, Alessio; Da Ros, Valerio; Morosetti, Daniele; Onofrio, Silvia D; Rovella, Valentina; Di Daniele, Nicola; Simonetti, Giovanni

    2014-01-01

    We describe our preliminary experience with percutaneous renal denervation in end-stage renal disease patients with resistant hypertension and challenging anatomy, in terms of the feasibility, safety, and efficacy of this procedure. Four patients with end-stage renal disease patients with resistant hypertension (mean hemodialysis time, 2.3 years) who had been taking at least four antihypertensive medications underwent percutaneous renal denervation. Renal artery eligibility included the absence of prior renal artery interventions, vessel stenosis renal denervation is a feasible approach for end-stage renal disease patients with resistant hypertension with encouraging short-term preliminary results in terms of procedural efficacy and safety.

  3. Renal plasticity in response to feeding in the Burmese python, Python molurus bivittatus.

    Science.gov (United States)

    Esbaugh, A J; Secor, S M; Grosell, M

    2015-10-01

    Burmese pythons are sit-and-wait predators that are well adapted to go long periods without food, yet subsequently consume and digest single meals that can exceed their body weight. These large feeding events result in a dramatic alkaline tide that is compensated by a hypoventilatory response that normalizes plasma pH; however, little is known regarding how plasma HCO3(-) is lowered in the days post-feeding. The current study demonstrated that Burmese pythons contain the cellular machinery for renal acid-base compensation and actively remodel the kidney to limit HCO3(-) reabsorption in the post-feeding period. After being fed a 25% body weight meal plasma total CO2 was elevated by 1.5-fold after 1 day, but returned to control concentrations by 4 days post-feeding (d pf). Gene expression analysis was used to verify the presence of carbonic anhydrase (CA) II, IV and XIII, Na(+) H(+) exchanger 3 (NHE3), the Na(+) HCO3(-) co-transporter (NBC) and V-type ATPase. CA IV expression was significantly down-regulated at 3 dpf versus fasted controls. This was supported by activity analysis that showed a significant decrease in the amount of GPI-linked CA activity in isolated kidney membranes at 3 dpf versus fasted controls. In addition, V-type ATPase activity was significantly up-regulated at 3 dpf; no change in gene expression was observed. Both CA II and NHE3 expression was up-regulated at 3 dpf, which may be related to post-prandial ion balance. These results suggest that Burmese pythons actively remodel their kidney after feeding, which would in part benefit renal HCO3(-) clearance. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Continuous renal replacement therapy improves renal recovery from acute renal failure.

    Science.gov (United States)

    Jacka, Michael J; Ivancinova, Xenia; Gibney, R T Noel

    2005-03-01

    Acute renal failure (ARF) occurs in up to 10% of critically ill patients, with significant associated morbidity and mortality. The optimal mode of renal replacement therapy (RRT) remains controversial. This retrospective study compared continuous renal replacement therapy (CRRT) and intermittent hemodialysis (IHD) for RRT in terms of intensive care unit (ICU) and hospital mortality, and renal recovery. We reviewed the records of all patients undergoing RRT for the treatment of ARF over a 12-month period. Patients were compared according to mode of RRT, demographics, physiologic characteristics, and outcomes of ICU and hospital mortality and renal recovery using the Chi square, Student's t test, and multiple logistic regression as appropriate. 116 patients with renal insufficiency underwent RRT during the study period. Of these, 93 had ARF. The severity of illness of CRRT patients was similar to that of IHD patients using APACHE II (25.1 vs 23.5, P = 0.37), but they required significantly more intensive nursing (therapeutic intervention scale 47.8 vs 37.6, P = 0.0001). Mortality was associated with lower pH at presentation (P = 0.003) and increasing age (P = 0.03). Renal recovery was significantly more frequent among patients initially treated with CRRT (21/24 vs 5/14, P = 0.0003). Further investigation to define optimal timing, dose, and duration of RRT may be beneficial. Although further study is needed, this study suggests that renal recovery may be better after CRRT than IHD for ARF. Mortality was not affected significantly by RRT mode.

  5. Renal manifestations in children with Alagille syndrome.

    Science.gov (United States)

    Di Pinto, Diana; Adragna, Marta

    2018-04-01

    Alagille syndrome (AS) is a cholestatic disease secondary to scarcity of interlobular bile ducts. It is associated with extrahepatic manifestations, and renal involvement is frequent. To describe the prevalence, type and outcome of renal pathology in children with AS. The presence and outcome of renal pathology was retrospectively studied in 21 children who met AS criteria. Renal pathology was observed in 18 patients (85.7%): (1) ultrasound variations in 7 patients (6 cases of bilateral renal dysplasia and 1 case of renal agenesis); (2) distal renal tubular acidosis in 2 patients; (3) a drop in glomerular filtration and/or proteinuria in 16 patients. The frequency of a drop in glomerular filtration was similar between patients with and without pathological kidney ultrasound findings. Our study confirms a high prevalence of renal involvement, which enhances the importance of diagnosis and renal function follow-up in children with AS. Sociedad Argentina de Pediatría.

  6. Renal failure in patients with multiple myeloma.

    Science.gov (United States)

    Almueilo, Samir H

    2015-01-01

    Renal dysfunction is encountered in 20-25% of patients with multiple myeloma (MM) at the time of diagnosis. There is often a precipitating event. Several biochemical and clinical correlations with renal failure in MM have been reported. Renal failure in MM is associated with worse outcome of the disease. We retrospectively analyzed the medical records of 64 patients with MM admitted to our institution during the period January 1992 to December 2012. Abnormal renal function was observed in 24 (37.5%) patients and 17 (26.6%) of them had renal failure; 14 of the 17 (82.4%) of patients with renal failure had Stage III MM. Urine Bence- Jones protein was positive in ten (58.8%) patients with renal failure versus ten (21.3%) patients without renal failure (P = 0.004). Potential precipitating factors of renal failure were determined in nine patients. Renal function normalized in 11 patients with simple measures, while six patients required hemodialysis; one remained dialysis dependent till time of death. Early mortality occurred in five (29.4%) patients with renal failure as compared with two (4.3%) patients in the group without renal failure (P = 0.005). In conclusion, renal failure is associated with a higher tumor burden and Bence-Jones proteinuria in patients with MM. It is reversible in the majority of patients; however, early mortality tends to be higher in patients with persistent renal failure.

  7. Renal vasculitis presenting with acute kidney injury.

    Science.gov (United States)

    Villacorta, Javier; Diaz-Crespo, Francisco; Acevedo, Mercedes; Cavero, Teresa; Guerrero, Carmen; Praga, Manuel; Fernandez-Juarez, Gema

    2017-06-01

    Renal failure secondary to ANCA-associated vasculitis represents a clinical and therapeutic challenge. In this study, we aimed to assess the treatment response rates and long-term outcomes of vasculitis patients presenting with renal failure. This retrospective study included 151 patients with renal vasculitis from three hospitals who underwent a renal biopsy between 1997 and 2014. Patients with renal failure which required dialysis at the onset were compared to those presenting with more preserved renal function. The primary end point was treatment response and patient surivival. Patients with severe renal involvement had a lower response to treatment compared to those having preserved renal function (26.6 versus 93.4%; p renal recovery (41.6 versus 12.5%; p = 0.05). A higher incidence of severe infections was observed among patients with severe renal involvement (38.4 versus 18.1%, p = 0.01). The mortality rate was significantly higher among vasculitis patients presenting with renal failure (53.8 versus 22.2%, p = 0.001). Global survival at 1 and 5 years was 60 and 47% in patients requiring dialysis compared with 90 and 80% among those with more preserved renal function (p renal dysfunction represents an independent risk factor for patient survival in renal vasculitis. Patients requiring dialysis associate a lower response rate to immunosuppressive therapy and a higher incidence of severe infections.

  8. Effects of adenosine infusion into renal interstitium on renal hemodynamics

    International Nuclear Information System (INIS)

    Pawlowska, D.; Granger, J.P.; Knox, F.G.

    1987-01-01

    This study was designed to investigate the hemodynamic effects of exogenous adenosine in the interstitium of the rat kidney. Adenosine or its analogues were infused into the renal interstitium by means of chronically implanted capsules. In fusion of adenosine decreased glomerular filtration rate (GFR) from 0.81 +/- 0.06 to 0.37 +/- 0.06 ml/min while having no effect on renal blood flow (RBF). The metabolically stable analogue, 2-chloradenosine (2-ClAdo), decreased GFR from 0.73 +/- 0.07 to 021 +/- 0.06 ml/min. Interstitial infusion of theophylline, an adenosine receptor antagonist, completely abolished the effects of adenosine and 2-ClAdo on GFR. The distribution of adenosine, when infused into the renal interstitium, was determined using radiolabeled 5'-(N-ethyl)-carboxamidoadenosine (NECA), a metabolically stable adenosine agonist. After continuous infusion, [ 3 H]NECA was distributed throughout the kidney. The effects of NECA to reduce GFR were similar to those of adenosine and 2-ClAdo. They conclude that increased levels of adenosine in the renal interstitium markedly decrease GFR without affecting RBF in steady-state conditions. The marked effects of adenosine agonists during their infusion into the renal interstitium and the complete blockade of these effects by theophylline suggest an extracellular action of adenosine

  9. Crisis de esclerodermia renal normotensiva

    Directory of Open Access Journals (Sweden)

    M. Villaverde

    2003-01-01

    Full Text Available Paciente de sexo masculino de 60 años con esclerosis sistémica que evolucionó con crisis de esclerodermia renal normotensiva. Tenía compromiso poliarticular, esofágico, pulmonar y cutáneo. Antes de internarse en nuestro hospital recibió tratamiento con altas dosis de corticoides, lo que probablemente precipitó el daño renal que presentó en su evolución, caracterizado por falla renal, anemia hemolítica microangiopática sin elevación de la presión arterial. La ausencia de hipertensión se observa sólo en el 10% de los casos de esclerodermia renal. Recibió tratamiento con enalapril y hemodiálisis. Evolucionó en forma desfavorable, sin respuesta a la terapeútica y falleció a los siete días de internado.A 60 year old male patient having systemic scleroderma and normotensive scleroderma renal crisis was admitted in our hospital. He presented polyarticular, esophagic, lung and skin compromise. Before admission he had been treated with high doses of corticosteroids. We believe corticosteroids led to the worsening of renal damage with renal failure, microangiopathic hemolytic anemia without high blood pressure. The 10% of these cases have normal blood pressure. The patient was treated with enalapril and hemodyalisis. There was no favourable response to this treatment and he died seven days after admission.

  10. Dynamic CT of the renal parenchyma

    International Nuclear Information System (INIS)

    Ohyama, Yukio; Imanishi, Yoshimasa; Ishikawa, Tohru; Fujii, Masamichi; Uji, Teruyuki

    1985-01-01

    Normal renal dynamic CT findings of 57 cases were analysed in termes of sequential change of renal parenchymal CT image. Cortex, outer medulla and inner medulla were delineated and their sequential CT image was well correlated with the anatomicophysiological character of the kidney. Dynamic CT of 32 abnormal cases showed abnormal sequential CT findings explaining the mechanism of the abnormalities. Especially, delayed enhancement of renal cortex was noted in 17 of 19 kidneys with arterial obstruction and delayed enhancement of renal medulla in 22 of 25 cases with renal dysfunction. Compaired with excretory urography in 11 cases with renal dysfunction, advantage of dynamic CT were noted. (author)

  11. CT imaging spectrum of infiltrative renal diseases.

    Science.gov (United States)

    Ballard, David H; De Alba, Luis; Migliaro, Matias; Previgliano, Carlos H; Sangster, Guillermo P

    2017-11-01

    Most renal lesions replace the renal parenchyma as a focal space-occupying mass with borders distinguishing the mass from normal parenchyma. However, some renal lesions exhibit interstitial infiltration-a process that permeates the renal parenchyma by using the normal renal architecture for growth. These infiltrative lesions frequently show nonspecific patterns that lead to little or no contour deformity and have ill-defined borders on CT, making detection and diagnosis challenging. The purpose of this pictorial essay is to describe the CT imaging findings of various conditions that may manifest as infiltrative renal lesions.

  12. CT differentiation of infiltrating renal cell carcinoma and renal urothelial tumor

    International Nuclear Information System (INIS)

    Choi, Hyo Kyeong; Goo, Dong Erk; Bang, Sun Woo; Lee, Moon Gyu; Cho, Kyoung Sik; Auh, Yong Ho

    1994-01-01

    It may be difficult to differentiate renal cell carcinoma involving collecting system from renal urothelial tumor invading into renal parenchyma. The purpose of this study was to assess the differences of CT findings between two conditions. CT findings of 5 cases of renal cell carcinoma involving the renal collecting systems and 10 cases of renal urothelial tumors invading the renal parenchyma were compared, and analyzed about the presence or absence of hydronephrosis, normal or abnormal CT nephrogram, renal contour changes due to mass and tentative diagnosis. The diagnoses were confirmed at surgery. Renal cell carcinoma showed hydronephrosis in only 20% and normal CT nephrogram and outward contour bulging in all cases. In contrast, renal urothelial tumor showed hydronephrosis(70%), abnormal CT nephrogram(60%), and preservation of reinform shape(100%). Renal contour changes and CT nephrogram may be useful in distinguishing both disease entities

  13. Reversed electrogenic sodium bicarbonate cotransporter 1 is the major acid loader during recovery from cytosolic alkalosis in mouse cortical astrocytes.

    Science.gov (United States)

    Theparambil, Shefeeq M; Naoshin, Zinnia; Thyssen, Anne; Deitmer, Joachim W

    2015-08-15

    The regulation of H(+) i from cytosolic alkalosis has generally been attributed to the activity of Cl(-) -coupled acid loaders/base extruders in most cell types, including brain cells. The present study demonstrates that outwardly-directed sodium bicarbonate cotransport via electrogenic sodium bicarbonate cotransporter 1 (NBCe1) mediates the major fraction of H(+) i regulation from cytosolic alkalosis in mouse cortical astrocytes. Cl(-) -coupled acid-loading transporters play only a minor role in the regulation of H(+) i from alkalosis in mouse cortical astrocytes. NBCe1-mediated H(+) i regulation from alkalosis was dominant, with the support of intracellular carbonic anhydrase II, even when the intra- and extracellular [HCO3 (-) ] was very low (sodium bicarbonate cotransporter 1 (NBCe1) and for carbonic anhydrase (CA) isoform II. An acute cytosolic alkalosis was induced by the removal of either CO2 /HCO3 (-) or butyric acid, and the subsequent acid loading was analysed by monitoring changes in cytosolic H(+) or Na(+) using ion-sensitive fluorescent dyes. We have identified that NBCe1 reverses during alkalosis and contributes more than 70% to the rate of recovery from alkalosis by extruding Na(+) and HCO3 (-) . After CA inhibition or in CAII-knockout (KO) cells, the rate of recovery was reduced by 40%, and even by 70% in the nominal absence of CO2 /HCO3 (-) . Increasing the extracellular K(+) concentration modulated the rate of acid loading in wild-type cells, but not in NBCe1-KO cells. Removing chloride had only a minor effect on the recovery from alkalosis. Reversal of NBCe1 by reducing pH/[HCO3 (-) ] was demonstrated in astrocytes and in Xenopus oocytes, in which human NBCe1 was heterologously expressed. The results obtained suggest that reversed NBCe1, supported by CAII activity, plays a major role in acid-loading cortical astrocytes to support recovery from cytosolic alkalosis. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

  14. Hyperdense renal masses: a CT manifestation of hemorrhagic renal cysts

    International Nuclear Information System (INIS)

    Sussman, S.; Cochran, S.T.; Pagani, J.J.; McArdle, C.; Wong, W.; Austin, R.; Curry, N.; Kelly, K.M.

    1984-01-01

    Eleven patients with sharply circumscribed round to ovoid renal cysts measuring 70-90 H on CT are reported. The cysts were hyperdense on unenhanced scans, measuring 30-60 H greater than the adjacent parenchyma, and either hypodense, isodense, or hyperdense on enhanced scans. Four patients had polycystic kidney disease; of the other 7 patients, the cysts were cortical in 6 and parapelvic in 1. Eight patients had a solitary cyst and 3 had multiple cysts. Sonography demonstrated internal echoes and/or lack of increased through-transmission in 6 patients. Pathological analysis was available in 6 cases and indicated a benign, hemorrhagic renal cyst. This hyperdense CT appearance is characteristic of some hemorrhagic renal cysts, though differentiation between benign and malignant cysts requires cyst puncture and/or surgery

  15. [Renal hemorrhage after ESWL: From small hematoma to renal blowout].

    Science.gov (United States)

    Panach-Navarrete, Jorge; Palmero Martí, Jose Luis; Ganau Ituren, Amparo; Pastor Lence, Juan Carlos; Benedicto Redón, Antonio

    2016-04-01

    To report two cases of renal hemorrhage after extracorporeal shock wave lithotripsy (ESWL) and their therapeutic management. Description of the clinical cases, together with the diagnosis and therapeutic management of these complications. We present two cases of patients with renal hemorrhage after ESWL, which were performed without immediate complications. One of the cases, after detecting an important laceration of the renal parenchyma, needed two embolization sessions for its short-term resolution; however, the patient finally passed away due to the complications derived from hemorrhage. The other case was solved through conservative management. Even though hemorrhage is an infrequent complication after ESWL, it should be suspected when the patient presents compatible clinical symptoms, since even though most cases are resolved in a conservative manner, on some occasions specific treatments for the hemorrhage are necessary. Old age and the presence of vascular comorbidities seem to be related to a higher risk of hemorrhage after ESWL.

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

    Science.gov (United States)

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

    2018-06-01

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

  17. Acute renal failure in rats

    International Nuclear Information System (INIS)

    Cederholm, C.; Almen, T.; Bergquist, D.; Golman, K.; Takolander, R.; Malmoe Allmaenna Sjukhus

    1989-01-01

    It was demonstrated in rats that renal injury which follows transient renal hypoxia is potentiated by the contrast media metrizoate, ioxaglate, iopamidol and iohexol. Intravenous injection of 1 g I/kg of all four media alone to 82 rats caused no significant increase in serum urea 1, 3 and 7 days later. The percentage increase of serum urea is given in median values and interquartile range (in parentheses). Bilateral renal arterial occlusion alone for 40 minutes in 42 rats increased serum urea one day later by 40% (20-130). Intravenous injection of the media followed in one hour by bilateral renal arterial occlusion for 40 minutes in 104 rats caused serum urea to increase one day later by 130% (70-350) after metrizoate, by 220% (50-380) after ioxaglate, by 290 % (60-420) after iopamidol and by 160% (50-330) after iohexol. There were no significant differences between the potentiating effects of the various media on ischemic renal failure. (orig.)

  18. Using Bacterial Surrogates to Assess Pathogen Transport in the Subsurface: Laboratory and Field Indications of Co-Transport Considerations

    Science.gov (United States)

    Emelko, M.; Stimson, J. R.; McLellan, N. L.; Mesquita, M.

    2009-12-01

    processes such as RBF. Here, duplicate column studies were conducted to evaluate the transport of nano- and micro-sized polystyrene micropsheres, aerobic spores of Bacillus subtilis, PR772 bacteriophage, and pathogenic Salmonella typhimurium bacteria in a well-sorted fine sand (d 50 = 0.6 mm). A field validation experiment investigating transport of 1.5 µm polystyrene micropsheres and aerobic spores in and RBF system comprised of unconsolidated silty sand, gravel, and boulders was conducted. The column studies demonstrated that the presence of the aerobic spores resulted in increased removal of 4.5 µm microspheres from< 2 log to ~4 log, and 1.5 µm microsphere removal from <0.5 log to ~1 log removal. Microscopic examination of the samples also revealed extensive clumping of microspheres and microorganisms during the experiments conducted with aerobic spores. A field trial during which microspheres and spores of B. subtilis were injected into the subsurface provided corroborating evidence of a co-transport effect of aerobic spores by demonstrating ~1.6 log increase in 1.5 µm microsphere removal in the presence of aerobic spores.

  19. Massive postpartum right renal hemorrhage.

    Science.gov (United States)

    Kiracofe, H L; Peterson, N

    1975-06-01

    All reported cases of massive postpartum right renal hemorrhage have involved healthy young primigravidas and blacks have predominated (4 of 7 women). Coagulopathies and underlying renal disease have been absent. Hematuria was painless in 5 of 8 cases. Hemorrhage began within 24 hours in 1 case, within 48 hours in 4 cases and 4 days post partum in 3 cases. Our first case is the only report in which hemorrhage has occurred in a primipara. Failure of closure or reopening of pyelovenous channels is suggested as the pathogenesis. The hemorrhage has been self-limiting, requiring no more than 1,500 cc whole blood replacement. Bleeding should stop spontaneously, and rapid renal pelvic clot lysis should follow with maintenance of adequate urine output and Foley catheter bladder decompression. To date surgical intervention has not been necessary.

  20. Renal Myxoma, an Incidental Finding

    Directory of Open Access Journals (Sweden)

    Parth Thakker

    2017-07-01

    Full Text Available Myxomas are mesenchymal tumors commonly found in the heart and skin. Renal myxomas are rare, having only been documented 14 times. Our case is a 55-year-old woman who presented to our clinic after a right renal mass was incidentally found on CT. Evaluation with MRI showed a mass that appeared to arise from the supero-medial cortex of the right kidney. As the imaging was concerning for renal cell carcinoma, the patient underwent a partial nephrectomy. Microscopic examination showed a well-circumscribed mass with polygonal to spindle-shaped cells in a granular eosinophilic cytoplasm. Immunohistochemical staining for CD-10, Desmin, HMB-45, and Pankeratin were negative.

  1. Renal diseases in AIDS patients

    OpenAIRE

    Álvarez Escobar, María del Carmen; Alfonso de León, José Alberto; Lima Gutiérrez, Héctor; Torres Álvarez, Armella; Torres Álvarez, Arling Yuliett

    2009-01-01

    La afectación renal en el SIDA es un tema poco abordado a pesar de su frecuencia, la misma depende de la acción directa e indirecta del virus, así como de las complicaciones y del tratamiento. La más frecuente de las complicaciones es la Insuficiencia Renal Aguda. La forma más típica de nefropatía asociada al VIH (NAVIH) se caracteriza por alto grado de proteinuria con progresión rápida a Insuficiencia Renal Terminal. En el SIDA se presentan diversas formas de glomerulopatías cuya expresión c...

  2. CT of the renal infarction

    International Nuclear Information System (INIS)

    Tazawa, Satoru; Ito, Hisao; Tange, Isamu

    1984-01-01

    We have five cases of the global renal infarction, four of which resulted from post-transarterial embolization(TAE) of the hypernephroma, the remaining one was probably caused by the cardiac disease. Generally speaking, CE-CT is useful for the diagnosis of the acute renal infarction, because the ''rim sign'' which represents viable subcapsular parenchyma is helpful for the diagnosis. It seems that band-like enhancement from the renal sinus to the periphery in the low-attenuation-parenchyma on CE-CT, named as ''band sign'', is useful for the diagnosis. ''Band sign'' may also be valuable for distinguishing the neoplastic area from the non-neoplastic one after TAE of the hypernephroma. (author)

  3. Radiologic observation of renal tuberculosis

    International Nuclear Information System (INIS)

    Kim, S. W.; Ra, Y. W.; Kim, Y. J.

    1981-01-01

    Radiographic findings of thirty eight cases of renal tuberculosis treated at this hospital during last 4 years were analysed with following results. The cases examined were 24 male and 14 female patients. Age distribution was broad and evenly distributed ranging from 2nd decades to 5th decades. Main symptoms complained were urinary frequency, hematuria, dysuria and flank pain. Findings of physical examination revealed tenderness of costovertebral angle, palpable mass on flank area and epididymal indutration. The simple chest films showed pulmonary tuberculosis in 22 cases including 6 cases of active military type. Thirty one cases showed increased ESR, 8 cases showed AFB positive in urine and 12 cases showed bilateral renal tuberculosis. Through urographic findings nonvisualization, cyceopelviectasis, motheaten appearance of minor calyx, contracted bladder, delayed visualization, ureteral stricture and beading were observed in order of frequency. Five cases with miliary tuberculosis showed advanced renal lesion on urogram

  4. Renal replacement therapy in Europe

    DEFF Research Database (Denmark)

    Noordzij, Marlies; Kramer, Anneke; Abad Diez, José M

    2014-01-01

    the Mediterranean Sea were used. From 27 registries, individual patient data were received, whereas 17 registries contributed data in aggregated form. We present the incidence and prevalence of RRT, and renal transplant rates in 2011. In addition, survival probabilities and expected remaining lifetimes were....... The overall unadjusted prevalence of RRT for ESRD on 31 December 2011 was 692 pmp (n = 425 824). The highest prevalence was reported by Portugal (1662 pmp) and the lowest by Ukraine (131 pmp). Among all registries, a total of 22 814 renal transplantations were performed (37 pmp). The highest overall.......6-47.0], and on dialysis 39.3% (95% CI 39.2-39.4). The unadjusted 5-year patient survival after the first renal transplantation performed between 2002 and 2006 was 86.7% (95% CI 86.2-87.2) for kidneys from deceased donors and 94.3% (95% CI 93.6-95.0) for kidneys from living donors....

  5. CT diagnosis of simple renal cysts

    International Nuclear Information System (INIS)

    Nanakawa, Seito; Yasunaga, Tadamasa; Tsuchigame, Tadatoshi; Kawano, Shoji; Takahashi, Mutsumasa; Fukui, Koutaro.

    1987-01-01

    CT is indispensable in the evaluation of renal masses, providing noninvasive and clear transverse images. With wider clinical application of CT, renal cysts have been found more frequently. CT examinations on 500 patients, who underwent CT for the diagnosis of renal diseases except for renal cysts, have been reviewed and analysed. The incidence of renal cysts was 9.6 % without prediction for sexes, but the incidence and sizes of the cysts increased with the advancing age. The upper portion of the kidneys was more frequently involved, but there was no relationship between number, sex and age of the patients. Since renal cysts produce mass effect in the kidneys, understanding of the nature and incidence of the renal cysts is important in diagnosing renal mass lesions. (author)

  6. Drugs Approved for Kidney (Renal Cell) Cancer

    Science.gov (United States)

    ... Your Treatment Research Drugs Approved for Kidney (Renal Cell) Cancer This page lists cancer drugs approved by the ... not listed here. Drugs Approved for Kidney (Renal Cell) Cancer Afinitor (Everolimus) Aldesleukin Avastin (Bevacizumab) Axitinib Bevacizumab Cabometyx ( ...

  7. Radionuclide renal dynamic and function study

    International Nuclear Information System (INIS)

    Guan Liang

    1991-01-01

    The radionuclide dynamic and function study, glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were reported in 14 cases of renal and ureteral calculi patients before and after extracorporeal shock wave lithotripsy (ESWL). In 12 cases with normal renal blood flow, within 3 months after ESWL, the GFR of shock and non-shock side decreased with different extent, while the individual ERPF had little change. In 5 cases followed up 1 year after ESWL, the individual GFR and ERPF were normal. In 2 cases of severe renal function insufficiency, there was no improvement in renal function in shock side, after 5 months and 1 year, the renal function was still at low level. Thereby it is considered that ESWL is not suitable for the renal calculi patients with severe renal function insufficiency

  8. Physiology and pathophysiology of Na+/H+ exchange and Na+-K+-2Cl- cotransport in the heart, brain, and blood

    DEFF Research Database (Denmark)

    Pedersen, S. F.; O´Donnell, M. E.; Anderson, S. E.

    2006-01-01

    Maintenance of a stable cell volume and intracellular pH is critical for normal cell function. Arguably, two of the most important ion transporters involved in these processes are the Na+/H+ exchanger isoform 1 (NHE1) and Na+-K+-2Cl- cotransporter isoform 1 (NKCC1). Both NHE1 and NKCC1....... The aim is to provide a comprehensive overview of the mechanisms and consequences of stress-induced stimulation of these transporters with focus on the heart, brain, and blood. The physiological stressors reviewed are metabolic/exercise stress, osmotic stress, and mechanical stress, conditions in which...... are stimulated by cell shrinkage and by numerous other stimuli, including a wide range of hormones and growth factors, and for NHE1, intracellular acidification. Both transporters can be important regulators of cell volume, yet their activity also, directly or indirectly, affects the intracellular concentrations...

  9. In vitro characterization of luseogliflozin, a potent and competitive sodium glucose co-transporter 2 inhibitor: Inhibition kinetics and binding studies

    Directory of Open Access Journals (Sweden)

    Saeko Uchida

    2015-05-01

    Full Text Available In this study, we evaluated an inhibition model of luseogliflozin on sodium glucose co-transporter 2 (SGLT2. We also analyzed the binding kinetics of the drug to SGLT2 protein using [3H]-luseogliflozin. Luseogliflozin competitively inhibited human SGLT2 (hSGLT2-mediated glucose uptake with a Ki value of 1.10 nM. In the absence of glucose, [3H]-luseogliflozin exhibited a high affinity for hSGLT2 with a Kd value of 1.3 nM. The dissociation half-time was 7 h, suggesting that luseogliflozin dissociates rather slowly from hSGLT2. These profiles of luseogliflozin might contribute to the long duration of action of this drug.

  10. Renal endothelial function and blood flow predict the individual susceptibility to adriamycin-induced renal damage

    NARCIS (Netherlands)

    Ochodnicky, Peter; Henning, Robert H.; Buikema, Hendrik; Kluppel, Alex C. A.; van Wattum, Marjolein; de Zeeuw, Dick; van Dokkum, Richard P. E.

    2009-01-01

    Susceptibility to renal injury varies among individuals. Previously, we found that individual endothelial function of healthy renal arteries in vitro predicted severity of renal damage after 5/6 nephrectomy. Here we hypothesized that individual differences in endothelial function in vitro and renal

  11. The renal arterial resistive index and stage of chronic kidney disease in patients with renal allograft

    DEFF Research Database (Denmark)

    Winther, Stine O; Thiesson, Helle C; Poulsen, Lene N

    2012-01-01

    The study investigated the optimal threshold value of renal arterial resistive index as assessed by Doppler ultrasonography determining chronic kidney disease stage 4 or higher in patients with renal allograft.......The study investigated the optimal threshold value of renal arterial resistive index as assessed by Doppler ultrasonography determining chronic kidney disease stage 4 or higher in patients with renal allograft....

  12. Bumetanide kinetics in renal failure

    International Nuclear Information System (INIS)

    Pentikaeinen, P.J.P.; Pasternack, A.; Lampainen, E.; Neuvonen, P.J.; Penttilae, A.

    1985-01-01

    To study the effects of renal failure on bumetanide kinetics, the authors administered single intravenous doses of 1.0 mg/3.08 microCi 14 C-bumetanide to six healthy subjects and 22 patients with variable degrees of renal failure. The kinetics of 14 C-bumetanide and total 14 C were adequately described by a two-compartment open model in the control subjects and in the patients. The volume of the central compartment and the distribution t1/2 were of the same order in both groups, whereas the mean (+/- SE) volume at steady state was larger (22.1 +/- 1.6 and 16.9 +/- 1.0 L) and the elimination t1/2 was longer (1.9 +/- 0.2 and 1.4 +/- 0.1 hours) in patients with renal failure than in healthy controls. Bumetanide renal clearance was lower (10 +/- 3 and 90 +/- 13 ml/min) in patients than in subjects and correlated with creatinine clearance (r = 0.784) and log serum creatinine level (r = -0.843), whereas nonrenal clearance was significantly higher in the patients (153 +/- 14 and 99 +/- 6 ml/min). Bumetanide total plasma clearance did not significantly change. The non-protein-bound, free fraction of bumetanide was higher in patients and correlated with plasma albumin levels (r = -0.777). The kinetics of total 14 C showed similar but greater changes than those of 14C-bumetanide. Thus the most important changes in bumetanide kinetics in patients with renal failure are low renal clearance and a high free fraction, with a consequent increase in nonrenal clearance, volume of distribution, and elimination t1/2

  13. Molecular mechanisms of renal aging.

    Science.gov (United States)

    Schmitt, Roland; Melk, Anette

    2017-09-01

    Epidemiologic, clinical, and molecular evidence suggest that aging is a major contributor to the increasing incidence of acute kidney injury and chronic kidney disease. The aging kidney undergoes complex changes that predispose to renal pathology. The underlying molecular mechanisms could be the target of therapeutic strategies in the future. Here, we summarize recent insight into cellular and molecular processes that have been shown to contribute to the renal aging phenotype.The main clinical finding of renal aging is the decrease in glomerular filtration rate, and its structural correlate is the loss of functioning nephrons. Mechanistically, this has been linked to different processes, such as podocyte hypertrophy, glomerulosclerosis, tubular atrophy, and gradual microvascular rarefaction. Renal functional recovery after an episode of acute kidney injury is significantly worse in elderly patients. This decreased regenerative potential, which is a hallmark of the aging process, may be caused by cellular senescence. Accumulation of senescent cells could explain insufficient repair and functional loss, a view that has been strengthened by recent studies showing that removal of senescent cells results in attenuation of renal aging. Other potential mechanisms are alterations in autophagy as an important component of a disturbed renal stress response and functional differences in the inflammatory system. Promising therapeutic measures to counteract these age-related problems include mimetics of caloric restriction, pharmacologic renin-angiotensin-aldosterone system inhibition, and novel strategies of senotherapy with the goal of reducing the number of senescent cells to decrease aging-related disease in the kidney. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  14. The Role of Na:K:2Cl Cotransporter 1 (NKCC1/SLC12A2) in Dental Epithelium during Enamel Formation in Mice

    Science.gov (United States)

    Jalali, Rozita; Lodder, Johannes C.; Zandieh-Doulabi, Behrouz; Micha, Dimitra; Melvin, James E.; Catalan, Marcelo A.; Mansvelder, Huibert D.; DenBesten, Pamela; Bronckers, Antonius

    2017-01-01

    Na+:K+:2Cl− cotransporters (NKCCs) belong to the SLC12A family of cation-coupled Cl− transporters. We investigated whether enamel-producing mouse ameloblasts express NKCCs. Transcripts for Nkcc1 were identified in the mouse dental epithelium by RT-qPCR and NKCC1 protein was immunolocalized in outer enamel epithelium and in the papillary layer but not the ameloblast layer. In incisors of Nkcc1-null mice late maturation ameloblasts were disorganized, shorter and the mineral density of the enamel was reduced by 10% compared to wild-type controls. Protein levels of gap junction protein connexin 43, Na+-dependent bicarbonate cotransporter e1 (NBCe1), and the Cl−-dependent bicarbonate exchangers SLC26A3 and SLC26A6 were upregulated in Nkcc1-null enamel organs while the level of NCKX4/SLC24A4, the major K+, Na+ dependent Ca2+ transporter in maturation ameloblasts, was slightly downregulated. Whole-cell voltage clamp studies on rat ameloblast-like HAT-7 cells indicated that bumetanide increased ion-channel activity conducting outward currents. Bumetanide also reduced cell volume of HAT-7 cells. We concluded that non-ameloblast dental epithelium expresses NKCC1 to regulate cell volume in enamel organ and provide ameloblasts with Na+, K+ and Cl− ions required for the transport of mineral- and bicarbonate-ions into enamel. Absence of functional Nkcc1 likely is compensated by other types of ion channels and ion transporters. The increased amount of Cx43 in enamel organ cells in Nkcc1-null mice suggests that these cells display a higher number of gap junctions to increase intercellular communication. PMID:29209227

  15. Essential role of the electroneutral Na+-HCO3- cotransporter NBCn1 in murine duodenal acid-base balance and colonic mucus layer build-up in vivo.

    Science.gov (United States)

    Singh, Anurag Kumar; Xia, Weiliang; Riederer, Brigitte; Juric, Marina; Li, Junhua; Zheng, Wen; Cinar, Ayhan; Xiao, Fang; Bachmann, Oliver; Song, Penghong; Praetorius, Jeppe; Aalkjaer, Christian; Seidler, Ursula

    2013-04-15

    Duodenal epithelial cells need efficient defence strategies during gastric acidification of the lumen, while colonic mucosa counteracts damage by pathogens by building up a bacteria-free adherent mucus layer. Transport of HCO3(-) is considered crucial for duodenal defence against acid as well as for mucus release and expansion, but the transport pathways involved are incompletely understood. This study investigated the significance of the electroneutral Na(+)-HCO3(-) cotransporter NBCn1 for duodenal defence against acid and colonic mucus release. NBCn1 was localized to the basolateral membrane of duodenal villous enterocytes and of colonic crypt cells, with predominant expression in goblet cells. Duodenal villous enterocyte intracellular pH was studied before and during a luminal acid load by two-photon microscopy in exteriorized, vascularly perfused, indicator (SNARF-1 AM)-loaded duodenum of isoflurane-anaesthetized, systemic acid-base-controlled mice. Acid-induced HCO3(-) secretion was measured in vivo by single-pass perfusion and pH-stat titration. After a luminal acid load, NBCn1-deficient duodenocytes were unable to recover rapidly from intracellular acidification and could not respond adequately with protective HCO3(-) secretion. In the colon, build-up of the mucus layer was delayed, and a decreased thickness of the adherent mucus layer was observed, suggesting that basolateral HCO3(-) uptake is essential for optimal release of mucus. The electroneutral Na(+)-HCO3(-) cotransporter NBCn1 displays a differential cellular distribution in the murine intestine and is essential for HCO3(-)-dependent mucosal protective functions, such as recovery of intracellular pH and HCO3(-) secretion in the duodenum and secretion of mucus in the colon.

  16. Phosphorylation and transport in the Na-K-2Cl cotransporters, NKCC1 and NKCC2A, compared in HEK-293 cells.

    Directory of Open Access Journals (Sweden)

    Anke Hannemann

    2011-03-01

    Full Text Available Na-K-2Cl cotransporters help determine cell composition and volume. NKCC1 is widely distributed whilst NKCC2 is only found in the kidney where it plays a vital role reabsorbing 20% of filtered NaCl. NKCC2 regulation is poorly understood because of its restricted distribution and difficulties with its expression in mammalian cell cultures. Here we compare phosphorylation of the N-termini of the cotransporters, measured with phospho-specific antibodies, with bumetanide-sensitive transport of K(+ ((86Rb(+ (activity in HEK-293 cells stably expressing fNKCC1 or fNKCC2A which were cloned from ferret kidney. Activities of transfected transporters were distinguished from those of endogenous ones by working at 37 °C. fNKCC1 and fNKCC2A activities were highest after pre-incubation of cells in hypotonic low-[Cl(-] media to reduce cell [Cl(-] and volume during flux measurement. Phosphorylation of both transporters more than doubled. Pre-incubation with ouabain also strongly stimulated fNKCC1 and fNKCC2A and substantially increased phosphorylation, whereas pre-incubation in Na(+-free media maximally stimulated fNKCC1 and doubled its phosphorylation, but inhibited fNKCC2A, with a small increase in its phosphorylation. Kinase inhibitors halved phosphorylation and activity of both transporters whereas inhibition of phosphatases with calyculin A strongly increased phosphorylation of both transporters but only slightly stimulated fNKCC1 and inhibited fNCCC2A. Thus kinase inhibition reduced phosphorylation and transport, and transport stimulation was only seen when phosphorylation increased, but transport did not always increase with phosphorylation. This suggests phosphorylation of the N-termini determines the transporters' potential capacity to move ions, but final activity also depends on other factors. Transport cannot be reliably inferred solely using phospho-specific antibodies on whole-cell lysates.

  17. Phosphorylation and transport in the Na-K-2Cl cotransporters, NKCC1 and NKCC2A, compared in HEK-293 cells.

    Science.gov (United States)

    Hannemann, Anke; Flatman, Peter W

    2011-03-25

    Na-K-2Cl cotransporters help determine cell composition and volume. NKCC1 is widely distributed whilst NKCC2 is only found in the kidney where it plays a vital role reabsorbing 20% of filtered NaCl. NKCC2 regulation is poorly understood because of its restricted distribution and difficulties with its expression in mammalian cell cultures. Here we compare phosphorylation of the N-termini of the cotransporters, measured with phospho-specific antibodies, with bumetanide-sensitive transport of K(+) ((86)Rb(+)) (activity) in HEK-293 cells stably expressing fNKCC1 or fNKCC2A which were cloned from ferret kidney. Activities of transfected transporters were distinguished from those of endogenous ones by working at 37 °C. fNKCC1 and fNKCC2A activities were highest after pre-incubation of cells in hypotonic low-[Cl(-)] media to reduce cell [Cl(-)] and volume during flux measurement. Phosphorylation of both transporters more than doubled. Pre-incubation with ouabain also strongly stimulated fNKCC1 and fNKCC2A and substantially increased phosphorylation, whereas pre-incubation in Na(+)-free media maximally stimulated fNKCC1 and doubled its phosphorylation, but inhibited fNKCC2A, with a small increase in its phosphorylation. Kinase inhibitors halved phosphorylation and activity of both transporters whereas inhibition of phosphatases with calyculin A strongly increased phosphorylation of both transporters but only slightly stimulated fNKCC1 and inhibited fNCCC2A. Thus kinase inhibition reduced phosphorylation and transport, and transport stimulation was only seen when phosphorylation increased, but transport did not always increase with phosphorylation. This suggests phosphorylation of the N-termini determines the transporters' potential capacity to move ions, but final activity also depends on other factors. Transport cannot be reliably inferred solely using phospho-specific antibodies on whole-cell lysates.

  18. Renal dysplasia in a Rhodesian Ridgeback dog

    International Nuclear Information System (INIS)

    Lobetti, R.G.; Pearson, J.; Jimenez, M.

    1996-01-01

    A six-month-old Rhodesian ridgeback dog was presented for evaluation of facial swelling. Chronic renal failure was clinically diagnosed based on urinalysis, biochemical changes and ultrasonography. The facial swelling was due to fibrous osteodystrophy, which was evident on survey radiographs of the skull. On post mortem examination, chronic renal failure as a result of renal dysplasia was confirmed. This is the first reported case of renal dysplasia in this breed of dog

  19. Study of acute renal insufficiency and chronic renal insufficiency using radioisotopes

    International Nuclear Information System (INIS)

    Raynaud, C.

    1976-01-01

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

  20. Acute renal infarction Secondary to Atrial Fibrillation Mimicking Renal Stone Picture

    International Nuclear Information System (INIS)

    Salih, Salih Bin; Al-Durihim, H.; Al-Jizeeri, A.; Al-Maziad, G.

    2006-01-01

    Acute renal infarction presents in a similar clinical picture to that of a renal stone. We report a 55-year-old Saudi female, known to have atrial fibrillation secondary to mitral stenosis due to rheumatic heart disease. She presented with a two day history of right flank pain that was treated initially as renal stone. Further investigations confirmed her as a case of renal infarction. Renal infarction is under-diagnosed because the similarity of its presentation to renal stone. Renal infarction should be considered in the differential diagnosis of loin pain, particularly in a patient with atrial fibrillation. (author)

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

    DEFF Research Database (Denmark)

    Hornum, Mads; Feldt-Rasmussen, Bo

    2017-01-01

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

  2. Sonographic findings of renal tuberculosis

    International Nuclear Information System (INIS)

    Yoon, Chong Hyun; Lee, Chang Joon; Kim, Seung Hyun

    1990-01-01

    In order to determine sonographic characteristic of renal tuberculosis, we retrospectively collected 27 cases during a 5 year period. Infected kidneys showed large size (52%) and lobulating contour (76%). In 19 cases of increased parenchymal echogenicity, most of them (16 cases) showed decreased parenchymal thickness. We divided hydronephrotic patterns into 4 categories; predominant calyceal dilatation with mild or no pelvic dilatation (67%), focal calyectasis without pelvic dilation (15%), parenchymal cavitation without hydronephrosis (11%) and proportional hydronephrosis with calyceal deformity (7%). Our findings suggest that disproportional hydronephrosis would be the characteristic finding of renal tuberculosis

  3. Renal pelvis urothelial carcinoma of the upper moiety in complete right renal duplex: a case report.

    Science.gov (United States)

    Zhang, Yiran; Yu, Quanfeng; Zhang, Zhihong; Liu, Ranlu; Xu, Yong

    2015-01-01

    Urothelial carcinoma (UC) originated from renal pelvis is the common tumor of the urinary system, however, neoplasia of the renal pelvis in duplex kidneys is extremely rare, especially in the complete renal and ureteral duplex cases. We present the first case of renal pelvis UC of the upper moiety in a complete right renal duplex. This male patient has bilateral complete renal and ureteral duplex. To the best of our knowledge, this is the first reported case of renal pelvis UC in a complete renal duplex system. After this experience we feel that the diagnosis of renal pelvis UC in duplex kidneys is not so easy, and once the diagnosis is determined, the whole renal duplex units and bladder cuff or ectopic orifice should be excised radically.

  4. Salvageability of renal function following renal revascularisation in ...

    African Journals Online (AJOL)

    reported on the outcome of hypertension in a cohort of patients with Takayasu's ... Against Rheumatism/Paediatric Rheumatology European Society ... Association guidelines for reporting of renal artery revascularisation .... reversing the dialysis dependence of 2 of the 3 patients who were .... Clinical Practice Guidelines.

  5. Maternal drugs and neonatal renal failure

    Directory of Open Access Journals (Sweden)

    M Sahay

    2014-01-01

    Full Text Available Maternal use of drugs during pregnancy may cause irreversible renal failure in the newborn. This report highlights the adverse effect of telmisartan during the last trimester of pregnancy. The neonate presented with oliguric renal failure and the renal histology showed proximal tubular dysgenesis.

  6. Hypogonadism and renal failure: An update.

    Science.gov (United States)

    Thirumavalavan, Nannan; Wilken, Nathan A; Ramasamy, Ranjith

    2015-01-01

    The prevalence of both hypogonadism and renal failure is increasing. Hypogonadism in men with renal failure carries with it significant morbidity, including anemia and premature cardiovascular disease. It remains unclear whether testosterone therapy can affect the morbidity and mortality associated with renal failure. As such, in this review, we sought to evaluate the current literature addressing hypogonadism and testosterone replacement, specifically in men with renal failure. The articles chosen for this review were selected by performing a broad search using Pubmed, Embase and Scopus including the terms hypogonadism and renal failure from 1990 to the present. This review is based on both primary sources as well as review articles. Hypogonadism in renal failure has a multifactorial etiology, including co-morbid conditions such as diabetes, hypertension, old age and obesity. Renal failure can lead to decreased luteinizing hormone production and decreased prolactin clearance that could impair testosterone production. Given the increasing prevalence of hypogonadism and the potential morbidity associated with hypogonadism in men with renal failure, careful evaluation of serum testosterone would be valuable. Testosterone replacement therapy should be considered in men with symptomatic hypogonadism and renal failure, and may ameliorate some of the morbidity associated with renal failure. Patients with all stages of renal disease are at an increased risk of hypogonadism that could be associated with significant morbidity. Testosterone replacement therapy may reduce some of the morbidity of renal failure, although it carries risk.

  7. Relationship Between Adult Renal Dimensions and Biometric ...

    African Journals Online (AJOL)

    We measured renal dimensions sonographically and correlated the values obtained with some anthropometric parameters in order to identify the best estimate of renal size in a clinical setting. The renal dimensions of 200 adult subjects referred for abdomino-pelvic scan at University of Nigeria Teaching Hospital, Enugu ...

  8. Protein restriction in chronic renal failure

    NARCIS (Netherlands)

    ECHTEN, JEKT; NAUTA, J; HOP, WCJ; de Jong, MCJ; REITSMABIERENS, WCC; VANAMSTEL, SLBP; VANACKER, KJ; NOORDZIJ, CM; WOLFF, ED

    The aim of the study was to investigate the effect of a protein restricted diet on renal function and growth of children with chronic renal failure. In a multicentre prospective study 56 children (aged 2-18 years) with chronic renal failure were randomly assigned to the protein restricted (0.8-1.1

  9. Primary Renal Carcinoid - A Case Report

    LENUS (Irish Health Repository)

    O’Sullivan, M

    2018-01-01

    Carcinoid tumours in the abdomen are uncommon, but typically occur in the gastrointestinal tract. Primary renal carcinoid is an extremely rare tumour, poorly described in the literature. We describe an unusual case where an atypical renal mass on imaging led to a preoperative diagnosis of renal carcinoid on imaging guiding biopsy.

  10. Dynamic renal scintigraphy in aortic disorders

    International Nuclear Information System (INIS)

    Terae, Satoshi; Itoh, Kazuo; Tsukamoto, Eriko; Nakada, Kunihiro; Fujimori, Kenji; Hashimoto, Masato; Tanabe, Tatsuzo; Furudate, Masayori; Irie, Goro

    1986-01-01

    Dynamic renal scintigraphy has been reviewed for evaluation of renal arterial involvement in aortic disorders such as arteriosclerosis obliterans, abdominal aortic aneurysm and dissecting aneurysm. As a diagnostic finding and parameters, we used blood perfusion images of both kidneys and relative split renal function index obtained with analysis of the time-activity curves which were generated using a renal region of interest. In the diagnosis of unilateral renal arterial involvement, sensitivity and specificity of blood perfusion images were 100 % (9/9) and 77 % (10/13) and those of relative split renal function index were 78 % (7/9) and 92 % (12/13), respectively. Dynamic renal scintigraphy was useful for evaluating unilateral renal arterial involvement in aortic diseases. However, scintigraphic diagnosis of bilateral renal arterial involvement were difficult. And in a severe case, we could not differentiate renal parenchymal damage due to renovascular involvement from senile renal dysfunction or hypertensive renal disease which is often a cause of aortic disorders. (author)

  11. Renal rescue of dopamine D2 receptor function reverses renal injury and high blood pressure

    Science.gov (United States)

    Konkalmatt, Prasad R.; Asico, Laureano D.; Zhang, Yanrong; Yang, Yu; Drachenberg, Cinthia; Zheng, Xiaoxu; Han, Fei; Jose, Pedro A.; Armando, Ines

    2016-01-01

    Dopamine D2 receptor (DRD2) deficiency increases renal inflammation and blood pressure in mice. We show here that long-term renal-selective silencing of Drd2 using siRNA increases renal expression of proinflammatory and profibrotic factors and blood pressure in mice. To determine the effects of renal-selective rescue of Drd2 expression in mice, the renal expression of DRD2 was first silenced using siRNA and 14 days later rescued by retrograde renal infusion of adeno-associated virus (AAV) vector with DRD2. Renal Drd2 siRNA treatment decreased the renal expression of DRD2 protein by 55%, and DRD2 AAV treatment increased the renal expression of DRD2 protein by 7.5- to 10-fold. Renal-selective DRD2 rescue reduced the expression of proinflammatory factors and kidney injury, preserved renal function, and normalized systolic and diastolic blood pressure. These results demonstrate that the deleterious effects of renal-selective Drd2 silencing on renal function and blood pressure were rescued by renal-selective overexpression of DRD2. Moreover, the deleterious effects of 45-minute bilateral ischemia/reperfusion on renal function and blood pressure in mice were ameliorated by a renal-selective increase in DRD2 expression by the retrograde ureteral infusion of DRD2 AAV immediately after the induction of ischemia/reperfusion injury. Thus, 14 days after ischemia/reperfusion injury, the renal expression of profibrotic factors, serum creatinine, and blood pressure were lower in mice infused with DRD2 AAV than in those infused with control AAV. These results indicate an important role of renal DRD2 in limiting renal injury and preserving normal renal function and blood pressure. PMID:27358912

  12. Role of RENAL nephrometry scoring system in planning surgical intervention in patients with localized renal mas

    OpenAIRE

    Mohamed Samir Shaaban; Tamer Mohammed Abou Youssif; Ahmed Mostafa; Hossam Eldin Hegazy; Mohammed Adel Atta

    2015-01-01

    Purpose: The study was designed to validate the value of preoperative planning using RENAL nephrometry scoring system in patients having organ confined renal tumors and undergoing surgical intervention and to assess its correlation with the surgical technique. Patient and methods: Forty patients with organ-confined renal masses underwent RENAL nephrometry scoring which was correlated with the surgical technique either radical or nephron-sparing surgery. Result: RENAL nephrometry scoring...

  13. Chemical Renal Denervation in the Rat

    Energy Technology Data Exchange (ETDEWEB)

    Consigny, Paul M., E-mail: paul.consigny@av.abbott.com; Davalian, Dariush, E-mail: dariush.davalian@av.abbott.com [Abbott Vascular, Innovation Incubator (United States); Donn, Rosy, E-mail: rosy.donn@av.abbott.com; Hu, Jie, E-mail: jie.hu@av.abbott.com [Abbott Vascular, Bioanalytical and Material Characterization (United States); Rieser, Matthew, E-mail: matthew.j.rieser@abbvie.com; Stolarik, DeAnne, E-mail: deanne.f.stolarik@abbvie.com [Abbvie, Analytical Pharmacology (United States)

    2013-12-03

    Introduction: The recent success of renal denervation in lowering blood pressure in drug-resistant hypertensive patients has stimulated interest in developing novel approaches to renal denervation including local drug/chemical delivery. The purpose of this study was to develop a rat model in which depletion of renal norepinephrine (NE) could be used to determine the efficacy of renal denervation after the delivery of a chemical to the periadventitial space of the renal artery. Methods: Renal denervation was performed on a single renal artery of 90 rats (n = 6 rats/group). The first study determined the time course of renal denervation after surgical stripping of a renal artery plus the topical application of phenol in alcohol. The second study determined the efficacy of periadventitial delivery of hypertonic saline, guanethidine, and salicylic acid. The final study determined the dose–response relationship for paclitaxel. In all studies, renal NE content was determined by liquid chromatography–mass spectrometry. Results: Renal NE was depleted 3 and 7 days after surgical denervation. Renal NE was also depleted by periadventitial delivery of all agents tested (hypertonic saline, salicylic acid, guanethidine, and paclitaxel). A dose response was observed after the application of 150 μL of 10{sup −5} M through 10{sup −2} M paclitaxel. Conclusion: We developed a rat model in which depletion of renal NE was used to determine the efficacy of renal denervation after perivascular renal artery drug/chemical delivery. We validated this model by demonstrating the efficacy of the neurotoxic agents hypertonic saline, salicylic acid, and guanethidine and increasing doses of paclitaxel.

  14. Chemical Renal Denervation in the Rat

    International Nuclear Information System (INIS)

    Consigny, Paul M.; Davalian, Dariush; Donn, Rosy; Hu, Jie; Rieser, Matthew; Stolarik, DeAnne

    2014-01-01

    Introduction: The recent success of renal denervation in lowering blood pressure in drug-resistant hypertensive patients has stimulated interest in developing novel approaches to renal denervation including local drug/chemical delivery. The purpose of this study was to develop a rat model in which depletion of renal norepinephrine (NE) could be used to determine the efficacy of renal denervation after the delivery of a chemical to the periadventitial space of the renal artery. Methods: Renal denervation was performed on a single renal artery of 90 rats (n = 6 rats/group). The first study determined the time course of renal denervation after surgical stripping of a renal artery plus the topical application of phenol in alcohol. The second study determined the efficacy of periadventitial delivery of hypertonic saline, guanethidine, and salicylic acid. The final study determined the dose–response relationship for paclitaxel. In all studies, renal NE content was determined by liquid chromatography–mass spectrometry. Results: Renal NE was depleted 3 and 7 days after surgical denervation. Renal NE was also depleted by periadventitial delivery of all agents tested (hypertonic saline, salicylic acid, guanethidine, and paclitaxel). A dose response was observed after the application of 150 μL of 10 −5  M through 10 −2  M paclitaxel. Conclusion: We developed a rat model in which depletion of renal NE was used to determine the efficacy of renal denervation after perivascular renal artery drug/chemical delivery. We validated this model by demonstrating the efficacy of the neurotoxic agents hypertonic saline, salicylic acid, and guanethidine and increasing doses of paclitaxel

  15. Chemical renal denervation in the rat.

    Science.gov (United States)

    Consigny, Paul M; Davalian, Dariush; Donn, Rosy; Hu, Jie; Rieser, Matthew; Stolarik, Deanne

    2014-02-01

    The recent success of renal denervation in lowering blood pressure in drug-resistant hypertensive patients has stimulated interest in developing novel approaches to renal denervation including local drug/chemical delivery. The purpose of this study was to develop a rat model in which depletion of renal norepinephrine (NE) could be used to determine the efficacy of renal denervation after the delivery of a chemical to the periadventitial space of the renal artery. Renal denervation was performed on a single renal artery of 90 rats (n = 6 rats/group). The first study determined the time course of renal denervation after surgical stripping of a renal artery plus the topical application of phenol in alcohol. The second study determined the efficacy of periadventitial delivery of hypertonic saline, guanethidine, and salicylic acid. The final study determined the dose-response relationship for paclitaxel. In all studies, renal NE content was determined by liquid chromatography-mass spectrometry. Renal NE was depleted 3 and 7 days after surgical denervation. Renal NE was also depleted by periadventitial delivery of all agents tested (hypertonic saline, salicylic acid, guanethidine, and paclitaxel). A dose response was observed after the application of 150 μL of 10(-5) M through 10(-2) M paclitaxel. We developed a rat model in which depletion of renal NE was used to determine the efficacy of renal denervation after perivascular renal artery drug/chemical delivery. We validated this model by demonstrating the efficacy of the neurotoxic agents hypertonic saline, salicylic acid, and guanethidine and increasing doses of paclitaxel.

  16. Sequential Scintigraphy in Renal Transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Winkel, K. zum; Harbst, H.; Schenck, P.; Franz, H. E.; Ritz, E.; Roehl, L.; Ziegler, M.; Ammann, W.; Maier-Borst, W. [Institut Fuer Nuklearmedizin, Deutsches Krebsforschungszentrum, Heidelberg, Federal Republic of Germany (Germany)

    1969-05-15

    Based on experience gained from more than 1600 patients with proved or suspected kidney diseases and on results on extended studies with dogs, sequential scintigraphy was performed after renal transplantation in dogs. After intravenous injection of 500 {mu}Ci. {sup 131}I-Hippuran scintiphotos were taken during the first minute with an exposure time of 15 sec each and thereafter with an exposure of 2 min up to at least 16 min.. Several examinations were evaluated digitally. 26 examinations were performed on 11 dogs with homotransplanted kidneys. Immediately after transplantation the renal function was almost normal arid the bladder was filled in due time. At the beginning of rejection the initial uptake of radioactive Hippuran was reduced. The intrarenal transport became delayed; probably the renal extraction rate decreased. Corresponding to the development of an oedema in the transplant the uptake area increased in size. In cases of thrombosis of the main artery there was no evidence of any uptake of radioactivity in the transplant. Similar results were obtained in 41 examinations on 15 persons. Patients with postoperative anuria due to acute tubular necrosis showed still some uptake of radioactivity contrary to those with thrombosis of the renal artery, where no uptake was found. In cases of rejection the most frequent signs were a reduced initial uptake and a delayed intrarenal transport of radioactive Hippuran. Infarction could be detected by a reduced uptake in distinct areas of the transplant. (author)

  17. Contemporary treatment of renal tumors

    DEFF Research Database (Denmark)

    Nisen, Harry; Järvinen, Petrus; Fovaeus, Magnus

    2017-01-01

    Objective: The five Nordic countries comprise 25 million people, and have similar treatment traditions and healthcare systems. To take advantage of these similarities, a collaborative group (Nordic Renal Cancer Group, NORENCA) was founded in 2015. Materials and methods: A questionnaire of 17...

  18. Novel genes in renal aging

    NARCIS (Netherlands)

    Noordmans, Gerda Anke

    2015-01-01

    Renal aging is characterized by structural changes and functional decline. These changes make the elderly more vulnerable to chronic kidney disease, hypertension, and cardiovascular disease. Furthermore, they also make it more difficult to cope with stress factors, such as dehydration, toxicity, and

  19. Renal involvement in Gaucher's disease.

    Science.gov (United States)

    Siegal, A.; Gutman, A.; Shapiro, M. S.; Griffel, B.

    1981-01-01

    A patient with chronic Gaucher's disease is described who developed glomerulopathy 24 years after splenectomy terminating in renal failure. The pathological changes of this very rare complication of Gaucher's disease are described. The few similar cases reported in the literature are reviewed and the possible pathogenetic pathways discussed. Images Fig. 1 Fig. 2 Fig. 3 PMID:7301691

  20. The Radiology of Renal Trauma

    African Journals Online (AJOL)

    1974-05-15

    May 15, 1974 ... Retrograde pyelography was performed in 3 patients and renal angio- graphy in 22. Of the 210 cases referred, abnormal radio- logical signs were observed in 112. All the radiological in- vestigations were reviewed to assess the frequency of the various findings. RESULTS. The Plain Film of the Abdomen.

  1. Renal sympathetic denervation in hypertension.

    Science.gov (United States)

    Doumas, Michael; Faselis, Charles; Papademetriou, Vasilios

    2011-11-01

    Despite the abundance of antihypertensive drugs, resistant hypertension remains a major clinical problem. Recent technological advances render interventional management of resistant hypertension one of the hottest topics in the hypertension field. The aim of this review is to present the pathophysiologic background and the mechanisms mediating blood pressure reduction after renal sympathetic denervation, to analyze recent findings with this fascinating approach and to critically suggest future research directions. Catheter-based, ablation-induced renal sympathetic denervation was initially studied in 45 patients with resistant hypertension in a proof-of-concept study. Impressive blood pressure reductions of about 30/15  mmHg were achieved at 6 months, without serious complications. A second, controlled, randomized (but not blinded) study confirmed the results, verifying the efficacy and safety of the procedure. A recent report revealed the 2-year durability of blood pressure reduction. Data published so far indicate that ablation-induced renal denervation is a feasible, effective, and well tolerated interventional approach for the management of resistant hypertension. The groundbreaking studies of renal denervation in drug-resistant hypertension pave the way for further research in other disease conditions in which sympathetic overactivity seems to play a critical role. This initial wave of enthusiasm needs to be followed by rigorous investigation, for the proper identification of the potential and the limitations, indications, and contraindications of this approach.

  2. More about... renal and urology

    African Journals Online (AJOL)

    [3,4]. Although the incidence of ESRD is high in the elderly, progression to renal failure tends to be low.[3[. The Kidney Disease .... to loosely it will fall off. • When ulceration occurs, the patient needs to stop using the urinary sheath .... If the patient has a history of retrograde ejaculation, it is necessary to prepare the bladder by ...

  3. Metastatic renal cell carcinoma management

    Directory of Open Access Journals (Sweden)

    Flavio L. Heldwein

    2009-06-01

    Full Text Available PURPOSE: To assess the current treatment of metastatic renal cell carcinoma, focusing on medical treatment options. MATERIAL AND METHODS: The most important recent publications have been selected after a literature search employing PubMed using the search terms: advanced and metastatic renal cell carcinoma, anti-angiogenesis drugs and systemic therapy; also significant meeting abstracts were consulted. RESULTS: Progress in understanding the molecular basis of renal cell carcinoma, especially related to genetics and angiogenesis, has been achieved mainly through of the study of von Hippel-Lindau disease. A great variety of active agents have been developed and tested in metastatic renal cell carcinoma (mRCC patients. New specific molecular therapies in metastatic disease are discussed. Sunitinib, Sorafenib and Bevacizumab increase the progression-free survival when compared to therapy with cytokines. Temsirolimus increases overall survival in high-risk patients. Growth factors and regulatory enzymes, such as carbonic anhydrase IX may be targets for future therapies. CONCLUSIONS: A broader knowledge of clear cell carcinoma molecular biology has permitted the beginning of a new era in mRCC therapy. Benefits of these novel agents in terms of progression-free and overall survival have been observed in patients with mRCC, and, in many cases, have become the standard of care. Sunitinib is now considered the new reference first-line treatment for mRCC. Despite all the progress in recent years, complete responses are still very rare. Currently, many important issues regarding the use of these agents in the management of metastatic renal cancer still need to be properly addressed.

  4. Live Donor Renal Anatomic Asymmetry and Posttransplant Renal Function.

    Science.gov (United States)

    Tanriover, Bekir; Fernandez, Sonalis; Campenot, Eric S; Newhouse, Jeffrey H; Oyfe, Irina; Mohan, Prince; Sandikci, Burhaneddin; Radhakrishnan, Jai; Wexler, Jennifer J; Carroll, Maureen A; Sharif, Sairah; Cohen, David J; Ratner, Lloyd E; Hardy, Mark A

    2015-08-01

    Relationship between live donor renal anatomic asymmetry and posttransplant recipient function has not been studied extensively. We analyzed 96 live kidney donors, who had anatomical asymmetry (>10% renal length and/or volume difference calculated from computerized tomography angiograms) and their matching recipients. Split function differences (SFD) were quantified with technetium-dimercaptosuccinic acid renography. Implantation biopsies at time 0 were semiquantitatively scored. A comprehensive model using donor renal volume adjusted to recipient weight (Vol/Wgt), SFD, and biopsy score was used to predict recipient estimated glomerular filtration rate (eGFR) at 1 year. Primary analysis consisted of a logistic regression model of outcome (odds of developing eGFR>60 mL/min/1.73 m(2) at 1 year), a linear regression model of outcome (predicting recipient eGFR at one-year, using the chronic kidney disease-epidemiology collaboration formula), and a Monte Carlo simulation based on the linear regression model (N=10,000 iterations). In the study cohort, the mean Vol/Wgt and eGFR at 1 year were 2.04 mL/kg and 60.4 mL/min/1.73 m(2), respectively. Volume and split ratios between 2 donor kidneys were strongly correlated (r = 0.79, P 10%) were not different (P = 0.190). On multivariate models, only Vol/Wgt was significantly associated with higher odds of having eGFR > 60 mL/min/1.73 m (odds ratio, 8.94, 95% CI 2.47-32.25, P = 0.001) and had a strong discriminatory power in predicting the risk of eGFR less than 60 mL/min/1.73 m(2) at 1 year [receiver operating curve (ROC curve), 0.78, 95% CI, 0.68-0.89]. In the presence of donor renal anatomic asymmetry, Vol/Wgt appears to be a major determinant of recipient renal function at 1 year after transplantation. Renography can be replaced with CT volume calculation in estimating split renal function.

  5. Microwave treatment of renal cell carcinoma adjacent to renal sinus

    International Nuclear Information System (INIS)

    Gao, Yongyan; Liang, Ping; Yu, Xiaoling; Yu, Jie; Cheng, Zhigang; Han, Zhiyu; Duan, Shaobo; Huang, Hui

    2016-01-01

    Highlights: • This study shows US-guided microwave ablation appears to be a promising method to treat renal cell carcinoma adjacent to renal sinus. • The estimated 1-, 3- and 5-year RCC-related survival were 100%, 93.3% and 93.3%, respectively. • The estimated 1-, 3- and 5-year overall survival were 97.1%, 87.8%, 83.6%, respectively. • For patients with RCC ≤4 cm, initial ablation success was 100% (29/29) and the estimated 5-year disease-free survival were 81.5%. - Abstract: Purpose: To evaluate the efficacy and safety of ultrasound (US)-guided percutaneous microwave ablation (MWA) for renal cell carcinoma (RCC) adjacent to renal sinus. Materials and methods: This retrospective study included 41 patients who underwent US-guided percutaneous MWA of 41 RCCs adjacent to the renal sinus from April 2006 to December 2015. Contrast-enhanced images of US and computed tomography (CT) or magnetic resonance (MR) imaging were performed at pre-ablation and 1 day, 1 month, 3 months, and every 6 months after ablation. Initial ablation success (IAS), disease-free survival (DFS), RCC-related survival (RRS), and overall survival (OS) were recorded at the follow-up visits. Results: IAS was achieved in 92.7% (38/41) of the study subjects. The IAS significantly differed between patients with RCCs ≤4 cm (100%, 29/29) and RCCs >4 cm (75%, 9/12, p = 0.021). During the median follow-up of 37.6 (range, 3.0–97.3) months, the estimated 1-, 3-, and 5-year DFS of patients with an initial tumor of ≤4 cm were 100%, 89.7%, and 81.5%, respectively. The 1-, 3-, and 5-year RRS were 100%, 93.3%, and 93.3%, respectively. The 1-, 3-, and 5-year OS were 97.1%, 87.8%, and 83.6%, respectively. The multivariate analysis using the Cox proportional hazard model revealed no independent predictor of recurrence among all the variables. There were no MWA-related deaths among the study subjects. One patient developed a retroperitoneal abscess after ablation. Conclusion: US-guided percutaneous MWA

  6. Microwave treatment of renal cell carcinoma adjacent to renal sinus

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Yongyan, E-mail: gaoyongyan7@163.com [Department of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853 (China); Department of Ultrasound, The General Hospital of Chinese People’s Armed Police Forces, 69 Yongding Road, Beijing, 100039 (China); Liang, Ping, E-mail: liangping301@hotmail.com [Department of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853 (China); Yu, Xiaoling, E-mail: 784107477@qq.com [Department of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853 (China); Yu, Jie, E-mail: 1411495161@qq.com [Department of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853 (China); Cheng, Zhigang, E-mail: 13691367317@163.com [Department of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853 (China); Han, Zhiyu, E-mail: hanzhiyu122@163.com [Department of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853 (China); Duan, Shaobo, E-mail: Dustin2662@163.com [Department of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853 (China); Huang, Hui, E-mail: 309hh@sina.com [Department of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853 (China)

    2016-11-15

    Highlights: • This study shows US-guided microwave ablation appears to be a promising method to treat renal cell carcinoma adjacent to renal sinus. • The estimated 1-, 3- and 5-year RCC-related survival were 100%, 93.3% and 93.3%, respectively. • The estimated 1-, 3- and 5-year overall survival were 97.1%, 87.8%, 83.6%, respectively. • For patients with RCC ≤4 cm, initial ablation success was 100% (29/29) and the estimated 5-year disease-free survival were 81.5%. - Abstract: Purpose: To evaluate the efficacy and safety of ultrasound (US)-guided percutaneous microwave ablation (MWA) for renal cell carcinoma (RCC) adjacent to renal sinus. Materials and methods: This retrospective study included 41 patients who underwent US-guided percutaneous MWA of 41 RCCs adjacent to the renal sinus from April 2006 to December 2015. Contrast-enhanced images of US and computed tomography (CT) or magnetic resonance (MR) imaging were performed at pre-ablation and 1 day, 1 month, 3 months, and every 6 months after ablation. Initial ablation success (IAS), disease-free survival (DFS), RCC-related survival (RRS), and overall survival (OS) were recorded at the follow-up visits. Results: IAS was achieved in 92.7% (38/41) of the study subjects. The IAS significantly differed between patients with RCCs ≤4 cm (100%, 29/29) and RCCs >4 cm (75%, 9/12, p = 0.021). During the median follow-up of 37.6 (range, 3.0–97.3) months, the estimated 1-, 3-, and 5-year DFS of patients with an initial tumor of ≤4 cm were 100%, 89.7%, and 81.5%, respectively. The 1-, 3-, and 5-year RRS were 100%, 93.3%, and 93.3%, respectively. The 1-, 3-, and 5-year OS were 97.1%, 87.8%, and 83.6%, respectively. The multivariate analysis using the Cox proportional hazard model revealed no independent predictor of recurrence among all the variables. There were no MWA-related deaths among the study subjects. One patient developed a retroperitoneal abscess after ablation. Conclusion: US-guided percutaneous MWA

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

    Science.gov (United States)

    Vallon, Volker; Thomson, Scott C

    2017-02-01

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

  8. “Transcollateral” Renal Angioplasty for a Completely Occluded Renal Artery

    International Nuclear Information System (INIS)

    Chandra, Subash; Chadha, Davinder S.; Swamy, Ajay

    2011-01-01

    Percutaneous transluminal renal angioplasty with stenting has been effective in the control of hypertension, renal function, and pulmonary edema caused by atherosclerotic renal artery stenosis. However, the role of the procedure has not been fully established in the context of chronic total occlusion of renal artery. We report the successful use of this procedure in 57-year-old male patient who reported for evaluation of a recent episode of accelerated hypertension. A renal angiogram in this patient showed ostial stenosis of the right renal artery, which was filling by way of the collateral artery. Renal angioplasty for chronic total occlusion of right renal artery was successfully performed in a retrograde fashion through a collateral artery, thereby leading to improvement of renal function and blood pressure control.

  9. ROS activate KCl cotransport in nonadherent Ehrlich ascites cells but K+ and Cl- channels in adherent Ehrlich Lettré and NIH3T3 cells

    DEFF Research Database (Denmark)

    Lambert, Ian Henry; Klausen, Thomas Kjær; Bergdahl, Andreas

    2009-01-01

    Addition of H2O2 (0.5 mM) to Ehrlich ascites tumor cells under isotonic conditions results within 25 min in a substantial (22 +/- 1 %) reduction in cell volume. The cell shrinkage is paralleled by net loss of K(+), which was significant within 8 min, whereas no concomitant increase in the K......(+) or Cl(-) conductances could be observed. The H2O2-induced cell shrinkage was unaffected by the presence of clofilium and clotrimazole, that block volume-sensitive and Ca(2+)-activated K(+) channels, respectively, and unaffected by a raise in extracellular K(+) concentration to a value which eliminates...... the electrochemical driving force for K(+). On the other hand, the H2O2-induced cell shrinkage was impaired in the presence of the KCl cotransport inhibitor DIOA, following substitution of NO3(-) for Cl(-), and when the driving force for KCl cotransport was omitted. It is suggested that H2O2 activates electro neutral...

  10. Superselective transcatheter renal arterial embolization for acute renal bleeding in patients with renal insufficiency: its clinical efficacy and safety

    International Nuclear Information System (INIS)

    Hu Tingyang; Zhou Bing; Yu Wenqiang; Luo Zuyan; Mao Yingmin; Chen Fanghong; Li Bo; Yuan Jianhua

    2010-01-01

    Objective: To discuss the clinical efficacy and complications of super selective renal arterial embolization in treating acute renal arterial bleeding in patients with renal insufficiency, and to evaluate the influence of the treatment on the renal function. Methods: During the period of January 2000 December 2009, super selective renal arterial embolization was performed in our institution for acute renal bleeding in 13 patients with renal insufficiency. The complete clinical and imaging materials of all patients were properly collected. The clinical effectiveness, the renal function, the extent of embolization and the complications were observed and the relationship between each other was analyzed. Results: The embolization procedure was successfully completed in all patients with a technical success rate of 100%. The mean embolized territory was 22% of a single kidney. Three days after the procedure, the hemoglobin level, hematocrit, blood pressure and heart rate were considerably improved in all patients. Compared to the corresponding preoperative data, all the differences were statistically significant (P 0.05), while the blood urea nitrogen was markedly decreased (P=0.011). Post embolization syndrome occurred in 5 patients and progressive aggravation of the renal function was observed in one patient, who had to receive hemodialysis finally. The embolized territory in patients occurring complications was larger than that in patients without occurring complications (U=1.500, P=0.006). Conclusion: Super selective renal arterial embolization is an effective and safe treatment for acute renal arterial bleeding in patients with renal insufficiency, the therapy will not significantly worsen the renal function. Appropriate and reasonable extent of embolization, as small as possible, is the key point for reducing the complications. (authors)

  11. Renal replacement therapy in sepsis-induced acute renal failure

    Directory of Open Access Journals (Sweden)

    Rajapakse Senaka

    2009-01-01

    Full Text Available Acute renal failure (ARF is a common complication of sepsis and carries a high mortality. Renal replacement therapy (RRT during the acute stage is the mainstay of therapy. Va-rious modalities of RRT are available. Continuous RRT using convective methods are preferred in sepsis-induced ARF, especially in hemodynamically unstable patients, although clear evidence of benefit over intermittent hemodialysis is still not available. Peritoneal dialysis is clearly inferior, and is not recommended. Early initiation of RRT is probably advantageous, although the optimal timing of dialysis is yet unknown. Higher doses of RRT are more likely to be beneficial. Use of bio-compatible membranes and bicarbonate buffer in the dialysate are preferred. Anticoagulation during dialysis must be carefully adjusted and monitored.

  12. Renal and post-renal causes of acute renal failure in children

    International Nuclear Information System (INIS)

    Jamal, A.; Ramzan, A.

    2004-01-01

    Objective: To identify the causes of acute renal failure (ARF) in pediatric population along with the identification of the age and gender most affected by the failure. Subjects and Methods: The study included children under the age of 12 years who presented with signs and symptoms suggestive of ARF (oliguria/anuria, vomiting, acidotic breathing etc.) along with raised blood urea nitrogen (BUN) serum creatinine and metabolic acidosis as shown by arterial blood gases (ABGs). Patients were divided into two group on the basis of age; group A consisting of 0-2 years and group B from >2 years. Patients presenting with transient pre-renal azotaemia were excluded from the study. After providing initial emergency cover, detailed history, physical examination and investigations were carried out according to a proforma specially designed to ascertain the cause of ARF. Patients were managed for ARF as per standard recommendations and investigations completed or repeated as and when required. Results: A total of 119 patients with ARF were admitted in the ward over a period of two years constituting 1.36% of the total admissions and 16.39% of the admissions due to renal pathology. Mean age of presentation was 4.5 years 16.7% of the patients under the age of 5 years. Male predominance was noted in all ages with an overall male to female ratio of 2.3:1. Most common cause leading to ARF in younger age group was found to be hemolytic uremic syndrome [25(54.34%)] followed by septicemia [7(15.21 %)]. In older patients renal calculus disease was the most common [22(30.13%)] underlying pathology followed by pre-existing, undiagnosed chronic renal failure [16(21.91 %)]. Conclusion: ARF is fairly cotton in children especially under the age of 5 years showing a male predominance. More than 90% of the cases can be prevented by improving primary health care and by early and prompt treatment of infections. (author)

  13. Microwave treatment of renal cell carcinoma adjacent to renal sinus.

    Science.gov (United States)

    Gao, Yongyan; Liang, Ping; Yu, Xiaoling; Yu, Jie; Cheng, Zhigang; Han, Zhiyu; Duan, Shaobo; Huang, Hui

    2016-11-01

    To evaluate the efficacy and safety of ultrasound (US)-guided percutaneous microwave ablation (MWA) for renal cell carcinoma (RCC) adjacent to renal sinus. This retrospective study included 41 patients who underwent US-guided percutaneous MWA of 41 RCCs adjacent to the renal sinus from April 2006 to December 2015. Contrast-enhanced images of US and computed tomography (CT) or magnetic resonance (MR) imaging were performed at pre-ablation and 1day, 1 month, 3 months, and every 6 months after ablation. Initial ablation success (IAS), disease-free survival (DFS), RCC-related survival (RRS), and overall survival (OS) were recorded at the follow-up visits. IAS was achieved in 92.7% (38/41) of the study subjects. The IAS significantly differed between patients with RCCs ≤4cm (100%, 29/29) and RCCs >4cm (75%, 9/12, p=0.021). During the median follow-up of 37.6 (range, 3.0-97.3) months, the estimated 1-, 3-, and 5-year DFS of patients with an initial tumor of ≤4cm were 100%, 89.7%, and 81.5%, respectively. The 1-, 3-, and 5-year RRS were 100%, 93.3%, and 93.3%, respectively. The 1-, 3-, and 5-year OS were 97.1%, 87.8%, and 83.6%, respectively. The multivariate analysis using the Cox proportional hazard model revealed no independent predictor of recurrence among all the variables. There were no MWA-related deaths among the study subjects. One patient developed a retroperitoneal abscess after ablation. US-guided percutaneous MWA appears to be a promising method for RCCs adjacent to renal sinus, especially for tumors ≤4cm. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  14. Does Renal Artery Supply Indicate Treatment Success of Renal Denervation?

    International Nuclear Information System (INIS)

    Schmid, Axel; Ditting, Tilmann; Sobotka, Paul A.; Veelken, Roland; Schmieder, Roland E.; Uder, Michael; Ott, Christian

    2013-01-01

    PurposeRenal denervation (RDN) emerged as an innovative interventional antihypertensive therapy. With the exception of pretreatment blood pressure (BP) level, no other clear predictor for treatment efficacy is yet known. We analyzed whether the presence of multiple renal arteries has an impact on BP reduction after RDN.MethodsFifty-three patients with treatment-resistant hypertension (office BP ≥ 140/90 mmHg and 24-h ambulatory BP monitoring (≥130/80 mmHg) underwent bilateral catheter-based RDN. Patients were stratified into one-vessel (OV) (both sides) and at least multivessel (MV) supply at one side. Both groups were treated on one vessel at each side; in case of multiple arteries, only the dominant artery was treated on each side.ResultsBaseline clinical characteristics (including BP, age, and estimated glomerular filtration rate) did not differ between patients with OV (n = 32) and MV (n = 21). Office BP was significantly reduced in both groups at 3 months (systolic: OV −15 ± 23 vs. MV −16 ± 20 mmHg; diastolic: OV −10 ± 12 vs. MV −8 ± 11 mmHg, both p = NS) as well as 6 months (systolic: OV −18 ± 18 vs. MV −17 ± 22 mmHg; diastolic: OV −10 ± 10 vs. −10 ± 12 mmHg, both p = NS) after RDN. There was no difference in responder rate (rate of patients with office systolic BP reduction of at least 10 mmHg after 6 months) between the groups.ConclusionIn patients with multiple renal arteries, RDN of one renal artery—namely, the dominant one—is sufficient to induce BP reduction in treatment-resistant hypertension

  15. Does Renal Artery Supply Indicate Treatment Success of Renal Denervation?

    Energy Technology Data Exchange (ETDEWEB)

    Schmid, Axel, E-mail: axel.schmid@uk-erlangen.de [University of Erlangen-Nuremberg, Department of Radiology (Germany); Ditting, Tilmann, E-mail: tilmann.ditting@uk-erlangen.de [University of Erlangen-Nuremberg, Department of Nephrology and Hypertension (Germany); Sobotka, Paul A., E-mail: sobotka@alumni.stanford.edu [Ohio State University (United States); Veelken, Roland, E-mail: roland.veelken@uk-erlangen.de; Schmieder, Roland E., E-mail: roland.schmieder@uk-erlangen.de [University of Erlangen-Nuremberg, Department of Nephrology and Hypertension (Germany); Uder, Michael, E-mail: michael.uder@uk-erlangen.de [University of Erlangen-Nuremberg, Department of Radiology (Germany); Ott, Christian, E-mail: christian.ott@uk-erlangen.de [University of Erlangen-Nuremberg, Department of Nephrology and Hypertension (Germany)

    2013-08-01

    PurposeRenal denervation (RDN) emerged as an innovative interventional antihypertensive therapy. With the exception of pretreatment blood pressure (BP) level, no other clear predictor for treatment efficacy is yet known. We analyzed whether the presence of multiple renal arteries has an impact on BP reduction after RDN.MethodsFifty-three patients with treatment-resistant hypertension (office BP {>=} 140/90 mmHg and 24-h ambulatory BP monitoring ({>=}130/80 mmHg) underwent bilateral catheter-based RDN. Patients were stratified into one-vessel (OV) (both sides) and at least multivessel (MV) supply at one side. Both groups were treated on one vessel at each side; in case of multiple arteries, only the dominant artery was treated on each side.ResultsBaseline clinical characteristics (including BP, age, and estimated glomerular filtration rate) did not differ between patients with OV (n = 32) and MV (n = 21). Office BP was significantly reduced in both groups at 3 months (systolic: OV -15 {+-} 23 vs. MV -16 {+-} 20 mmHg; diastolic: OV -10 {+-} 12 vs. MV -8 {+-} 11 mmHg, both p = NS) as well as 6 months (systolic: OV -18 {+-} 18 vs. MV -17 {+-} 22 mmHg; diastolic: OV -10 {+-} 10 vs. -10 {+-} 12 mmHg, both p = NS) after RDN. There was no difference in responder rate (rate of patients with office systolic BP reduction of at least 10 mmHg after 6 months) between the groups.ConclusionIn patients with multiple renal arteries, RDN of one renal artery-namely, the dominant one-is sufficient to induce BP reduction in treatment-resistant hypertension.

  16. Renal oncocytoma in a cat with chronic renal failure

    OpenAIRE

    Sora Lee; Hyun-Ji Choi; Han-Byul Lee; Sung-Min Jo; Ji-hye Mun; Woo-Chan Son

    2017-01-01

    Case summary A 9-year-old male neutered domestic shorthair cat presented with anorexia. Ultrasonography showed an irregularly shaped hypoechoic mass in the cranial pole of the right kidney. Ultrasound-guided fine-needle aspiration of the renal mass was performed. Cytology revealed moderate cellularity smears composed of epithelial cell clusters, which consisted of an exclusive population of oncocytic cells seen in sheets and papillary clusters along with abundant single cells. A moderate-to-a...

  17. [Orthotopic renal transplant: our experience].

    Science.gov (United States)

    De Gracia, R; Jiménez, C; Gil, F; Escuin, F; Tabernero, A; Sanz, A; Hidalgo, L

    2007-01-01

    Orthotopic renal transplant (ORT) is useful in cases of severe atherosclerosis, heterotopic bilateral transplant, unsuitable pelvic vessels and in aortic thrombosis, but it is not available in all the institutions and it is only realized of exceptional form. To review the indication, surgical technique and outcome of the ORT at our hospital. The studied included five cases between January 1990 and December 2005. We analyzed several variables: demographic characteristics, characteristics of the donor, ischemia times, evolution of renal function and morbi-mortality associated. Left ORT was performed in three men and two women. Mean patient age was 52+/-5 years, all the patients received kidneys from cadaveric donors. Mean creatinine and urea one month postoperative were 2.2+/-0.72 mg/dl and 103+/-17.2 mg/dl and at 6 months postoperative were 1.8+/-0.59 mg/dl and 78+/-14 mg/dl respectively. Immediately all patients received prophylaxis with low molecular weight heparin but it was indicated antiaggregation to two patients when they left the hospital, anticoagulation to two patients and to one of them was decided to anticoagulation nor antiagregation for history of bled digestive. A patient died for bleeding episode at level of the renal graft six months after the transplant, she was in treatment with dicumarinics, they were indicated by venous deep thrombosis in right leg. The survival a year is 80 % of the graft and the patient. Only two patients returned to hospital later, one of them for presenting an episode of diverticulitis and the other one for renal obstructive failure that needed laying of catheter pig-tail. Four patients presented stenosis of renal native vassels detected in control magnetic nuclear resonance, not symptomatic. There are two patients who take more than three years transplanted with renal stable function (creatinina 1.3 mg/dl and 1.4 mg/dl respectively). ORT is an excellent option in patients with co-morbidity increased for atherosclerosis and

  18. Nutritional support in the tertiary care of patients affected by chronic renal insufficiency: report of a step-wise, personalized, pragmatic approach.

    Science.gov (United States)

    Cupisti, Adamasco; D'Alessandro, Claudia; Di Iorio, Biagio; Bottai, Anna; Zullo, Claudia; Giannese, Domenico; Barsotti, Massimiliano; Egidi, Maria Francesca

    2016-09-06

    Dietary treatment is helpful in CKD patients, but nutritional interventions are scarcely implemented. The main concern of the renal diets is its feasibility with regards to daily clinical practice especially in the elderly and co-morbid patients. This study aimed to evaluate the effects of a pragmatic, step-wise, personalized nutritional support in the management of CKD patients on tertiary care. This is a case-control study. It included 823 prevalent out-patients affected by CKD stage 3b to 5 not-in-dialysis, followed by tertiary care in nephrology clinics; 305 patients (190 males, aged 70 ± 12 years) received nutritional support (nutritional treatment Group, NTG); 518 patients (281 males, aged 73 ± 13 years) who did not receive any dietary therapy, formed the control group (CG). In the NTG patients the dietary interventions were assigned in order to prevent or correct abnormalities and to maintain a good nutritional status. They included manipulation of sodium, phosphate, energy and protein dietary intakes while paying special attention to each patient's dietary habits. Phosphate and BUN levels were lower in the NTG than in the CG, especially in stage 4 and 5. The prevalence of hyperphosphatemia was lower in the NTG than in CG in stage 5 (13.3 % vs 53.3 %, p < 001, respectively), in stage 4 (4.1 % vs 18.3 % vs, p < 0.001) and stage 3b (2.8 % vs 9.5 % p < 0.05). Serum albumin was higher in NTG than in CG especially in stage 5 . The use of calcium-free intestinal phosphate binders was significantly lower in NTG than in CG (11 % vs 19 % p < 0.01), as well as that of Erythropoiesis stimulating agents (11 % vs 19 %, p < 0.01), and active Vitamin D preparations (13 % vs 21 %, p < 0.01). This case-control study shows the usefulness of a nutritional support in addition to the pharmacological good practice in CKD patients on tertiary care. Lower phosphate and BUN levels are obtained together with maintenance of serum albumin

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

    OpenAIRE

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

    2014-01-01

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

  20. Does complete renal denervation translate into superior clinical outcomes? Lessons learned from denervation of accessory renal arteries

    OpenAIRE

    Mendelsohn, Farrell O.

    2014-01-01

    Pre-clinical studies of renal denervation would suggest that the extent of renal nerve injury correlates with outcomes. The “completeness” of renal nerve injury following renal denervation correlates with treatment-based variables such as the depth of ablation, the number of ablations along the length of the artery, and the number of renal arteries successfully ablated. Renal denervation techniques targeting only main renal arteries may lead to suboptimal results in patients with accessory re...

  1. Focus on renal congestion in heart failure.

    Science.gov (United States)

    Afsar, Baris; Ortiz, Alberto; Covic, Adrian; Solak, Yalcin; Goldsmith, David; Kanbay, Mehmet

    2016-02-01

    Hospitalizations due to heart failure are increasing steadily despite advances in medicine. Patients hospitalized for worsening heart failure have high mortality in hospital and within the months following discharge. Kidney dysfunction is associated with adverse outcomes in heart failure patients. Recent evidence suggests that both deterioration in kidney function and renal congestion are important prognostic factors in heart failure. Kidney congestion in heart failure results from low cardiac output (forward failure), tubuloglomerular feedback, increased intra-abdominal pressure or increased venous pressure. Regardless of the cause, renal congestion is associated with increased morbidity and mortality in heart failure. The impact on outcomes of renal decongestion strategies that do not compromise renal function should be explored in heart failure. These studies require novel diagnostic markers that identify early renal damage and renal congestion and allow monitoring of treatment responses in order to avoid severe worsening of renal function. In addition, there is an unmet need regarding evidence-based therapeutic management of renal congestion and worsening renal function. In the present review, we summarize the mechanisms, diagnosis, outcomes, prognostic markers and treatment options of renal congestion in heart failure.

  2. [Computation of the K+, Na+ and Cl- fluxes through plasma membrane of animal cell with Na+/K+ pump, NKCC, NC cotransporters, and ionic channels with and without non-Goldman rectification in K+ channels. Norma and apoptosis].

    Science.gov (United States)

    Rubashkin, A A; Iurinskaia, V E; Vereninov, A A

    2010-01-01

    The balance of K+, Na+ and Cl- fluxes through cell membrane with the Na+/K+ pump, ion channels and NKCC and NC cotransporters is considered. It is shown that all unidirectional K+, Na+ and Cl- fluxes through cell membrane, permeability coefficients of ion channels and membrane potential can be computed for balanced ion distribution between cell and the medium if K+, Na+ and Cl- concentration in cell water and three fluxes are known: total Cl- flux, total K+ influx and ouabain-inhibitable "pump" component of the K+ influx. Changes in the mortovalent ion balance in lymphoid cells U937 induced to apoptosis by 1 microM staurosporine are analyzed as an example. It is found that the apoptotic shift in ion and water balance in studied cells is caused by a decrease in the pump activity which is accompanied by a decrease in the integral permeability of Na+ channels without significant increase in K+ and Cl- channel permeabilities. Computation shows that only a small part of the total fluxes of K+, Na+ and Cl- accounts for the fluxes via NKCC and NC cotransporters. Therefore, cotransport fluxes can not be studied using inhibitors.

  3. Retrograde Renal Cooling to Minimize Ischemia

    Directory of Open Access Journals (Sweden)

    Janet L. Colli

    2013-01-01

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

  4. Renal aneurysm and arteriovenous fistula

    International Nuclear Information System (INIS)

    Savastano, S.; Feltrin, G.P.; Miotto, D.; Chiesura-Corona, M.; Padua Univ.

    1990-01-01

    Embolization was performed in six patients with renal artery aneurysms (n=2) and arteriovenous fistulas (AVF) (n=5). The aneurysms were observed in one patient with fibromuscular dysplasia and in another with Ehlers-Danlos syndrome. All the AVFs were intraparenchymal and secondary to iatrogenic trauma. Elective embolization was performed in five patients with good clinical results at follow-up between 1 and 9 years. Because of rupture of the aneurysm emergency embolization was attempted without success in the patient with Ehlers-Danlos syndrome, and nephrectomy was carried out. A postembolization syndrome complicated three procedures in which Gelfoam and polyvinyl alcohol were used; in two of these cases unexpected reflux of the particulate material occurred, resulting in limited undesired ablation of the ipsilateral renal parenchyma. Embolization is the most reliable and effective treatment for intrarenal vascular abnormalities since it minimizes the parenchymal damage. (orig.)

  5. Bone scintigraphy in renal osteopathy

    International Nuclear Information System (INIS)

    Hermann, H.J.; Gahl, G.; Freie Univ. Berlin

    1976-01-01

    25 patients with chronic renal disease are investigated. In 16 cases with conservative treatment the bone scintigram showed pathological uptake according to the creatinine level, mainly in the joints of iliosacrum, hip, knee and ankles. In three patients increased uptake in the skull was found. The bone uptake found by scintigraphy was highly pronounced in the patients treated by dialysis. The most frequently involved regions were the joints of iliocacrum and hip, facial cranium, skull, pelvis and metatarsus. The count-rate ratio of cranium to chest was significantly increased in 6 patients. The investigations 6 months later showed in 4 cases a further increase compared with the first values. Count-rates of the skull were found to be comparable to the highly increased uptake in Paget's disease. Bone scintigraphy is a suitable method to estimate semiquantitatively the bone turnover in renal disease. (orig.) [de

  6. Dynamic renal scintigraphy at hydronephrosis

    International Nuclear Information System (INIS)

    Petrov, T.; Chukov, I.; Svrakova, E.

    1998-01-01

    The aim of the study was to estimate the clinical relevance and accuracy of dynamic renal scintigraphy (DRS) in case of obstructed kidneys as hydronephrosis is among the complications at different renal diseases, like nephrolithiasis and urolithiasis. Twenty-one patients mainly with unilateral hydronephrosis were studied. DRS with 99m Tc-MAG3 or 99m Tc-EC was done and quantitative parameters of the morphological and functional status of every kidney were assessed. At 24 % of the patients accumulation curves typical for obstructed by hydronephrosis kidneys were obtained. At 38 % the type of renograms of the affected kidneys was intermediate one, closer to that at the cases with nephrosclerosis, with lower uptake and severe parenchymal changes. The rest 38 % of the cases showed normal renograms or slightly delayed downslope. DRS is a very precise and sensitive method for evaluation of the degree of kidney damage in cases with hydronephrosis

  7. Renal allograft rupture: US diagnosis

    International Nuclear Information System (INIS)

    Maklad, N.F.

    1987-01-01

    The US appearances in seven pathologically and/or surgically proved cases of renal allograft rupture are presented. These include a triangular or amorphous echogenic area in the cortex and medulla in a polar location, an echogenic band or wavy, branching anechoic lines in the hyperechoic region, a subcapsular hematoma, and an extrarenal hematoma in direct continuity with the echogenic area. Duplex Doppler examination in renal allograft rupture shows marked reduction of absence of the diastolic component of the velocity waveform in the arcuate and interlobar arteries, with reduction in amplitude of the systolic wave form. Correlation of the US appearances with gross and microscopic pathologic findings indicates that the echogenic area is due to an intrarenal hematoma, while the echogenic band represents the cortical laceration with adherent blood clots. The US-duplex Doppler examination should be the primary diagnostic modality in this life-threatening condition

  8. Impaired nutrient signaling and body weight control in a Na+ neutral amino acid cotransporter (Slc6a19)-deficient mouse.

    Science.gov (United States)

    Bröer, Angelika; Juelich, Torsten; Vanslambrouck, Jessica M; Tietze, Nadine; Solomon, Peter S; Holst, Jeff; Bailey, Charles G; Rasko, John E J; Bröer, Stefan

    2011-07-29

    Amino acid uptake in the intestine and kidney is mediated by a variety of amino acid transporters. To understand the role of epithelial neutral amino acid uptake in whole body homeostasis, we analyzed mice lacking the apical broad-spectrum neutral (0) amino acid transporter B(0)AT1 (Slc6a19). A general neutral aminoaciduria was observed similar to human Hartnup disorder which is caused by mutations in SLC6A19. Na(+)-dependent uptake of neutral amino acids into the intestine and renal brush-border membrane vesicles was abolished. No compensatory increase of peptide transport or other neutral amino acid transporters was detected. Mice lacking B(0)AT1 showed a reduced body weight. When adapted to a standard 20% protein diet, B(0)AT1-deficient mice lost body weight rapidly on diets containing 6 or 40% protein. Secretion of insulin in response to food ingestion after fasting was blunted. In the intestine, amino acid signaling to the mammalian target of rapamycin (mTOR) pathway was reduced, whereas the GCN2/ATF4 stress response pathway was activated, indicating amino acid deprivation in epithelial cells. The results demonstrate that epithelial amino acid uptake is essential for optimal growth and body weight regulation.

  9. Renal artery pulsatility index and renal volume: Normal fetuses versus growth-retarded fetuses

    International Nuclear Information System (INIS)

    Lee, Kyung Soon; Woo, Bock Hi

    2001-01-01

    To evaluate the blood flow velocity waveform of the renal artery and renal volume of growth-retarded fetuses and to compare them with those of normal fetuses. Pulsatility index of the renal artery and renal volume measured by three-dimensional ultrasonography were obtained from seventy eight normal fetuses at the gestational age from twenty five to thirty nine weeks and eighteen intrauterine growth retarded fetuses whose weight was below ten percentile at birth. We studied changes of the pulsatility index of the renal artery and renal volume according to the gestational age and compared with those of growth-retarded fetuses. Pulsatility index (PI) of the fetal renal artery decreased throughout the gestational period (r=0.703, p<0.0001). In growth-retarded fetuses, despite of abnormal doppler velocity waveform of the middle cerebral artery, which was showing fetal hypoxia, the renal PI was not increased significantly. The fetal renal volume increased throughout the gestational period (r=0.834, p<0.0001) whereas in growth-retarded fetuses, all renal volume was below fifth percentile of normal fetuses. In growth-retarded fetuses, fetal renal volume was decreased significantly without change of the renal vascular flow. Therefore, the fetal renal volume measured by three-dimensional ultrasonography may be a helpful parameter in the diagnosis of growth-retarded fetuses.

  10. [Aortic dissection spread to the renal arteries: role of renal volumetry after angioplasty].

    Science.gov (United States)

    Vautrin, E; Thony, F; Chavanon, O; Hannachi, I; Barone-Rochette, G; Pierre, H; Baguet, J-P

    2012-06-01

    Type A or B aortic dissection can extend to renal arteries, causing a renal ischemia which treatment is usually endovascular. The aim of our study is to show the interest of the renal volumetry in the follow-up of these patients. Twenty-two patients (16 men, mean age 63.4±11.8years, BMI 25.2±3.4kg/m(2)) with a type A or B aortic dissection spread to one or to both renal arteries and followed at Grenoble university hospital were consecutively included. All patients underwent renal angiography with aorto-renal pressure gradients measurements and follow-up by renal volumetry (scanner Siemens(®)). A renal ischemia was defined by a decrease of 20% or more of the volumetry. Sixteen patients (73%) were hypertensive before the aortic dissection among which ten (62%) were treated. Eight patients (36%) have a significant renal pressure gradient among which five (62%) underwent renal endovascular therapy. The renal volumetry of these five patients remained unchanged while six of 17 patients (36%) without angioplasty have a decreasing volumetry. Renal volumetry appeared an effective and attractive option for the follow-up of the patients with aortic dissection spread to the renal arteries. These results should be taken into account to put the indication of an endovascular treatment. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  11. Renal artery pulsatility index and renal volume: Normal fetuses versus growth-retarded fetuses

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Kyung Soon; Woo, Bock Hi [Ewha Womans University College of Medicine, Seoul (Korea, Republic of)

    2001-06-15

    To evaluate the blood flow velocity waveform of the renal artery and renal volume of growth-retarded fetuses and to compare them with those of normal fetuses. Pulsatility index of the renal artery and renal volume measured by three-dimensional ultrasonography were obtained from seventy eight normal fetuses at the gestational age from twenty five to thirty nine weeks and eighteen intrauterine growth retarded fetuses whose weight was below ten percentile at birth. We studied changes of the pulsatility index of the renal artery and renal volume according to the gestational age and compared with those of growth-retarded fetuses. Pulsatility index (PI) of the fetal renal artery decreased throughout the gestational period (r=0.703, p<0.0001). In growth-retarded fetuses, despite of abnormal doppler velocity waveform of the middle cerebral artery, which was showing fetal hypoxia, the renal PI was not increased significantly. The fetal renal volume increased throughout the gestational period (r=0.834, p<0.0001) whereas in growth-retarded fetuses, all renal volume was below fifth percentile of normal fetuses. In growth-retarded fetuses, fetal renal volume was decreased significantly without change of the renal vascular flow. Therefore, the fetal renal volume measured by three-dimensional ultrasonography may be a helpful parameter in the diagnosis of growth-retarded fetuses.

  12. Leiomyoma in a Renal Allograft

    Directory of Open Access Journals (Sweden)

    Yan Jun Li

    2016-01-01

    Full Text Available Leiomyomas are smooth muscle tumours that are rarely found in the kidney. There is one report of a leiomyoma in a kidney transplant in a paediatric recipient. Here, we report an adult renal transplant recipient who developed an Epstein-Barr virus-positive leiomyoma in his allograft 15 years after transplantation. The patient was converted to everolimus for posttransplant immunosuppression management and there was no sign of progression over a year.

  13. Congenital hypopituitarism and renal failure

    Directory of Open Access Journals (Sweden)

    Gaurav Atreja

    2011-01-01

    Full Text Available Congenital hypopituitarism is potentially fatal in the newborn period but treatable if the diagnosis is made early. We report a neonate who presented with hypothermia and severe hypoglycemia. He also had undescended testis and micropenis. Initial screening revealed panhypopituitarism, which was corrected promptly. He developed renal failure due to initial cardiovascular compromise related to hypotension but recovered quickly with standard management. Magnetic resonance imaging revealed absent stalk of anterior pituitary.

  14. Renal manifestations of primary hyperparathyroidism

    OpenAIRE

    Lila, Anurag Ranjan; Sarathi, Vijaya; Jagtap, Varsha; Bandgar, Tushar; Menon, Padma S.; Shah, Nalini Samir

    2012-01-01

    Primary hyperparathyroidism (PHPT) is associated with nephrolithiasis and nephrocalcinosis. Hypercalciuria is one of the multiple factors that is implicated in the complex pathophysiology of stone formation. The presence of a renal stone (symptomatic or asymptomatic) categorizes PHPT as symptomatic and is an indication for parathyroid adenomectomy. Progression of nephrocalcinosis is largely reversible after successful surgery, but the residual risk persists. PHPT is also associated with decli...

  15. Pulmonary complications in renal transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Jung Bin; Choi, Yo Won; Jeon, Seok Chol; Park, Choong Ki; Lee, Seung Rho; Hahm, Chang Kok; Joo, Kyung Bin [Hanyang University College of Medicine, Seoul (Korea, Republic of)

    2003-04-01

    To evaluate the radiographic and CT findings of pulmonary complications other than pulmonary edema arising from renal transplantation. Among 393 patients who had undergone renal transplantation at our hospital during a previous ten-year period, 23 with pulmonary complications other than pulmonary edema were included in this study. The complications involved were infection caused by CMV (n=6), bacteria (n=4), fungus (n=4), tuberculosis (n=2), varicella (n=1) or chlamydia (n=1), and malignancy involving lung cancer (n=4) or Kaposi's sarcoma (n=1). Two chest radiologists reviewed all images. The complications manifesting mainly as pulmonary nodules were lung cancer (4/4), tuberculosis (1/2), and Kaposi's sarcoma (1/1). Pulmonary consolidation was a main feature in bacterial infection (4/4), fungal infection (3/4), tuberculosis (1/2), chlamydial infection (1/1), and varicellar pneumonia (1/1). Ground-glass attenuation was a main CT feature in CMV pneumonia (4/6), and increased interstitial making was a predominant radiographic feature in CMV pneumonia (2/6). The main radiologic features described above can be helpful for differential diagnosis of the pulmonary complications of renal transplantation.

  16. Pregnancy in renal transplant recipients.

    Science.gov (United States)

    Bouattar, T; Hakim, H; Rhou, H; Benamar, L; Bayahia, R; Ouzeddoun, N

    2009-06-01

    Renal transplantation with a well-functioning graft leads to a rapid restoration of endocrine and sexual functions. The aim of this study was to examine our experience with pregnancies among renal transplant patients, particularly with regard to their impact on graft function. We analyzed 10 pregnancies in 7 renal transplant recipients for long-term graft outcomes in terms of clinical and biological data. The mean patient age was 28.5 +/- 4 years. They all received a living donor kidney. The time between transplantation and the onset of pregnancy was 33.4 +/- 23.2 months. Regarding the immunosuppressive therapy, all patients received steroids and cyclosporine; 4 patients received in addition azathioprine and 2 received mycophenolate mofetil that was changed at 1 month before conception to azathioprine. There was no significant difference between the serum creatinine before and during pregnancy. We did not observe any acute rejection episode. Pregnancy complications were preclampsia in 1 case, hypertension in 1 case, urinary tract infection in 2 cases, and anemia in 80% of patients during the third trimester. Premature rupture of membranes occurred in 1 case and preterm delivery in 2 cases. Two cases of neonatal death were registered. Cesarean section was performed in 50% of cases. The follow-up revealed 2 cases of chronic rejection. A multidisciplinary approach is necessary for pregnancy which generally occurs at 2 years after kidney transplantation.

  17. Renal disease and mitochondrial genetics.

    Science.gov (United States)

    Rötig, Agnès

    2003-01-01

    Respiratory chain (RC) deficiencies have long been regarded as neuromuscular diseases mainly originating from mutations in the mitochondrial DNA. Oxidative phosphorylation, i.e. adenosine triphosphate (ATP) synthesis-coupled electron transfer from substrate to oxygen through the RC, does not occur only in the neuromuscular system. Therefore, a RC deficiency can theoretically give rise to any symptom, in any organ or tissue, at any age and with any mode of inheritance, owing to the dual genetic origin of RC enzymes (nuclear DNA and mitochondrial DNA). Mitochondrial diseases can give rise to various syndromes or association, namely, neurologic and neuromuscular diseases, cardiac, renal, hepatic, hematological and endocrin or dermatological presentations. The most frequent renal symptom is proximal tubular dysfunction with a more or less complete de Toni-Debre-Fanconi Syndrome. A few patients have been reported with tubular acidosis, Bartter Syndrome, chronic tubulointerstitial nephritis or nephrotic syndrome. The diagnosis of a RC deficiency is difficult when only renal symptoms are present, but should be easier when another, seemingly unrelated symptom is observed. Metabolic screening for abnormal oxidoreduction status in plasma, including lactate/pyruvate and ketone body molar ratios, can help to identify patients for further investigations. These include the measurement of oxygen consumption by mitochondria and the assessment of mitochondrial respiratory enzyme activities by spectrophotometric studies. Any mode of inheritance can be observed: sporadic, autosomal dominant or recessive, or maternal inheritance.

  18. Detection of acute renal allograft rejection by analysis of renal tissue proteomics in rat models of renal transplantation

    Directory of Open Access Journals (Sweden)

    Dai Yong

    2008-01-01

    Full Text Available At present, the diagnosis of renal allograft rejection requires a renal biopsy. Clinical management of renal transplant patients would be improved if rapid, noninvasive and reliable biomarkers of rejection were available. This study is designed to determine whether such protein biomarkers can be found in renal-graft tissue proteomic approach. Orthotopic kidney transplantations were performed using Fisher (F344 or Lewis rats as donors and Lewis rats as recipients. Hence, there were two groups of renal transplant models: one is allograft (from F344 to Lewis rats; another is syngrafts (from Lewis to Lewis rats serving as control. Renal tissues were collected 3, 7 and 14 days after transplantation. As many as 18 samples were analyzed by 2-D Electrophoresis and mass spectrometry (MALDI-TOF-TOF-MS. Eleven differentially expressed proteins were identified between groups. In conclusion, proteomic technology can detect renal tissue proteins associated with acute renal allograft rejection. Identification of these proteins as diagnostic markers for rejection in patients′ urine or sera may be useful and non-invasive, and these proteins might serve as novel therapeutic targets that also help to improve the understanding of mechanism of renal rejection.

  19. Increase in SGLT1-mediated transport explains renal glucose reabsorption during genetic and pharmacological SGLT2 inhibition in euglycemia

    Science.gov (United States)

    Rieg, Timo; Masuda, Takahiro; Gerasimova, Maria; Mayoux, Eric; Platt, Kenneth; Powell, David R.; Thomson, Scott C.; Koepsell, Hermann

    2013-01-01

    In the kidney, the sodium-glucose cotransporters SGLT2 and SGLT1 are thought to account for >90 and ∼3% of fractional glucose reabsorption (FGR), respectively. However, euglycemic humans treated with an SGLT2 inhibitor maintain an FGR of 40–50%, mimicking values in Sglt2 knockout mice. Here, we show that oral gavage with a selective SGLT2 inhibitor (SGLT2-I) dose dependently increased urinary glucose excretion (UGE) in wild-type (WT) mice. The dose-response curve was shifted leftward and the maximum response doubled in Sglt1 knockout (Sglt1−/−) mice. Treatment in diet with the SGLT2-I for 3 wk maintained 1.5- to 2-fold higher urine glucose/creatinine ratios in Sglt1−/− vs. WT mice, associated with a temporarily greater reduction in blood glucose in Sglt1−/− vs. WT after 24 h (−33 vs. −11%). Subsequent inulin clearance studies under anesthesia revealed free plasma concentrations of the SGLT2-I (corresponding to early proximal concentration) close to the reported IC50 for SGLT2 in mice, which were associated with FGR of 64 ± 2% in WT and 17 ± 2% in Sglt1−/−. Additional intraperitoneal application of the SGLT2-I (maximum effective dose in metabolic cages) increased free plasma concentrations ∼10-fold and reduced FGR to 44 ± 3% in WT and to −1 ± 3% in Sglt1−/−. The absence of renal glucose reabsorption was confirmed in male and female Sglt1/Sglt2 double knockout mice. In conclusion, SGLT2 and SGLT1 account for renal glucose reabsorption in euglycemia, with 97 and 3% being reabsorbed by SGLT2 and SGLT1, respectively. When SGLT2 is fully inhibited by SGLT2-I, the increase in SGLT1-mediated glucose reabsorption explains why only 50–60% of filtered glucose is excreted. PMID:24226519

  20. Prenatal programming of renal salt wasting resets postnatal salt appetite, which drives food intake in the rat.

    Science.gov (United States)

    Alwasel, Saleh H; Barker, David J P; Ashton, Nick

    2012-03-01

    Sodium retention has been proposed as the cause of hypertension in the LP rat (offspring exposed to a maternal low-protein diet in utero) model of developmental programming because of increased renal NKCC2 (Na+/K+/2Cl- co-transporter 2) expression. However, we have shown that LP rats excrete more rather than less sodium than controls, leading us to hypothesize that LP rats ingest more salt in order to maintain sodium balance. Rats were fed on either a 9% (low) or 18% (control) protein diet during pregnancy; male and female offspring were studied at 4 weeks of age. LP rats of both sexes held in metabolism cages excreted more sodium and urine than controls. When given water to drink, LP rats drank more and ate more food than controls, hence sodium intake matched excretion. However, when given a choice between saline and water to drink, the total volume of fluid ingested by LP rats fell to control levels, but the volume of saline taken was significantly larger [3.8±0.1 compared with 8.8±1.3 ml/24 h per 100 g of body weight in control and LP rats respectively; Psodium content and ECF (extracellular fluid) volumes were greater in LP rats. These results show that prenatal programming of renal sodium wasting leads to a compensatory increase in salt appetite in LP rats. We speculate that the need to maintain salt homoeostasis following malnutrition in utero stimulates greater food intake, leading to accelerated growth and raised BP (blood pressure).