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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 a

  2. Luminal fructose inhibits rat intestinal sodium-phosphate cotransporter gene expression and phosphate uptake24

    Science.gov (United States)

    Kirchner, Séverine; Muduli, Anjali; Casirola, Donatella; Prum, Kannitha; Douard, Véronique; Ferraris, Ronaldo P

    2008-01-01

    Background While searching by microarray for sugar-responsive genes, we inadvertently discovered that sodium-phosphate cotransporter 2B (NaPi-2b) mRNA concentrations were much lower in fructose-perfused than in glucose-perfused intestines of neonatal rats. Changes in NaPi-2b mRNA abundance by sugars were accompanied by similar changes in NaPi-2b protein abundance and in rates of inorganic phosphate (Pi) uptake. Objective We tested the hypothesis that luminal fructose regulates NaPi-2b. Design We perfused into the intestine fructose, glucose, and non-metabolizable or poorly transported glucose analogs as well as phlorizin. Results NaPi-2b mRNA concentrations and Pi uptake rates in fructose-perfused intestines were ≈30% of those in glucose and its analogs. NaPi-2b inhibition by fructose is specific because the mRNA abundance and activity of the fructose transporter GLUT5 (glucose transporter 5) increased with fructose perfusion, whereas those of other transporters were independent of the perfusate. Plasma Pi after 4 h of perfusion was independent of the perfusate, probably because normal kidneys can maintain normophosphatemia. Inhibiting glucose-6-phosphatase, another fructose-responsive gene, with tungstate or vanadate nonspecifically inhibited NaPi-2b mRNA expression and Pi uptake in both glucose- or fructose-perfused intestines. The AMP kinase (AMPK)–activator AICAR (5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside) enhanced and the fatty acid synthase–AMPK inhibitor C75 (3-carboxy-4-octyl-2-methylene-butyrolactone trans-4-carboxy-5-octyl-3-methylenebutyrolactone) prevented fructose inhibition of NaPi-2b but had no effect on expression of other transporters. NaPi-2b expression decreased markedly with age and was inhibited by fructose in all age groups. Conclusions Energy levels in enterocytes may play a role in NaPi-2b inhibition by luminal fructose. Consumption of fructose that supplies ≈10% of caloric intake by Americans clearly affects absorption of

  3. Calcium oxalate crystal deposition in kidneys of hypercalciuric mice with disrupted type IIa sodium-phosphate cotransporter

    OpenAIRE

    Khan, Saeed R.; Glenton, Patricia A.

    2008-01-01

    The most common theories about the pathogenesis of idiopathic kidney stones consider precipitation of calcium phosphate (CaP) within the kidneys critical for the development of the disease. We decided to test the hypothesis that a CaP substrate can promote the deposition of calcium oxalate (CaOx) in the kidneys. Experimental hyperoxaluria was induced by feeding glyoxylate to male mice with knockout (KO) of NaPi IIa (Npt2a), a sodium-phosphate cotransporter. Npt2a KO mice are hypercalciuric an...

  4. Expression of Pit2 sodium-phosphate cotransporter during murine odontogenesis is developmentally regulated.

    Science.gov (United States)

    Zhao, Dawei; Vaziri Sani, Forugh; Nilsson, Jeanette; Rodenburg, Michaela; Stocking, Carol; Linde, Anders; Gritli-Linde, Amel

    2006-12-01

    Different sodium-dependent inorganic phosphate (P(i)) uptake mechanisms play a major role in cellular P(i) homeostasis. The function and detailed distribution patterns of the type III Na(+)-phosphate cotransporter, PiT-2, in different organs during development are still largely unknown. We therefore examined the temporospatial expression patterns of Pit2 during murine odontogenesis. Odontoblasts were always devoid of Pit2 expression, whereas a transient, but strong, expression was detected in young secretory ameloblasts. However, the stratum intermedium and, later on, the papillary layer and cells of the subodontoblastic layer, exhibited high levels of Pit2 mRNA, which increased gradually as the tooth matured. Hormonal treatment or P(i) starvation of tooth germs in vitro did not alter Pit2 levels or patterns of expression, indicating mechanisms of regulation different from those of PiT-1 or other cell types. PiT-2 also functions as a retroviral receptor, and functional membrane-localized protein was confirmed throughout the dental papilla/pulp by demonstrating cellular permissiveness to infection by a gammaretrovirus that uses PiT-2 as a receptor. The distinct pattern of Pit2 expression during odontogenesis suggests that its P(i)-transporter function may be important for homeostasis of dental cells and not specifically for mineralization of the dental extracellular matrices. The expression of viral receptors in enamel-forming cells and the dental pulp may be of pathological significance.

  5. Sodium Phosphate

    Science.gov (United States)

    Sodium phosphate is used in adults 18 years of age or older to empty the colon (large intestine, bowel) ... view of the walls of the colon. Sodium phosphate is in a class of medications called saline ...

  6. Change in renal function after sodium phosphate preparation for screening colonoscopy

    Institute of Scientific and Technical Information of China (English)

    Dong; Choon; Seol; Sung; Noh; Hong; Jeong; Hwan; Kim; In; Kyung; Sung; Hyung; Seok; Park; Jung; Hyun; Lee; Chan; Sup; Shim

    2010-01-01

    AIM:To investigate the changes in renal function at 12-24 mo in patients following sodium phosphate(NaP) preparation for screening colonoscopy.METHODS:We carried out a retrospective study on the results from patients who received health check-up services as part of an employer-provided wellness program performed between August 2006 and May 2008 and who were followed up for 12-24 mo.Prior to screening colonoscopy,224 patients underwent bowel cleansing with NaP(NaP group) and 113 patients with polyethylene gl...

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

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    Naziha Bakouh

    Full Text Available BACKGROUND: 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. METHODOLOGY/FINDINGS: 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. CONCLUSION/PERSPECTIVES: 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

  8. 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.

  9. Changes in Renal Function Following Administration of Oral Sodium Phosphate or Polyethylene Glycol for Colon Cleansing before Colonoscopy

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    Ramy Abaskharoun

    2007-01-01

    Full Text Available Changes in renal function were compared in patients receiving oral sodium phosphate (NaP for colon cleansing and those receiving large-volume polyethylene glycol (PEG solution to determine whether oral NaP resulted in frequent renal damage that had gone clinically undetected. From 1995 to 2004, a cohort of consecutive patients who had serum creatinine (Cr drawn immediately before colonoscopy and again after subsequent procedures three months to nine years later (almost 80% of patients between the first and fifth year were identified. Chronic renal failure (CRF was defined as an abnormal Cr at repeat measurement or an abnormal Cr clearance as estimated by the Cockroft-Gault equation at the time of repeat Cr measurement. Medications and medical comorbid conditions were recorded. Seven hundred sixty-seven patients (51% female and 49% male; 81% oral NaP and 19% PEG with normal baseline Cr levels were identified through the endoscopy unit database at the Hotel Dieu Hospital, Queen’s University (Kingston, Ontario. Of these, 55 (7% developed CRF. Forty-two (6.8% patients receiving oral NaP developed renal failure compared with 13 patients (8.7% receiving PEG (Fisher’s exact test; P=0.382, but the magnitude of CRF was small in each group (Cr level lower than 160 μmol/L. Using logistic regression analysis with the choice of preparation, medications and medical comorbid conditions as independent variables, only age and blood pressure were predictive of the development of renal failure (P=0.014 and P=0.001, respectively. Baseline Cr clearance was similiar in both the NaP and PEG groups and the absolute difference after colonoscopy did not differ. The present study concluded that the ingestion of oral NaP for colon cleansing before colonoscopy did not result in frequent renal damage that went clinically undetected.

  10. 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 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....... 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...

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

    DEFF Research Database (Denmark)

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

    2000-01-01

    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....... 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...

  12. Regulation of renal Na-(K)-Cl cotransporters by vasopressin.

    Science.gov (United States)

    Bachmann, Sebastian; Mutig, Kerim

    2017-08-01

    Vasopressin (AVP) induces antidiuresis, thus playing an essential role in body water and electrolyte homeostasis. Its antidiuretic effects are mediated chiefly by V2 vasopressin receptors (V2R) expressed along the distal nephron and collecting duct epithelia. NaCl reabsorption in the distal nephron, which includes the thick ascending limb (TAL) and distal convoluted tubule (DCT), largely depends on the activity of two structurally related Na-(K)-Cl cotransporters, NKCC2 in TAL and NCC in DCT. AVP-induced activation of these transporters contributes to urine concentration and renal electrolyte reabsorption. Previous work has specified molecular pathways mediating the effects of V2R activation in TAL and DCT, and protein networks involved in intracellular trafficking and phosphoregulation of the two transporters have been identified. This review summarizes recent progress in understanding AVP signalling mechanisms that are responsible for the activation of NKCC2 and NCC. Implications in the pathophysiology of diseases such as nephrogenic diabetes insipidus, diabetes mellitus and salt-sensitive hypertension are discussed in this context.

  13. 21 CFR 182.1778 - Sodium phosphate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Sodium phosphate. 182.1778 Section 182.1778 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR... Substances § 182.1778 Sodium phosphate. (a) Product. Sodium phosphate (mono-, di-, and tribasic)....

  14. 21 CFR 582.6778 - Sodium phosphate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Sodium phosphate. 582.6778 Section 582.6778 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Sodium phosphate. (a) Product. Sodium phosphate (mono-, di-, and tribasic). (b) Conditions of use....

  15. 21 CFR 582.1778 - Sodium phosphate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Sodium phosphate. 582.1778 Section 582.1778 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Additives § 582.1778 Sodium phosphate. (a) Product. Sodium phosphate (mono-, di-, and tribasic)....

  16. 21 CFR 582.5778 - Sodium phosphate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Sodium phosphate. 582.5778 Section 582.5778 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Supplements 1 § 582.5778 Sodium phosphate. (a) Product. Sodium phosphate (mono-, di-, and tribasic)....

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

    OpenAIRE

    Mizerski Grzegorz; Kicinski Pawel; Jaroszynski Andrzej

    2015-01-01

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

  18. 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.

  19. 21 CFR 182.8778 - Sodium phosphate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Sodium phosphate. 182.8778 Section 182.8778 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR... phosphate. (a) Product. Sodium phosphate (mono-, di-, and tribasic). (b) Conditions of use. This...

  20. 21 CFR 182.6778 - Sodium phosphate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Sodium phosphate. 182.6778 Section 182.6778 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR... phosphate. (a) Product. Sodium phosphate (mono-, di-, and tribasic). (b) Conditions of use. This...

  1. Sodium phosphate as an ergogenic aid.

    Science.gov (United States)

    Buck, Christopher L; Wallman, Karen E; Dawson, Brian; Guelfi, Kym J

    2013-06-01

    Legal nutritional ergogenic aids can offer athletes an additional avenue to enhance their performance beyond what they can achieve through training. Consequently, the investigation of new nutritional ergogenic aids is constantly being undertaken. One emerging nutritional supplement that has shown some positive benefits for sporting performance is sodium phosphate. For ergogenic purposes, sodium phosphate is supplemented orally in capsule form, at a dose of 3-5 g/day for a period of between 3 and 6 days. A number of exercise performance-enhancing alterations have been reported to occur with sodium phosphate supplementation, which include an increased aerobic capacity, increased peak power output, increased anaerobic threshold and improved myocardial and cardiovascular responses to exercise. A range of mechanisms have been posited to account for these ergogenic effects. These include enhancements in 2,3-Diphosphoglycerate (2,3-DPG) concentrations, myocardial efficiency, buffering capacity and adenosine triphosphate/phosphocreatine synthesis. Whilst there is evidence to support the ergogenic benefits of sodium phosphate, many studies researching this substance differ in terms of the administered dose and dosing protocol, the washout period employed and the fitness level of the participants recruited. Additionally, the effect of gender has received very little attention in the literature. Therefore, the purpose of this review is to critically examine the use of sodium phosphate as an ergogenic aid, with a focus on identifying relevant further research.

  2. 21 CFR 522.1883 - Prednisolone sodium phosphate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Prednisolone sodium phosphate. 522.1883 Section... § 522.1883 Prednisolone sodium phosphate. (a) Specifications. Each milliliter of solution contains 20 milligrams (mg) prednisolone sodium phosphate (equivalent to 14.88 mg of prednisolone). (b) Sponsor. See...

  3. Renal Expression and Urinary Excretion of Na-K-2Cl Cotransporter in Obstructive Nephropathy

    Directory of Open Access Journals (Sweden)

    Anabel Brandoni

    2017-01-01

    Full Text Available Renal damage due to urinary tract obstruction accounts for up to 30% of acute kidney injury in paediatrics and adults. Bilateral ureteral obstruction (BUO is associated with polyuria and reduced urinary concentrating capacity. We investigated the renal handling of water and electrolytes together with the renal expression and the urinary excretion of the Na-K-Cl cotransporter (NKCC2 after 1 (BUO-1, 2 (BUO-2, and 7 (BUO-7 days of release of BUO. Immunoblotting and immunohistochemical studies showed that NKCC2 expression was upregulated in apical membranes both from BUO-2 and from BUO-7 rats. The apical membrane expression, where NKCC2 is functional, may be sufficient to normalize water, potassium, sodium, and osmolytes tubular handling. NKCC2 abundance in homogenates and mRNA levels of NKCC2 was significantly decreased in almost all groups suggesting a decrease in the synthesis of the transporter. Urinary excretion of NKCC2 was increased in BUO-7 groups. These data suggest that the upregulation in the expression of NKCC2 in apical membranes during the postobstructive phase of BUO could contribute to improving the excretion of sodium and consequently also the excretion of potassium, osmolytes, and water. Moreover, the increase in urinary excretion of NKCC2 in BUO-7 group could be a potential additional biomarker of renal function recovery.

  4. Calcineurin inhibitor cyclosporine A activates renal Na-K-Cl cotransporters via local and systemic mechanisms.

    Science.gov (United States)

    Blankenstein, K I; Borschewski, A; Labes, R; Paliege, A; Boldt, C; McCormick, J A; Ellison, D H; Bader, M; Bachmann, S; Mutig, K

    2017-03-01

    Calcineurin dephosphorylates nuclear factor of activated T cells transcription factors, thereby facilitating T cell-mediated immune responses. Calcineurin inhibitors are instrumental for immunosuppression after organ transplantation but may cause side effects, including hypertension and electrolyte disorders. Kidneys were recently shown to display activation of the furosemide-sensitive Na-K-2Cl cotransporter (NKCC2) of the thick ascending limb and the thiazide-sensitive Na-Cl cotransporter (NCC) of the distal convoluted tubule upon calcineurin inhibition using cyclosporin A (CsA). An involvement of major hormones like angiotensin II or arginine vasopressin (AVP) has been proposed. To resolve this issue, the effects of CsA treatment in normal Wistar rats, AVP-deficient Brattleboro rats, and cultured renal epithelial cells endogenously expressing either NKCC2 or NCC were studied. Acute administration of CsA to Wistar rats rapidly augmented phosphorylation levels of NKCC2, NCC, and their activating kinases suggesting intraepithelial activating effects. Chronic CsA administration caused salt retention and hypertension, along with stimulation of renin and suppression of renal cyclooxygenase 2, pointing to a contribution of endocrine and paracrine mechanisms at long term. In Brattleboro rats, CsA induced activation of NCC, but not NKCC2, and parallel effects were obtained in cultured cells in the absence of AVP. Stimulation of cultured thick ascending limb cells with AVP agonist restored their responsiveness to CsA. Our results suggest that the direct epithelial action of calcineurin inhibition is sufficient for the activation of NCC, whereas its effect on NKCC2 is more complex and requires concomitant stimulation by AVP. Copyright © 2017 the American Physiological Society.

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

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    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.

  6. 40 CFR 422.60 - Applicability; description of the sodium phosphates subcategory.

    Science.gov (United States)

    2010-07-01

    ... sodium phosphates subcategory. 422.60 Section 422.60 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS PHOSPHATE MANUFACTURING POINT SOURCE CATEGORY Sodium Phosphates Subcategory § 422.60 Applicability; description of the sodium phosphates subcategory....

  7. The renal thiazide-sensitive Na-Cl cotransporter as mediator of the aldosterone-escape phenomenon.

    Science.gov (United States)

    Wang, X Y; Masilamani, S; Nielsen, J; Kwon, T H; Brooks, H L; Nielsen, S; Knepper, M A

    2001-07-01

    The kidneys "escape" from the Na-retaining effects of aldosterone when circulating levels of aldosterone are inappropriately elevated in the setting of normal or expanded extracellular fluid volume, e.g., in primary aldosteronism. Using a targeted proteomics approach, we screened renal protein extracts with rabbit polyclonal antibodies directed to each of the major Na transporters expressed along the nephron to determine whether escape from aldosterone-mediated Na retention is associated with decreased abundance of one or more of renal Na transporters. The analysis revealed that the renal abundance of the thiazide-sensitive Na-Cl cotransporter (NCC) was profoundly and selectively decreased. None of the other apical solute-coupled Na transporters displayed decreases in abundance, nor were the total abundances of the three ENaC subunits significantly altered. Immunocytochemistry showed a strong decrease in NCC labeling in distal convoluted tubules of aldosterone-escape rats with no change in the cellular distribution of NCC. Ribonuclease protection assays (RPAs) revealed that the decrease in NCC protein abundance was not associated with altered NCC mRNA abundance. Thus, the thiazide-sensitive Na-Cl cotransporter of the distal convoluted tubule appears to be the chief molecular target for regulatory processes responsible for mineralocorticoid escape, decreasing in abundance via a posttranscriptional mechanism.

  8. 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.

  9. Effect of hepatic or renal impairment on the pharmacokinetics of canagliflozin, a sodium glucose co-transporter 2 inhibitor.

    Science.gov (United States)

    Devineni, Damayanthi; Curtin, Christopher R; Marbury, Thomas C; Smith, William; Vaccaro, Nicole; Wexler, David; Vandebosch, An; Rusch, Sarah; Stieltjes, Hans; Wajs, Ewa

    2015-03-01

    Canagliflozin is a sodium-glucose cotransporter 2 inhibitor approved for the treatment of type 2 diabetes mellitus (T2DM). Because T2DM is often associated with renal or hepatic impairment, understanding the effects of these comorbid conditions on the pharmacokinetics of canagliflozin, and further assessing its safety, in these special populations is essential. Two open-label studies evaluated the pharmacokinetics, pharmacodynamics (renal study only), and safety of canagliflozin in participants with hepatic or renal impairment. Participants in the hepatic study (8 in each group) were categorized based on their Child-Pugh score (normal hepatic function, mild impairment [Child-Pugh score of 5 or 6], and moderate impairment [Child-Pugh score of 7-9]) and received a single oral dose of canagliflozin 300 mg. Participants in the renal study (8 in each group) were categorized based on their creatinine clearance (CLCR) (normal renal function [CLCR ≥80 mL/min]; mild [CLCR 50 to canagliflozin 200 mg; the exception was those with ESRD, who received 1 dose postdialysis and 1 dose predialysis (10 days later). Canagliflozin's pharmacokinetics and pharmacodynamics (urinary glucose excretion [UGE] and renal threshold for glucose excretion [RTG]) were assessed at predetermined time points. Mean maximum plasma concentration (Cmax) and area under the plasma concentration-time curve from time zero to infinite (AUC)0-∞ values differed by Canagliflozin's pharmacokinetics were not affected by mild or moderate hepatic impairment. Systemic exposure to canagliflozin increased in the renal impairment groups relative to participants with normal renal function. Pharmacodynamic response to canagliflozin, measured by using UGE and RTG, declined with increasing severity of renal impairment. A single oral dose of canagliflozin was well tolerated by participants in both studies. ClinicalTrials.gov identifiers: NCT01186588 and NCT01759576. Copyright © 2015 Elsevier HS Journals, Inc. All rights

  10. 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.

  11. Serum electrolyte shifts following administration of sodium phosphates enema.

    Science.gov (United States)

    Jacobson, Robert M; Peery, Jessica; Thompson, William O; Kanapka, Joseph A; Caswell, Michael

    2010-01-01

    The misuse of sodium phosphates enemas has resulted in reports of potentially severe metabolic and hemodynamic disturbances. Despite their long availability, these products have not been fully characterized pharmacokinetically. This trial sought to evaluate changes in the metabolic and hemodynamic parameters following the administration of one of two standard sodium phosphates enemas. Enema Casen (250 ml) is available only in Spain, and Fleet Enema (133 ml) is available in 66 countries in six continents of the world. These changes were correlated with scientific literature reports of hyperphosphatemia following phosphate enema use. Forty-five adult participants aged 50 years or older enrolled in the trial. Twenty-five participants were given one Enema Casen, whereas 20 participants received one Fleet Enema. Blood pressure, pulse, and serum chemistries were evaluated at screening; baseline; and 10, 60, and 120 minutes after receiving the enema. Each participant had a bowel movement within 10 minutes of receiving his enema. Asymptomatic, transient hyperphosphatemia was associated with increase in retention time but not with increase in volume of sodium phosphates enemas. Increased serum phosphate concentration and increased area under the curve of serum phosphate were associated with increased enema retention time. The Enema Casen induced a greater mean AUC of serum sodium concentration than did the Fleet Enema. There were no drug-related adverse events. Transient hyperphosphatemia following the use of sodium phosphates enemas correlates with retention time but not with dose. A scientific literature review of serious adverse events revealed that overdose, concomitant use of oral and rectal sodium phosphates products, and use in a contraindicated patient were associated with sodium phosphates enema and hyperphosphatemia.

  12. Renal Safety of Canagliflozin, a Sodium Glucose Co-transporter 2 Inhibitor, in Patients With Type 2 Diabetes Mellitus.

    Science.gov (United States)

    Desai, Mehul; Yavin, Yshai; Balis, Dainius; Sun, Don; Xie, John; Canovatchel, William; Rosenthal, Norm

    2017-01-12

    The incidence of renal-related adverse events (AEs) with canagliflozin in patients with type 2 diabetes mellitus from a pooled population of patients in 7 active- and placebo-controlled trials (N = 5,598) and in a 104-week study versus glimepiride (N = 1,450) was low and similar in canagliflozin and non-canagliflozin groups. In the study versus glimepiride, canagliflozin was associated with an initial acute decrease in estimated glomerular filtration rate (eGFR) that attenuated over time, while eGFR declined progressively over 104 weeks with glimepiride; the incidence of renal-related AEs with canagliflozin was generally stable over time, while the incidence with glimepiride increased over 104 weeks. In the analysis reported in this manuscript based on postmarketing reports from the US Food and Drug Administration Adverse Event Reporting System, a potential signal was identified for acute kidney injury with all approved sodium glucose co-transporter 2 (SGLT2) inhibitors (ie, canagliflozin, dapagliflozin, empagliflozin). The early onset of acute kidney injury events with SGLT2 inhibitors in postmarketing reports likely reflects the acute changes in eGFR due to the known renal haemodynamic effects of SGLT2 inhibition.

  13. Ovarian hormones and prolactin increase renal NaCl cotransporter phosphorylation.

    Science.gov (United States)

    Rojas-Vega, Lorena; Reyes-Castro, Luis A; Ramírez, Victoria; Bautista-Pérez, Rocío; Rafael, Chloe; Castañeda-Bueno, María; Meade, Patricia; de Los Heros, Paola; Arroyo-Garza, Isidora; Bernard, Valérie; Binart, Nadine; Bobadilla, Norma A; Hadchouel, Juliette; Zambrano, Elena; Gamba, Gerardo

    2015-04-15

    Unique situations in female physiology require volume retention. Accordingly, a dimorphic regulation of the thiazide-sensitive Na(+)-Cl(-) cotransporter (NCC) has been reported, with a higher activity in females than in males. However, little is known about the hormones and mechanisms involved. Here, we present evidence that estrogens, progesterone, and prolactin stimulate NCC expression and phosphorylation. The sex difference in NCC abundance, however, is species dependent. In rats, NCC phosphorylation is higher in females than in males, while in mice both NCC expression and phosphorylation is higher in females, and this is associated with increased expression and phosphorylation of full-length STE-20 proline-alanine-rich kinase (SPAK). Higher expression/phosphorylation of NCC was corroborated in humans by urinary exosome analysis. Ovariectomy in rats resulted in decreased expression and phosphorylation of the cotransporter and promoted the shift of SPAK isoforms toward the short inhibitory variant SPAK2. Conversely, estradiol or progesterone administration to ovariectomized rats restored NCC phosphorylation levels and shifted SPAK expression and phosphorylation towards the full-length isoform. Estradiol administration to male rats induced a significant increase in NCC phosphorylation. NCC is also modulated by prolactin. Administration of this peptide hormone to male rats induced increased phosphorylation of NCC, an effect that was observed even using the ex vivo kidney perfusion strategy. Our results indicate that estradiol, progesterone, and prolactin, the hormones that are involved in sexual cycle, pregnancy and lactation, upregulate the activity of NCC.

  14. 21 CFR 524.1883 - Prednisolone sodium phosphate-neomycin sulfate ophthalmic ointment.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Prednisolone sodium phosphate-neomycin sulfate... DOSAGE FORM NEW ANIMAL DRUGS § 524.1883 Prednisolone sodium phosphate-neomycin sulfate ophthalmic ointment. (a) Specifications. Prednisolone sodium phosphate-neomycin sulfate ophthalmic ointment...

  15. Osmoregulation Requires Brain Expression of the Renal Na-K-2Cl Cotransporter NKCC2

    Science.gov (United States)

    Konopacka, Agnieszka; Qiu, Jing; Yao, Song T.; Greenwood, Michael P.; Greenwood, Mingkwan; Lancaster, Thomas; Inoue, Wataru; de Souza Mecawi, Andre; Vechiato, Fernanda M.V.; de Lima, Juliana B.M.; Coletti, Ricardo; Hoe, See Ziau; Martin, Andrew; Lee, Justina; Joseph, Marina; Hindmarch, Charles; Paton, Julian; Antunes-Rodrigues, Jose; Bains, Jaideep

    2015-01-01

    The Na-K-2Cl cotransporter 2 (NKCC2) was thought to be kidney specific. Here we show expression in the brain hypothalamo-neurohypophyseal system (HNS), wherein upregulation follows osmotic stress. The HNS controls osmotic stability through the synthesis and release of the neuropeptide hormone, arginine vasopressin (AVP). AVP travels through the bloodstream to the kidney, where it promotes water conservation. Knockdown of HNS NKCC2 elicited profound effects on fluid balance following ingestion of a high-salt solution—rats produced significantly more urine, concomitant with increases in fluid intake and plasma osmolality. Since NKCC2 is the molecular target of the loop diuretics bumetanide and furosemide, we asked about their effects on HNS function following disturbed water balance. Dehydration-evoked GABA-mediated excitation of AVP neurons was reversed by bumetanide, and furosemide blocked AVP release, both in vivo and in hypothalamic explants. Thus, NKCC2-dependent brain mechanisms that regulate osmotic stability are disrupted by loop diuretics in rats. PMID:25834041

  16. Deafness and renal tubular acidosis in mice lacking the K-Cl co-transporter Kcc4.

    Science.gov (United States)

    Boettger, Thomas; Hübner, Christian A; Maier, Hannes; Rust, Marco B; Beck, Franz X; Jentsch, Thomas J

    2002-04-25

    Hearing depends on a high K(+) concentration bathing the apical membranes of sensory hair cells. K(+) that has entered hair cells through apical mechanosensitive channels is transported to the stria vascularis for re-secretion into the scala media(). K(+) probably exits outer hair cells by KCNQ4 K(+) channels(), and is then transported by means of a gap junction system connecting supporting Deiters' cells and fibrocytes() back to the stria vascularis. We show here that mice lacking the K(+)/Cl(-) (K-Cl) co-transporter Kcc4 (coded for by Slc12a7) are deaf because their hair cells degenerate rapidly after the beginning of hearing. In the mature organ of Corti, Kcc4 is restricted to supporting cells of outer and inner hair cells. Our data suggest that Kcc4 is important for K(+) recycling() by siphoning K(+) ions after their exit from outer hair cells into supporting Deiters' cells, where K(+) enters the gap junction pathway. Similar to some human genetic syndromes(), deafness in Kcc4-deficient mice is associated with renal tubular acidosis. It probably results from an impairment of Cl(-) recycling across the basolateral membrane of acid-secreting alpha-intercalated cells of the distal nephron.

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

    DEFF Research Database (Denmark)

    Poulsen, Søren Brandt; Christensen, Birgitte M

    2016-01-01

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

  18. Double knockout of pendrin and Na-Cl cotransporter (NCC) causes severe salt wasting, volume depletion, and renal failure.

    Science.gov (United States)

    Soleimani, Manoocher; Barone, Sharon; Xu, Jie; Shull, Gary E; Siddiqui, Faraz; Zahedi, Kamyar; Amlal, Hassane

    2012-08-14

    The Na-Cl cotransporter (NCC), which is the target of inhibition by thiazides, is located in close proximity to the chloride-absorbing transporter pendrin in the kidney distal nephron. Single deletion of pendrin or NCC does not cause salt wasting or excessive diuresis under basal conditions, raising the possibility that these transporters are predominantly active during salt depletion or in response to excess aldosterone. We hypothesized that pendrin and NCC compensate for loss of function of the other under basal conditions, thereby masking the role that each plays in salt absorption. To test our hypothesis, we generated pendrin/NCC double knockout (KO) mice by crossing pendrin KO mice with NCC KO mice. Pendrin/NCC double KO mice displayed severe salt wasting and sharp increase in urine output under basal conditions. As a result, animals developed profound volume depletion, renal failure, and metabolic alkalosis without hypokalemia, which were all corrected with salt replacement. We propose that the combined inhibition of pendrin and NCC can provide a strong diuretic regimen without causing hypokalemia for patients with fluid overload, including patients with congestive heart failure, nephrotic syndrome, diuretic resistance, or generalized edema.

  19. Circadian exosomal expression of renal thiazide-sensitive NaCl cotransporter (NCC) and prostasin in healthy individuals.

    Science.gov (United States)

    Castagna, Annalisa; Pizzolo, Francesca; Chiecchi, Laura; Morandini, Francesca; Channavajjhala, Sarath Kiran; Guarini, Patrizia; Salvagno, Gianluca; Olivieri, Oliviero

    2015-06-01

    A circadian timing system is involved in the maintenance of fluid and electrolyte balance and blood pressure control. Aldosterone and vasopressin modulate ion transporters and channels crucial in sodium (Na) and water reabsorption such as the epithelium Na channel and the renal thiazide-sensitive NaCl cotransporter (NCC). We analyzed in urinary exosomes the intraday variations of NCC and prostasin expression and the association with electrolytes and water balance parameters. Blood and urine samples were collected at five time points during the day from five healthy subjects. Blood renin, aldosterone, cortisol, ACTH, and plasmatic and urinary Na, potassium, creatinine, adiuretin (ADH), NCC, and prostasin were evaluated. ACTH and cortisol showed a circadian pattern, similarly to aldosterone, while exosomal NCC and prostasin pattern were similar to urinary ADH, decreased in the morning and subsequently increased in the afternoon and evening. In urinary exosomes, NCC and prostasin had a diurnal pattern parallel to ADH and aquaporin 2, confirming that, in healthy subjects, both prostasin and NCC relate to water balance. These results provide suggestions for a possible chronotherapeutic approach in patients treated with thiazides, diuretic drugs acting as specific inhibitors of NCC-mediated Na reabsorption. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

    Science.gov (United States)

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

    2017-03-01

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

  1. 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; Lapointe, Jean-Yves

    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. Copyright © 2016 by the American Society of Nephrology.

  2. Effects of sodium phosphate and caffeine loading on repeated-sprint ability.

    Science.gov (United States)

    Buck, Christopher; Guelfi, Kym; Dawson, Brian; McNaughton, Lars; Wallman, Karen

    2015-01-01

    The effects of sodium phosphate and caffeine supplementation were assessed on repeated-sprint ability. Using a randomised, double-blind, Latin-square design, 12 female, team-sport players participated in four trials: (1) sodium phosphate and caffeine, (2) sodium phosphate and placebo (for caffeine), (3) caffeine and placebo (for sodium phosphate) and (4) placebo (for sodium phosphate and caffeine), with ~21 days separating each trial. After each trial, participants performed a simulated team-game circuit (4 × 15 min quarters) with 6 × 20-m repeated-sprints performed once before (Set 1), at half-time (Set 2), and after end (Set 3). Total sprint times were faster after sodium phosphate and caffeine supplementation compared with placebo (Set 1: P = 0.003; Set 2: d = -0.51; Set 3: P sprint times were faster after sodium phosphate supplementation compared with placebo (Set 1: d = -0.52; Set 3: d = -0.58). Best sprint results were faster after sodium phosphate and caffeine supplementation compared with placebo (Set 3: P = 0.007, d = -0.90) and caffeine (Set 3: P = 0.024, d = -0.73). Best sprint times were also faster after sodium phosphate supplementation compared with placebo (d = -0.54 to -0.61 for all sets). Sodium phosphate and combined sodium phosphate and caffeine loading improved repeated-sprint ability.

  3. Incretins and selective renal sodium-glucose co-transporter 2 inhibitors in hypertension and coronary heart disease

    Institute of Scientific and Technical Information of China (English)

    Ramiro; A; Sanchez; Hugo; Sanabria; Cecilia; de; los; Santos; Agustin; J; Ramirez

    2015-01-01

    Hyperglycemia is associated with an increased risk of cardiovascular disease,and the consequences ofintensive therapy may depend on the mechanism of the anti-diabetic agent(s)used to achieve a tight control.In animal models,stable analogues of glucagon-like peptide-1(GLP-1)were able to reduce body weight and blood pressure and also had favorable effects on ischemia following coronary reperfusion.In a similar way,dipeptidyl peptidase IV(DPPIV)showed to have favorable effects in animal models of ischemia/reperfusion.This could be due to the fact that DPPIV inhibitors were able to prevent the breakdown of GLP-1 and glucose-dependent insulinotropic polypeptide,but they also decreased the degradation of several vasoactive peptides.Preclinical data for GLP-1,its derivatives and inhibitors of the DPPIV enzyme degradation suggests that these agents may be able to,besides controlling glycaemia,induce cardio-protective and vasodilator effects.Notwithstanding the many favorable cardiovascular effects of GLP-1/incretins reported in different studies,many questions remain unanswered due the limited number of studies in human beings that aim to examine the effects of GLP-1 on cardiovascular endpoints.For this reason,long-term trials searching for positive cardiovascular effects are now in process,such as the CAROLINA and CARMELINA trials,which are supported by small pilot studies performed in humans(and many more animal studies)with incretin-based therapies.On the other hand,selective renal sodium-glucose co-transporter 2 inhibitors were also evaluated in the prevention of cardiovascular outcomes in type 2 diabetes.However,it is quite early to draw conclusions,since data on cardiovascular outcomes and cardiovascular death are limited and long-term studies are still ongoing.In this review,we will analyze the mechanisms underlying the cardiovascular effects of incretins and,at the same time,we will present a critical position about the real value of these compounds in the

  4. 21 CFR 201.307 - Sodium phosphates; package size limitation, warnings, and directions for over-the-counter sale.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Sodium phosphates; package size limitation... Requirements for Specific Drug Products § 201.307 Sodium phosphates; package size limitation, warnings, and... and Drug Administration indicate that multiple container sizes of sodium phosphates oral...

  5. Altered expression of renal bumetanide-sensitive sodium-pota-ssium-2 chloride cotransporter and Cl- channel -K2 gene in angiotensin Ⅱ-infused hypertensive rats

    Institute of Scientific and Technical Information of China (English)

    YE Tao; LIU Zhi-quan; SUN Chao-feng; ZHENG Yong; MA Ai-qun; FANG Yuan

    2005-01-01

    Background Little information is available regarding the effect of angiotensin Ⅱ (Ang Ⅱ) on the bumetanide-sensitive sodium-potassium-2 chloride cotransporter (NKCC2), the thiazide-sensitive sodium-chloride cotransporter (NCC), and the Cl- channel (CLC)-K2 at both mRNA and protein expression level in Ang Ⅱ-induced hypertensive rats. This study was conducted to investigate the influence of Ang Ⅱ with chronic subpressor infusion on nephron-specific gene expression of NKCC2, NCC and CLC-K2. Results Ang Ⅱ significantly increased blood pressure and up-regulated NKCC2 mRNA and protein expression in the kidney. Expression of CLC-K2 mRNA in the kidney increased 1.6 fold (P<0.05).There were no changes in NCC mRNA or protein expression in AngII-treated rats versus control. Conclusions Chronic subpressor Ang Ⅱ infusion can significantly alter NKCC2 and CLC-K2 mRNA expression in the kidney, and protein abundance of NKCC2 in kidney is positively regulated by Ang Ⅱ. These effects may contribute to enhanced renal Na+ and Cl- reabsorption in response to Ang Ⅱ.

  6. 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.

  7. 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%.

  8. Upregulation of renal sodium transporters in D5 dopamine receptor-deficient mice.

    Science.gov (United States)

    Wang, Xiaoyan; Luo, Yingjin; Escano, Crisanto S; Yang, Zhiwei; Asico, Laureano; Li, Hewang; Jones, John E; Armando, Ines; Lu, Quansheng; Sibley, David R; Eisner, Gilbert M; Jose, Pedro A

    2010-06-01

    D(5) dopamine receptor (D(5)R)-deficient (D(5)(-/-)) mice have hypertension that is aggravated by an increase in sodium intake. The present experiments were designed to test the hypothesis that a dysregulation of renal sodium transporters is related to the salt sensitivity in D(5)(-/-) mice. D(5)R was expressed in the renal proximal tubule, thick ascending limb, distal convoluted tubule, and cortical and outer medullary collecting ducts in D(5)(+/+) mice. On a control Na(+) diet, renal protein expressions of NKCC2 (sodium-potassium-2 chloride cotransporter), sodium chloride cotransporter, and alpha and gamma subunits of the epithelial sodium channel were greater in D(5)(-/-) than in D(5)(+/+) mice. Renal renin abundance and urine aldosterone levels were similar but renal angiotensin II type 1 receptor (AT(1)R) protein expression was increased in D(5)(-/-) mice. An elevated Na(+) diet increased further the elevated blood pressure of D(5)(-/-) mice but did not affect the normal blood pressure of D(5)(+/+) mice. The increased levels of NKCC2, sodium chloride cotransporter, and alpha and gamma subunits of the epithelial sodium channel persisted with the elevated Na(+) diet and unaffected by chronic AT(1)R blockade (losartan) in D(5)(-/-) mice. The expressions of proximal sodium transporters NHE3 (sodium hydrogen exchanger type 3) and NaPi2 (sodium phosphate cotransporter type 2) were increased by the elevated Na(+) diet in D(5)(-/-) mice; the increased expression of NHE3 but not NaPi2 was abolished by AT(1)R blockade. Our findings suggest that the increased protein expression of sodium transporters/channels in distal nephron segments may be the direct consequence of the disruption of D(5)R, independent of the renin-angiotensin aldosterone system.

  9. 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.

  10. Angiotensin II signaling increases activity of the renal Na-Cl cotransporter through a WNK4-SPAK-dependent pathway.

    NARCIS (Netherlands)

    San-Cristobal, P.; Pacheco-Alvarez, D.; Richardson, C.; Ring, A.M.; Vazquez, N.; Rafiqi, F.H.; Chari, D.; Kahle, K.T.; Leng, Q.; Bobadilla, N.A.; Hebert, S.C.; Alessi, D.R.; Lifton, R.P.; Gamba, G.

    2009-01-01

    Mutations in the kinase WNK4 cause pseudohypoaldosteronism type II (PHAII), a syndrome featuring hypertension and high serum K(+) levels (hyperkalemia). WNK4 has distinct functional states that regulate the balance between renal salt reabsorption and K(+) secretion by modulating the activities of

  11. Angiotensin II signaling increases activity of the renal Na-Cl cotransporter through a WNK4-SPAK-dependent pathway.

    NARCIS (Netherlands)

    San-Cristobal, P.; Pacheco-Alvarez, D.; Richardson, C.; Ring, A.M.; Vazquez, N.; Rafiqi, F.H.; Chari, D.; Kahle, K.T.; Leng, Q.; Bobadilla, N.A.; Hebert, S.C.; Alessi, D.R.; Lifton, R.P.; Gamba, G.

    2009-01-01

    Mutations in the kinase WNK4 cause pseudohypoaldosteronism type II (PHAII), a syndrome featuring hypertension and high serum K(+) levels (hyperkalemia). WNK4 has distinct functional states that regulate the balance between renal salt reabsorption and K(+) secretion by modulating the activities of re

  12. The renal thiazide-sensitive Na-Cl cotransporter as mediator of the aldosterone-escape phenomenon

    OpenAIRE

    Wang, Xiao-Yan; Masilamani, Shyama; Nielsen, Jakob; Kwon, Tae-Hwan; Brooks, Heddwen L.; Nielsen, Søren; Knepper, Mark A.

    2001-01-01

    The kidneys “escape” from the Na-retaining effects of aldosterone when circulating levels of aldosterone are inappropriately elevated in the setting of normal or expanded extracellular fluid volume, e.g., in primary aldosteronism. Using a targeted proteomics approach, we screened renal protein extracts with rabbit polyclonal antibodies directed to each of the major Na transporters expressed along the nephron to determine whether escape from aldosterone-mediated Na retention is associated with...

  13. Magnesium citrate with a single dose of sodium phosphate for colonoscopy bowel preparation

    Institute of Scientific and Technical Information of China (English)

    Yong Sung Choi; Jung Pil Suh; Jong Kyu Kim; In Taek Lee; Eui Gon Youk; Doo Seok Lee; Do Sun Kim; Doo Han Lee

    2011-01-01

    AIM: To evaluate the efficacy and acceptability of magnesium citrate and a single dose of oral sodium phosphate (45 mL) solution for morning colonoscopy bowel preparation.METHODS: A total of 159 patients were randomly assigned to receive two split doses of 90 mg of sodium phosphate (Group Ⅰ, n = 79) or magnesium citrate (250 mL,the day before the procedure) followed by 45 mL of sodium phosphate (the day of procedure, Group Ⅱ, n =80). The quality of bowel cleansing and the acceptability of each regimen were compared, including the satisfaction,taste, willing to repeat and adverse effects of each regimen.RESULTS: The quality of bowel cleansing of Group Ⅱ was as good as that of Group Ⅰ (An Aronchick scale score of good or excellent: 70.9% vs 81.0%, respectively,P = 0.34; the Ottawa system score: 4.4 ± 2.6 vs 3.8± 3.0, respectively, P = 0.76). There was no statistically significant difference between both groups with regard to acceptability, including the satisfaction, taste and willingness to repeat the regimen. A significantly greater number of older patients (over 65 years old) in Group Ⅱ graded the overall satisfaction as satisfactory (48.1%vs 78.1%, respectively; Group Ⅰ vs Group Ⅱ, P = 0.01).There were no significant adverse reactions. CONCLUSION: Magnesium citrate and a single dose of sodium phosphate was as effective and tolerable as the conventional sodium phosphate regimen and is a satisfactory option.

  14. Recognizing the Clinical Contraindications to the Use of Oral Sodium Phosphate for Colon Cleansing: A Case Study

    Directory of Open Access Journals (Sweden)

    Lawrence C Hookey

    2004-01-01

    Full Text Available Oral sodium phosphate has been demonstrated in numerous clinical trials to be an effective and well-tolerated colonic cleansing agent. However, there exists a potential to induce shifts in intravascular volume. The phosphate load often results in hyperphosphatemia, which may precipitate hypocalcemia. A review at the authors' institution identified four patients with adverse events related to oral sodium phosphate. Three of these cases had pre-existing comorbidities that predisposed them to the adverse event, or had received doses higher than that used or recommended in previous trials. Recommendations for relative and absolute contraindications to the use of oral sodium phosphate are described.

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

    Science.gov (United States)

    Oi, Katsuyuki; Sohara, Eisei; Rai, Tatemitsu; Misawa, Moko; Chiga, Motoko; Alessi, Dario R; Sasaki, Sei; Uchida, Shinichi

    2012-02-15

    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.

  16. 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.

  17. Improving quality of colonoscopy by adding simethicone to sodium phosphate bowel preparation

    Institute of Scientific and Technical Information of China (English)

    Sasinee Tongprasert; Abhasnee Sobhonslidsuk; Sasivimol Rattanasiri

    2009-01-01

    AIM: To evaluate the effectiveness of simethicone in enhancing visibility and efficacy during colonoscopy. METHODS: A prospective, double-blind, randomized, placebo-controlled study was conducted. One hundred and twenty-four patients were allocated to receive 2 doses of sodium phosphate plus 240 mg of tablet simethicone or placebo as bowel preparation. Visibility was blindly assessed for the amount of air bubbles and adequacy of colon preparation. Total colonoscopic time, side effects of the medication, endoscopist and patient satisfaction were also compared. RESULTS: Sodium phosphate plus simethicone, compared to sodium phosphate plus placebo, improved visibility by diminishing air bubbles (100.00% vs 42.37%, P < 0.0001) but simethicone failed to demonstrate improvement in adequacy of colon preparation (90.16% vs 81.36%, P = 0.17). Endoscopist and patient satisfaction were increased significantly in the simethicone group. However, there was no difference in the total duration of colonoscopy and side effects of the medication. CONCLUSION: The addition of simethicone is of benefit for colonoscopic bowel preparation by diminishing air bubbles, which results in enhanced visibility. Endoscopist and patient satisfaction is also increased.

  18. Fourier Transform Infrared Spectroscopic Study of Sodium Phosphate Solids and Solutions

    Institute of Scientific and Technical Information of China (English)

    龚文琪

    2001-01-01

    Solids and solutions of sodium phosphates with various chain lengths have been studied by using the techniques of diffuse reflectance infrared Fourier transform (DRIFT) spectroscopy and attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy, respectively. A systematic study of the infrared spectra of the solid sodium phosphates has been conducted on the basis of the information available in the literatures to establish the assignments of the infrared vibrations of the different groups in the phosphate molecules. The infrared spectra of the solutions of sodium phosphates have been analyzed according to the infrared study on the relevant solids, in conjunction with the study of the phosphate species distribution in solution on the basis of the acid-base reaction equilibria. The results obtained have revealed the correlations between the infrared absorption spectra and the structure of the different P-O groups in different kinds of phosphates and are useful in the analysis of phosphate solids and solutions widely used in the various operations of mineral processing.

  19. 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

  20. Crystal Growth Models of Dexamethasone Sodium Phosphate in a MSMPR Reactive Crystallizer

    Institute of Scientific and Technical Information of China (English)

    郝红勋; 王静康; 王永莉; 侯宝红

    2005-01-01

    The reactive crystallization process of dexamethasone sodium phosphate was investigated in a continuous mixed-suspension, mixed-product-removal(MSMPR) crystallizer. Analyzing experimental data, it was found that the growth of product crystal was size-dependent. The Bransom, CR, ASL, M J2 and M J3 size-dependent growth models were discussed in details. Using experimental steady state population density data of dexamethasone sodium phosphate, parameters of five size-dependent growth models were determined by the method of non-linear least-squares. By comparison of experimental population density and linear growth rate data with those obtained from the five size-dependent growth models, it was found that the MJ3 model predicts the growth more accurately than do the other four models. Based on the theory of population balance, the crystal nucleation and growth rate equations of dexamethasone sodium phosphate were determined by non-linear regression method. The effects of different operation parameters such as supersaturation, magma density and temperature on the quality of product crystal were also discussed, and the optimal operation conditions were derived.

  1. Inactivation of the Na-Cl co-transporter (NCC) gene is associated with high BMD through both renal and bone mechanisms: analysis of patients with Gitelman syndrome and Ncc null mice.

    Science.gov (United States)

    Nicolet-Barousse, Laurence; Blanchard, Anne; Roux, Christian; Pietri, Laurence; Bloch-Faure, May; Kolta, Sami; Chappard, Christine; Geoffroy, Valérie; Morieux, Caroline; Jeunemaitre, Xavier; Shull, Gary E; Meneton, Pierre; Paillard, Michel; Houillier, Pascal; De Vernejoul, Marie-Christine

    2005-05-01

    Chronic thiazide treatment is associated with high BMD. We report that patients and mice with null mutations in the thiazide-sensitive NaCl cotransporter (NCC) have higher renal tubular Ca reabsorption, higher BMD, and lower bone remodeling than controls, as well as abnormalities in Ca metabolism, mainly caused by Mg depletion. Chronic thiazide treatment decreases urinary Ca excretion (UVCa) and increases BMD. To understand the underlying mechanisms, Ca and bone metabolism were studied in two models of genetic inactivation of the thiazide-sensitive NaCl cotransporter (NCC): patients with Gitelman syndrome (GS) and Ncc knockout (Ncc(-/-)) mice. Ca metabolism was analyzed in GS patients and Ncc(-/-) mice under conditions of low dietary Ca. BMD was measured by DXA in patients and mice, and bone histomorphometry was analyzed in mice. GS patients had low plasma Mg. They exhibited reduced UVCa, but similar serum Ca and GFR as control subjects, suggesting increased renal Ca reabsorption. Blood PTH was lower despite lower serum ionized Ca, and Mg repletion almost corrected both relative hypoparathyroidism and low UVCa. BMD was significantly increased in GS patients at both lumbar (+7%) and femoral (+16%) sites, and osteocalcin was reduced. In Ncc(-/-) mice, serum Ca and GFR were unchanged, but UVCa was reduced and PTH was elevated; Mg repletion largely corrected both abnormalities. Trabecular and cortical BMD were higher than in Ncc(+/+) mice (+4% and +5%, respectively), and despite elevated PTH, were associated with higher cortical thickness and lower endosteal osteoclastic surface. Higher BMD is observed in GS patients and Ncc(-/-) mice. Relative hypoparathyroidism (human) and bone resistance to PTH (mice), mainly caused by Mg depletion, can explain the low bone remodeling and normal/low serum Ca despite increased renal Ca reabsorption.

  2. Corrosion Inhibition of Sodium Phosphate for Coarse and Near Ultrafined-Grain Mild steel surface

    Directory of Open Access Journals (Sweden)

    Kazem Sabet Bokati

    2017-06-01

    Full Text Available An ultrafine grain surface layer with average crystallite size of 28 nm was produced on annealed mild steel through a wire brushing process. The effects of grain size reduction on the inhibition performance of sodium phosphate were investigated using polarization and electrochemical impedance spectroscopy (EIS measurements. The crystal grain size of wire brushed surface was analyzed by X-ray diffractometry (XRD and field emission scanning electron microscopy (FESEM. The electrochemical tests were conducted in artificial sea water (ASW in the presence and absence of 250 mg/lit sodium phosphate (SP. The wire brushed surface indicated considerable deformed plastic flows and high surface roughness. Due to the accumulated strains, a deformed layer with thickness of 20±5 μm was produced and the crystal grain size of severe deformed zone was about 28 nm. Wire brushed surface increased uniform corrosion rate of mild steel due to enhanced surface roughness and preferential sites to adsorption of corrosive ions. However, the wire brushed surface showed a positive effect on inhibition performance of sodium phosphate. The electrochemical results revealed that average inhibition efficiency increased from 65 to about 80 percent in ASW solution containing 1.5 mM Na3PO4 for coarse grained samples in comparison to that of ultra-fined grain samples respectively .The wire brushing process encouraged passivity on the surface in SP-containing solution due to a high density of nucleation sites which increased the adsorption of phosphate ions leading to a high fraction of passive layers and low corrosion rates.

  3. Microanalyses of the hydroxyl—poly—calcium sodium phosphate coatings produced by ion beam assisted deposition

    Institute of Scientific and Technical Information of China (English)

    LIUZhong-Yang; WANGChang-Xing; 等

    2002-01-01

    Thin calcium phosphate catings on titanium alloy substrates were prepared by Ar+ ion beam assisted deposition(IBAD) from hydroxyl-poly-calcium sodium phosphate(HPPA) target.The coatings were analyzed by XRD,FTIR,XPS,These analyses revealed that the as-deposited films were amorphous or no apparent crystallinity.No distinct absorption band of the hydroxyl group was observed in FTIR spectra of the coatings but new absorption bands were presented for CO3-2,The calcium to phosphorous ratio of these catings in different IBAD conditions varied from 0.46 to 3.36.

  4. Gamma ray interactions with V{sub 2}O{sub 5}-doped sodium phosphate glasses

    Energy Technology Data Exchange (ETDEWEB)

    ElBatal, F.H. [Glass Research Department, National Research Center, Cairo (Egypt); Hamdy, Y.M. [Spectroscopy Department, National Research Center, Cairo (Egypt)], E-mail: yousry_m_h@yahoo.com; Marzouk, S.Y. [Electron Microscope and Thin Film Department, National Research Center, Cairo (Egypt)

    2008-12-20

    Undoped and V{sub 2}O{sub 5}-doped sodium phosphate glasses of various compositions and with varying progressive V{sub 2}O{sub 5} contents were prepared. UV-vis and infrared, Raman and electron spin resonance spectroscopic studies were measured before and after successive gamma irradiation. Experimental results indicate that vanadium ions exist in three possible valencies in sodium phosphate glasses, namely, the trivalent, tetravalent and pentavalent states. The first two lower valencies are predominant in this glass system. The changes in UV-vis and infrared spectral data are discussed in relation to the structural evolution caused by the change in the V{sub 2}O{sub 5} content or glass composition. Raman and ESR measurements are taken as confirmative tools to support our assumptions relating to the states of vanadium and structural groups arrangements in the studied glasses. Gamma irradiation produces induced defects depending on the host glass and the concentration of V{sub 2}O{sub 5} content together with the sharing of unavoidable trace iron impurities. Vanadium ions when present in high doping level, have been found to exhibit a shielding behaviour towards the effects of progressive gamma irradiation causing a retardation of the growth of the induced defects caused by irradiation.

  5. Sodium-glucose cotransport

    Science.gov (United States)

    Poulsen, Søren Brandt; Fenton, Robert A.; Rieg, Timo

    2017-01-01

    Purpose of review Sodium-glucose cotransporters (SGLTs) are important mediators of glucose uptake across apical cell membranes. SGLT1 mediates almost all sodium-dependent glucose uptake in the small intestine, while in the kidney SGLT2, and to a lesser extent SGLT1, account for more than 90% and nearly 3%, respectively, of glucose reabsorption from the glomerular ultrafiltrate. Although the recent availability of SGLT2 inhibitors for the treatment of diabetes mellitus has increased the number of clinical studies, this review has a focus on mechanisms contributing to the cellular regulation of SGLTs. Recent findings Studies have focused on the regulation of SGLT expression under different physiological/pathophysiological conditions, for example diet, age or diabetes mellitus. Several studies provide evidence of SGLT regulation via cyclic adenosine monophosphate/protein kinase A, protein kinase C, glucagon-like peptide 2, insulin, leptin, signal transducer and activator of transcription-3 (STAT3), phosphoinositide-3 kinase (PI3K)/Akt, mitogen-activated protein kinases (MAPKs), nuclear factor-kappaB (NF-kappaB), with-no-K[Lys] kinases/STE20/SPS1-related proline/alanine-rich kinase (Wnk/SPAK) and regulatory solute carrier protein 1 (RS1) pathways. Summary SGLT inhibitors are important drugs for glycemic control in diabetes mellitus. Although the contribution of SGLT1 for absorption of glucose from the intestine as well as SGLT2/SGLT1 for renal glucose reabsorption has been comprehensively defined, this review provides an up-to-date outline for the mechanistic regulation of SGLT1/SGLT2. PMID:26125647

  6. Zinc(II) oxide stability in alkaline sodium phosphate solutions at elevated temperatures

    Energy Technology Data Exchange (ETDEWEB)

    Ziemniak, S.E.; Opalka, E.P.

    1993-04-01

    Zinc oxide (ZnO) is shown to transform into either of two phosphate-containing compounds in relatively dilute alkaline sodium phosphate solutions at elevated temperatures via ZnO(s) + Na{sup +} + H{sub 2}PO{sub 4}{sup {minus}} {r_reversible} NaZnPO{sub 4}(s) + H{sub 2}O or 2 ZnO(s) + H{sub 3}PO{sub 4}(aq) {r_reversible} Zn{sub 2}(OH)PO{sub 4}(s) + H{sub 2}O. X-ray diffraction analyses indicate that NaZnPO{sub 4} possesses an orthorhombic unit cell having lattice parameters a = 8.710 {+-} 0.013, b = 15.175 {+-} 0.010, and c = 8.027 {+-} 0.004 {angstrom}. The thermodynamic equilibria for these reactions were defined in the system ZnO-Na{sub 2}O-P{sub 2}O{sub 5}-H{sub 2}O for Na/P molar ratios between 2.1 and 3. Based on observed reaction threshold values for sodium phosphate concentration and temperature, the standard entropy (S{degrees}) and free energy of formation ({Delta}G{sub f}{degrees}) for NaZnPO{sub 4} were calculated to be 169.0 J/mol-K and {minus}1510.6 kJ/mol, respectively; similar values for Zn{sub 2}(OH)PO{sub 4} (tarbuttite) were 235.9 J/mol-K and {minus}1604.6 kJ/mol. Additions of sodium sulfite and sulfate did not alter the above reactions.

  7. Preparation of photocatalytic ZnO nanoparticles and application in photochemical degradation of betamethasone sodium phosphate using taguchi approach

    Science.gov (United States)

    Giahi, M.; Farajpour, G.; Taghavi, H.; Shokri, S.

    2014-07-01

    In this study, ZnO nanoparticles were prepared by a sol-gel method for the first time. Taguchi method was used to identify the several factors that may affect degradation percentage of betamethasone sodium phosphate in wastewater in UV/K2S2O8/nano-ZnO system. Our experimental design consisted of testing five factors, i.e., dosage of K2S2O8, concentration of betamethasone sodium phosphate, amount of ZnO, irradiation time and initial pH. With four levels of each factor tested. It was found that, optimum parameters are irradiation time, 180 min; pH 9.0; betamethasone sodium phosphate, 30 mg/L; amount of ZnO, 13 mg; K2S2O8, 1 mM. The percentage contribution of each factor was determined by the analysis of variance (ANOVA). The results showed that irradiation time; pH; amount of ZnO; drug concentration and dosage of K2S2O8 contributed by 46.73, 28.56, 11.56, 6.70, and 6.44%, respectively. Finally, the kinetics process was studied and the photodegradation rate of betamethasone sodium phosphate was found to obey pseudo-first-order kinetics equation represented by the Langmuir-Hinshelwood model.

  8. Safety and efficacy of aspartame-based liquid versus sucrose-based liquids used for dilution in oral sodium phosphate solutions for colonoscopy preparations.

    Science.gov (United States)

    Chamberlain, Sherman M; Balart, J Carter; Sideridis, Kostas; Salek, Jefrey; Sridhar, Subbaramiah; Thompson, William O

    2007-11-01

    The aim of this study was to investigate whether an oral sodium phosphate solution (OSPS) mixed with aspartame-based clear liquids as the diluent would yield improved colon cleansing results compared to an OSPS mixed with sucrose-based liquids as the diluent. Fifty-one patients undergoing colonoscopy were prospectively randomized into two groups to receive different OSPS colonoscopy preparations, with sucrose-based or aspartame-based liquids used as diluents. The primary end point was the quality of the colonoscopy preparation and secondary end points were serum electrolytes before and after preparations. No significant difference in colonoscopy preparation quality was seen between the two OSPS diluent groups (Mantel-Haenzel chi (2) = 0.795, P = 0.484). There were no significant differences in mean electrolyte shifts of sodium, potassium, blood urea nitrogen (BUN), creatinine (Cr), or BUN/Cr ratios between the two groups. There was a statistically significant increase in serum phosphorous in the aspartame-based group compared to the sucrose-based diluent group (P = 0.021). In conclusion, there was no clinically detectable difference in colonoscopy preparation quality between the two OSPS diluent groups. This study suggests that passive fluid transport by aquaporins may well be the major mediator of fluid shifts in the study subjects. This result suggests the potential importance of aquaporins and minimizes the importance of sodium glucose cotransporter SGLT1 in fluid and electrolyte transport in the human gastrointestinal tract. Aspartame or its constituent amino acids may enhance phosphate absorption across the human small intestine.

  9. Canagliflozin, a sodium glucose co-transporter 2 inhibitor, reduces post-meal glucose excursion in patients with type 2 diabetes by a non-renal mechanism: results of a randomized trial.

    Science.gov (United States)

    Stein, Peter; Berg, Jolene K; Morrow, Linda; Polidori, David; Artis, Eunice; Rusch, Sarah; Vaccaro, Nicole; Devineni, Damayanthi

    2014-10-01

    Canagliflozin is a sodium glucose co-transporter 2 inhibitor approved for treating patients with type 2 diabetes. This study evaluated renal and non-renal effects of canagliflozin on postprandial plasma glucose (PG) excursion in patients with type 2 diabetes inadequately controlled with metformin. Patients (N=37) were randomized to a four-period crossover study with 3-day inpatient stays in each period and 2-week wash-outs between periods. Patients received Treatments (A) placebo/placebo, (B) canagliflozin 300 mg/placebo, (C) canagliflozin 300 mg/canagliflozin 300 mg, or (D) canagliflozin 300 mg/canagliflozin 150 mg on Day 2/Day 3 in one of four treatment sequences (similar urinary glucose excretion [UGE] expected for Treatments B-D). A mixed-meal tolerance test (MMTT) was given 20 minutes post-dose on Day 3 of each period. A single dose of canagliflozin 300 mg reduced both fasting and postprandial PG compared with placebo, with generally similar effects on fasting PG and UGE observed for Treatments B-D. An additional dose of canagliflozin 300 mg (Treatment C), but not 150 mg (Treatment D), prior to the MMTT on Day 3 provided greater postprandial PG reduction versus placebo (difference in incremental glucose AUC0-2h, -7.5% for B vs A; -18.5% for C vs A; -12.0% [P = 0.012] for C vs B), leading to modestly greater reductions in total glucose AUC0-2h with Treatment C versus Treatment B or D. Canagliflozin was generally well tolerated. These findings suggest that a non-renal mechanism (ie, beyond UGE) contributes to glucose lowering for canagliflozin 300 mg, but not 150 mg. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  10. Efficacy of riboflavin sodium phosphate in treating radiation proctitis%核黄素磷酸钠对放射性直肠黏膜炎的疗效观察

    Institute of Scientific and Technical Information of China (English)

    隋晓梅; 朱勤伟; 杨兆禄; 孙瑞美; 张启富

    2014-01-01

    Objective to observe the efficacy of treating radiation proctitis with riboflavin sodium phosphate. Methods Eighty patients undergoing radiotherapy for uterine cervix cancer for the ifrst time were divided randomly into two groups. Ribolfavin sodium phosphate 20 mg IV qd was used during radiotherapy in group A( 40 cases) , which was not in group B ( 40 cases ) . Results The incidence of radiation proctitis was signiifcantly lower in group A than that in group B. The efifcacy was signiifcantly higher in group A than in group B ( P<0. 05) . Conclusion the incidence of radiotherapy induced can be reduced radiation proctitis effectively by simultaneous infusion of ribolfavin sodium phosphate without any adverse effect on liver and renal function.%目的:观察核黄素磷酸钠对放射性直肠黏膜炎的治疗效果。方法80例接受首次放射治疗的宫颈癌患者随机分为两组:治疗组(a组)40例,放疗期间每日静滴核黄素磷酸钠20mg;对照组(组)40例,未用核黄素磷酸钠。结果治疗组放射性直肠黏膜炎的发生率明显低于对照组,其治疗有效率明显高于对照组( P<0.05)。结论宫颈癌患者放疗过程中应用核黄素磷酸钠可有效预防和减轻放射性直肠炎,对肝肾功能无明显不良反应。

  11. Prospective randomized comparison of oral sodium phosphate and polyethylene glycol lavage for colonoscopy preparation

    Institute of Scientific and Technical Information of China (English)

    Kai-Lin Hwang; William Tzu-Liang Chen; Koung-Hong Hsiao; Hong-Chang Chen; Ting-Ming Huang; Chien-Ming Chiu; Ger-Haur Hsu

    2005-01-01

    AIM: To compare the effectiveness, patient acceptability, and physical tolerability of two oral lavage solutions prior to colonoscopy in a Taiwanese population. METHODS: Eighty consecutive patients were randomized to receive either standard 4 L of polyethylene glycol (PEG) or 90 mL of sodium phosphate (NaP) in a split regimen of two 45 mL doses separated by 12 h, prior to colonoscopic evaluation. The primary endpoint was the percent of subjects who had completed the preparation. Secondary endpoints included colonic cleansing evaluated with an overall assessment and segmental evaluation, the tolerance and acceptability assessed by a selfadministered structured questionnaire, and a safety profile such as any unexpected adverse events, electrolyte tests, physical exams, vital signs, and body weights. RESULTS: A significantly higher completion rate was found in the NaP group compared to the PEG group(84.2% vs 27.5%, P<0.001). The amount of fluid suctioned was significantly less in patients taking NaP vs PEG (50.13±54.8 cc vs 121.13±115.4 cc, P<0.001),even after controlling for completion of the oral solution(P = 0.031). The two groups showed a comparable overall assessment of bowel preparation with a rate of "good" or "excellent" in 78.9% of patients in the NaPgroup and 82.5% in PEG group (P = 0.778). Patients taking NaP tended to have significantly better colonic segmental cleansing relative to stool amount observedin the descending (94.7% vs 70%, P = 0.007) andtransverse (94.6% vs 74.4%, P = 0.025) colon. Slightly more patients graded the taste of NaP as "good" or "very good" compared to the PEG patients (32.5% vs 12.5%;P = 0.059). Patients' willingness to take the same preparation in the future was 68.4% in the NaP compared to 75% in the PEG group (P = 0.617). There was a significant increase in serum sodium and a significant decrease in phosphate and chloride levels in NaP group on the day following the colonoscopy without any clinical sequelae. Prolonged (

  12. Ex vivo encapsulation of dexamethasone sodium phosphate into human autologous erythrocytes using fully automated biomedical equipment.

    Science.gov (United States)

    Mambrini, Giovanni; Mandolini, Marco; Rossi, Luigia; Pierigè, Francesca; Capogrossi, Giovanni; Salvati, Patricia; Serafini, Sonja; Benatti, Luca; Magnani, Mauro

    2017-01-30

    Erythrocyte-based drug delivery systems are emerging as potential new solutions for the release of drugs into the bloodstream. The aim of the present work was to assess the performance of a fully automated process (EDS) for the ex-vivo encapsulation of the pro-drug dexamethasone sodium phosphate (DSP) into autologous erythrocytes in compliance with regulatory requirements. The loading method was based on reversible hypotonic hemolysis, which allows the opening of transient pores in the cell membrane to be crossed by DSP. The efficiency of encapsulation and the biochemical and physiological characteristics of the processed erythrocytes were investigated in blood samples from 34 healthy donors. It was found that the processed erythrocytes maintained their fundamental properties and the encapsulation process was reproducible. The EDS under study showed greater loading efficiency and reduced variability compared to previous EDS versions. Notably, these results were confirmed using blood samples from Ataxia Telangiectasia (AT) patients, 9.33±1.40 and 19.41±2.10mg of DSP (mean±SD, n=134) by using 62.5 and 125mg DSP loading quantities, respectively. These results support the use of the new EDS version 3.2.0 to investigate the effect of erythrocyte-delivered dexamethasone in regulatory trials in patients with AT.

  13. Effects of sodium phosphate and beetroot juice supplementation on repeated-sprint ability in females.

    Science.gov (United States)

    Buck, Christopher L; Henry, Timothy; Guelfi, Kym; Dawson, Brian; McNaughton, Lars R; Wallman, Karen

    2015-10-01

    Sodium phosphate (SP) and beetroot juice (BJ) supplementation was assessed on repeated-sprint ability (RSA). Thirteen female team-sport participants completed four trials: (1) SP and BJ (SP + BJ), (2) SP and placebo (for BJ), (3) BJ and placebo (for SP) and (4) placebo (for SP + BJ), with ~21 days separating each trial. After each trial, participants performed a simulated team-game circuit (STGC) consisting of four 15 min quarters, with a 6 × 20-m repeated-sprint set performed at the start, half-time and end. Total sprint times were between 0.95-1.30 and 0.83-1.12 s faster for each RSA set and 3.25 and 3.12 s faster overall (~5% improvement) after SP compared with placebo and BJ, respectively (p = 0.02 for sets 1, 2 and overall; Cohen's effect size: d = -0.51 to -0.90 for all sets and overall). Additionally, total sprint times were 0.48 s faster after SP + BJ compared with placebo (set 2; p = 0.05, ~2% improvement). Furthermore, best sprints were 0.13-0.23 and 0.15-0.20 s faster (~6% improvement; p sprint times were faster after SP compared with placebo and BJ.

  14. Zinc(II) oxide solubility and phase behavior in aqueous sodium phosphate solutions at elevated temperatures

    Energy Technology Data Exchange (ETDEWEB)

    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/phase behavior of zinc(II) oxide in aqueous sodium phosphate solutions at temperatures between 290 and 560 K. ZnO solubilities are observed to increase continuously with temperature and phosphate concentration. At higher phosphate concentrations, a solid phase transformation to NaZnPO{sub 4} is observed. NaZnPO{sub 4} solubilities are retrograde with temperature. The measured solubility behavior is examined via a Zn(II) ion hydrolysis/complexing model and thermodynamic functions for the hydrolysis/complexing reaction equilibria are obtained from a least-squares analysis of the data. The existence of two new zinc(II) ion complexes is reported for the first time: Zn(OH){sub 2}(HPO{sub 4}){sup 2{minus}} and Zn(OH){sub 3}(H{sub 2}PO{sub 4}){sup 2{minus}}. A summary of thermochemical properties for species in the systems ZnO-H{sub 2}O and ZnO-Na{sub 2}O-P{sub 2}O{sub 5}-H{sub 2}O is also provided. 21 refs., 10 figs., 7 tabs.

  15. Prospective evaluation of small bowel preparation with bisacodyl and sodium phosphate for capsule endoscopy

    Institute of Scientific and Technical Information of China (English)

    Andreas Franke; Frank Hummel; Phillip Knebel; Christoph Antoni; Ulrich Bocker; Manfred V Singer; Matthias Lohr

    2008-01-01

    AIM: To determine the effect of Prepacol?, a combination of sodium phosphate and bisacodyl, on transit and quality of capsule endoscopy (CE).METHODS: Fivety two consecutive patients were included in this prospective study. CE was performed following a 12 h fasting period. Twenty six patients were randomized for additional preparation with Prepacor. The quality of CE was assessed separately for the proximal and the distal small bowel by 3 experienced endoscopists on the basis of a graduation which was initially developed with 20 previous CE.RESULTS: Preparation with Prepacol? accelerated small bowel transit time (262 ± 55 min vs 287 ± 97 min), but had no effect on the quality of CE. Visibility was significantly reduced in the distal compared to the proximal small bowel.CONCLUSION: The significantly reduced visibility of CE in the distal small bowel allocates the need for a good preparation. Since Prepacol? has no beneficial effect on CE the modality of preparation and the ideal time of application remains unclear. Further standardized examinations are necessary to identify sufficient preparation procedures and to determine the impact of the volume of the preparation solution.

  16. Iontophoresis successfully delivers dexamethasone sodium phosphate to dermis as measured by microdialysis.

    Science.gov (United States)

    Joshi, Abhay; Stagni, Grazia; Cleary, Ann; Patel, Komal; Weiss, David S; Hagins, Marshall

    2014-01-01

    Despite its widespread and long term use, the effectiveness of iontophoresis to increase the delivery of dexamethasone sodium phosphate (DSP) remains controversial. The goal of this study was to quantitatively compare the DSP concentrations in dermis' dialysates in two delivery scenarios: with and without iontophoresis. Interstitial fluid concentrations were measured by cutaneous microdialysis. Passive and active iontophoresis were applied simultaneously on the skin of the forearm in eight healthy adult participants using each participant as his/her own control. The iontophoresis apparatus and procedures were identical to those used in common clinical practice. Iontophoresis electrodes were loaded with 2 mL of 4.4 mg/mL of preservative-free DSP solution. Electric current (4 mA) was applied for 20 min. Dialysate samples were collected for 2 h and analyzed for DSP and its active metabolite dexamethasone (DXM). Seven out of eight iontophoresis sites contained quantifiable levels of DSP and DXM, whereas none of the samples collected at the passive site contained either form of the drug. In conclusion, this study demonstrates that iontophoresis significantly (p < 0.0001) increases delivery of DSP to the dermis compared with passive delivery of the same, and that microdialysis can be used to monitor DSP delivery and DXM formation in skin.

  17. Cellular distribution of the renal bumetanide-sensitive Na-K-2Cl cotransporter BSC-1 in the inner stripe of the outer medulla during the development of hypertension in the spontaneously hypertensive rat.

    Science.gov (United States)

    Sonalker, Prajakta A; Tofovic, Stevan P; Jackson, Edwin K

    2007-12-01

    1. The renal bumetanide-sensitive Na-K-2Cl cotransporter (BSC-1) is expressed only in the thick ascending limb and selectively traffics from intracellular vesicles (IVs) to apical plasma membranes (PMs), where BSC-1 regulates sodium reabsorption. We showed previously that in kidneys from adult spontaneously hypertensive rats (SHR; model of essential hypertension) total protein expression of BSC-1 was higher compared with kidneys from normotensive Wistar-Kyoto (WKY) rats. However, whether this change is associated with an increased trafficking of BSC-1 from IVs to PMs is unknown. The goal of the present study was to test the hypothesis that the increase in total renal BSC-1 protein expression in SHR is accompanied by an augmented distribution of BSC-1 from IVs to PMs. 2. To test the hypothesis, we obtained renal tissue from the inner stripe of the outer medulla (ISOM; enriched in thick ascending limbs) and isolated IVs and PMs from this tissue by differential centrifugation. Total BSC-1 protein expression in ISOM and BSC-1 protein expression in ISOM IVs and PMs were measured by semiquantitative western blotting in SHR and aged-matched WKY rats at different ages and stages of hypertension. 3. At 5 weeks of age, SHR were prehypertensive (mean arterial blood pressure (MABP) 97 mmHg). At this age, both the total abundance and cellular distribution of BSC-1 were similar in ISOM from SHR and WKY rats. 4. As SHR aged, their hypertension progressed (MABP 137 and 195 mmHg at 8 and 14 weeks of age, respectively). Associated with the increase in MABP was an increase in both steady state protein levels of ISOM BSC-1 and the distribution of ISOM BSC-1 to PMs (four- and sixfold increases at 8 and 14 weeks of age, respectively, compared with age-matched WKY rats; P BSC-1 mRNA was measured and was found not to differ between SHR and WKY rat ISOM at any age or level of MABP. 6. We conclude that as SHR transition from prehypertensive to established hypertension, there is a marked

  18. 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.

  19. Type II Na+-Pi cotransporters in osteoblast mineral formation: regulation by inorganic phosphate.

    Science.gov (United States)

    Lundquist, Patrik; Murer, Heini; Biber, Jürg

    2007-01-01

    During calcification of bone, large amounts of phosphate (P(i)) must be transported from the circulation to the osteoid. Likely candidates for osteoblast P(i) transport are the type II sodium-phosphate cotransporters NaPi-IIa and NaPi-IIb that facilitate transcellular P(i) flux in kidney and intestine, respectively. We have therefore determined the 'cotransporters' expression in osteoblast-like cells. We have also studied the 'cotransporters' regulation by P(i) and during mineralization in vitro. Phosphate uptake and cotransporter protein expression was investigated at early, late and mineralizing culture stages of mouse (MC3T3-E1) and rat (UMR-106) osteoblast-like cells. Both NaPi-IIa and NaPi-IIb were expressed by both osteoblast-like cell lines. NaPi-IIa was upregulated in both cell lines one week after confluency. After 7 days in 3mM P(i) NaPi-IIa was strongly upregulated in both cell lines. NaPi-IIb expression was unaffected by both culture stage and P(i) supplementation. The expression of both cotransporters was unaffected by P(i) deprivation. In vitro mineralization at 1.5mM P(i) was preceded by a three-fold increase in osteoblast sodium-dependent P(i) uptake and a corresponding upregulation of both NaPi-IIa and NaPi-IIb. Their expression thus seem regulated by phosphate in a manner consistent with their playing a role in transcellular P(i) flux during mineralization.

  20. 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.

  1. Bone-specific poly(ethylene sodium phosphate)-bearing biodegradable nanoparticles.

    Science.gov (United States)

    Hirano, Yuya; Iwasaki, Yasuhiko

    2017-05-01

    Chemotherapy is the most reliable treatment for osteoporosis and osseous metastases. To facilitate better drug delivery for bone treatments, a novel preparation of polymeric nanoparticles with high affinity to bone has been prepared. Two-step synthesis of cholesteryl-functionalized poly(ethylene sodium phosphate) (Ch-PEPn·Na) was performed via ring-opening polymerization of cyclic phosphoesters and the demethylation. The molecular weight of Ch-PEPn·Na could be well controlled by changing the ratio of cholesterol and cyclic phosphoesters. Because Ch-PEPn·Na exhibits an amphiphilic nature in aqueous media, Ch-PEPn·Na-bearing nanoparticles (PEPn·Na NPs) were prepared by a solvent evaporation technique. The size of the nanoparticles investigated in the current study is approximately 100nm, which was determined by dynamic light scattering (DLS) and transmission electron microscopy (TEM). Due to the presence of highly water-soluble polymer chains, dispersion of PEPn·Na NPs in aqueous media was stable for at least 1 week. Hemolytic activity of PEPn·Na NPs was found to be low and PEPn·Na NPs did not disintegrate mammalian cell membranes. Additionally, cytotoxicity of PEPn·Na NPs was not observed at concentrations below 100μg/mL. The adsorption of PEPn·Na NPs on hydroxyapatite (HAp) microparticles was studied in comparison with poly(ethylene glycol) nanoparticles (PEG NPs). Both PEPn·Na NPs and PEG NPs adsorbed well onto HAp microparticles in distilled water with binding equilibrium constants (KHAp) for PEPn·Na NPs and PEG NPs of 3.6×10(6) and 7.9×10(6), respectively. In contrast, only PEPn·Na NPs adsorbed onto HAp microparticles in a saline phosphate buffer. Moreover, the adsorption of PEPn·Na NPs onto HAp microparticles occurred even in the presence of 1.2mM calcium ions or low-pH media. The affinity of the nanoparticles to bovine bone slices was also studied, with the result that large quantities of adsorbed PEPn·Na NPs were observed on the slices by

  2. Exploring the intricate regulatory network controlling the thiazide-sensitive NaCl cotransporter (NCC)

    DEFF Research Database (Denmark)

    Dimke, Henrik Anthony

    2011-01-01

    The thiazide-sensitive NaCl cotransporter (NCC) plays key roles in renal electrolyte transport and blood pressure maintenance. Regulation of this cotransporter has received increased attention recently, prompted by the discovery that mutations in the with-no-lysine (WNK) kinases are the molecular...... by acting as a scaffold between the dephosphorylated cotransporter and the regulatory kinase. As more molecular regulators of NCC are identified, the system-controlling NCC activity is becoming increasingly complex. This intricacy confers an ability to integrate a variety of stimuli, thereby regulating NCC...

  3. 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.

  4. 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.

  5. 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.

  6. Effect of Sodium Phosphate Supplementation on Cycling Time Trial Performance and VO2 1 and 8 Days Post Loading.

    Science.gov (United States)

    Brewer, Cameron P; Dawson, Brian; Wallman, Karen E; Guelfi, Kym J

    2014-09-01

    This study examined the effect of 6 days of sodium phosphate (SP) (50 mg·kg·FFM(-1)·day(-1)) or placebo (PL) supplementation in trained cyclists on either 100 kJ (23.9 Kcal) (~3-4 min) or 250 kJ (59.7 Kcal) (~10-12 min) time trials performances both 1 and 8 days post-supplementation. Trials were performed in a counterbalanced crossover design, with a 28-day washout period between supplementation phases. No significant differences, moderate-large ES (d) or likely (or greater) smallest worthwhile change (SWC) values were recorded for time to completion and mean power output on days 1 and 8 post-supplementation, both within and between SP and PL for either the 100 or 250 kJ (23.9 or 59.7 Kcal) trials. In the 100 kJ (23.9 Kcal) trial (only) first minute VO2 tended to be higher in SP8 than both PL8 (d = 0.60; 88/10/2 SWC) and SP1 (d = 0.47: 82/15/3 SWC), as was mean VO2 (PL8: d = 0.77; 93/6/1 SWC and SP1: d = 0.84; 90/8/3 SWC). No significant differences were found for heart rate, ratings of perceived exertion and blood lactate post-exercise within or between any trials, while serum phosphate values were not different before or after supplementation with SP or PL. In conclusion, this study showed a tendency for increased VO2 in a short duration (100 kJ/ 23.9 Kcal: ~3-4 min) cycling test on day 8 after SP supplementation, but no differences in 100 or 250 kJ (23.9 or 59.7 Kcal) time trials performances were observed. Key PointsStudies investigating the effects of sodium phosphate loading on shorter duration (ergogenic effect may last.Loading did not improve cycling time trial (~3-4 min and 10-12 min) performance either 1 or 8 days after supplementation.Future studies should investigate the effect of sodium phosphate loading on repeated sprints and simulated cycling road race performance over extended durations (>30 min), where it may be likely to have a more beneficial effect.

  7. Estudo prospectivo e randomizado comparando solução de fosfato de sódio oral e manitol para o preparo de cólon para colonoscopia Mechanical bowel preparation with oral sodium phosphate solution for colonoscopy. A new small volume solution compared to the traditional mannitol

    Directory of Open Access Journals (Sweden)

    Lúcia Câmara Castro Oliveira

    1999-12-01

    Full Text Available Realizamos um estudo prospectivo e randomizado comparando a utilização do fosfato de sódio oral e manitol como preparo para colonoscopia. Apresentamos a introdução do fosfato de sódio, em uma das formas nacionais (Fleet Enema, para utilização por via oral. Entre abril de 1996 e abril de 1998, 220 pacientes foram prospectivamente randomizados. A tolerância para ambos os preparos foi similar em relação à maioria dos sintomas estudados, com exceção de sensação de plenitude, cólica ou dor abdominal que ocorreram em maior freqüência com o uso de manitol. A única desvantagem em relação ao fosfato oral foi a má tolerância quanto ao sabor (p=O,O043. A avaliação do endoscopista julgou o preparo como excelente ou bom em 84% dos pacientes que fizeram uso de fosfato de sódio e em 78% dos que tomaram manitol (p=0,76, n.s., porém o exame foi interrompido por preparo inadequado em oito e em cinco pacientes que fizeram uso de manitol e fosfato de sódio, respectivamente (p=0,56. Não ocorreram, nesta série, lesões iatrogênicas ou morbidade relacionadas com o método ou a sedação. Embora não tenham ocorrido diferenças estatisticamente significantes em relação à qualidade de ambos os preparos, o fosfato de sódio foi o de melhor tolerância, de uma maneira geral, com um número menor de efeitos colaterais.The aim of this study was to compare the cleansing ability, patient compliance, and safety of two oral solutions or colonoscopy. All eligible patients were prospectively randomized to receive either a standard mannitol solution or a 260 ml 01 sodium phosphate for bowel preparation for colonoscopy. Parameters evaluated included patient's tolerance or taste and volume 01 solutions, gastrointestinal and cardiac side effects and quality 01 preparation. Exclusion criteria included pregnancy, ascites, symptomatic congestive heart disease and pre-existent renal disease. Statistical analysis was performed using the Wilcoxón 's rank

  8. Characterization of the interaction between chitosan and inorganic sodium phosphates by means of rheological and optical microscopy studies.

    Science.gov (United States)

    Casettari, Luca; Cespi, Marco; Palmieri, Giovanni Filippo; Bonacucina, Giulia

    2013-01-16

    The physicochemical and rheological properties of chitosan and two different inorganic sodium phosphate dispersions (NaH(2)PO(4) and Na(3)PO(4)) were investigated in order to elucidate the role of different factors, such as ratios between polymer and sodium inorganic phosphates, different pHs and storage stability, on the gelling properties of chitosan. This was deemed opportune since physico-chemical characterizations of chitosan in the literature often appear incomplete and questionable. We also compared the elastic modulus values of the different chitosan/inorganic phosphate systems and examined their behaviour through optical microscopy analyses. The most efficient formulations that showed a thermogelling capacity with a significant gel transition behaviour after 24h were the NaH(2)PO(4)/chitosan and Na(3)PO(4)/chitosan systems at ratio 2 and pH 7.0. These results confirmed the importance of the pH value and ratio selection for the final systems.

  9. Lower body weight and female gender: Hyperphosphatemia risk factors after sodium phosphate preparations Parakkal Deepak, Eli D Ehrenpreis

    Institute of Scientific and Technical Information of China (English)

    Parakkal Deepak; Eli D Ehrenpreis

    2011-01-01

    Casais et al have reported an inverse correlation between serum phosphate and body weight after administration of sodium phosphate at a dose of 60 g. Our group has already described the relationship between body weight and hyperphosphatemia with these preparations, although our study was not quoted by Casais. We performed a pharmacokinetic study involving 13 volunteers who were divided into two groups on the basis of body weight: group Ⅰ consisting of seven women with a median weight of 60 kg and group Ⅱconsisting due to a diminished volume of distribution of the high dose of ingested phosphate. Decreased volume of distribution in women is due to diminished body weight. This is further compounded by decreased creatinine clearance in females.

  10. 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...

  11. 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.

  12. Stabilization/solidification of mercury-contaminated waste ash using calcium sodium phosphate (CNP) and magnesium potassium phosphate (MKP) processes.

    Science.gov (United States)

    Cho, Jae Han; Eom, Yujin; Lee, Tai Gyu

    2014-08-15

    This study examined the stabilization and solidification (S/S) of mercury (Hg)-contaminated waste ash generated from an industrial waste incinerator using chemically bonded phosphate ceramic (CBPC) technology. A magnesium potassium phosphate (MKP; MgKPO4 · 6H2O) ceramic, fabricated from MgO and KH2PO4, and a calcium sodium phosphate (CNP; CaNaPO4) ceramic, fabricated from CaO and Na2HPO4, were used as solidification binders in the CBPC process, and Na2S or FeS was added to each solidification binder to stabilize the Hg-contaminated waste ash. The S/S processes were conducted under various operating conditions (based on the solidification binder and stabilization reagent, stabilization reagent dosage, and waste loading ratio), and the performance characteristics of the S/S sample under each operating condition were compared, including the Hg leaching value and compressive strength. The Hg leaching value of untreated Hg-contaminated waste ash was 231.3 μg/L, whereas the S/S samples treated using the MKP and CNP processes exhibited Hg leaching values below the universal treatment standard (UTS) limit (25 μg/L). Although the compressive strengths of the S/S samples decreased as the sulfide dosage and waste loading ratio were increased, most of the S/S samples fabricated by the MKP and CNP processes exhibited good mechanical properties.

  13. pH-Sensitive cationic copolymers of different macromolecular architecture as potential dexamethasone sodium phosphate delivery systems.

    Science.gov (United States)

    Georgieva, Dilyana; Kostova, Bistra; Ivanova, Sijka; Rachev, Dimitar; Tzankova, Virginia; Kondeva-Burdina, Magdalena; Christova, Darinka

    2014-08-01

    This paper describes the synthesis and characterization of cationic copolymers with different macromolecular architecture and drug delivery properties of the corresponding dexamethasone sodium phosphate (DSP)-loaded systems. Copolyelectrolytes comprising poly[2-(acryloyloxy)ethyl] trimethylammonium chloride (PAETMAC) and poly(ethylene glycol) blocks as well as a tri-arm star-shaped PAETMAC were synthesized using cerium(IV) ion-mediated polymerization method. The obtained copolyelectrolytes and corresponding ionic associates with DSP have been characterized by (1)H NMR, Fourier Transform Infrared spectroscopy, and differential scanning calorimetry. The average diameter, size distribution, and ζ-potential of the copolymers and DSP-copolymer ionic associates were determined by dynamic light scattering, and particles were visualized by scanning electron microscopy and transmission electron microscopy. The biocompatibility and cytotoxicity of obtained copolymers were determined. In vitro drug release experiments were carried out to estimate the ability of the obtained nanoparticles for sustained release of DSP for a period of 24 h. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  14. 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...

  15. gamma-Adducin stimulates the thiazide-sensitive NaCl cotransporter

    NARCIS (Netherlands)

    Dimke, H.; San Cristobal, P.; Graaf, M.J. de; Lenders, J.W.M.; Deinum, J.; Hoenderop, J.G.J.; Bindels, R.J.M.

    2011-01-01

    The thiazide-sensitive NaCl cotransporter (NCC) plays a key role in renal salt reabsorption and the determination of systemic BP, but the molecular mechanisms governing the regulation of NCC are not completely understood. Here, through pull-down experiments coupled to mass spectrometry, we found

  16. The effect of 6 days of sodium phosphate supplementation on appetite, energy intake, and aerobic capacity in trained men and women.

    Science.gov (United States)

    West, Jessica S; Ayton, Tom; Wallman, Karen E; Guelfi, Kym J

    2012-12-01

    Ingestion of an acute dose of phosphate has been shown to attenuate energy intake in the subsequent meal. This raises the question of whether the practice of phosphate supplementation over a number of days by athletes to enhance performance also influences energy intake. This study investigated the effect of 6 d of phosphate supplementation on appetite and energy intake, as well as aerobic capacity, in trained individuals. Twenty participants completed two 6-d phases of supplementation with either sodium phosphate (50 mg/kg of fat-free mass per day) or a placebo in a double-blinded, counterbalanced design. On Days 1, 2, and 6 of supplementation, a laboratory meal was provided to assess appetite and ad libitum energy intake. All other food and drink consumed during each supplementation phase were recorded in a food diary. After the 6 d of supplementation, peak aerobic capacity (VO(2peak)) was assessed. There was no difference in energy intake at the laboratory meal after an acute dose (i.e., on Day 1; placebo 2,471 ± 919 kJ, phosphate 2,353 ± 987 kJ; p = .385) or prolonged supplementation with sodium phosphate (p = .581) compared with placebo. Likewise, there was no difference in VO(2peak) with phosphate supplementation (placebo 52.6 ± 5.2 ml · kg(-1) · min(-1), phosphate 53.3 ± 6.1 ml · kg(-1) · min(-1); p = .483). In summary, 6 d of sodium phosphate supplementation does not appear to influence energy intake. Therefore, athletes supplementing with sodium phosphate can do so without hindering their nutritional status. However, given that phosphate supplementation failed to improve aerobic capacity, the ergogenic benefit of this supplement remains questionable.

  17. Effect of Sodium Phosphate Supplementation on Cycling Time Trial Performance and VO2 1 and 8 Days Post Loading

    Directory of Open Access Journals (Sweden)

    Cameron P. Brewer, Brian Dawson, Karen E. Wallman, Kym J. Guelfi

    2014-09-01

    Full Text Available This study examined the effect of 6 days of sodium phosphate (SP (50 mg·kg·FFM-1·day-1 or placebo (PL supplementation in trained cyclists on either 100 kJ (23.9 Kcal (~3-4 min or 250 kJ (59.7 Kcal (~10-12 min time trials performances both 1 and 8 days post-supplementation. Trials were performed in a counterbalanced crossover design, with a 28-day washout period between supplementation phases. No significant differences, moderate-large ES (d or likely (or greater smallest worthwhile change (SWC values were recorded for time to completion and mean power output on days 1 and 8 post-supplementation, both within and between SP and PL for either the 100 or 250 kJ (23.9 or 59.7 Kcal trials. In the 100 kJ (23.9 Kcal trial (only first minute VO2 tended to be higher in SP8 than both PL8 (d = 0.60; 88/10/2 SWC and SP1 (d = 0.47: 82/15/3 SWC, as was mean VO2 (PL8: d = 0.77; 93/6/1 SWC and SP1: d = 0.84; 90/8/3 SWC. No significant differences were found for heart rate, ratings of perceived exertion and blood lactate post-exercise within or between any trials, while serum phosphate values were not different before or after supplementation with SP or PL. In conclusion, this study showed a tendency for increased VO2 in a short duration (100 kJ/ 23.9 Kcal: ~3-4 min cycling test on day 8 after SP supplementation, but no differences in 100 or 250 kJ (23.9 or 59.7 Kcal time trials performances were observed.

  18. 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.

  19. 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.

  20. Sodium Phosphate Rectal

    Science.gov (United States)

    ... a blockage or tear in your stomach or intestine, inflammatory bowel disease (IBD; a group of conditions in which the lining of the lining of the intestines is swollen, irritated, or has sores), paralytic ileus ( ...

  1. Bowel preparation for colonoscopy using standard vs reduced doses of sodium phosphate: A single-blind randomized controlled study

    Institute of Scientific and Technical Information of China (English)

    Tatsuya; Koshitani; Mayumi; Kawada; Toshikazu; Yoshikawa

    2014-01-01

    AIM: To evaluate the efficacy of a colonoscopy prepa-ration that utilizes a reduced dose of sodium phosphate(NaP) and an adjunct.METHODS: Sixty-two patients requiring screening colonoscopies were studied. Each patient was randomly allocated to receive either 50 NaP tablets(50 g) or 30 NaP tablets(30 g) with 10 mL of 0.75% sodium pico-sulfate for bowel preparation. NaP was administered at a rate of five tablets(5 g) or three tablets(3 g) every 15 min with 200 mL of water, beginning five to six hours before colonoscopy. The sodium picosulfate was administered with 200 mL of water on the night before the procedure. Both groups were compared in term of the efficacies of colonic cleansing, the time required for completion of the bowel preparation, and acceptability of the preparation.RESULTS: Sixty patients(n = 30 for each group) were analyzed. The cleansing efficacy tended to be higher in the 30 g NaP plus sodium picosulfate group as as-sessed by the mean total Ottawa scale score(50 g NaP6.70 ± 1. 42 vs 30 g NaP plus sodium picosulfate 6.17 ± 1.18 P = 0.072). The mean time for bowel prepara-tion tended to be shorter in the 30 g NaP plus sodium picosulfate group(50 g NaP 189.9 ± 64.0 min vs 30 g NaP plus sodium picosulfate 161.8 ± 57.6 min, P = 0.065). There were no significant differences between the two groups in the acceptability of the preparations(50 g NaP 83.3% vs 30 g NaP plus sodium picosulfate 86.7%, P = 0.500). There were no adverse events re-lated to bowel preparation in either of the groups.CONCLUSION: The colonoscopy preparation that uti-lized 30 g NaP with sodium picosulfate was comparable to that utilizing 50 g NaP. This novel bowel preparation might be useful before colonoscopy.

  2. Hydrochlorothiazide treatment increases the abundance of the NaCl cotransporter in urinary extracellular vesicles of essential hypertensive patients.

    NARCIS (Netherlands)

    Pathare, G.T.; Tutakhel, O.A.Z.; Wel, M.C. van der; Shelton, L.M.; Deinum, J.; Lenders, J.W.M.; Hoenderop, J.G.J.; Bindels, R.J.M.

    2017-01-01

    The thiazide-sensitive NaCl cotransporter (NCC), located apically in distal convoluted tubule epithelia, regulates the fine-tuning of renal sodium excretion. Three isoforms of NCC are generated through alternative splicing of the transcript, of which the third isoform has been the most extensively

  3. NaCl cotransporter abundance in urinary vesicles is increased by calcineurin inhibitors and predicts thiazide sensitivity

    NARCIS (Netherlands)

    Tutakhel, O.A.Z.; Moes, A.D.; Valdez Flores, M.A.; Kortenoeven, M.L.A.; Vrie, M. van de; Jelen, S.K.; Fenton, R.A.; Zietse, R.; Hoenderop, J.G.J.; Hoorn, E.J.; Hilbrands, L.B.; Bindels, R.J.M.

    2017-01-01

    Animal studies have shown that the calcineurin inhibitors (CNIs) cyclosporine and tacrolimus can activate the thiazide-sensitive NaCl cotransporter (NCC). A common side effect of CNIs is hypertension. Renal salt transporters such as NCC are excreted in urinary extracellular vesicles (uEVs) after

  4. NaCl cotransporter abundance in urinary vesicles is increased by calcineurin inhibitors and predicts thiazide sensitivity

    NARCIS (Netherlands)

    Tutakhel, O.A.Z. (Omar A. Z.); A.D. Moes (Arthur); Valdez-Flores, M.A. (Marco A.); Kortenoeven, M.L.A. (Marleen L. A.); Vrie, M.V.D. (Mathijs V.D.); Jelen, S. (Sabina); R.A. Fenton (Robert); R. Zietse (Bob); J.G.J. Hoenderop (Joost); E.J. Hoorn (Ewout); L.B. Hilbrands (Luuk); Bindels, R.J.M. (Reneâ J. M.)

    2017-01-01

    textabstractAnimal studies have shown that the calcineurin inhibitors (CNIs) cyclosporine and tacrolimus can activate the thiazide-sensitive NaCl cotransporter (NCC). A common side effect of CNIs is hypertension. Renal salt transporters such as NCC are excreted in urinary extracellular vesicles

  5. 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...

  6. Exploring the intricate regulatory network controlling the thiazide-sensitive NaCl cotransporter (NCC).

    Science.gov (United States)

    Dimke, Henrik

    2011-12-01

    The thiazide-sensitive NaCl cotransporter (NCC) plays key roles in renal electrolyte transport and blood pressure maintenance. Regulation of this cotransporter has received increased attention recently, prompted by the discovery that mutations in the with-no-lysine (WNK) kinases are the molecular explanation for pseudohypoaldosteronism type II (PHAII). Studies suggest that WNK4 regulates NCC via two distinct pathways, depending on its state of activation. Furthermore, an intact STE20-related proline-alanine-rich kinase (SPAK)/oxidative stress response 1 kinase (OSR1) pathway was found to be necessary for a WNK4 PHAII mutation to increase NCC phosphorylation and blood pressure in mice. The mouse protein 25α is a novel regulator of the SPAK/OSR1 kinase family, which greatly increases their activity. The phosphorylation status of NCC and the WNK is regulated by the serum- and glucocorticoid-inducible kinase 1, suggesting novel mechanisms whereby aldosterone modulates NCC activity. Dephosphorylation of NCC by protein phosphatase 4 strongly influences the activity of the cotransporter, confirming an important role for NCC phosphorylation. Finally, γ-adducin increases NCC activity. This stimulatory effect is dependent on the phosphorylation status of the cotransporter. γ-Adducin only binds the dephosphorylated cotransporter, suggesting that phosphorylation of NCC causes the dissociation of γ-adducin. Since γ-adducin is not a kinase, it is tempting to speculate that the protein exerts its function by acting as a scaffold between the dephosphorylated cotransporter and the regulatory kinase. As more molecular regulators of NCC are identified, the system-controlling NCC activity is becoming increasingly complex. This intricacy confers an ability to integrate a variety of stimuli, thereby regulating NCC transport activity and ultimately blood pressure.

  7. DAPAGLIFLOZIN: SELECTIVE SODIUM-GLUCOSE CO-TRANSPORTER-2 INHIBITOR IN TYPE 2 DIABETES

    Directory of Open Access Journals (Sweden)

    Sudhakar Pemminati

    2011-11-01

    Full Text Available Dapagliflozin is a promising new drug that targets the so far untapped renal glucose reabsorption. By inhibiting sodium-glucose co-transporter-2 (SGLT2 which is mainly localized in the S1 segment of the proximal tubule, Dapagliflozin promotes renal glucose excretion and reduces hyperglycemia in an insulin-independent manner. Dapagliflozin also produces pronounced weight loss which may be an advantage in patients on sulfonylureas and insulin. Dapagliflozin has the potential to be used as monotherapy, as well as in combination with all approved antidiabetic agents.

  8. Leptin stimulates fibroblast growth factor 23 expression in bone and suppresses renal 1alpha,25-dihydroxyvitamin D3 synthesis in leptin-deficient mice.

    Science.gov (United States)

    Tsuji, Kiyomi; Maeda, Toyonobu; Kawane, Tetsuya; Matsunuma, Ayako; Horiuchi, Noboru

    2010-08-01

    Leptin is the LEP (ob) gene product secreted by adipocytes. We previously reported that leptin decreases renal expression of the 25-hydroxyvitamin D(3) 1alpha-hydroxylase (CYP27B1) gene through the leptin receptor (ObRb) by indirectly acting on the proximal tubules. This study focused on bone-derived fibroblast growth factor 23 (FGF-23) as a mediator of the influence of leptin on renal 1alpha-hydroxylase mRNA expression in leptin-deficient ob/ob mice. Exposure to leptin (200 ng/mL) for 24 hours stimulated FGF-23 expression by primary cultured rat osteoblasts. Administration of leptin (4 mg/kg i.p. at 12-hour intervals for 2 days) to ob/ob mice markedly increased the serum FGF-23 concentration while significantly reducing the serum levels of calcium, phosphate, and 1alpha,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)]. Administration of FGF-23 (5 microg i.p. at 12-hour intervals for 2 days) to ob/ob mice suppressed renal 1alpha-hydroxylase mRNA expression. The main site of FGF-23 mRNA expression was the bone, and leptin markedly increased the FGF-23 mRNA level in ob/ob mice. In addition, leptin significantly reduced 1alpha-hydroxylase and sodium-phosphate cotransporters (NaP(i)-IIa and NaP(i)-IIc) mRNA levels but did not affect Klotho mRNA expression in the kidneys of ob/ob mice. Furthermore, the serum FGF-23 level and renal expression of 1alpha-hydroxylase mRNA were not influenced by administration of leptin to leptin receptor-deficient (db/db) mice. These results indicate that leptin directly stimulates FGF-23 synthesis by bone cells in ob/ob mice, suggesting that inhibition of renal 1,25(OH)(2)D(3) synthesis in these mice is at least partly due to elevated bone production of FGF-23.

  9. A quantitative description of the Na-K-2Cl cotransporter and its conformity to experimental data.

    Science.gov (United States)

    Benjamin, B A; Johnson, E A

    1997-09-01

    In epithelia, the Na-K-2Cl cotransporter cooperates with other transport mechanisms to produce transepithelial NaCl transport. The reaction cycle for the Na-K-2Cl cotransporter has been established experimentally, but whether it accounts, quantitatively, for experimental findings has yet to be established. The differential equations that describe the reaction cycle were formulated, and the steady-state solutions were obtained by digital computation. Conformity between this description and the experimental data obtained from the literature was explored by automatic searches for the sets of rate constants that yielded statistical best-fits to the experimental data. Fits were obtained from renal epithelial cell lines, HeLa cells, and duck erythrocytes. Results show that the reaction cycle for the Na-K-2Cl cotransporter conforms well, quantitatively, with the experimental data.

  10. 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.

  11. A Randomized Prospective Study of Bowel Preparation for Colonoscopy with Low-Dose Sodium Phosphate Tablets versus Polyethylene Glycol Electrolyte Solution

    Directory of Open Access Journals (Sweden)

    Erina Kumagai

    2014-01-01

    Full Text Available Optimal bowel preparation is essential for the safety and outcome of colonoscopy. A solution containing polyethylene glycol (PEG is often used as a bowel cleansing agent, but some patients are intolerant of PEG, and this may lead to discontinuation of colonoscopy. Sodium phosphates (NaP tablets are designed to improve patient acceptance and compliance. The objective of this study was to compare bowel preparation efficiency and patient acceptance of a 30 NaP tablet preparation (L-NaP and a 2 L PEG preparation. Patients were randomized into either the L-NaP or PEG group. The primary endpoint was the efficiency of colon cleansing as assessed by a validated four-point scale according to the Aronchick scale by endoscopists and was verified by blinded investigators. The secondary endpoints were patients’ tolerability and acceptance. Colon-cleansing efficiency was not significantly different between the two preparations. However, patients’ overall judgment was significantly in favor of L-NaP, reflecting better acceptance of L-NaP than PEG. Additionally, more patients favored L-NaP over PEG in a hypothetical future occasion requiring colonoscopy.

  12. Comparison of beclomethasone dipropionate (2 and 3 mg) and prednisolone sodium phosphate enemas (30 mg) in the treatment of ulcerative proctitis. An adrenocortical approach.

    Science.gov (United States)

    Mulder, C J; Endert, E; van der Heide, H; Houthoff, H J; Wiersinga, W; Wiltink, E H; Tytgat, G N

    1989-08-01

    Twenty-three patients with attacks of distal ulcerative colitis were treated randomly with either 2 or 3 mg of topically administered beclomethasone dipropionate (BDP) or 30 mg of prednisolone sodium phosphate (PP). The effect of the steroid enemas on adrenocortical function was assessed by ACTH tests, which were performed before and after treatment. Endoscopic, clinical and histological scores were comparable in the three treatment groups in this pilot trial. Fasting cortisol in the PP group decreased significantly from 0.47 +/- 0.12 mumol/l before to 0.22 +/- 0.14 mumol/l (P less than 0.05) after therapy; in the BDP group no significant changes were found. Urinary cortisol excretion in the PP group was not detectable after therapy; in the BDP group no changes were found. It is concluded that in the topical treatment of ulcerative colitis, BDP may be preferable to PP because it exerts a promising anti-inflammatory action without affecting adrenocortical function.

  13. Microstructure of Temporomandibular Joint Cartilage after Intra-Articular Betamethasone Sodium Phosphate/Betamethasone Dipropionate Injection during the Early Stage of Experimental Osteoarthrosis

    Directory of Open Access Journals (Sweden)

    Irina N. Kostina

    2014-06-01

    Full Text Available Objective: to study the morphological changes in cartilage after a single intra-articular betamethasone sodium phosphate (BSP/betamethasone dipropionate (BDP injection during the early stage of experimental osteoarthrosis (OA of the temporomandibular joint (TMJ. Material and Methods: The experiment was performed on 18 male rabbits aged 6 months .The first group consisted of 9 healthy rabbits. The second group included 9 rabbits with mechanically induced TMJ OA. For 5 days, 3 hours daily, a load (with a force of 200N on the TMJ was imposed. In the left TMJ of the second group of rabbits, betamethasone was injected intra-articularly in different doses: 0.1 ml (n=3, 0.3 ml (n=3, and 0.5 ml (n=3. The right TMJ was used for comparison. A combined anesthesia was applied each experimental day. Rabbits of both groups were sacrificed on days 7, 14, and 30 with introductory combined anesthesia and intravenous injection of Zoletil 100® 20 mg/kg to stop their breathing. Results: Betamethasone caused destruction of the chondrocytes, fragmentation of collagen fibers, deficit of proteoglycans (PGs and glycosaminoglycans (GAGs, thinning of the cartilage, and contributed to the progression of TMJ OA. Conclusion: The optimal dose of BSP/BDP for intra-articular injection in the early stages of TMJ OA must be within the range of 0.1-0.3 ml|0.7-1.5 mg.

  14. Loss of K-Cl co-transporter KCC3 causes deafness, neurodegeneration and reduced seizure threshold

    OpenAIRE

    Boettger, Thomas; Rust, Marco B.; Maier, Hannes; Seidenbecher, Thomas; Schweizer, Michaela; Damien J. Keating; Faulhaber, Jörg; Ehmke, Heimo; Pfeffer, Carsten; Scheel, Olaf; Lemcke, Beate; Horst, Jürgen; Leuwer, Rudolf; Pape, Hans-Christian; Völkl, Harald

    2003-01-01

    K-Cl co-transporters are encoded by four homologous genes and may have roles in transepithelial transport and in the regulation of cell volume and cytoplasmic chloride. KCC3, an isoform mutated in the human Anderman syndrome, is expressed in brain, epithelia and other tissues. To investigate the physiological functions of KCC3, we disrupted its gene in mice. This severely impaired cell volume regulation as assessed in renal tubules and neurons, and moderately raised intraneuronal Cl– concentr...

  15. Sodium Glucose Co-transporter Type 2 (SGLT2) Inhibitors: Targeting the Kidney to Improve Glycemic Control in Diabetes Mellitus

    OpenAIRE

    Bays, Harold

    2013-01-01

    Although hyperglycemia is a key therapeutic focus in the management of patients with type 2 diabetes mellitus (T2DM), many patients experience sub-optimal glycemic control. Current glucose-lowering agents involve the targeting of various body organs. Sodium glucose co-transporter type 2 (SGLT2) inhibitors target the kidney, reduce renal glucose reabsorption, and increase urinary glucose elimination, thus lowering glucose blood levels. This review examines some of the key efficacy and safety d...

  16. Passive water and ion transport by cotransporters

    DEFF Research Database (Denmark)

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

    1999-01-01

    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...... the changes in oocyte volume in response to osmotic gradients. The specific SGLT1 and GAT1 Lp values were obtained by measuring Lp in the presence and absence of blockers (phlorizin and SKF89976A). In the presence of the blockers, the Lp values of oocytes expressing SGLT1 and GAT1 were indistinguishable from...... 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...

  17. 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

    DAVP significantly increased pS124-NCC abundance, with no changes in total NCC plasma membrane abundance. pS124-NCC levels also increased in abundance in rats after stimulation of the renin-angiotensin-aldosterone system by dietary low sodium intake. In contrast to other NCC phosphorylation sites, the STE20/SPS1......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...

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

    NARCIS (Netherlands)

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

    2004-01-01

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

  19. Genistein affects parathyroid gland and NaPi 2a cotransporter in an animal model of the andropause.

    Science.gov (United States)

    Pantelic, J; Ajdzanovic, V; Medigovic, I; Mojic, M; Trifunovic, S; Milosevic, V; Filipovic, B

    2013-06-01

    This study aimed to examine the effects of genistein on the structural and functional changes in parathyroid glands (PTG) and sodium phosphate cotransporter 2a (NaPi 2a) in orchidectomized rats. Sixteen-month-old Wistar rats were divided into sham-operated (SO), orchidectomized (Orx) and genistein-treated orchidectomized (Orx+G) groups. Genistein (30 mg/kg/day) was administered subcutaneously for 3 weeks, while the controls received vehicle alone. PTG was analyzed histomorphometrically, while the expressions of NaPi 2a mRNA/protein levels from kidneys were determined by real time PCR and Western blots. Serum and urine parameters were determined biochemically. The PTG volume in Orx rats was increased by 30% (p<0.05), compared to the SO group. Orx+G treatment increased the PTG volume by 35% and 75% (p<0.05) respectively, comparing to Orx and SO animals. Orchidectomy led to increment of serum PTH by 27% (p<0.05) compared to the SO group, Orx+G decreased it by 18% (p<0.05) comparing to Orx animals. NaPi 2a expression in Orx animals was reduced in regards to its abundance in SO animals, although it was increased in Orx+G group compared to the Orx. Phosphorus urine content of Orx animals was raised by 12% (p<0.05) compared to that for the SO group, while Orx+G induced a 17% reduction (p<0.05) in regards to Orx animals. Our study shows that Orx increases PTG volume and serum PTH level, while protein expression of NaPi 2a is reduced. Application of genistein attenuates the orchidectomy-induced changes in serum PTH level, stimulates the expression of NaPi 2a and reduces urinary Pi excretion, implying potential beneficial effects on andropausal symptoms.

  20. Exon loss accounts for differential sorting of Na-K-Cl cotransporters in polarized epithelial cells.

    Science.gov (United States)

    Carmosino, Monica; Giménez, Ignacio; Caplan, Michael; Forbush, Biff

    2008-10-01

    The renal Na-K-Cl cotransporter (NKCC2) is selectively expressed in the apical membranes of cells of the mammalian kidney, where it is the target of the clinically important loop diuretics. In contrast, the "secretory" NKCC1 cotransporter is localized in the basolateral membranes of many epithelia. To identify the sorting signal(s) that direct trafficking of NKCCs, we generated chimeras between the two isoforms and expressed these constructs in polarized renal epithelial cell lines. This analysis revealed an amino acid stretch in NKCC2 containing apical sorting information. The NKCC1 C terminus contains a dileucine motif that constitutes the smallest essential component of its basolateral sorting signal. NKCC1 lacking this motif behaves as an apical protein. Examination of the NKCC gene structure reveals that this dileucine motif is encoded by an additional exon in NKCC1 absent in NKCC2. Phylogenetic analysis of this exon suggests that the evolutionary loss of this exon from the gene encoding the basolateral NKCC1 constitutes a novel mechanism that accounts for the apical sorting of the protein encoded by the NKCC2 gene.

  1. Quantitative determination of betamethasone sodium phosphate and betamethasone dipropionate in human plasma by UPLC-MS/MS and a bioequivalence study.

    Science.gov (United States)

    Chen, Man-Yun; Tang, Yong-Jun; Wang, Yi-Cheng; Wang, Chong-Zhi; Yuan, Chun-Su; Chen, Yao; Tan, Zhi-Rong; Huang, Wei-Hua; Zhou, Hong-Hao

    2016-05-07

    The compound medicine of betamethasone sodium phosphate (BSP) and betamethasone dipropionate (BDP) is widely used for diverse glucocorticoid-sensitive acute and chronic diseases such as asthma, rheumatoid arthritis and systemic lupus erythematosus. It will be useful and beneficial to validate sensitive method for the determination of BSP, BDP and their metabolites for their pharmacokinetic study. Hereby, an ultra-high pressure liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) has been validated for the determination of BSP, BDP and their metabolites betamethasone (BOH), betamethasone 17-monodipropionate (B17P) and betamethasone 21-monodipropionate (B21P) in human plasma. Liquid-liquid extraction with ether and n-hexane (v/v, 4:1) was used for sample preparation of BDP, BOH, B17P and B21P with beclomethasone dipropionate as internal standard (IS), while solid phase extraction was adopted for sample preparation of BSP using prednisolone as IS. The chromatographic separation was performed on a Hypurity C18 column (150 mm×2.1 mm, 5 μm) for BOH, BDP, B21P and B17P, and a Luna C18 (2) column (150 mm×2.0 mm, 5 μm) for BSP. Electrospray ionization interfaced with positive multiple reaction monitoring (MRM) scan mode was used for mass spectrometric detection. The standard calibration curves were linear within the range of 2.525 × 10(-9)-403.9 × 10(-9) mol·dm(-3) for BSP, 0.125 × 10(-9)-55.81 × 10(-9) mol·dm(-3) for BDP, 0.278 × 10(-9)-74.95 × 10(-9) mol·dm(-3) for BOH, 0.098 × 10(-9)-4.688 × 10(-9) mol·dm(-3) for B17P and 0.226 × 10(-9)-5.411 × 10(-9) mol·dm(-3) for B21P, respectively. The validated method was successfully applied to a bioequivalence study in 23 healthy subjects after they were injected with this compound medicine BSP and BDP.

  2. 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

  3. EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion on the substantiation of health claims related to sodium phosphate and increase in endurance performance (ID 318, 2887) and increase in endurance capacity (ID 318, 2887) pursuant to Article 13(1) of Regulation (EC

    DEFF Research Database (Denmark)

    Tetens, Inge

    Following a request from the European Commission, the Panel on Dietetic Products, Nutrition and Allergies was asked to provide a scientific opinion on a list of health claims pursuant to Article 13 of Regulation (EC) No 1924/2006. This opinion addresses the scientific substantiation of health...... claims in relation to sodium phosphate and increase in endurance performance and increase in endurance capacity. The scientific substantiation is based on the information provided by the Member States in the consolidated list of Article 13 health claims and references that EFSA has received from Member...... States or directly from stakeholders. The food constituent that is the subject of the health claims is sodium phosphate. The Panel considers that sodium phosphate is sufficiently characterised....

  4. With no lysine L-WNK1 isoforms are negative regulators of the K+-Cl- cotransporters.

    Science.gov (United States)

    Mercado, Adriana; de Los Heros, Paola; Melo, Zesergio; Chávez-Canales, María; Murillo-de-Ozores, Adrián R; Moreno, Erika; Bazúa-Valenti, Silvana; Vázquez, Norma; Hadchouel, Juliette; Gamba, Gerardo

    2016-07-01

    The K(+)-Cl(-) cotransporters (KCC1-KCC4) encompass a branch of the SLC12 family of electroneutral cation-coupled chloride cotransporters that translocate ions out of the cell to regulate various factors, including cell volume and intracellular chloride concentration, among others. L-WNK1 is an ubiquitously expressed kinase that is activated in response to osmotic stress and intracellular chloride depletion, and it is implicated in two distinct hereditary syndromes: the renal disease pseudohypoaldosteronism type II (PHAII) and the neurological disease hereditary sensory neuropathy 2 (HSN2). The effect of L-WNK1 on KCC activity is unknown. Using Xenopus laevis oocytes and HEK-293 cells, we show that the activation of KCCs by cell swelling was prevented by L-WNK1 coexpression. In contrast, the activity of the Na(+)-K(+)-2Cl(-) cotransporter NKCC1 was remarkably increased with L-WNK1 coexpression. The negative effect of L-WNK1 on the KCCs is kinase dependent. Elimination of the STE20 proline-alanine rich kinase (SPAK)/oxidative stress-responsive kinase (OSR1) binding site or the HQ motif required for the WNK-WNK interaction prevented the effect of L-WNK1 on KCCs, suggesting a required interaction between L-WNK1 molecules and SPAK. Together, our data support that NKCC1 and KCCs are coordinately regulated by L-WNK1 isoforms.

  5. 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.

  6. γ-Adducin stimulates the thiazide-sensitive NaCl cotransporter

    DEFF Research Database (Denmark)

    Dimke, Henrik Anthony; San-Cristobal, Pedro; de Graaf, Mark

    2011-01-01

    The thiazide-sensitive NaCl cotransporter (NCC) plays a key role in renal salt reabsorption and the determination of systemic BP, but the molecular mechanisms governing the regulation of NCC are not completely understood. Here, through pull-down experiments coupled to mass spectrometry, we found...... that γ-adducin interacts with the NCC transporter. γ-Adducin colocalized with NCC to the distal convoluted tubule. (22)Na(+) uptake experiments in the Xenopus laevis oocyte showed that γ-adducin stimulated NCC activity in a dose-dependent manner, an effect that occurred upstream from With No Lysine (WNK......) 4 kinase. The binding site of γ-adducin mapped to the N terminus of NCC and encompassed three previously reported phosphorylation sites. Supporting this site of interaction, competition with the N-terminal domain of NCC abolished the stimulatory effect of γ-adducin on the transporter. γ...

  7. 气相色谱法测定地塞米松磷酸钠注射液中丙三醇含量%Determination the Assay of Glycerol in Dexamethasone Sodium Phosphate Injection by GC

    Institute of Scientific and Technical Information of China (English)

    耿倩; 赵云鹏; 王建明

    2013-01-01

    建立地塞米松磷酸钠注射液中丙三醇含量的GC检测方法。色谱柱为HP-1毛细管柱,载气为高纯氮气,采用氢火焰离子化检测器(FID),外标法计算丙三醇的含量。在试验范围内峰面积和浓度呈现良好的线性关系,相关系数为0.999,平均回收率为97%(n=9),RSD为0.8%。本法专属性强、重现性好、准确度和灵敏度高,可用于地塞米松磷酸钠注射液中丙三醇含量的测定。%To establish a method for determination the assay of glycerin in Dexamethasone Sodium Phosphate Injection, use GC with column of HP-1, nitrogen as the carrier gas, and FID as the detector, use external standard method to calculate the assay of glycerin. Peak area and concentration presents good linearity in experimental range, the correlation coef icient is 0.999, the average recovery is 97%(n=9),RSD is 0.8%.The method has a good specificity, reproducibility, accurancy and high sensitivity, can use to determination the assay of glycerin in Dexamethasone Sodium Phosphate Injection.

  8. FGF23 regulates renal sodium handling and blood pressure

    OpenAIRE

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

    2014-01-01

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

  9. Na+,2Cl-,K+ cotransport system as a marker of antihypertensive activity of new torasemide derivatives.

    Science.gov (United States)

    Masereel, B; Ferrari, P; Ferrandi, M; Pirotte, B; Schynts, M; Parenti, P; Delarge, J

    1992-09-04

    A series of compounds related to torasemide, a loop diuretic, were synthesized and examined for their diuretic potency and inhibitory activity on the erythrocyte and renal medullary thick ascending limb vesicle Na+,2Cl-,K+ cotransport in Milan hypertensive (MHS) and normotensive (MNS) rat strains, where previous studies had demonstrated an alteration of the cotransport system genetically related to hypertension. From the results of the screening, structure-activity relationships were drawn and two compounds, JDL 961 and C 2921 were selected. Their IC50 on renal vesicle cotransport were similar in the two strains (JDL 961: MHS = 1.8 microM; MNS = 1.2 microM; C 2921: MHS = 4 microM; MNS = 3.8 microM), and were 4-8 times lower than those of torasemide (MHS = 13 microM; MNS = 31 microM, P less than 0.01) and 50-60 times lower than those of bumetanide (MHS = 145 microM; MNS = 206 microM, P less than 0.05) taken as reference compounds. Their ability to reduce the development rate of hypertension was tested both in MHS and in Okamoto spontaneously hypertensive rats (SHR) strain, in which cotransport alterations are opposite to those of MHS. Both torasemide derivatives (7.5 mg.kg-1 os per day) prevented development of hypertension in the two strains. The time course of this hypotensive activity was faster and the percentage of blood pressure fall greater in MHS (20-25%) than in SHR rats (12-15%), even though the absolute value of blood pressure fall was similar in MHS (JDL 961 = -17 mm Hg; C 2921 = -30 mm Hg) and SHR (JDL 961 = -25 mm Hg; C 2921 = -20 mm Hg). A superimposable effect of bumetanide was observed in the two strains, but at 8 times higher daily dose (60 mg.kg-1). These results suggest that new loop diuretics can be selected for their antihypertensive activity on the basis of their in vitro potency in inhibiting the Na+,2Cl-,K+.

  10. 核黄素磷酸钠注射液在手足口病中的应用%Application of Rlboflavin Sodium Phosphate Injection in the treatment of hand, foot and mouth disease

    Institute of Scientific and Technical Information of China (English)

    陈军; 王险峰; 王艳荣; 李志辉

    2013-01-01

    Objective To evaluate clinical efficacy of Rlboflavin Sodium Phosphate Injection in the treatment of hand, foot and mouth disease (HFMD). Methods Sixty-four children of HFMD in Shenzhen Third People's Hospital from Mar. 2011 to July 2012 were collected and divided into the treatment group (n=33) and the control group (n=31) according to methods of treatment. The patients in the two groups were both treated by normal fluid infusion and symptomatic treatment, and those in the treatment group were additionally treated by Rlboflavin Sodium Phosphate Injection simultaneously, once per day, 5~7 d via injection. The change in the time of herpes repressed, appetite, temperature and side effects were analyzed. Results The time of herpes repressed, and the time of recovering normal appetite and normal temperature in treatment group [(4.45±0.51) d, (3.11±0.1) d, (3.19±0.6) d, respectively] was significantly shorter than those in the control group [(6.55±1.51) d, (4.09±0.8) d, (35.0±1.29) d, respectively], P< 0.05. The apparent effective rate (72.7%) and total effective rate (90.9%) in the treatment group were both significantly higher than those in the control group (41.9%, 90.3%), P<0.05. There was no obvious side effects during treatment. Conclusion There was apparent response using Rlboflavin Sodium Phosphate Injection for treating HFMD.%目的 观察核黄素磷酸钠注射液治疗手足口病的临床疗效.方法 选取2011 年3 月至2012 年7月在深圳市第三人民医院确诊为手足口病的64 例住院患儿,根据治疗方法分为治疗组(33 例)和对照组(31 例),两组均接受常规补液及对症治疗,治疗组加用核黄素磷酸钠注射液10 mg/d,1 次/d,静脉滴注5~7 d 后,对两组患儿的疱疹消失时间、食欲、体温等变化及药物不良反应进行临床分析.结果 治疗组患儿疱疹好转消失时间为食欲和体温恢复正常时间分别为(4.45±0.51) d、(3.11±0.1) d、(3.19±0.6) d,均短于对照组相应

  11. [Canagliflozin (Invokana): kidney SGLT2 cotransporter inhibitor for treating type 2 diabetes].

    Science.gov (United States)

    Scheen, A J

    2014-12-01

    Canagliflozin is an inhibitor of sodium-glucose cotransporters type 2 (SGLT2) that are present in renal tubules. This specific insulin-independent mechanism promotes glucosuria, which results in a reduction in fasting and postprandial glycaemia and a decrease of glycated haemoglobin (HbA(1c)). Furthermore, canagliflozin promotes weight loss and lowers arterial (mainly systolic) blood pressure. Its efficacy is decreased in patients with renal insufficiency and the treatment should be stopped if estimated glomerular filtration rate is below 45 ml/min/1.73 m2. Both the efficacy and safety of canagliflozin have been investigated in 24 to 104-week controlled trials versus placebo or versus an active comparator (glimepiride or sitagliptin). The mean reduction in HbA(1c) averages 0.75% when added to other treatments, as compared to placebo. The 100 mg dose is as active as sitagliptin 100 mg while the 300 mg canagliflozin dose is even more efficacious. Adverse events are mostly mycotic genital infections and more rarely mild urinary tract infections. Caution is required in elderly patients and the risk of volume depletion should be checked (hypotension). Hypoglycaemia may occur only in patients already treated with an insulin-secreting agent or insulin. Canagliflozin is commercialized under the trade name Invokana, at the doses of 100 mg and 300 mg once daily, for the treatment of type 2 diabetes.

  12. Effect of Sodium-Glucose Cotransport Inhibition on Polycystic Kidney Disease Progression in PCK Rats.

    Directory of Open Access Journals (Sweden)

    Sarika Kapoor

    Full Text Available The sodium-glucose-cotransporter-2 (SGLT2 inhibitor dapagliflozin (DAPA induces glucosuria and osmotic diuresis via inhibition of renal glucose reabsorption. Since increased diuresis retards the progression of polycystic kidney disease (PKD, we investigated the effect of DAPA in the PCK rat model of PKD. DAPA (10 mg/kg/d or vehicle was administered by gavage to 6 week old male PCK rats (n=9 per group. Renal function, albuminuria, kidney weight and cyst volume were assessed after 6 weeks of treatment. Treatment with DAPA markedly increased glucose excretion (23.6 ± 4.3 vs 0.3 ± 0.1 mmol/d and urine output (57.3 ± 6.8 vs 19.3 ± 0.8 ml/d. DAPA-treated PCK rats had higher clearances for creatinine (3.1 ± 0.1 vs 2.6 ± 0.2 ml/min and BUN (1.7 ± 0.1 vs 1.2 ± 0.1 ml/min after 3 weeks, and developed a 4-fold increase in albuminuria. Ultrasound imaging and histological analysis revealed a higher cyst volume and a 23% higher total kidney weight after 6 weeks of DAPA treatment. At week 6 the renal cAMP content was similar between DAPA and vehicle, and staining for Ki67 did not reveal an increase in cell proliferation. In conclusion, the inhibition of glucose reabsorption with the SGLT2-specific inhibitor DAPA caused osmotic diuresis, hyperfiltration, albuminuria and an increase in cyst volume in PCK rats. The mechanisms which link glucosuria to hyperfiltration, albuminuria and enhanced cyst volume in PCK rats remain to be elucidated.

  13. Effect of Sodium-Glucose Cotransport Inhibition on Polycystic Kidney Disease Progression in PCK Rats.

    Science.gov (United States)

    Kapoor, Sarika; Rodriguez, Daniel; Riwanto, Meliana; Edenhofer, Ilka; Segerer, Stephan; Mitchell, Katharyn; Wüthrich, Rudolf P

    2015-01-01

    The sodium-glucose-cotransporter-2 (SGLT2) inhibitor dapagliflozin (DAPA) induces glucosuria and osmotic diuresis via inhibition of renal glucose reabsorption. Since increased diuresis retards the progression of polycystic kidney disease (PKD), we investigated the effect of DAPA in the PCK rat model of PKD. DAPA (10 mg/kg/d) or vehicle was administered by gavage to 6 week old male PCK rats (n=9 per group). Renal function, albuminuria, kidney weight and cyst volume were assessed after 6 weeks of treatment. Treatment with DAPA markedly increased glucose excretion (23.6 ± 4.3 vs 0.3 ± 0.1 mmol/d) and urine output (57.3 ± 6.8 vs 19.3 ± 0.8 ml/d). DAPA-treated PCK rats had higher clearances for creatinine (3.1 ± 0.1 vs 2.6 ± 0.2 ml/min) and BUN (1.7 ± 0.1 vs 1.2 ± 0.1 ml/min) after 3 weeks, and developed a 4-fold increase in albuminuria. Ultrasound imaging and histological analysis revealed a higher cyst volume and a 23% higher total kidney weight after 6 weeks of DAPA treatment. At week 6 the renal cAMP content was similar between DAPA and vehicle, and staining for Ki67 did not reveal an increase in cell proliferation. In conclusion, the inhibition of glucose reabsorption with the SGLT2-specific inhibitor DAPA caused osmotic diuresis, hyperfiltration, albuminuria and an increase in cyst volume in PCK rats. The mechanisms which link glucosuria to hyperfiltration, albuminuria and enhanced cyst volume in PCK rats remain to be elucidated.

  14. 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

  15. Model analysis of effect of canagliflozin (Invokana), a sodium-glucose cotransporter 2 inhibitor, to alter plasma 1,5-anhydroglucitol.

    Science.gov (United States)

    Fortuna, Danielle; McCloskey, Laura J; Stickle, Douglas F

    2016-01-15

    Renal reabsorption of 1,5-anhydroglucitol (AG) is competitively inhibited by elevated glucose and leads to depleted plasma AG in diabetes. Plasma AG recovery in diabetes normally correlates with improved glycemic control. However, use of sodium-glucose co-transporter 2 (SGLT2) inhibitors (e.g., canagliflozin) to treat diabetes by inhibition of renal glucose reabsorption can negate this correlation, via an indirect effect (increase of renal filtrate glucose concentration) to inhibit AG reabsorption by sodium-glucose co-transporter 4 (SGLT4). Conversely, then, AG measurement might be useful as an independent marker for SGLT2 inhibitor activity. Using an AG mass balance model, we analyzed literature data on plasma AG before and after initiation of canagliflozin therapy (CT) to quantitatively characterize the effect of CT on AG reabsorption. According to model calculations, modest decreases (<5%) in fractional reabsorption of AG account for the drastic decrease in [AG] observed during CT. Decreases are predicted to be rapid (t1/2<3days) after CT initiation. CT negates the usual premise of AG measurement (that [AG] should increase with improved glycemic control). However, according to model calculations, a substantial and likely rapid effect of CT on [AG] means that AG measurement might provide an early marker for CT activity. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Inhibition of Na(+)-K(+)-2Cl(-) cotransport by mercury.

    Science.gov (United States)

    Jacoby, S C; Gagnon, E; Caron, L; Chang, J; Isenring, P

    1999-10-01

    Mercury alters the function of proteins by reacting with cysteinyl sulfhydryl (SH(-)) groups. The inorganic form (Hg(2+)) is toxic to epithelial tissues and interacts with various transport proteins including the Na(+) pump and Cl(-) channels. In this study, we determined whether the Na(+)-K(+)-Cl(-) cotransporter type 1 (NKCC1), a major ion pathway in secretory tissues, is also affected by mercurial substrates. To characterize the interaction, we measured the effect of Hg(2+) on ion transport by the secretory shark and human cotransporters expressed in HEK-293 cells. Our studies show that Hg(2+) inhibits Na(+)-K(+)-Cl(-) cotransport, with inhibitor constant (K(i)) values of 25 microM for the shark carrier (sNKCC1) and 43 microM for the human carrier. In further studies, we took advantage of species differences in Hg(2+) affinity to identify residues involved in the interaction. An analysis of human-shark chimeras and of an sNKCC1 mutant (Cys-697-->Leu) reveals that transmembrane domain 11 plays an essential role in Hg(2+) binding. We also show that modification of additional SH(-) groups by thiol-reacting compounds brings about inhibition and that the binding sites are not exposed on the extracellular face of the membrane.

  17. 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

    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......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...

  18. Effects of a 250-mL enema containing sodium phosphate on electrolyte concentrations in healthy volunteers: An open-label, randomized, controlled, two-period, crossover clinical trial*

    Science.gov (United States)

    Sédaba, Belén; Azanza, Josh R.; Campanero, Miguel A.; Garcia-Quetglas, Emilio; Muñoz, Maria Josh; Marco, Santiago

    2006-01-01

    Background: Enemas are used by individuals with constipation and are often required before certain medical diagnostic procedures and surgical interventions. However, abnormalities in serum electrolyte concentrations have been associated with enema use. Objective: The aim of this study was to determine the changes in serum electrolyte concentrations (phosphorus, calcium, sodium, and potassium) and urinary phosphorus elimination after the administration of a sodium phosphate enema. Methods: Healthy volunteers aged 35 to 70 years were eligible for this open-label, randomized, controlled, 2-period, crossover clinical trial at the Clinical Research Unit of the University Hospital of Navarra, Pamplona, Spain. The study comprised 2 one-day periods separated by a 7-day washout. All subjects were randomly assigned in a 1:1 ratio to 1 of 2 study sequences: (1) a single dose of Enema Casen® 250 mL in the first period followed by no treatment (control) in the second period, or (2) no treatment in the first period followed by a single dose of the study drug in the second period. The sequence of treatment was assigned using a randomization table that was prepared before the beginning of the study. Serum concentrations of phosphorus, sodium, potassium, and calcium were measured in both periods. Urinary phosphorus elimination was measured for 12 hours after enema administration (Ae0–12) in a subset of the subjects in the second period. Adverse events (AEs) were monitored by the investigators throughout the study. Normal ranges for the electrolytes were as follows: phosphorus, 2.5 to 5 mg/dL; calcium, 8.5 to 10.5 mg/dL; sodium, 135 to 145 mEq/L; and potassium, 3.5 to 5 mEq/L. Results: Twenty-four subjects (12 men, 12 women; mean [SD] age, 47.8 [9.6] years [range, 36–68 years]) participated in the study. All of the subjects were white and none were smokers. Twelve hours after enema administration, mean serum phosphorus and sodium concentrations increased by a mean of 1.18 mg

  19. Canagliflozin Slows Progression of Renal Function Decline Independently of Glycemic Effects

    NARCIS (Netherlands)

    Heerspink, Hiddo J. L.; Desai, Mehul; Jardine, Meg; Balis, Dainius; Meininger, Gary; Perkovic, Vlado

    Sodium-glucose cotransporter 2 inhibition with canagliflozin decreases HbA1c, body weight, BP, and albuminuria, implying that canagliflozin confers renoprotection. We determined whether canagliflozin decreases albuminuria and reduces renal function decline independently of its glycemic effects in a

  20. Direct control of Na(+)-K(+)-2Cl(-)-cotransport protein (NKCC1) expression with aldosterone.

    Science.gov (United States)

    Ding, Bo; Frisina, Robert D; Zhu, Xiaoxia; Sakai, Yoshihisa; Sokolowski, Bernd; Walton, Joseph P

    2014-01-01

    Sodium/potassium/chloride cotransporter (NKCC1) proteins play important roles in Na(+) and K(+) concentrations in key physiological systems, including cardiac, vascular, renal, nervous, and sensory systems. NKCC1 levels and functionality are altered in certain disease states, and tend to decline with age. A sensitive, effective way of regulating NKCC1 protein expression has significant biotherapeutic possibilities. The purpose of the present investigation was to determine if the naturally occurring hormone aldosterone (ALD) could regulate NKCC1 protein expression. Application of ALD to a human cell line (HT-29) revealed that ALD can regulate NKCC1 protein expression, quite sensitively and rapidly, independent of mRNA expression changes. Utilization of a specific inhibitor of mineralocorticoid receptors, eplerenone, implicated these receptors as part of the ALD mechanism of action. Further experiments with cycloheximide (protein synthesis inhibitor) and MG132 (proteasome inhibitor) revealed that ALD can upregulate NKCC1 by increasing protein stability, i.e., reducing ubiquitination of NKCC1. Having a procedure for controlling NKCC1 protein expression opens the doors for therapeutic interventions for diseases involving the mis-regulation or depletion of NKCC1 proteins, for example during aging.

  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. Mutations in the Na-Cl cotransporter reduce blood pressure in humans.

    Science.gov (United States)

    Cruz, D N; Simon, D B; Nelson-Williams, C; Farhi, A; Finberg, K; Burleson, L; Gill, J R; Lifton, R P

    2001-06-01

    The relationship between salt homeostasis and blood pressure has remained difficult to establish from epidemiological studies of the general population. Recently, mendelian forms of hypertension have demonstrated that mutations that increase renal salt balance lead to higher blood pressure, suggesting that mutations that decrease the net salt balance might have the converse effect. Gitelman's syndrome, caused by loss of function mutations in the Na-Cl cotransporter of the distal convoluted tubule (NCCT), features inherited hypokalemic alkalosis with so-called "normal" blood pressure. We hypothesized that the mild salt wasting of Gitelman's syndrome results in reduced blood pressure and protection from hypertension. We have formally addressed this question through the study of 199 members of a large Amish kindred with Gitelman's syndrome. Through genetic testing, family members were identified as inheriting 0 (n=60), 1 (n=113), or 2 (n=26) mutations in NCCT, permitting an unbiased assessment of the clinical consequences of inheriting these mutations by comparison of the phenotypes of relatives with contrasting genotypes. The results demonstrate high penetrance of hypokalemic alkalosis, hypomagnesemia, and hypocalciuria in patients inheriting 2 mutant NCCT alleles. In addition, the NCCT genotype was a significant predictor of blood pressure, with homozygous mutant family members having significantly lower age- and gender-adjusted systolic and diastolic blood pressures than those of their wild-type relatives. Moreover, both homozygote and heterozygote subjects had significantly higher 24-hour urinary Na(+) than did wild-type subjects, reflecting a self-selected higher salt intake. Finally, heterozygous children, but not adults, had significantly lower blood pressures than those of the wild-type relatives. These findings provide formal demonstration that inherited mutations that impair renal salt handling lower blood pressure in humans.

  3. [EMPAGLIFLOZIN (JARDIANCE) :Nw SGLT2 COTRANSPORTER INHIBITOR FOR TREATING TYPE 2 DIABETES].

    Science.gov (United States)

    Scheen, A J

    2015-09-01

    Empagliflozin is a new inhibitor of sodiumglucose cotransporters type 2 (SGLT2) for the treatment of type 2 diabetes mellitus (T2DM). Its specific action inhibits glucose reabsorption in renal tubules and thus promotes glucosuria. This effect results in a reduction in fasting and postprandial glycaemia and a decrease of glycated haemoglobin (HbA(Ic)), independently of insulin. Furthermore, calorie urinary loss promotes weight reduction and osmotic diuresis lowers arterial blood pressure. The efficacy of empagliflozin increases according to the level of hyperglycaemia but decreases in patients with renal insufficiency. In 24 to 104-week controlled trials versus placebo, empagliflozin reduces HbA(1c) (approximately 0.8%), without hypoglycaemia (except in patients already treated with insulin or sulphonylureas). This improvement in glucose control is rather similar to that observed with active comparators (metformin, glimepiride or sitagliptin), with the advantage for empagliflozin of reducing body weight (approximately 2 kg) and blood pressure (systolic approximately 4 mm Hg and diastolic approximately 2 mm Hg). Empagliflozin has shown a cardiovascular protection in the EMPA-REG OUTCOME trial. Mycotic genital infections occur more frequently, especially in women, while a negligible increase in mild urinary tract infections may be observed. The risk of hypotension and volume depletion is low, although it should be carefully checked in more fragile and at risk patients. Empagliflozin (Jardiance), which is commercialized at the doses of 10 mg and 25 mg once daily, is indicated for the treatment of T2DM and reimbursed in Belgium with conditions as add-on to a background glucose-lowering therapy.

  4. Pharmacokinetic and pharmacodynamic profile of empagliflozin, a sodium glucose co-transporter 2 inhibitor.

    Science.gov (United States)

    Scheen, André J

    2014-03-01

    Empagliflozin is an orally active, potent and selective inhibitor of sodium glucose co-transporter 2 (SGLT2), currently in clinical development to improve glycaemic control in adults with type 2 diabetes mellitus (T2DM). SGLT2 inhibitors, including empagliflozin, are the first pharmacological class of antidiabetes agents to target the kidney in order to remove excess glucose from the body and, thus, offer new options for T2DM management. SGLT2 inhibitors exert their effects independently of insulin. Following single and multiple oral doses (0.5-800 mg), empagliflozin was rapidly absorbed and reached peak plasma concentrations after approximately 1.33-3.0 h, before showing a biphasic decline. The mean terminal half-life ranged from 5.6 to 13.1 h in single rising-dose studies, and from 10.3 to 18.8 h in multiple-dose studies. Following multiple oral doses, increases in exposure were dose-proportional and trough concentrations remained constant after day 6, indicating a steady state had been reached. Oral clearance at steady state was similar to corresponding single-dose values, suggesting linear pharmacokinetics with respect to time. No clinically relevant alterations in pharmacokinetics were observed in mild to severe hepatic impairment, or in mild to severe renal impairment and end-stage renal disease. Clinical studies did not reveal any relevant drug-drug interactions with several other drugs commonly prescribed to patients with T2DM, including warfarin. Urinary glucose excretion (UGE) rates were higher with empagliflozin versus placebo and increased with dose, but no relevant impact on 24-h urine volume was observed. Increased UGE resulted in proportional reductions in fasting plasma glucose and mean daily glucose concentrations.

  5. Dapagliflozin, SGLT2 Inhibitor, Attenuates Renal Ischemia-Reperfusion Injury

    OpenAIRE

    Yoon-Kyung Chang; Hyunsu Choi; Jin Young Jeong; Ki-Ryang Na; Kang Wook Lee; Beom Jin Lim; Dae Eun Choi

    2016-01-01

    Dapagliflozin, a new type of drug used to treat diabetes mellitus (DM), is a sodium/glucose cotransporter 2 (SGLT2) inhibitor. Although some studies showed that SGLT2 inhibition attenuated reactive oxygen generation in diabetic kidney the role of SGLT2 inhibition is unknown. We evaluated whether SLT2 inhibition has renoprotective effects in ischemia-reperfusion (IR) models. We evaluated whether dapagliflozin reduces renal damage in IR mice model. In addition, hypoxic HK2 cells were treated wi...

  6. Water transport between CNS compartments: contributions of aquaporins and cotransporters

    DEFF Research Database (Denmark)

    MacAulay, N; Zeuthen, T

    2010-01-01

    review we introduce another family of transport proteins as water transporters, namely the cotransporters and the glucose uniport GLUT1. In direct contrast to the aquaporins, these proteins have an inherent ability to transport water against an osmotic gradient. Some of them may also function as water...... or hydrocephalus. The molecular pathways by which water molecules cross the cell membranes of the brain are not well-understood, although the discovery of aquaporin 4 (AQP4) in the brain improved our understanding of some of these transport processes, particularly under pathological conditions. In the present...

  7. 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

  8. Inflammatory cytokine TNF-α inhibits Na(+)-glutamine cotransport in intestinal epithelial cells.

    Science.gov (United States)

    Talukder, Jamilur R; Boyd, Brittney; Griffin, Ashley; Jaima, Antara; Rajendran, Vazhaikkurichi M

    2013-04-01

    Glutamine (Gln), a preferred fuel source for enterocytes, is critical for intestinal epithelial cell integrity and barrier function. Chronic enteritis inhibits apical Na(+)-Gln cotransport. It is not known whether inflammatory cytokines that are secreted during inflammation inhibit Na(+)-Gln cotransport. Thus, this study aimed to examine whether TNF-α would affect apical Na(+)-Gln cotransport in intestinal epithelial cells. In this study, the presence of Na(+)-Gln cotransport was established by measuring Gln uptake in 10 days postconfluent IEC-6 cells grown on transwell plates. Cation, amino acid specificity, and siRNA transfection studies established that Na(+)-Gln cotransport is mediated via B(0)AT1. Immunoblotting and immunofluorescence studies established the apical membrane localization of B(0)AT1 in IEC-6 cells. Tumour necrosis factor α (TNF-α) inhibited Na(+)-Gln cotransport in a concentration- and time-dependent manner with an inhibitory concentration of 1.53 nmol·L(-1). Quantitative real-time PCR and Western blot analyses indicated that TNF-α did not alter B(0)AT1-specific transcripts or protein expression level. Kinetic studies revealed that TNF-α inhibited Na(+)-Gln cotransport by reducing the affinity of the cotransporters for Gln, and this effect was antagonized by genistein. Thus, we conclude that the TNF-α inhibition of Na(+)-Gln cotransport occurs at the post-translational level, and that the IEC-6 cell line is an excellent system to study the role of cytokines in Na(+)-Gln cotransport.

  9. The clinical significance of K-Cl cotransport activity in red cells of patients with HbSC disease.

    Science.gov (United States)

    Rees, David C; Thein, Swee Lay; Osei, Anna; Drasar, Emma; Tewari, Sanjay; Hannemann, Anke; Gibson, John S

    2015-05-01

    HbSC disease is the second commonest form of sickle cell disease, with poorly understood pathophysiology and few treatments. We studied the role of K-Cl cotransport activity in determining clinical and laboratory features, and investigated its potential role as a biomarker. Samples were collected from 110 patients with HbSC disease and 41 with sickle cell anemia (HbSS). K-Cl cotransport activity was measured in the oxygenated (K-Cl cotransport(100)) and deoxygenated (K-Cl cotransport(0)) states, using radioactive tracer studies. K-Cl cotransport activity was high in HbSC and decreased significantly on deoxygenation. K-Cl cotransport activity correlated significantly and positively with the formation of sickle cells. On multiple regression analysis, K-Cl cotransport increased significantly and independently with increasing reticulocyte count and age. K-Cl cotransport activity was increased in patients who attended hospital with acute pain in 2011 compared to those who did not (K-Cl cotransport(100): mean 3.87 versus 3.20, P=0.009, independent samples T-test; K-Cl cotransport(0): mean 0.96 versus 0.68, P=0.037). On logistic regression only K-Cl cotransport was associated with hospital attendance. Increased K-Cl cotransport activity was associated with the presence of retinopathy, but this effect was confounded by age. This study links variability in a fundamental aspect of cellular pathology with a clinical outcome, suggesting that K-Cl cotransport is central to the pathology of HbSC disease. Increased K-Cl cotransport activity is associated with increasing age, which may be of pathophysiological significance. Effective inhibition of K-Cl cotransport activity is likely to be of therapeutic benefit.

  10. WNK kinases regulate thiazide-sensitive Na-Cl cotransport.

    Science.gov (United States)

    Yang, Chao-Ling; Angell, Jordan; Mitchell, Rose; Ellison, David H

    2003-04-01

    Pseudohypoaldosteronism type II (PHAII) is an autosomal dominant disorder of hyperkalemia and hypertension. Mutations in two members of the WNK kinase family, WNK1 and WNK4, cause the disease. WNK1 mutations are believed to increase WNK1 expression; the effect of WNK4 mutations remains unknown. The clinical phenotype of PHAII is opposite to Gitelman syndrome, a disease caused by dysfunction of the thiazide-sensitive Na-Cl cotransporter. We tested the hypothesis that WNK kinases regulate the mammalian thiazide-sensitive Na-Cl cotransporter (NCC). Mouse WNK4 was cloned and expressed in Xenopus oocytes with or without NCC. Coexpression with WNK4 suppressed NCC activity by more than 85%. This effect did not result from defects in NCC synthesis or processing, but was associated with an 85% reduction in NCC abundance at the plasma membrane. Unlike WNK4, WNK1 did not affect NCC activity directly. WNK1, however, completely prevented WNK4 inhibition of NCC. Some WNK4 mutations that cause PHAII retained NCC-inhibiting activity, but the Q562E WNK4 demonstrated diminished activity, suggesting that some PHAII mutations lead to loss of NCC inhibition. Gain-of-function WNK1 mutations would be expected to inhibit WNK4 activity, thereby activating NCC, contributing to the PHAII phenotype. Together, these results identify WNK kinases as a previously unrecognized sodium regulatory pathway of the distal nephron. This pathway likely contributes to normal and pathological blood pressure homeostasis.

  11. Trauma renal Renal trauma

    Directory of Open Access Journals (Sweden)

    Gerson Alves Pereira Júnior

    1999-02-01

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

  12. Renal arteriography

    Science.gov (United States)

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

  13. Investigation of the stability of the dexamethasone sodium phosphate injection and mecobalamin injection in sodium chloride injection%地塞米松磷酸钠注射剂与甲钴胺注射剂在氯化钠注射剂中的稳定性考察

    Institute of Scientific and Technical Information of China (English)

    黄滔敏; 陈念祖; 王东蕾; 赖永华; 马勤; 闫晶超

    2012-01-01

    AIM To investigate the stability of dexamethasone sodium phosphate injection and mecobalamin injection in sodium chloride injection. METHODS Dexamethasone sodium phosphate and mecobalamin were determined by RP-HPLC method at 4℃ and normal temperature under natural illumination and nonillumination within 12 h. The appearance of the solution was observed and its pH value was determined. RESULTS No significant change was found in the terms of the appearance and the contents of the mixed solution, the changes of pH value were not more than 1.0 under nonillumination within 12 h. No significant change was found in the terms of the content of dexamethasone sodium phosphate under illumination within 12 h. However, more than 50% mecobalamin was degraded under natural illumination within 5 min. CONCLUSION The dexamethasone sodium phosphate injection and mecobalamin injection should not be simultaneously put in the sodium chloride injection for intravenous infusion.%目的 考察地塞米松磷酸钠注射剂与甲钴胺注射剂在氯化钠注射剂中的稳定性.方法 监测地塞米松磷酸钠注射剂与甲钴胺注射剂在氯化钠注射剂中配伍后于4℃、常温时自然光照射下及避光条件下12 h内的含量变化,同时考察配伍液pH值与外观的变化情况.结果 与配伍后0h比较,在避光条件下12 h内,pH、外观及两者含量均无显著变化;未避光条件下,地塞米松磷酸钠在12 h内无显著变化,5min内甲钴胺含量有显著变化,50%以上已降解.结论 建议地塞米松磷酸钠注射剂不要与甲钴胺注射剂在氯化钠注射剂中配伍后用于静脉滴注.

  14. Effects Observation on Different Doses of Sodium Phosphate Clearance in Pediatric Intestinal Bowel Preparation Before Colorectal Treatment%不同剂量磷酸钠盐清肠液用于小儿结直肠治疗前肠道准备的效果观察

    Institute of Scientific and Technical Information of China (English)

    唐斯文

    2016-01-01

    Objective To explore the different doses of sodium phosphate salt qing intestinal juice for infantile bowel preparation before colorectal treatment.MethodsOur hospital from January 2013 to February 2014,60 cases of colorectal children were randomly assigned to A,B two groups,group A given half A bottle of children (1/2) sodium phosphate salt clear clear bowel intestinal juice,B group was given with A bottle of sodium phosphate salt intestinal juice clear bowel,and observe two groups of children with colorectal intestinal cleaning and incidence of adverse reactions.Results Group B with intestinal cleaning condition was better than that of group A,P0.05).Conclusion For children with clear clear bowel intestinal juice,1 bottle of sodium phosphate salt,its effect is good.%目的:探讨不同剂量磷酸钠盐清肠液用于小儿结直肠治疗前肠道准备的效果。方法我院将2013年1月~2014年2月收治的60例结直肠患儿进行随机分组为A、B两组,A组给予患儿半瓶(1/2)磷酸钠盐清肠液进行清肠,B组给予患儿一瓶磷酸钠盐清肠液清肠,并观察两组结直肠患儿的肠道清洁情况及不良反应发生率。结果 B组患儿的肠道清洁情况优于A组,P<0.05,不良反应发生率差异无统计学意义(P>0.05)。结论给予患儿1瓶磷酸钠盐清肠液进行清肠,其效果良好。

  15. Analgesic effect of intrathecal bumetanide is accompanied by changes in spinal sodium-potassium-chloride co-transporter 1 and potassium-chloride co-transporter 2 expression in a rat model of incisional pain

    Institute of Scientific and Technical Information of China (English)

    Yanbing He; Shiyuan Xu; Junjie Huang; Qingjuan Gong

    2014-01-01

    Accumulating evidence has demonstrated that the sodium-potassium-chloride co-transporter 1 and potassium-chloride co-transporter 2 have a role in the modulation of pain transmission at the spinal level through chloride regulation in the pain pathway and by effecting neuronal excitability and pain sensitization. The present study aimed to investigate the analgesic effect of the speciifc sodium-potassium-chloride co-transporter 1 inhibitor bumetanide, and the change in spinal sodium-potassium-chloride co-transporter 1 and potassium-chloride co-transporter 2 expression in a rat model of incisional pain. Results showed that intrathecal bumetanide could decrease cumulative pain scores, and could increase thermal and mechanical pain thresholds in a rat model of incisional pain. Sodium-potassium-chloride co-transporter 1 expression in-creased in neurons from dorsal root ganglion and the deep laminae of the ipsilateral dorsal horn following incision. By contrast, potassium-chloride co-transporter 2 expression decreased in neurons of the deep laminae from the ipsilateral dorsal horn. These ifndings suggest that spinal sodium-potassium-chloride co-transporter 1 expression was up-regulated and spinal potassi-um-chloride co-transporter 2 expression was down-regulated following incision. Intrathecal bumetanide has analgesic effects on incisional pain through inhibition of sodium-potassi-um-chloride co-transporter 1.

  16. Structural and functional significance of water permeation through cotransporters

    DEFF Research Database (Denmark)

    Zeuthen, Thomas; Gorraitz, Edurne; Her, Ka

    2016-01-01

    and mutated residues lining the sugar transport pathway to cysteine. The mutants were expressed in Xenopus oocytes, and the unitary water and urea permeabilities were determined before and after modifying the cysteine side chain with reversible methanethiosulfonate reagents. The results demonstrate that water......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...

  17. The Electrogenic Na+/HCO3- Cotransporter, NBC

    Directory of Open Access Journals (Sweden)

    Romero MF

    2001-07-01

    Full Text Available Electrogenic Na(+/HCO(3(- (NBC function has been characterized in many mammalian tissues including, kidney, pancreas, and brain. Cloning efforts identified a single cDNA, NBC/NBC1, that possesses all the functional attributes of the electrogenic Na(+/HCO(3(- cotransporter. This NBC clone is related to the anion exchangers and thus forms a bicarbonate transporter superfamily. Presently two N-terminal and one C-terminal isoforms are known. All three isoforms appear to arise from the same gene and seem to have identical function. NBC antibodies have localized NBC isoforms in kidney, pancreas, brain, small intestine, colon, epididymis, eye, heart, liver, salivary glands, stomach, and testis. Functionally, NBC appears HCO(3(- and Na(+ selective. NBC stoichiometry in Xenopus oocytes is 1 Na(+ : 2 HCO(3(-, implicating a possible accessory protein interaction.

  18. Emerging roles of sodium-glucose cotransporter 2 inhibitors in cardiology.

    Science.gov (United States)

    Tanaka, Atsushi; Node, Koichi

    2017-03-01

    The ultimate goal of treatment in people with diabetes mellitus is to prevent development of cardiovascular (CV) disease, resulting in prolongation of healthy life expectancy. Although impaired glycemic metabolism has a central role in its pathology, a number of studies have demonstrated that remedy for its imbalance cannot necessarily be accomplished as a therapeutic goal. A comprehensive medical approach against multi-factorial pathologies in diabetes, such as insulin resistance, obesity, hypertension, and dyslipidemia, in addition to diet and exercise therapy should be rather performed in the routine clinical setting. Along with such conceptual transition, what is required in anti-diabetes agents has also changed, and several anti-diabetes agents have been newly placed on the market in this decade. Such agents are required to undergo global pre- or post-marketing clinical trials assessing CV safety. A growing body of clinical evidence from those trials is now accumulating, and empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, has first demonstrated significant risk reduction, relative to placebo, in CV death, overall mortality, and hospitalization for worsened heart failure in high-risk patients with diabetes mellitus. An SGLT2 inhibitor is a unique glucose-lowering agent and at the same time has multifaceted effects on hemodynamic and metabolic parameters beyond glycemic control. A major mode of action of SGLT2 inhibitors appears to be 'glycosuria' and 'natriuresis,' leading to amelioration of systemic glycemic homeostasis and potential cardio-renal protection. However, the precise mechanisms by which SGLT2 inhibitors affect benefits on the CV systems are yet to be fully elucidated. Thus, although we are now facing several unanswered concerns lurking behind the successful trial, SGLT2 inhibitors surely play several important roles in high-quality management of not only diabetes, but also CV medicine. This review summarizes our current

  19. 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...... 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...... 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....

  20. Water permeability of Na+-K+-2C1- cotransporters in mammalian epithelial cells

    DEFF Research Database (Denmark)

    Hammann, Steffen; Herrera-Perez, J.J.; 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...... changes of the cotransporter and interaction with Na+, K+ and Cl-. Similar measurements were performed on immortalized cell cultures from the thick ascending limb of the loop of Henle (TALH). Given similar overall transport rates of bumetanide-sensitive 86Rb+, the NKCCs of this tissue did not contribute...... any bumetanide-sensitive Lp. This suggests that the cotransporters of the two tissues are either different isoforms or the same cotransporter but in two different transport modes....

  1. Tolerancia, seguridad y eficacia de la preparación para colonoscopia con fosfato de sodio: el papel de la edad Tolerability, safety and efficacy of sodium phosphate preparation for colonoscopy: The role of age

    Directory of Open Access Journals (Sweden)

    D. Rodríguez-Alcalde

    2008-01-01

    Full Text Available Objetivos: comparar la tolerancia subjetiva y los efectos adversos secundarios a la preparación para colonoscopia con dos productos, polietilenglicol (PEG y fosfato de sodio (NaP, en pacientes adultos y en aquellos de 65 años o más. Material y métodos: estudio retrospectivo apareado, tras escoger aleatoriamente a 140 pacientes de todos los que se sometieron a colonoscopia entre marzo de 2004 y mayo de 2005. Se investigó la presencia de los siguientes efectos adversos durante la preparación para la colonoscopia: fiebre, rectorragia, dolor abdominal, dolor perianal, náuseas, vómitos, sed, somnolencia, agitación, temblor y convulsiones. Se consideró mala tolerancia objetiva si el paciente presentó uno cualquiera de estos efectos. Asimismo, se recogió la tolerancia subjetiva al proceso de limpieza. Resultados: se incluyeron 70 pacientes preparados con PEG y 70 pacientes con NaP (69 mujeres y 71 hombres, con edad media de 60,6 ± 14,8 años. No se demostró relación entre la tolerancia subjetiva o la presencia de efectos adversos y la limpieza con uno de los dos productos, ni en la población general ni en los pacientes de 65 años o más (p = 0,09 y p = 0,45 en los ancianos, respectivamente. A pesar de ello, los pacientes preparados con NaP presentaron más náuseas que los tratados con PEG (p Objectives: to compare subjective tolerance and secondary adverse events to bowel cleansing prior to colonoscopy with polyethylene glycol (PEG and sodium phosphate (NaP in adult patients and in those 65 or more years old. Material and methods: retrospective matched study, choosing 140 patients among all of those who underwent colonoscopy from March 2004 to May 2005. We investigated the presence of the next adverse events during bowel preparation: Fever, low digestive bleeding, abdominal pain, perianal pain, nausea, vomiting, thirst, somnolence, agitation, tremor and convulsions. We considered bad objective tolerance if the patient presented any

  2. 苯并三氮唑和磷酸钠对锌的协同缓蚀%Synergistic Inhibition of Zinc Corrosion by Benzotriazole in Combination with Sodium Phosphate

    Institute of Scientific and Technical Information of China (English)

    柳松; 钟燕; 蒋荣英; 冯自平; 肖睿

    2011-01-01

    The inhibition behaviors of benzotriazole (BTA), sodium phosphate (SP) and their mixture on zinc corrosion in 17% (0. 534 mol/L) aqueous tetra-n-butylammonium bromide (TBAB) solution were investigated by means of static weight-loss test, potentiodynamic polarization curve method, electrochemical impedance spectroscopy (EIS), SEM and XPS. The results indicate that BTA, SP and their mixture all protect zinc from corrosion in aqueous TBAB solution, with an inhibition efficiency increasing with BTA or SP content, and that the mixture consisting of 0. 1 g/L BTA and 1 g/L SP is of an inhibition efficiency higher than 93%. Moreover, according to the results of SEM and XPS, it is found that the synergistic inhibition of zinc corrosion by benzotriazole in combination with SP is due to not only the formation of the protective film containing ZnO, Zn ( OH ) 2 and Zn3 ( PO4 ) 2 on the electrode surface but also the adsorption of BTA on the film surface or the inserting of BTA in the film.%采用静态失重法、动电位极化曲线法、电化学交流阻抗法、扫描电镜和X射线光电子能谱等方法,研究了在质量分数为17%(0.534mol/L)的四丁基溴化铵(TBAB)溶液中,苯并三氮唑(BTA)和Na3PO4(SP)单独和复配使用对锌腐蚀的抑制作用.结果表明,BTA和Na3PO4及其复配物对TBAB溶液中的锌具有缓蚀作用,BTA和Na3PO4对锌的缓蚀效率随缓蚀剂质量浓度的增大而提高;0.1g/L的BTA和1g/L的Na3PO4的复配物的缓蚀效率高于93%.文中还结合扫描电镜和X射线光电子能谱的结果对复配物的缓蚀机理进行了讨论,二者的协同效应在于Na3PO4在锌的表面形成含有ZnO、Zn(OH)2和Zn3(PO4)2的保护层,BTA吸附在该保护层的表面或者是镶嵌在保护层的内部.

  3. 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

    ionic and osmotic gradients. The coupling between salt and water transport in NKCC1 represents a novel aspect of cellular water homeostasis where cells can change their volume independently of the direction of an osmotic gradient across the membrane. This has relevance for both epithelial......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...... of external Na+ and Cl(-). The water influx could proceed uphill, against a transmembrane osmotic gradient, suggesting that energy contained in the ion fluxes can be transferred to the water flux. The influx of water induced by changes in external [Cl(-)] saturated in a sigmoidal fashion with a Km of 60 mm...

  4. 单一应用磷酸钠盐口服溶液在大肠癌术前肠道准备中的临床观察%Clinical observation of single oral sodium phosphate in preoperative bowel preparation for colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    袁强; 杜峻峰; 陈光; 徐一石; 魏晓军; 孙亮; 苑树俊; 陈纲; 于波

    2011-01-01

    目的 探讨单一应用磷酸钠盐口服溶液在大肠癌术前肠道准备中的清洁效果、不良反应和耐受性.方法 将212例需做术前肠道准备的大肠癌患者随机分为四组:A组53例,口服磷酸钠盐口服溶液;;B组55例,口服磷酸钠盐口服溶液联合磷酸钠盐灌肠液肛人;C组51例口服聚乙二醇电解质溶液;D组53例,口服硫酸镁溶液.观察4种不同肠道准备方法的肠道清洁有效率、不良反应率和耐受性.结果 A组患者的肠道清洁有效率显著优于C组(P=0.031),而与B组、D组相比均无统计学差异(P>0.05).A组患者在腹胀及恶心发生率方面显著低于D组(P =0.037,0.008),而在腹痛、腹胀、恶心、呕吐方面A组与B组、C组相比均无统计学差异(P>0.05),A组患者的耐受性显著优于D组(P=0.001),而与B组、C组比较均无统计学差异(P =0.570,0.379).结论 单一应用磷酸钠盐口服溶液用于大肠癌术前肠道准备的肠道清洁有效率高,且不良反应少,患者耐受性好.%Objective To explore the cleaning efficacy, tolerahility and safety of single oral sodium phosphate in preoperative bowel preparation for colorectal cancer.Methods 212 patients who underwent the operation of colorectal cancer were randomly divided into four groups: A, B, C and D.In A group, 53 eases took single oral sodium phosphate.In B group, 55 casos were given the combination of omi sodium phosphate and sodium phosphate clyster.51 cases took polyethylene glycol solution (PEG) in group C,and 53 eases was administrated magnesium sulfate in group D.The cleaning efficacy, tolerability and safety were evaluated after bowel preparation.Results The cleaning efficacy of A group was significantly superior to that of B group ( P = 0.031 ), however no statistical difference was observed as compared with B or C group ( P > 0.05 ).The incidence rate of bellyache, bloating and nausea in A group were all lower than those of D group(P =0.037,0.008).However, with

  5. 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....

  6. Establishing a definitive stoichiometry for the Na+/monocarboxylate cotransporter SMCT1.

    Science.gov (United States)

    Coady, Michael J; Wallendorff, Bernadette; Bourgeois, Francis; Charron, Francois; Lapointe, Jean-Yves

    2007-10-01

    Several different stoichiometries have been proposed for the Na(+)/monocarboxylate cotransporter SMCT1, including variable Na(+)/substrate stoichiometry. In this work, we have definitively established an invariant 2:1 cotransport stoichiometry for SMCT1. By using two independent means of assay, we first showed that SMCT1 exhibits a 2:1 stoichiometry for Na(+)/lactate cotransport. Radiolabel uptake experiments proved that, unlike lactate, propionic acid diffuses passively through oocyte membranes and, consequently, propionate is a poor candidate for stoichiometric determination by these methods. Although we previously determined SMCT1 stoichiometry by measuring reversal potentials, this technique produced erroneous values, because SMCT1 simultaneously mediates both an inwardly rectifying cotransport current and an outwardly rectifying anionic leak current; the leak current predominates in the range where reversal potentials are observed. We therefore employed a method that compared the effect of halving the external Na(+) concentration to the effect of halving the external substrate concentration on zero-current potentials. Both lactate and propionate were cotransported through SMCT1 using 2:1 stoichiometries. The leak current passing through the protein has a 1 osmolyte/charge stoichiometry. Identification of cotransporter stoichiometry is not always a trivial task and it can lead to a much better understanding of the transport activity mediated by the protein in question.

  7. Thiazide diuretics directly induce osteoblast differentiation and mineralized nodule formation by targeting a NaCl cotransporter in bone

    Science.gov (United States)

    Dvorak, Melita M; De Joussineau, Cyrille; Carter, D Howard; Pisitkun, Trairak; Knepper, Mark A; Gamba, Gerardo; Kemp, Paul J; Riccardi, Daniela

    2008-01-01

    Thiazide diuretics are used, worldwide, as the first-choice drug for patients with uncomplicated hypertension. In addition to their anti-hypertensive actions, they increase bone mineral density and reduce the prevalence of fractures, indicating that thiazides may have a role in the management of postmenopausal osteoporosis. Traditionally, the bone-protective effects of thiazides have been attributed to an increase in renal calcium reabsorption, secondary to the inhibition of the sodium chloride cotransporter, NCC, expressed in the kidney distal tubule. Whether thiazides exert a direct osteoanabolic effect independently of their renal action is controversial. Here we demonstrate that freshly frozen sections of human and rat bone express NCC, principally in bone-forming cells, the osteoblasts. In primary and established culture models of osteoblasts, fetal rat calvarial (FRC) and human MG63 cells, NCC protein is virtually absent in proliferating cells while its expression is dramatically increased during differentiation. Thiazides directly stimulate the production of osteoblast markers, runt-related transcription factor 2 (runx2) and osteopontin, in the absence of a proliferative effect. Using overexpression/knockdown studies in FRC cells, we show that thiazides, but not loop diuretics, increase mineralized nodule formation acting on NCC. Overall, our study demonstrates that thiazides stimulate osteoblast differentiation and bone mineral formation independently of their renal actions. In addition to their use as part of a therapeutic treatment plan for elderly, hypertensive individuals, our discovery opens up the possibility that bone-specific drug targeting by thiazides may be developed for the prevention and treatment of osteoporosis in the patient population as a whole. PMID:17656470

  8. 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.

  9. Differential expression patterns of chloride transporters, Na+-K+-2Cl--cotransporter and K+-Cl--cotransporter, in epilepsy-associated malformations of cortical development.

    NARCIS (Netherlands)

    Aronica, E.; Boer, K.; Redeker, S.; Spliet, W.G.; van Rijen, P.C.; Troost, D; Gorter, J.A.

    2007-01-01

    Malformations of cortical development are recognized causes of chronic medically intractable epilepsy. An increasing number of observations suggests an important role for cation-chloride co-transporters (CCTs) in controlling neuronal function. Deregulation of their expression may contribute to the

  10. Basolateral Na+/HCO3– cotransport activity is regulated by the dissociable Na+/H+ exchanger regulatory factor

    Science.gov (United States)

    Bernardo, Angelito A.; Kear, Felicidad T.; Santos, Anna V.P.; Ma, Jianfei; Steplock, Debra; Robey, R. Brooks; Weinman, Edward J.

    1999-01-01

    In the renal proximal tubule, the activities of the basolateral Na+/HCO3– cotransporter (NBC) and the apical Na+/H+ exchanger (NHE3) uniformly vary in parallel, suggesting that they are coordinately regulated. PKA-mediated inhibition of NHE3 is mediated by a PDZ motif–containing protein, the Na+/H+ exchanger regulatory factor (NHE-RF). Given the common inhibition of these transporters after protein kinase A (PKA) activation, we sought to determine whether NHE-RF also plays a role in PKA-regulated NBC activity. Renal cortex immunoblot analysis using anti-peptide antibodies directed against rabbit NHE-RF demonstrated the presence of this regulatory factor in both brush-border membranes (BBMs) and basolateral membranes (BLMs). Using a reconstitution assay, we found that limited trypsin digestion of detergent solubilized rabbit renal BLM preparations resulted in NBC activity that was unaffected by PKA activation. Co-reconstitution of these trypsinized preparations with a recombinant protein corresponding to wild-type rabbit NHE-RF restored the inhibitory effect of PKA on NBC activity in a concentration-dependent manner. NBC activity was inhibited 60% by 10–8M NHE-RF; this effect was not observed in the absence of PKA. Reconstitution with heat-denatured NHE-RF also failed to attenuate NBC activity. To establish further a physiologic role for NHE-RF in NBC regulation, the renal epithelial cell line B-SC-1, which lacks detectable endogenous NHE-RF expression, was engineered to express stably an NHE-RF transgene. NHE-RF–expressing B-SC-1 cells (B-SC-RF) exhibited markedly lower basal levels of NBC activity than did wild-type controls. Inhibition of NBC activity in B-SC-RF cells was enhanced after 10 μM of forskolin treatment, consistent with a postulated role for NHE-RF in mediating the inhibition of NBC activity by PKA. These findings not only suggest NHE-RF involvement in PKA-regulated NBC activity, but also provide a unique molecular mechanism whereby

  11. 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

  12. Expression of Na+-d-glucose cotransporter SGLT2 in rodents is kidney-specific and exhibits sex and species differences

    OpenAIRE

    Sabolić, Ivan; Vrhovac, Ivana; Eror, Daniela Balen; Gerasimova, Maria; Rose, Michael; Breljak, Davorka; Ljubojević, Marija; Brzica, Hrvoje; Sebastiani, Anne; Thal, Serge C.; Sauvant, Christoph; Kipp, Helmut; Vallon, Volker; Koepsell, Hermann

    2012-01-01

    With a novel antibody against the rat Na+-d-glucose cotransporter SGLT2 (rSGLT2-Ab), which does not cross-react with rSGLT1 or rSGLT3, the ∼75-kDa rSGLT2 protein was localized to the brush-border membrane (BBM) of the renal proximal tubule S1 and S2 segments (S1 > S2) with female-dominant expression in adult rats, whereas rSglt2 mRNA expression was similar in both sexes. Castration of adult males increased the abundance of rSGLT2 protein; this increase was further enhanced by estradiol and pr...

  13. Fosfato de sódio e cloreto de potássio na micropropagação de videira e amoreira-preta = Sodium phosphate and potassium chloride concentrations: micropropagation of grapevine and blackberry

    Directory of Open Access Journals (Sweden)

    Fabíola Villa

    2007-10-01

    Full Text Available Objetivou-se no presente trabalho testar diferentes concentrações de fosfato de sódio (NaH2PO4.H2O e cloreto de potássio (KCl do meio White e adicionadas ao meio Knudson, na multiplicação in vitro de videira e amoreira-preta. O meio foi constituído de sais doKnudson, acrescido de 25 g L-1 de sacarose e 6 g L-1 de ágar, e o pH ajustado para 5,8 antes da autoclavagem a 121ºC e 1 atm por 20 minutos. Os tratamentos consistiram de concentrações de NaH2PO4.H2O (0, 125, 250, 500 e 1.000 mg L-1 e de KCl (0, 125, 250, 500 e 1.000 mg L-1, em todas as combinações possíveis e do porta-enxerto de videira ‘R110’ e da amoreira-preta cv. Cherokee. Segmentos nodais, oriundos de plântulas preestabelecidas in vitro foram excisados eintroduzidos em tubos de ensaio contendo 15 mL do meio de cultura. Posteriormente, os tubos de ensaio foram transferidos para sala de crescimento a 25 ± 2ºC, irradiância de 32 mmol m–2 s–1 efotoperíodo de 16 horas diárias. O delineamento experimental foi inteiramente casualisado, utilizando-se 4 repetições com 12 plântulas cada. O experimento foi avaliado após 60 dias de cultivo in vitro e o maior comprimento da parte aérea e peso fresco de calos foram verificados em meio Knudson, na ausência de cloreto de potássio. A adição de cloreto de potássio ao meio Knudson não influenciou no aumento do comprimento da parte aérea das duas frutíferas e namassa fresca de calos do porta-enxerto de videira ‘R110’. Não é necessário adicionar fosfato de sódio ao meio para se obter maior massa fresca da parte aérea das frutíferas.This work aimed to test different concentrations of sodium phosphate (NaH2PO4.H2O and potassium chloride (KCl taken from the White medium and added to the Knudson culture medium, in the in vitro multiplication of grapevine rootstocks and blackberry. The culture medium was constituted of Knudson salts, added of 25 g L-1 of sucrose and 6 g L-1 of agar, and the adjusted pH to 5

  14. Renal perfusion scintiscan

    Science.gov (United States)

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

  15. A novel strategy for the treatment of diabetes mellitus - sodium glucose co-transport inhibitors.

    Science.gov (United States)

    Niazi, Asfandyar Khan; Niazi, Saad Hameed

    2010-12-01

    Diabetes is one of the most common chronic diseases, affecting almost 3 million in Canada alone and is characterized by increased blood glucose levels. Treatment varies from lifestyle changes to oral anti-diabetics and/or insulin. Sodium glucose co-transport inhibitors may offer promising treatment for patients suffering from diabetes. The inhibitors act by increasing the loss of glucose in urine by decreasing the reabsorption of glucose from the proximal tubules of nephrons. The aim of this review was to assess the efficacy of sodium glucose co-transport inhibitors in the treatment of diabetes as well as any adverse effects. Databases such as MEDLINE, COCHRANE and EMBASE were systematically searched for literature on the efficacy of sodium glucose co-transport inhibitors in improving the glycemic control of patients with diabetes. Research showed that sodium glucose co-transport inhibitors significantly decreased blood glucose levels by increasing glucosuria. Due to the diuretic effects of these inhibitors, diabetic patients who were suffering from hypertension showed a decrease in blood pressure. The caloric loss associated with these inhibitors resulted in weight loss as well. The most common adverse effect seen in patients on these medications was mycotic infection of the urinary or genital tract. Sodium glucose co-transport inhibitors may be an effective line of treatment for diabetes. Although short-term research has shown these drugs to be safe and well-tolerated, studies should be conducted to assess the long-term effects of these drugs.

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

    DEFF Research Database (Denmark)

    Zeuthen, Thomas; Macaulay, Nanna

    2012-01-01

    . The osmotic effects of NaCl were smaller than those of urea and mannitol. This supports the notion of interaction between ions and water in NKCC1 and allows for an estimate of around 600 water molecules transported per turnover of the protein. Osmotic gradients did not induce water transport in NKCC2. We...... increases in external K¿ concentration elicited abrupt inward water fluxes in NKCC1; the K¿ dependence obeyed one-site kinetics with a K0.5 of 7.5 mM. The water fluxes were blocked by bumetanide, had steep temperature dependence and could proceed uphill against an osmotic gradient of 20 mosmol l......¿¹. A comparison between ion and water fluxes indicates that 460 water molecules are cotransported for each turnover of the protein. In contrast, NKCC2 did not support water fluxes.Water transport in NKCC1 induced by increases in the external osmolarity had high activation energy and was blocked by bumetanide...

  17. Canagliflozin: a sodium glucose co-transporter 2 inhibitor for the treatment of type 2 diabetes mellitus.

    Science.gov (United States)

    Rosenthal, Norm; Meininger, Gary; Ways, Kirk; Polidori, David; Desai, Mehul; Qiu, Rong; Alba, Maria; Vercruysse, Frank; Balis, Dainius; Shaw, Wayne; Edwards, Robert; Bull, Scott; Di Prospero, Nicholas; Sha, Sue; Rothenberg, Paul; Canovatchel, William; Demarest, Keith

    2015-11-01

    The sodium glucose co-transporter 2 (SGLT2) inhibitor canagliflozin is a novel treatment option for adults with type 2 diabetes mellitus (T2DM). In patients with hyperglycemia, SGLT2 inhibition lowers plasma glucose levels by reducing the renal threshold for glucose (RTG ) and increasing urinary glucose excretion (UGE). Increased UGE is also associated with a mild osmotic diuresis and net caloric loss, which can lead to reductions in body weight and blood pressure (BP). After promising results from preclinical and phase I/II studies, the efficacy and safety of canagliflozin was evaluated in a comprehensive phase III development program in over 10,000 patients with T2DM on various background therapies. Canagliflozin improved glycemic control and provided reductions in body weight and BP versus placebo and active comparators in studies of up to 2 years' duration. Canagliflozin was generally well tolerated, with higher incidences of adverse events (AEs) related to the mechanism of action, including genital mycotic infections and AEs related to osmotic diuresis. Results from the preclinical and clinical studies led canagliflozin to be the first-in-class SGLT2 inhibitor approved in the United States, and support canagliflozin as a safe and effective therapeutic option across a broad range of patients with T2DM. © 2015 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals Inc. on behalf of The New York Academy of Sciences.

  18. Place of sodium-glucose co-transporter type 2 inhibitors for treatment of type 2 diabetes

    Institute of Scientific and Technical Information of China (English)

    Nasser; Mikhail

    2014-01-01

    Inhibitors of sodium-glucose co-transporter type 2(SGLT2), such as canagliflozin and dapagliflozin, are recently approved for treatment of type 2 diabetes. These agents lower blood glucose mainly by increasing urinary glucose excretion. Compared with placebo, SGLT2 inhibitors reduce hemoglobin A1c(Hb A1c) levels by an average of 0.5%-0.8% when used as monotherapy or add-on therapy. Advantages of this drug class include modest weight loss of approximately 2 kg, low risk of hypoglycemia, and decrease blood pressure of approximately 4 mm Hg systolic and 2 mm Hg diastolic. These characteristics make these agents potential add-on therapy in patients with Hb A1 c levels close to 7%-8.0%, particularly if these patients are obese, hypertensive, and/or prone for hypoglycemia. Meanwhile, these drugs are limited by high frequency of genital mycotic infections. Less common adverse effects include urinary tract infections, hypotension, dizziness, and worsening renal function. SGLT2 inhibitors should be used with caution in the elderly because of increased adverse effects, and should not be used in chronic kidney disease due to decreased or lack of efficacy and nephrotoxicity. Overall, SGLT2 inhibitors are useful addition for treatment of select groups of patients with type 2 diabetes,but their efficacy and safety need to be established in long-term clinical trials.

  19. Loss of K-Cl co-transporter KCC3 causes deafness, neurodegeneration and reduced seizure threshold.

    Science.gov (United States)

    Boettger, Thomas; Rust, Marco B; Maier, Hannes; Seidenbecher, Thomas; Schweizer, Michaela; Keating, Damien J; Faulhaber, Jörg; Ehmke, Heimo; Pfeffer, Carsten; Scheel, Olaf; Lemcke, Beate; Horst, Jürgen; Leuwer, Rudolf; Pape, Hans-Christian; Völkl, Harald; Hübner, Christian A; Jentsch, Thomas J

    2003-10-15

    K-Cl co-transporters are encoded by four homologous genes and may have roles in transepithelial transport and in the regulation of cell volume and cytoplasmic chloride. KCC3, an isoform mutated in the human Anderman syndrome, is expressed in brain, epithelia and other tissues. To investigate the physiological functions of KCC3, we disrupted its gene in mice. This severely impaired cell volume regulation as assessed in renal tubules and neurons, and moderately raised intraneuronal Cl(-) concentration. Kcc3(-/-) mice showed severe motor abnormalities correlating with a progressive neurodegeneration in the peripheral and CNS. Although no spontaneous seizures were observed, Kcc3(-/-) mice displayed reduced seizure threshold and spike-wave complexes on electrocorticograms. These resembled EEG abnormalities in patients with Anderman syndrome. Kcc3(-/-) mice also displayed arterial hypertension and a slowly progressive deafness. KCC3 was expressed in many, but not all cells of the inner ear K(+) recycling pathway. These cells slowly degenerated, as did sensory hair cells. The present mouse model has revealed important cellular and systemic functions of KCC3 and is highly relevant for Anderman syndrome.

  20. Defective membrane expression of the Na(+)-HCO(3)(-) cotransporter NBCe1 is associated with familial migraine.

    Science.gov (United States)

    Suzuki, Masashi; Van Paesschen, Wim; Stalmans, Ingeborg; Horita, Shoko; Yamada, Hideomi; Bergmans, Bruno A; Legius, Eric; Riant, Florence; De Jonghe, Peter; Li, Yuehong; Sekine, Takashi; Igarashi, Takashi; Fujimoto, Ichiro; Mikoshiba, Katsuhiko; Shimadzu, Mitsunobu; Shiohara, Masaaki; Braverman, Nancy; Al-Gazali, Lihadh; Fujita, Toshiro; Seki, George

    2010-09-07

    Homozygous mutations in SLC4A4, encoding the electrogenic Na(+)-HCO(3)(-) cotransporter NBCe1, have been known to cause proximal renal tubular acidosis (pRTA) and ocular abnormalities. In this study, we report two sisters with pRTA, ocular abnormalities, and hemiplegic migraine. Genetic analysis ruled out pathological mutations in the known genes for familial hemiplegic migraine, but identified a homozygous 65-bp deletion (Delta65bp) in the C terminus of NBCe1, corresponding to the codon change S982NfsX4. Several heterozygous members of this family also presented glaucoma and migraine with or without aura. Despite the normal electrogenic activity in Xenopus oocytes, the Delta65bp mutant showed almost no transport activity due to a predominant cytosolic retention in mammalian cells. Furthermore, coexpression experiments uncovered a dominant negative effect of the mutant through hetero-oligomer formation with wild-type NBCe1. Among other pRTA pedigrees with different NBCe1 mutations, we identified four additional homozygous patients with migraine. The immunohistological and functional analyses of these mutants demonstrate that the near total loss of NBCe1 activity in astrocytes can cause migraine potentially through dysregulation of synaptic pH.

  1. Defective membrane expression of the Na+-HCO3− cotransporter NBCe1 is associated with familial migraine

    Science.gov (United States)

    Suzuki, Masashi; Van Paesschen, Wim; Stalmans, Ingeborg; Horita, Shoko; Yamada, Hideomi; Bergmans, Bruno A.; Legius, Eric; Riant, Florence; De Jonghe, Peter; Li, Yuehong; Sekine, Takashi; Igarashi, Takashi; Fujimoto, Ichiro; Mikoshiba, Katsuhiko; Shimadzu, Mitsunobu; Shiohara, Masaaki; Braverman, Nancy; Al-Gazali, Lihadh; Fujita, Toshiro; Seki, George

    2010-01-01

    Homozygous mutations in SLC4A4, encoding the electrogenic Na+-HCO3− cotransporter NBCe1, have been known to cause proximal renal tubular acidosis (pRTA) and ocular abnormalities. In this study, we report two sisters with pRTA, ocular abnormalities, and hemiplegic migraine. Genetic analysis ruled out pathological mutations in the known genes for familial hemiplegic migraine, but identified a homozygous 65-bp deletion (Δ65bp) in the C terminus of NBCe1, corresponding to the codon change S982NfsX4. Several heterozygous members of this family also presented glaucoma and migraine with or without aura. Despite the normal electrogenic activity in Xenopus oocytes, the Δ65bp mutant showed almost no transport activity due to a predominant cytosolic retention in mammalian cells. Furthermore, coexpression experiments uncovered a dominant negative effect of the mutant through hetero-oligomer formation with wild-type NBCe1. Among other pRTA pedigrees with different NBCe1 mutations, we identified four additional homozygous patients with migraine. The immunohistological and functional analyses of these mutants demonstrate that the near total loss of NBCe1 activity in astrocytes can cause migraine potentially through dysregulation of synaptic pH. PMID:20798035

  2. Sodium-glucose co-transporter-2 inhibitors as add-on therapy to insulin: rationale and evidences.

    Science.gov (United States)

    Singh, Awadhesh Kumar; Singh, Ritu

    2016-01-01

    Sodium-glucose co-transporter-2 inhibitors (SGLT-2I) are recently approved class of anti-hyperglycaemic agents for the treatment of type 2 diabetes mellitus (T2DM). SGLT-2I inhibits renal glucose reabsorption, thereby ensuing urinary glucose excretion in a dose-dependent manner. This caloric loss and osmotic diuresis, secondary to increased urinary glucose excretion, has a unique potential to counter insulin induced weight gain and fluid retention, with little potential of hypoglycemic exacerbation. Also, as these agents act independently of insulin secretion or action, they are effective even in long-standing diabetes with depleted β-cell reserve. Improvement in insulin sensitivity, as observed with SGLT-2I can also facilitate insulin action. Furthermore, significant reduction in total daily insulin dosage and reduction of body weight as observed during combination therapy renders SGLT-2I, a near-ideal partner to insulin. This review aims to evaluate the safety and efficacy of currently used SGLT-2I as an add-on to insulin therapy in the treatment of T2DM.

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

    OpenAIRE

    Liu, Jiwen; 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 pharmacokineti...

  4. Interaction of the Sodium/Glucose Cotransporter (SGLT) 2 inhibitor Canagliflozin with SGLT1 and SGLT2.

    Science.gov (United States)

    Ohgaki, Ryuichi; Wei, Ling; Yamada, Kazunori; Hara, Taiki; Kuriyama, Chiaki; Okuda, Suguru; Ueta, Kiichiro; Shiotani, Masaharu; Nagamori, Shushi; Kanai, Yoshikatsu

    2016-07-01

    Canagliflozin, a selective sodium/glucose cotransporter (SGLT) 2 inhibitor, suppresses the renal reabsorption of glucose and decreases blood glucose level in patients with type 2 diabetes. A characteristic of canagliflozin is its modest SGLT1 inhibitory action in the intestine at clinical dosage. To reveal its mechanism of action, we investigated the interaction of canagliflozin with SGLT1 and SGLT2. Inhibition kinetics and transporter-mediated uptake were examined in human SGLT1- or SGLT2-expressing cells. Whole-cell patch-clamp recording was conducted to examine the sidedness of drug action. Canagliflozin competitively inhibited SGLT1 and SGLT2, with high potency and selectivity for SGLT2. Inhibition constant (Ki) values for SGLT1 and SGLT2 were 770.5 and 4.0 nM, respectively. (14)C-canagliflozin was suggested to be transported by SGLT2; however, the transport rate was less than that of α-methyl-d-glucopyranoside. Canagliflozin inhibited α-methyl-d-glucopyranoside-induced SGLT1- and SGLT2-mediated inward currents preferentially from the extracellular side and not from the intracellular side. Based on the Ki value, canagliflozin is estimated to sufficiently inhibit SGLT2 from the urinary side in renal proximal tubules. The Ki value for SGLT1 suggests that canagliflozin suppresses SGLT1 in the small intestine from the luminal side, whereas it does not affect SGLT1 in the heart and skeletal muscle, considering the maximal concentration of plasma-unbound canagliflozin. Similarly, SGLT1 in the kidney would not be inhibited, thereby aiding in the prevention of hypoglycemia. After binding to SGLT2, canagliflozin may be reabsorbed by SGLT2, which leads to the low urinary excretion and prolonged drug action of canagliflozin. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  5. Inhibition of Sodium-GlucoseCotransporter 2 with Dapagliflozin in Han: SPRD Rats with Polycystic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Daniel Rodriguez

    2015-12-01

    Full Text Available Background/Aims: Dapagliflozin (DAPA is a selective inhibitor of the sodium-glucose cotransporter 2 (SGLT2 which induces glucosuria and osmotic diuresis. The therapeutic effect of DAPA in progressing stages of polycystic kidney disease (PKD has not been studied. Methods: We examined the effect of DAPA in the Han: SPRD rat model of PKD. DAPA (10 mg/kg/day or vehicle (VEH was administered orally via gavage to 5 week old male Han: SPRD (Cy/+ or control (+/+ rats (n = 8-9 per group for 5 weeks. Blood and urine were collected at baseline and after 2.5 and 5 weeks of treatment to assess renal function and albuminuria. At the end of the treatment, rats were sacrificed and kidneys were excised for histological analysis. Results: After 5 weeks of treatment, DAPA-treated Cy/+ and +/+ rats exhibited significantly higher glucosuria, water intake and urine output than VEH-treated rats. DAPA-treated Cy/+ rats also exhibited significantly higher clearances for creatinine and BUN and less albuminuria than VEH-treated Cy/+ rats. DAPA treatment for 5 weeks resulted in a significant increase of the kidney weight in Cy/+ rats but no change in cyst growth. The degree of tubular epithelial cell proliferation, macrophage infiltration and interstitial fibrosis was also similar in DAPA-and VEH-treated Cy/+ rats. Conclusion: The induction of glucosuria with the SGLT2-specific inhibitor DAPA was associated with improved renal function and decreased albuminuria, but had no effect on cyst growth in Cy/+ rats. Overall the beneficial effects of DAPA in this PKD model were weaker than the previously described effects of the combined SGLT1/2 inhibitor phlorizin.

  6. Cotransport of bismerthiazol and montmorillonite colloids in saturated porous media.

    Science.gov (United States)

    Shen, Chongyang; Wang, Hong; Lazouskaya, Volha; Du, Yichun; Lu, Weilan; Wu, Junxue; Zhang, Hongyan; Huang, Yuanfang

    2015-01-01

    While bismerthiazol [N,N'-methylene-bis-(2-amino-5-mercapto-1,3,4-thiadiazole)] is one of the most widely used bactericides, the transport of bismerthiazol in subsurface environments is unclear to date. Moreover, natural colloids are ubiquitous in the subsurface environments. The cotransport of bismerthiazol and natural colloids has not been investigated. This study conducted laboratory column experiments to examine the transport of bismerthiazol in saturated sand porous media both in the absence and presence of montmorillonite colloids. Results show that a fraction of bismerthiazol was retained in sand and the retention was higher at pH7 than at pH 4 and 10. The retention did not change with ionic strength. The retention was attributed to the complex of bismerthiazol with metals/metal oxides on sand surfaces through ligand exchange. The transport of bismerthiazol was enhanced with montmorillonite colloids copresent in the solutions and, concurrently, the transport of montmorillonite colloids was facilitated by the bismerthiazol. The transport of montmorillonite colloids was enhanced likely because the bismerthiazol and the colloids competed for the attachment/adsorption sites on collector surfaces and the presence of bismerthiazol changed the Derjaguin-Landau-Verwey-Overbeek (DLVO) interaction energies between colloids and collectors. The transport of bismerthiazol was inhibited if montmorillonite colloids were pre-deposited in sand because bismerthiazol could adsorb onto the colloid surfaces. The adsorbed bismerthiazol could be co-remobilized with the colloids from primary minima by decreasing ionic strength. Whereas colloid-facilitated transport of pesticides has been emphasized, our study implies that transport of colloids could also be facilitated by the presence of pesticides. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Absence of Na +/sugar cotransport activity in Barrett's metaplasia

    Institute of Scientific and Technical Information of China (English)

    Lisa J Murray; Owen Tully; David S Rudolph; Marysue Whitby; Mary C Valenzano; Giancarlo Mercogliano; James J Thornton; James M Mullin

    2008-01-01

    AIM:To evaluate the presence of Na+-dependent,active,sugar transport in Barrett's epithelia as an intestinal biomarker,based on the well-documented,morphological intestinal phenotype of Barrett's esophagus (BE).METHODS:We examined uptake of the nonmeta-bolizable glucose analogue,alpha-methyl-D-glucoside (AMG),a substrate for the entire sodium glucose cotransporter (SGLT) family of transport proteins.During upper endoscopy,patients with BE or with uncomplicated gastroesophageal reflux disease (GERD)allowed for duodenal,gastric fundic,and esophageal mucosal biopsies to be taken.Biopsies were incubated in bicarbonate-buffered saline (KRB) containing 0.1 mmol/L 14C-AMG for 60 min at 20℃.Characterized by abundant SGLT,duodenum served as a positive control while gastric fundus and normal esophagus,known to lack SGLT,sewed as negative controls.RESULTS:Duodenal biopsies accumulated 249.84± 35.49 (SEM) picomoles AMG/μg DNA (n = 12),gastric fundus biopsies 36.20 ± 6.62 (n = 12),normal esophagus 12.10 ± 0.59 (n = 3) and Barrett's metaplasia 29.79 ± 5.77 (n = 8).There was a statistical difference (P<0.01) between biopsies from duodenum and each other biopsy site but there was no statistically significant difference between normal esophagus and BE biopsies.0.5 mmol/L phlorizin (PZ) inhibited AMG uptake into duodenal mucosa by over 89%,but had no significant effect on AMG uptake into gastric fundus,normal esophagus,or Barrett's tissue.In the absence of Na+ (all Na+ salts replaced by Li+ salts),AMG uptake in duodenum was decreased by over 90%,while uptake into gastric,esophageal or Barrett's tissue was statistically unaffected.CONCLUSION:Despite the intestinal enterocyte phenotype of BE,Na+-dependent,sugar transport activity is not present in bhese cells.

  8. Characterization of a novel phosphorylation site in the sodium–chloride cotransporter, NCC

    Science.gov (United States)

    Rosenbaek, L L; Assentoft, M; Pedersen, N B; MacAulay, N; Fenton, R A

    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 antibodies targeting pS124-NCC demonstrated a band of 160 kDa in the kidney cortex, but not medulla, which was preabsorbed by a corresponding phosphorylated peptide. Confocal microscopy with kidney tubule segment-specific markers localized pS124-NCC to all distal convoluted tubule cells. Double immunogold electron microscopy demonstrated that pS124-NCC co-localized with total NCC in the apical plasma membrane of distal convoluted tubule cells and intracellular vesicles. Acute treatment of Munich–Wistar rats or vasopressin-deficient Brattleboro rats with the vasopressin type 2 receptor-specific agonist dDAVP significantly increased pS124-NCC abundance, with no changes in total NCC plasma membrane abundance. pS124-NCC levels also increased in abundance in rats after stimulation of the renin–angiotensin–aldosterone system by dietary low sodium intake. In contrast to other NCC phosphorylation sites, the STE20/SPS1-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 mTOR/FRAP) showed weak but significant phosphorylation activity at S124. In oocytes, 36Cl uptake studies combined with biochemical analysis showed decreased activity of plasma membrane-associated NCC when replacing S124 with alanine (A) or aspartic acid (D). In novel tetracycline-inducible MDCKII-NCC cell lines, S124A and S124D mutants were able to traffic to the plasma membrane similarly to wildtype NCC. PMID:22966159

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

    Science.gov (United States)

    Rosenbaek, L L; Assentoft, M; Pedersen, N B; MacAulay, N; Fenton, R A

    2012-12-01

    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 antibodies targeting pS124-NCC demonstrated a band of 160 kDa in the kidney cortex, but not medulla, which was preabsorbed by a corresponding phosphorylated peptide. Confocal microscopy with kidney tubule segment-specific markers localized pS124-NCC to all distal convoluted tubule cells. Double immunogold electron microscopy demonstrated that pS124-NCC co-localized with total NCC in the apical plasma membrane of distal convoluted tubule cells and intracellular vesicles. Acute treatment of Munich-Wistar rats or vasopressin-deficient Brattleboro rats with the vasopressin type 2 receptor-specific agonist dDAVP significantly increased pS124-NCC abundance, with no changes in total NCC plasma membrane abundance. pS124-NCC levels also increased in abundance in rats after stimulation of the renin-angiotensin-aldosterone system by dietary low sodium intake. In contrast to other NCC phosphorylation sites, the STE20/SPS1-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 mTOR/FRAP) showed weak but significant phosphorylation activity at S124. In oocytes, (36)Cl uptake studies combined with biochemical analysis showed decreased activity of plasma membrane-associated NCC when replacing S124 with alanine (A) or aspartic acid (D). In novel tetracycline-inducible MDCKII-NCC cell lines, S124A and S124D mutants were able to traffic to the plasma membrane similarly to wildtype NCC.

  10. Expression and phosphorylation of the Na+-Cl- cotransporter NCC in vivo is regulated by dietary salt, potassium, and SGK1.

    Science.gov (United States)

    Vallon, Volker; Schroth, Jana; Lang, Florian; Kuhl, Dietmar; Uchida, Shinichi

    2009-09-01

    The Na-Cl cotransporter NCC is expressed in the distal convoluted tubule, activated by phosphorylation, and has been implicated in renal NaCl and K(+) homeostasis. The serum and glucocorticoid inducible kinase 1 (SGK1) contributes to renal NaCl retention and K(+) excretion, at least in part, by stimulating the epithelial Na(+) channel and Na(+)-K(+)-ATPase in the downstream segments of aldosterone-sensitive Na(+)/K(+) exchange. In this study we confirmed in wild-type mice (WT) that dietary NaCl restriction increases renal NCC expression and its phosphorylation at Thr(53), Thr(58), and Ser(71), respectively. This response, however, was attenuated in mice lacking SGK1 (Sgk1(-/-)), which may contribute to impaired NaCl retention in those mice. Total renal NCC expression and phosphorylation at Thr(53), Thr(58), and Ser(71) in WT were greater under low- compared with high-K(+) diet. This finding is consistent with a regulation of NCC to modulate Na(+) delivery to downstream segments of Na(+)/K(+) exchange, thereby modulating K(+) excretion. Dietary K(+)-dependent variation in renal expression of total NCC and phosphorylated NCC were not attenuated in Sgk1(-/-) mice. In fact, high-K(+) diet-induced NCC suppression was enhanced in Sgk1(-/-) mice. The hyperkalemia induced in Sgk1(-/-) mice by a high-K(+) diet may have augmented NCC suppression, thereby increasing Na(+) delivery and facilitating K(+) excretion in downstream segments of impaired Na(+)/K(+) exchange. In summary, changes in NaCl and K(+) intake altered NCC expression and phosphorylation, an observation consistent with a role of NCC in NaCl and K(+) homeostasis. The two maneuvers dissociated plasma aldosterone levels from NCC expression and phosphorylation, implicating additional regulators. Regulation of NCC expression and phosphorylation by dietary NaCl restriction appears to involve SGK1.

  11. 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.

  12. Prolactin increases hepatic Na+/taurocholate co-transport activity and messenger RNA post partum.

    Science.gov (United States)

    Ganguly, T C; Liu, Y; Hyde, J F; Hagenbuch, B; Meier, P J; Vore, M

    1994-01-01

    We have shown that Na+/taurocholate co-transport activity is decreased in pregnancy, but rebounds post partum relative to non-pregnant controls, and that activity can be increased by treatment with ovine prolactin [Ganguly, Hyde and Vore (1993) J. Pharmacol. Exp. Ther. 267, 82-87]. To determine the basis for these effects, Na+/taurocholate co-transport was determined in purified basolateral liver plasma-membrane (bLPM) vesicles and compared with steady-state mRNA levels encoding the Na+/taurocholate-co-transporting polypeptide (Ntcp) in non-pregnant controls, pregnant rats (19-20 days pregnant), rats post partum (48 h post partum) and rats post partum treated with bromocriptine to inhibit prolactin secretion. Na+/taurocholate co-transport activity (nmol/5 s per mg of protein) in bLPM was decreased from 10.4 +/- 1.8 in non-pregnant controls to 7.9 +/- 0.6 in bLPM in pregnant rats, but rebounded to 17.5 +/- 1.3 post partum; treatment of rats post partum with bromocriptine to inhibit prolactin secretion decreased activity to 14.1 +/- 0.9. Northern and slot-blot analyses revealed similar changes in mRNA for Ntcp, so that a positive correlation was observed between Na+/taurocholate co-transport activity and Ntcp mRNA. Furthermore, treatment of ovariectomized rats with ovine prolactin increased Ntcp mRNA 10-fold compared with solvent-treated controls, consistent with the 2-fold increase in Vmax, for Na+/taurocholate co-transport in isolated hepatocytes. These data are the first to demonstrate endogenous physiological regulation by prolactin of Ntcp mRNA in parallel with Na+/taurocholate co-transport activity. Images Figure 2 PMID:7945260

  13. 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.

  14. Conformational Dynamics of hSGLT1 during Na+/Glucose Cotransport

    DEFF Research Database (Denmark)

    Loo, D. D.; Hirayama, B. A.; Karakossian, M. H.

    2006-01-01

    . voltage (Q-V) and fluorescence vs. voltage ( F-V) relations (for medium and slow components) obeyed Boltzmann relations with similar parameters: z (apparent valence of voltage sensor) 1; and V0.5 (midpoint voltage) between -15 and -40 mV. Sugar induced an inward current (Na+/glucose cotransport......This study examines the conformations of the Na+/glucose cotransporter (SGLT1) during sugar transport using charge and fluorescence measurements on the human SGLT1 mutant G507C expressed in Xenopus oocytes. The mutant exhibited similar steady-state and presteady-state kinetics as wild-type SGLT1...

  15. 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.

  16. Renal angiomyolipoma

    DEFF Research Database (Denmark)

    Holm-Nielsen, P; Sørensen, Flemming Brandt

    1988-01-01

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

  17. 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

  18. Renal cancer

    NARCIS (Netherlands)

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

    2007-01-01

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

  19. Renal fallure

    Institute of Scientific and Technical Information of China (English)

    1992-01-01

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

  20. 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

  1. Renal cancer

    NARCIS (Netherlands)

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

    2007-01-01

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

  2. 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...

  3. Alternative splice variant of the thiazide-sensitive NaCl cotransporter

    DEFF Research Database (Denmark)

    Tutakhel, Omar A Z; Jeleń, Sabina; Valdez-Flores, Marco;

    2016-01-01

    The thiazide-sensitive NaCl cotransporter (NCC) is an important pharmacological target in the treatment of hypertension. Human SLC12A3 gene, encoding NCC, gives rise to three isoforms. Only the 3(rd) isoform has been extensively investigated. The aim of the present study was, therefore, to establ...

  4. 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...

  5. RasGRP1 stimulation enhances ubiquitination and endocytosis of the sodium-chloride cotransporter.

    NARCIS (Netherlands)

    Ko, B.; Kamsteeg, E.J.; Cooke, L.L.; Moddes, L.N.; Deen, P.M.T.; Hoover, R.S.

    2010-01-01

    The sodium-chloride cotransporter (NCC) is the principal salt-absorptive pathway in the distal convoluted tubule. Recently, we described a novel pathway of NCC regulation in which phorbol esters (PE) stimulate Ras guanyl-releasing protein 1 (RasGRP1), triggering a cascade ultimately activating ERK1/

  6. Na+/D-glucose cotransporter based bilayer lipid membrane sensor for D-glucose.

    Science.gov (United States)

    Sugao, N; Sugawara, M; Minami, H; Uto, M; Umezawa, Y

    1993-02-15

    A new type of amperometric blosensor for glucose was fabricated using a Na+/D-glucose cotransporter as the signal-transducing sensory element that exploits the D-glucose-triggered Na+ ion current through bilayer lipid membranes (BLMs). The planar BLM was formed by the folding method across a small aperture of a thin Teflon film. The Na+/D-glucose cotransporter, isolated and purified from small intestinal brush border membrane of guinea pigs, was embedded into BLMs through proteoliposomes. The number of the protein molecules thus incorporated in the present sensing membrane was estimated to be ca. 10(7). The sensor response was measured as an ionic current through the BLM arising from cotransported Na+ ion flux under a constant applied potential and was only induced by D-glucose above 10(-9) M, but not by the other monosaccharides except for D-galactose. The effect of applied potentials, Na+ and K+ ion concentrations, and the addition of a competitive inhibitor, phlorizin, were scrutinized to characterize the sensor output. The results were briefly discussed in terms of the potential use of the Na+/D-glucose cotransporter as a sensory element for D-glucose.

  7. Choroid plexus potassium cotransport: modulation by osmotic stress and external potassium.

    Science.gov (United States)

    Keep, R F; Xiang, J

    1995-06-01

    The choroid plexuses are involved in CSF secretion and CSF K homeostasis. This study examines the potential role of K cotransport in these two processes using isolated rat lateral ventricle choroid plexuses. Bumetanide-sensitive 86Rb influx and efflux were measured to assess the response of K cotransport to changes in media osmolality and K concentration. Alterations in osmolality had no effect on K uptake (in the presence or absence of bumetanide). However, the efflux rate constant for K was 0.29 +/- 0.02, 0.44 +/- 0.04, and 0.84 +/- 0.06 min-1 in 240, 300, and 424 mOsm/kg solutions, respectively (p brain shrinkage during hyperosmotic stress if the cotransporter is present on the apical membrane. The rate of bumetanide-sensitive efflux was unaffected by changes in external [K]. However, the rate of K uptake (measured on return to normal [K] media) was reduced gradually by exposure to low [K]. It was 21 +/- 1, 19 +/- 3, 13 +/- 2, and 6 +/- 1 nmol/mg/min after 0, 10, 30, and 60-min exposure to 1 mM K. Sixty minutes of exposure to 1 mM [K] abolished the bumetanide-sensitive K uptake present in plexuses exposed continually to normal media. This modulation of K cotransport by external [K] may be important in CSF K homeostasis by limiting K loss from the CSF if CSF [K] is low.

  8. RasGRP1 stimulation enhances ubiquitination and endocytosis of the sodium-chloride cotransporter.

    NARCIS (Netherlands)

    Ko, B.; Kamsteeg, E.J.; Cooke, L.L.; Moddes, L.N.; Deen, P.M.T.; Hoover, R.S.

    2010-01-01

    The sodium-chloride cotransporter (NCC) is the principal salt-absorptive pathway in the distal convoluted tubule. Recently, we described a novel pathway of NCC regulation in which phorbol esters (PE) stimulate Ras guanyl-releasing protein 1 (RasGRP1), triggering a cascade ultimately activating

  9. Evidence for an apical Na-Cl cotransporter involved in ion uptake in a teleost fish

    Science.gov (United States)

    Hiroi, J.; Yasumasu, S.; McCormick, S.D.; Hwang, P.-P.; Kaneko, T.

    2008-01-01

    Cation-chloride cotransporters, such as the Na+/K +/2Cl- cotransporter (NKCC) and Na+/Cl - cotransporter (NCC), are localized to the apical or basolateral plasma membranes of epithelial cells and are involved in active ion absorption or secretion. The objectives of this study were to clone and identify 'freshwater-type' and 'seawater-type' cation-chloride cotransporters of euryhaline Mozambique tilapia (Oreochromis mossambicus) and to determine their intracellular localization patterns within mitochondria-rich cells (MRCs). From tilapia gills, we cloned four full-length cDNAs homologous to human cation-chloride cotransporters and designated them as tilapia NKCC1a, NKCC1b, NKCC2 and NCC. Out of the four candidates, the mRNA encoding NKCC1a was highly expressed in the yolk-sac membrane and gills (sites of the MRC localization) of seawater-acclimatized fish, whereas the mRNA encoding NCC was exclusively expressed in the yolk-sac membrane and gills of freshwater-acclimatized fish. We then generated antibodies specific for tilapia NKCC1a and NCC and conducted whole-mount immunofluorescence staining for NKCC1a and NCC, together with Na+/K+-ATPase, cystic fibrosis transmembrane conductance regulator (CFTR) and Na+/H+ exchanger 3 (NHE3), on the yolk-sac membrane of tilapia embryos acclimatized to freshwater or seawater. The simultaneous quintuple-color immunofluorescence staining allowed us to classify MRCs clearly into four types: types I, II, III and IV. The NKCC1a immunoreactivity was localized to the basolateral membrane of seawater-specific type-IV MRCs, whereas the NCC immunoreactivity was restricted to the apical membrane of freshwater-specific type-II MRCs. Taking account of these data at the level of both mRNA and protein, we deduce that NKCC1a is the seawater-type cotransporter involved in ion secretion by type-IV MRCs and that NCC is the freshwater-type cotransporter involved in ion absorption by type-II MRCs. We propose a novel ion-uptake model by MRCs in

  10. 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.

  11. 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.

  12. The Na+/PO4 cotransporter SLC20A1 gene labels distinct restricted subdomains of the developing pronephros in Xenopus and zebrafish embryos.

    Science.gov (United States)

    Nichane, Massimo; Van Campenhout, Claude; Pendeville, Hélène; Voz, Marianne L; Bellefroid, Eric J

    2006-10-01

    The embryonic pronephric kidneys of Xenopus and zebrafish serve as models to study vertebrate nephrogenesis. Recently, multiple subdomains within the Xenopus pronephros have been defined based on the expression of several transport proteins. In contrast, very few studies on the expression of renal transporters have been conducted in zebrafish. We have recently shown that the anterior and posterior segments of the zebrafish pronephric duct may correspond to the proximal tubule and distal tubule/duct compartments of the Xenopus and higher vertebrate pronephros, respectively. Here, we report the embryonic expression pattern of the Na(+)/PO(4) cotransporter SLC20A1 (PiT1/Glvr-1) gene encoding a type III sodium-dependent phosphate cotransporter in Xenopus and zebrafish. In Xenopus, SLC20A1 mRNA is expressed in the somitic mesoderm and lower level of expression is detected in the neural tube, eye, and neural crest cells. From stage 25, SLC20A1 is also detectable in the developing pronephros where expression is restricted to the late portion of the distal pronephric tubules. In zebrafish, SLC20A1 is transcribed from mid-somitogenesis in the anterior part of the pronephros where its expression corresponds to the rostral portion of the expression of other proximal tubule-specific markers. Outside the pronephros, lower level of SLC20A1 expression is also observed in the posterior cardinal and caudal veins. Based on the SLC20A1 expression domain and that of other transporters, four segments have been defined within the zebrafish pronephros. Together, our data reveal that the zebrafish and Xenopus pronephros have non-identical proximo-distal organizations.

  13. Preliminary X-ray diffraction analysis of the cytoplasmic N-terminal domain of the Na/HCO{sub 3} cotransporter NBCe1-A

    Energy Technology Data Exchange (ETDEWEB)

    Gill, Harindarpal S., E-mail: hs.gill@yale.edu; Boron, Walter F. [Department of Cellular and Molecular Physiology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520 (United States)

    2006-06-01

    The N-terminal, cytoplasmic domain of the Na{sup +}-coupled HCO{sub 3} cotransporter NBCe1-A crystallizes in the trigonal space group P3{sub 1}21 or P3{sub 1} with pseudo P3{sub 1}21 symmetry and diffracts X-rays to 3.0 Å resolution. The crystal packing demonstrates a domain-swap mechanism for dimerization. The N-terminal cytoplasmic domain of the Na{sup +}-coupled HCO cotransporter NBCe1-A (NtNBCe1) has been linked with proximal renal tubular acidosis. In a previous purification study of recombinant NtNBCe1, crystal growth at a suboptimal protein concentration (<1 mg ml{sup −1}) yielded small single diamond-shaped crystals that diffracted poorly. In the present study, by increasing the protein concentration 50-fold, the crystal size was doubled and robustness was also improved. Crystal annealing made the crystals suitable for X-ray diffraction. The crystals either belong to space group P3{sub 1}21 or P3{sub 1} with pseudo P3{sub 1}21 symmetry, with unit-cell parameters a = 51.7, b = 51.7, c = 200.6 Å, α = β = 90, γ = 120°, and diffract X-rays to 3.0 Å resolution. The calculated Matthews number is 1.9 Å{sup 3} Da{sup −1}, with two monomers of molecular weight ∼83 kDa in the asymmetric unit. The molecular- replacement packing solution shows that the molecules form dimers by a domain-swapping mechanism.

  14. Downregulation of NCC and NKCC2 cotransporters by kidney-specific WNK1 revealed by gene disruption and transgenic mouse models.

    Science.gov (United States)

    Liu, Zhen; Xie, Jian; Wu, Tao; Truong, Thao; Auchus, Richard J; Huang, Chou-Long

    2011-03-01

    WNK1 (with-no-lysine[K]-1) is a protein kinase of which mutations cause a familial hypertension and hyperkalemia syndrome known as pseudohypoaldosteronism type 2 (PHA2). Kidney-specific (KS) WNK1 is an alternatively spliced form of WNK1 kinase missing most of the kinase domain. KS-WNK1 downregulates the Na(+)-Cl(-) cotransporter NCC by antagonizing the effect of full-length WNK1 when expressed in Xenopus oocytes. The physiological role of KS-WNK1 in the regulation of NCC and potentially other Na(+) transporters in vivo is unknown. Here, we report that mice overexpressing KS-WNK1 in the kidney exhibited renal Na(+) wasting, elevated plasma levels of angiotensin II and aldosterone yet lower blood pressure relative to wild-type littermates. Immunofluorescent staining revealed reduced surface expression of total and phosphorylated NCC and the Na(+)-K(+)-2Cl(-) cotransporter NKCC2 in the distal convoluted tubule and the thick ascending limb of Henle's loop, respectively. Conversely, mice with targeted deletion of exon 4A (the first exon for KS-WNK1) exhibited Na(+) retention, elevated blood pressure on a high-Na(+) diet and increased surface expression of total and phosphorylated NCC and NKCC2 in respective nephron segments. Thus, KS-WNK1 is a negative regulator of NCC and NKCC2 in vivo and plays an important role in the control of Na(+) homeostasis and blood pressure. These results have important implications to the pathogenesis of PHA2 with WNK1 mutations.

  15. Effect of Sodium Glucose Cotransporter 2 Inhibitors With Low SGLT2/SGLT1 Selectivity on Circulating Glucagon-Like Peptide 1 Levels in Type 2 Diabetes Mellitus.

    Science.gov (United States)

    Takebayashi, Kohzo; Inukai, Toshihiko

    2017-09-01

    Sodium glucose cotransporter 2 (SGLT2) inhibitors are a new class of antidiabetic drugs that improve glycemic control by inhibiting reabsorption of glucose filtered through the renal glomerulus. Use of drugs in this class has increased because of their effect of decreasing body weight and a low risk for hypoglycemia, in addition to a relatively strong glucose-lowering effect. SGLT2 inhibitors such as canagliflozin and sotagliflozin (a SGLT1/SGLT2 dual inhibitor) also have a mild or moderate intestinal and renal SGLT1 inhibitory effect because of their relatively weak selectivity for SGLT2 over SGLT1. Recent evidence shows that these SGLT2 inhibitors with low SGLT2/SGLT1 selectivity elevate the level of circulating glucagon like peptide-1 (GLP-1), an incretin hormone that promotes insulin secretion in pancreatic β cells. This effect probably occurs partly via inhibition of intestinal SGLT1, and the elevation of active GLP-1 levels is especially apparent when these drugs are co-administered with dipeptidyl peptidase 4 (DPP4) inhibitors. These findings suggest that a combination of canagliflozin or sotagliflozin and a DPP4 inhibitor can provide a beneficial effect associated with elevation of circulating active GLP-1 and may serve as a treatment for patients with type 2 diabetes.

  16. Thiazide diuretics directly induce osteoblast differentiation and mineralized nodule formation by interacting with a sodium chloride co-transporter in bone.

    Science.gov (United States)

    Dvorak, Melita M; De Joussineau, Cyrille; Carter, D Howard; Pisitkun, Trairak; Knepper, Mark A; Gamba, Gerardo; Kemp, Paul J; Riccardi, Daniela

    2007-09-01

    Thiazide diuretics are used worldwide as a first-choice drug for patients with uncomplicated hypertension. In addition to their antihypertensive effect, thiazides increase bone mineral density and reduce the prevalence of fractures. Traditionally, these effects have been attributed to increased renal calcium reabsorption that occurs secondary to the inhibition of the thiazide-sensitive sodium chloride cotransporter (NCC) in the distal tubule. The aim of the current study was to determine whether thiazides exert a direct bone-forming effect independent of their renal action. We found that the osteoblasts of human and rat bone also express NCC, suggesting that these bone-forming cells may be an additional target for thiazides. In vitro, NCC protein was virtually absent in proliferating human and fetal rat osteoblasts, whereas its expression dramatically increased during differentiation. Thiazides did not affect osteoblast proliferation, but directly stimulated the production of the osteoblast differentiation markers runt-related transcription factor 2 (runx2) and osteopontin. Using overexpression/knockdown studies in fetal rat calvarial cells, we show that thiazides increase the formation of mineralized nodules, but loop diuretics do not. Overall, our study demonstrates that thiazides directly stimulate osteoblast differentiation and bone mineral formation independent of their effects in the kidney. Therefore, in addition to their use as antihypertensive drugs, our results suggest that thiazides may find a role in the prevention and treatment of osteoporosis.

  17. Activation of Renal (Pro)Renin Receptor Contributes to High Fructose-Induced Salt Sensitivity.

    Science.gov (United States)

    Xu, Chuanming; Lu, Aihua; Lu, Xiaohan; Zhang, Linlin; Fang, Hui; Zhou, Li; Yang, Tianxin

    2017-02-01

    A high-fructose diet is shown to induce salt-sensitive hypertension, but the underlying mechanism largely remains unknown. The major goal of the present study was to test the role of renal (pro)renin receptor (PRR) in this model. In Sprague-Dawley rats, high-fructose intake increased renal expression of full-length PRR, which were attenuated by allopurinol. High-fructose intake also upregulated renal mRNA and protein expression of sodium/hydrogen exchanger 3 and Na/K/2Cl cotransporter, as well as in vivo Na/K/2Cl cotransporter activity, all of which were nearly completely blocked by a PRR decoy inhibitor PRO20 or allopurinol treatment. Parallel changes were observed for indices of intrarenal renin-angiotensin-system including renal and urinary renin and angiotensin II levels. Radiotelemetry demonstrated that high-fructose or a high-salt diet alone did not affect mean arterial pressure, but the combination of the 2 maneuvers induced a ≈10-mm Hg increase of mean arterial pressure, which was blunted by PRO20 or allopurinol treatment. In cultured human kidney 2 cells, both fructose and uric acid increased protein expression of soluble PRR in a time- and dose-dependent manner; fructose-induced PRR upregulation was inhibited by allopurinol. Taken together, our data suggest that fructose via uric acid stimulates renal expression of PRR/soluble PRR that stimulate sodium/hydrogen exchanger 3 and Na/K/2Cl cotransporter expression and intrarenal renin-angiotensin system to induce salt-sensitive hypertension.

  18. Renal teratogens.

    Science.gov (United States)

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

    2014-09-01

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

  19. Sarcoidose renal

    Directory of Open Access Journals (Sweden)

    AQUINO MARIA ENEDINA CLAUDINO DE

    2001-01-01

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

  20. Renal failure

    Institute of Scientific and Technical Information of China (English)

    1993-01-01

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

  1. 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™.

  2. Use of sodium-glucose cotransporter 2 inhibitors in older patients with type 2 diabetes mellitus.

    Science.gov (United States)

    Kambara, Takahiro; Shibata, Rei; Osanai, Hiroyuki; Nakashima, Yoshihito; Asano, Hiroshi; Sakai, Kazuyoshi; Murohara, Toyoaki; Ajioka, Masayoshi

    2017-09-01

    Sodium-glucose cotransporter 2 (SGLT2) inhibitors are antidiabetic agents that act on the proximal renal tubules to lower blood glucose levels by inhibiting glucose reabsorption and promoting urinary glucose excretion. The present study assessed the long-term use of SGLT2 inhibitors in older patients with diabetes. A total of 117 older patients with type 2 diabetes who were given SGLT2 inhibitors were enrolled from April 2014 to March 2016. The mean age of the patients was 73.7 ± 10.0 years. During the follow-up period (mean 289.3 days), there was no event associated with oral administration of SGLT2 inhibitors. These drugs significantly lowered fasting blood glucose and glycosylated hemoglobin levels at 6 months, and did not affect the creatinine level, blood urea nitrogen/creatinine ratio or estimated glomerular filtration rate during treatment. Although the treatment significantly increased hemoglobin and hematocrit levels, it did not affect the ultrasonographically determined diameter of the inferior vena cava, and no signs of intravascular collapse were observed. Changes in brain natriuretic peptide levels during the follow-up period were assessed in 78 patients with a brain natriuretic peptide level exceeding the normal upper limit before treatment with SGLT2 inhibitors. The brain natriuretic peptide levels significantly decreased after 6 months of treatment. In older Japanese patients with diabetes, treatment with SGLT2 inhibitors for 6 months exerted a favorable hypoglycemic effect, while no sign of dehydration was observed. Geriatr Gerontol Int 2017; ••: ••-••. © 2017 Japan Geriatrics Society.

  3. 钠-葡萄糖协同转运蛋白与糖尿病%Sodium-glucose cotransporters and diabetes

    Institute of Scientific and Technical Information of China (English)

    朱蕾; 杨怡

    2011-01-01

    Sodium-glucose cotransporters (SGLTs) are carrier proteins which can help glucose to enter eukaryotic cells.Among them,the SGLT1 and SGLT2 are the most important ones and play major roles in dietary glucose absorption and renal glucose reabsorption respectively.In the state of diabetes,increased expression of SGLT1 in the intestine will enhance the glucose absorption and therefore accelerate hyperglycemia.Through decreasing salivary secretion,increased expression of SGLT1 in salivary glands will promote the development of diabetic oral complications.Meanwhile the expression of SGLT1 and SGLT2 in kidney are also increased which will enhance the glucose reabsorption and therefore accelerate hyperglycemia and deteriorate dial.tic nephropathy.At present,selective inhibitor of SGLT2 is becoming a new drug for diabetes.%钠-葡萄糖协同转运蛋白(SGLTs)在葡萄糖的跨细胞转运中发挥重要作用,其中SGLT1负责膳食葡萄糖的吸收,SGLT2负责肾脏中葡萄糖的重吸收.在糖尿病状态下,肠道SGLT1表达的增加将促进葡萄糖的吸收,从而加重了高血糖,而涎腺导管SGLT1表达的增加则使唾液分泌减少,促进了口腔并发症的发生;肾脏SGLT2和SGLT1表达的增加使葡萄糖的重吸收增加,加重了高血糖,并促进了糖尿病肾病的进展.目前,选择性SLGT2抑制剂已经成为新型的抗糖尿病药物.

  4. Renal failure

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

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

  5. Renal failure

    Institute of Scientific and Technical Information of China (English)

    1995-01-01

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

  6. Renal failure

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

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

  7. 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.

  8. 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

  9. 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 na

  10. Impaired renal H+ secretion and NH3 production in mineralocorticoid-deficient glucocorticoid-replete dogs.

    Science.gov (United States)

    Hulter, H N; Ilnicki, L P; Harbottle, J A; Sebastian, A

    1977-02-01

    When the administration of exogenous mineralocorticoid hormones was discontinued in adrenalectomized dogs maintained on glucocorticoid, net acid excretion decreased due largely to a reduction in urinary ammonium excretion (UNH4+V), and hyperchloremic hyperkalemic metabolic acidosis occurred and persisted. The reduction in UNH4+V was not associated with an increase in urine pH (UpH) or a decrease in urine flow, but correlated with the severity of hyperkalemia and was mitigated by dietary potassium restriction. UpH decreased to values as low as 5.3. During acidosis, UpH varied directly with UNH4+V, but in relation to UNH4+V, UpH exceeded that in acid-fed mineralocorticoid-replete dogs. Extrapolated to UNH4+V=0, however, UpH was not significantly different in the two groups (5.27 vs. 5.44). When distal delivery of sodium was increased by infusion of sodium phosphate, titratable acid excretion increased in both groups but pateaued at lower rates in the mineralocorticoid-deficient dogs. These results suggest that in mineralocorticoid-deficient dogs, renal ammonia production is diminished, in part due to potassium retention and hyperkalemia; renal hydrogen ion secretory capacity is reduced even when sodium and buffer delivery to the distal nephron is not reduced; and the ability of the kidney to generate normally steep urine-to-blood hydrogen ion concentration gradients is unimpaired.

  11. 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

    and placed in a perfusion chamber in which the solution facing the retinal membrane could be changed rapidly. Two types of experiments were performed: Changes in cell water volume were measured by self-quenching of the fluorescent dye Calcein, and changes in intracellular pH were measured ratiometrically......) 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....

  12. Antidiuretic effect of hydrochlorothiazide in lithium-induced nephrogenic diabetes insipidus is associated with upregulation of aquaporin-2, Na-Cl co-transporter, and epithelial sodium channel.

    Science.gov (United States)

    Kim, Gheun-Ho; Lee, Jay Wook; Oh, Yun Kyu; Chang, Hye Ryun; Joo, Kwon Wook; Na, Ki Young; Earm, Jae-Ho; Knepper, Mark A; Han, Jin Suk

    2004-11-01

    Thiazides have been used in patients with nephrogenic diabetes insipidus (NDI) to decrease urine volume, but the mechanism by which it produces the paradoxic antidiuretic effect remains unclear. Previous studies have reported that downregulation of aquaporin-2 (AQP2) is important for the development of lithium-induced (Li-induced) polyuria and that hydrochlorothiazide (HCTZ) increases renal papillary osmolality and Na(+) concentration in Brattleboro rats. For elucidating the molecular basis of the antidiuretic action of HCTZ in diabetes insipidus, whether administration of HCTZ may affect the expression of AQP2 and major renal Na(+) transporters in Li-induced NDI rats was investigated, using semiquantitative immunoblotting and immunohistochemistry. After feeding male Sprague-Dawley rats Li chloride-containing rat diet for 4 wk, HCTZ or vehicle was infused subcutaneously via osmotic minipump. Urine output was significantly decreased by HCTZ treatment, whereas it was not changed in vehicle-treated rats. Urine osmolality was also higher in HCTZ-treated rats than in vehicle-treated rats. Semiquantitative immunoblotting using whole-kidney homogenates revealed that HCTZ treatment caused a significant partial recovery in AQP2 abundance from Li-induced downregulation. AQP2 immunohistochemistry showed compatible findings with the immunoblot results in both cortex and medulla. The abundances of thiazide-sensitive NaCl co-transporter and alpha-epithelial sodium channel were increased by HCTZ treatment. Notably, HCTZ treatment induced a shift in molecular weight of gamma-epithelial sodium channel from 85 to 70 kD, consistent with previously demonstrated aldosterone stimulation. The upregulation of AQP2 and distal renal Na(+) transporters in response to HCTZ treatment may account for the antidiuretic action of HCTZ in NDI.

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

    OpenAIRE

    Mathew John; Deepa Gopinath; Rejitha Jagesh

    2016-01-01

    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...

  14. OVER-EXPRESSION OF THE SODIUM CHLORIDE COTRANSPORTER IS NOT SUFFICIENT TO CAUSE FAMILIAL HYPERKALEMIC HYPERTENSION

    OpenAIRE

    McCormick, James A.; Nelson, Joshua H.; Yang, Chao-Ling; Curry, Joshua N.; Ellison, David H.

    2011-01-01

    The sodium chloride co-transporter (NCC) is the primary target of thiazides diuretics, drugs used commonly for long-term hypertension therapy. Thiazides also completely reverse the signs of Familial Hyperkalemic Hypertension (FHHt), suggesting that the primary defect in FHHt is increased NCC activity. To test whether increased NCC abundance alone is sufficient to generate the FHHt phenotype, we generated NCC transgenic mice; surprisingly, these mice did not display an FHHt-like phenotype. Sys...

  15. Enhanced expression of potassium-chloride cotransporter KCC2 in human temporal lobe epilepsy

    OpenAIRE

    Karlócai, MR; Wittner, L; Tóth, K; Maglóczky, Z.; Katarova, Z.; Rásonyi, G; Erőss, L; Czirják, S; Halász, P; G. Szabó; Payne, JA; Kaila, K.; Freund, TF

    2015-01-01

    © 2015 Springer-Verlag Berlin Heidelberg Synaptic reorganization in the epileptic hippocampus involves altered excitatory and inhibitory transmission besides the rearrangement of dendritic spines, resulting in altered excitability, ion homeostasis, and cell swelling. The potassium-chloride cotransporter-2 (KCC2) is the main chloride extruder in neurons and hence will play a prominent role in determining the polarity of GABAA receptor-mediated chloride currents. In addition, KCC2 also interact...

  16. Euglycemic Diabetic Ketoacidosis: A Potential Complication of Treatment With Sodium–Glucose Cotransporter 2 Inhibition

    OpenAIRE

    Peters, Anne L.; Buschur, Elizabeth O.; Buse, John B.; Cohan, Pejman; Diner, Jamie C.; Hirsch, Irl B.

    2015-01-01

    OBJECTIVE Sodium–glucose cotransporter 2 (SGLT-2) inhibitors are the most recently approved antihyperglycemic medications. We sought to describe their association with euglycemic diabetic ketoacidosis (euDKA) in hopes that it will enhance recognition of this potentially life-threatening complication. RESEARCH DESIGN AND METHODS Cases identified incidentally are described. RESULTS We identified 13 episodes of SGLT-2 inhibitor–associated euDKA or ketosis in nine individuals, seven with type 1 d...

  17. Synthesis of novel l-rhamnose derived acyclic C-nucleosides with substituted 1,2,3-triazole core as potent sodium-glucose co-transporter (SGLT) inhibitors.

    Science.gov (United States)

    Putapatri, Siddamal Reddy; Kanwal, Abhinav; Banerjee, Sanjay K; Kantevari, Srinivas

    2014-03-15

    Sodium-glucose co-transporter (SGLT) inhibitors are a novel class of therapeutic agents for the treatment of type 2 diabetes by preventing renal glucose reabsorption. In our efforts to identify novel inhibitors of SGLT, we synthesized a series of l-rhamnose derived acyclic C-nucleosides with 1,2,3-triazole core. The key β-ketoester building block 4 prepared from l-rhamnose in five steps, was reacted with various aryl azides to produce the respective 1,2,3-triazole derivatives in excellent yields. Deprotection of acetonide group gave the desired acyclic C-nucleosides 7a-o. All the new compounds were screened for their sodium-glucose co-transporters (SGLT1 and SGLT2) inhibition activity using recently developed cell-based nonradioactive fluorescence glucose uptake assay. Among them, 7m with IC50: 125.9nM emerged as the most potent SGLT2 inhibitor. On the other hand compound 7d exhibited best selectivity for inhibition of SGLT2 (IC50: 149.1nM) over SGLT1 (IC50: 693.2nM). The results presented here demonstrated the utility of acyclic C-nucleosides as novel SGLT inhibitors for future investigations.

  18. Progress in Synthesis of C-Aryl Glucosides Sodium Glucose Co-Transporter 2 Inhibitors%C-芳基糖苷类SGLT2抑制剂的合成研究进展

    Institute of Scientific and Technical Information of China (English)

    杜铁奇; 郑亿; 朱灵龙; 钟为慧

    2015-01-01

    Sodium glucose Co-transporter 2 (SGLT2) has been a hot spot of research on the treatment for type II diabetes. Inhibiting SGLT2, which works in the kidney specially, can reduce renal glucose reab-sorption, excrete excess glucose through the urine and lower the plasma glucose. This paper briefly reviews the synthetic routes to the C-aryl glucosides sodium glucose Co-transporter 2 inhibitors on the market, such as Ipragliflozin, Empagliflozin.%钠-葡萄糖协同转运蛋白2(SGLT2)抑制剂是目前Ⅱ型糖尿病药物研究的热点之一。通过抑制这种在肾脏特异性表达的钠-葡萄糖协同转运蛋白2(SGLT2),可以减少肾脏对葡萄糖的重吸收,增加葡萄糖在尿中的排泄,从而降低血糖。本文将针对已上市的C-芳基糖苷类SGLT2抑制剂伊格列净和恩格列净的合成路线进行简要评述。

  19. 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.

  20. 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.

  1. Renal effects of canagliflozin in type 2 diabetes mellitus.

    Science.gov (United States)

    Perkovic, Vlado; Jardine, Meg; Vijapurkar, Ujjwala; Meininger, Gary

    2015-12-01

    Chronic kidney disease is commonly associated with type 2 diabetes mellitus (T2DM) and may impact the efficacy and safety of glucose-lowering therapies. Canagliflozin, a sodium glucose co-transporter 2 inhibitor, reduces blood glucose levels in patients with T2DM by lowering the renal threshold for glucose, thereby promoting urinary glucose excretion. This review describes the pharmacology, efficacy and safety of canagliflozin according to kidney function in participants with T2DM. Published articles that reported efficacy, safety and pharmacokinetics/pharmacodynamics data for canagliflozin in patients with T2DM and impaired renal function, and renal safety data with canagliflozin in various populations of patients with T2DM through May 2015 were included. Early transient reductions in estimated glomerular filtration rate were observed with canagliflozin; these changes generally stabilized or attenuated over time and reversed after discontinuation, suggesting no renal (glomerular or tubular) damage with canagliflozin treatment. Urinary albumin-to-creatinine ratios were reduced with canagliflozin. Canagliflozin was generally well tolerated in patients with normal or mild to moderately impaired renal function, with a modestly higher incidence of renal-related adverse events and volume depletion-related adverse events in patients with moderate renal impairment. Adverse events related to potassium elevations were infrequent with canagliflozin 100 mg regardless of kidney function status; however, patients with moderately impaired kidney function experienced hyperkalemia more frequently with canagliflozin 300 mg compared with patients treated with either canagliflozin 100 mg or placebo. Canagliflozin was not associated with increased cardiovascular risk across studies; however, relatively few events among patients with impaired renal function meant that the analysis was not adequately powered to examine this outcome, and results from separate trials are awaited

  2. Chloride-cotransport blockade desynchronizes neuronal discharge in the "epileptic" hippocampal slice.

    Science.gov (United States)

    Hochman, D W; Schwartzkroin, P A

    2000-01-01

    Antagonism of the chloride-cotransport system in hippocampal slices has been shown to block spontaneous epileptiform (i.e., hypersynchronized) discharges without diminishing excitatory synaptic transmission. Here we test the hypotheses that chloride-cotransport blockade, with furosemide or low-chloride (low-[Cl(-)](o)) medium, desynchronizes the firing activity of neuronal populations and that this desynchronization is mediated through nonsynaptic mechanisms. Spontaneous epileptiform discharges were recorded from the CA1 and CA3 cell body layers of hippocampal slices. Treatment with low-[Cl(-)](o) medium led to cessation of spontaneous synchronized bursting in CA1 >/=5-10 min before its disappearance from CA3. During the time that CA3 continued to burst spontaneously but CA1 was silent, electrical stimulation of the Schaffer collaterals showed that hyperexcited CA1 synaptic responses were maintained. Paired intracellular recordings from CA1 pyramidal cells showed that during low-[Cl(-)](o) treatment, the timing of action potential discharges became desynchronized; desynchronization was identified with phase lags in firing times of action potentials between pairs of neurons as well as a with a broadening and diminution of the CA1 field amplitude. Continued exposure to low-[Cl(-)](o) medium increased the degree of the firing-time phase shifts between pairs of CA1 pyramidal cells until the epileptiform CA1 field potential was abolished completely. Intracellular recordings during 4-aminopyridine (4-AP) treatment showed that prolonged low-[Cl(-)](o) exposure did not diminish the frequency or amplitude of spontaneous postsynaptic potentials. CA3 antidromic responses to Schaffer collateral stimulation were not significantly affected by prolonged low-[Cl(-)](o) exposure. In contrast to CA1, paired intracellular recordings from CA3 pyramidal cells showed that chloride-cotransport blockade did not cause a significant desynchronization of action potential firing times in the

  3. Modeling the co-transport of viruses and colloids in unsaturated porous media.

    Science.gov (United States)

    Seetha, N; Mohan Kumar, M S; Majid Hassanizadeh, S

    2015-10-01

    A mathematical model is developed to simulate the co-transport of viruses and colloids in unsaturated porous media under steady-state flow conditions. The virus attachment to the mobile and immobile colloids is described using a linear reversible kinetic model. Colloid transport is assumed to be decoupled from virus transport; that is, we assume that colloids are not affected by the presence of attached viruses on their surface. The governing equations are solved numerically using an alternating three-step operator splitting approach. The model is verified by fitting three sets of experimental data published in the literature: (1) Syngouna and Chrysikopoulos (2013) and (2) Walshe et al. (2010), both on the co-transport of viruses and clay colloids under saturated conditions, and (3) Syngouna and Chrysikopoulos (2015) for the co-transport of viruses and clay colloids under unsaturated conditions. We found a good agreement between observed and fitted breakthrough curves (BTCs) under both saturated and unsaturated conditions. Then, the developed model was used to simulate the co-transport of viruses and colloids in porous media under unsaturated conditions, with the aim of understanding the relative importance of various processes on the co-transport of viruses and colloids in unsaturated porous media. The virus retention in porous media in the presence of colloids is greater during unsaturated conditions as compared to the saturated conditions due to: (1) virus attachment to the air-water interface (AWI), and (2) co-deposition of colloids with attached viruses on its surface to the AWI. A sensitivity analysis of the model to various parameters showed that the virus attachment to AWI is the most sensitive parameter affecting the BTCs of both free viruses and total mobile viruses and has a significant effect on all parts of the BTC. The free and the total mobile viruses BTCs are mainly influenced by parameters describing virus attachment to the AWI, virus interaction

  4. Renal Cysts

    Science.gov (United States)

    ... as “simple” cysts, meaning they have a thin wall and contain water-like fluid. Renal cysts are fairly common in ... simple kidney cysts, meaning they have a thin wall and only water-like fluid inside. They are fairly common in ...

  5. Renal failure

    Institute of Scientific and Technical Information of China (English)

    1997-01-01

    970363 Effect on serum PTH and 1, 25(OH)2 D3levels of rapid correction of metabolic acidosis in CRFpatients with secondary hyperparathyroidism. YUANQunsheng(袁群生), et al. Renal Div, PUMC Hosp,Beijing, 100730. Chin J Nephrol 1996; 12(6): 328-331.

  6. Drug-induced renal injury

    African Journals Online (AJOL)

    Drugs can cause acute renal failure by causing pre-renal, intrinsic or post-renal toxicity. Pre-renal ... incidence of drug dose adjustment in renal impairment in the SAMJ. ... Fever, haemolytic anaemia, thrombocytopenia, renal impairment and.

  7. Expression of the sodium potassium chloride cotransporter (NKCC1) and sodium chloride cotransporter (NCC) and their effects on rat lens transparency.

    Science.gov (United States)

    Chee, K N; Vorontsova, I; Lim, J C; Kistler, J; Donaldson, P J

    2010-05-04

    To characterize the expression patterns of the Na+-K+-Cl(-) cotransporter (NKCC) 1 and NKCC2, and the Na+-Cl(-) cotransporter (NCC) in the rat lens and to determine if they play a role in regulating lens volume and transparency. RT-PCR was performed on RNA extracted from fiber cells to identify sodium dependent cotransporters expressed in the rat lens. Western blotting and immunohistochemistry, using NKCC1, NKCC2, and NCC antibodies, were used to verify expression at the protein level and to localize transporter expression. Organ cultured rat lenses were incubated in Artificial Aqueous Humor (AAH) of varying osmolarities or isotonic AAH that contained either the NKCC specific inhibitor bumetanide, or the NCC specific inhibitor thiazide for up to 18 h. Lens transparency was monitored with dark field microscopy, while tissue morphology and antibody labeling patterns were recorded using a confocal microscope. Molecular experiments showed that NKCC1 and NCC were expressed in the lens at both the transcript and protein levels, but NKCC2 was not. Immunohistochemistry showed that both NKCC1 and NCC were expressed in the lens cortex, but NCC expression was also found in the lens core. In the lens cortex the majority of labeling for both transporters was cytoplasmic in nature, while in the lens core, NCC labeling was associated with the membrane. Exposure of lenses to either hypotonic or hypertonic AAH had no noticeable effects on the predominantly cytoplasmic location of either transporter in the lens cortex. Incubation of lenses in isotonic AAH plus the NKCC inhibitor bumetanide for 18 h induced a cortical opacity that was initiated by a shrinkage of peripheral fiber cells and the dilation of the extracellular space between fiber cells in a deeper zone located some approximately 150 microm in from the capsule. In contrast, lenses incubated in isotonic AAH and the NCC inhibitor thiazide maintained both their transparency and their regular fiber cell morphology. We have

  8. cAMP-dependent and cholinergic regulation of the electrogenic intestinal/pancreatic Na+/HCO3- cotransporter pNBC1 in human embryonic kidney (HEK293 cells

    Directory of Open Access Journals (Sweden)

    Soleimani Manoocher

    2008-12-01

    Full Text Available Abstract Background The renal (kNBC1 and intestinal (pNBC1 electrogenic Na+/HCO3- cotransporter variants differ in their primary structure, transport direction, and response to secretagogues. Previous studies have suggested that regulatory differences between the two subtypes can be partially explained by unique consensus phosphorylation sites included in the pNBC1, but not the kNBC1 sequence. After having shown activation of NBC by carbachol and forskolin in murine colon, we now investigated these pathways in HEK293 cells transiently expressing a GFP-tagged pNBC1 construct. Results Na+- and HCO3--dependent pHi recovery from an acid load (measured with BCECF was enhanced by 5-fold in GFP-positive cells compared to the control cells in the presence of CO2/HCO3-. Forskolin (10-5 M had no effect in untransfected cells, but inhibited the pHi recovery in cells expressing pNBC1 by 62%. After preincubation with carbachol (10-4 M, the pHi recovery was enhanced to the same degree both in transfected and untransfected cells, indicating activation of endogenous alkalizing ion transporters. Acid-activated Na+/HCO3- cotransport via pNBC1 expressed in renal cells is thus inhibited by cAMP and not affected by cholinergic stimulation, as opposed to the findings in native intestinal tissue. Conclusion Regulation of pNBC1 by secretagogues appears to be not solely dependent on its primary structure, but also on properties of the cell type in which it is expressed.

  9. Renal failure (chronic)

    OpenAIRE

    Clase, Catherine

    2011-01-01

    Chronic renal failure is characterised by a gradual and sustained decline in renal clearance or glomerular filtration rate (GFR). Continued progression of renal failure will lead to renal function too low to sustain healthy life. In developed countries, such people will be offered renal replacement therapy in the form of dialysis or renal transplantation. Requirement for dialysis or transplantation is termed end-stage renal disease (ESRD).Diabetes, glomerulonephritis, hypertension, pyelone...

  10. Clinical observation of riboflavin sodium phosphate combined with interferon in treatment of children herpangina%核黄素磷酸钠联合干扰素治疗小儿疱疹性咽峡炎的疗效观察

    Institute of Scientific and Technical Information of China (English)

    黄蓉

    2016-01-01

    目的:观察核黄素磷酸钠联合干扰素治疗小儿疱疹性咽峡炎的疗效。方法选取2012年10月—2015年4月重庆市沙坪坝区妇幼保健计划生育服务中心收治的疱疹性咽峡炎患儿100例,随机分为对照组和治疗组,每组各50例。两组患者均给予物理或药物降温、补液支持、抗菌素治疗等常规治疗。对照组在此基础上雾化吸入重组人干扰素α1b注射液,6个月~1岁6μg/次,1~3岁10μg/次,3岁以上20μg/次,1次/d。治疗组在对照组基础上静脉滴注稀释后的核黄素磷酸钠5~10 mg,1次/d。观察两组患者的临床疗效,并比较两组患者疱疹溃疡消失时间、流涎消失时间、退热时间、住院时间和不良反应。结果治疗后,对照组和治疗组总有效率分别为76.0%、88.0%,两组比较差异具有统计学意义(P<0.05)。治疗组患者疱疹溃疡消失时间、流涎消失时间、退热时间、住院时间均低于对照组,两组比较差异具有统计学意义(P<0.05)。对照组和治疗组不良反应发生率分别为20.0%、8.0%,两组比较差异具有统计学意义(P<0.05)。结论核黄素磷酸钠联合干扰素治疗小儿疱疹性咽峡炎具有较好的临床疗效,可缩短疱疹溃疡消失时间、流涎消失时间、退热时间、住院时间,不良反应少,具有一定的临床推广应用价值。%Objective To observe the clinical effect of riboflavin sodium phosphate combined with interferon in the treatment of children herpangina. Methods Patients (100 cases) with herpangina in Maternal and Child Health Care Family Planning Service Center of Shapingba District of Chongqing from October 2012 to April 2015 were randomly divided into control and treatment groups, and each group had 50 cases. All patients were given conventional treatment including physical or drugs cooling, rehydration support and antibiotic therapy. The patients in the control group were

  11. 采用FACT-H & N评价核黄素磷酸钠对喉癌放疗患者生存质量的影响%Using FACT-H & N to evaluate the effect of riboflavin sodium phosphate on the qual- ity of life of patients with laryngeal carcinoma who received radiotherapy

    Institute of Scientific and Technical Information of China (English)

    丁荣楣; 王平; 马丽君; 田奕

    2015-01-01

    目的:采用FACT-H&N量表评价核黄素磷酸钠对喉癌放疗患者生存质量的影响。方法选取我院肿瘤科首次接受放射治疗的喉癌患者72例,随机分为观察组和对照组,每组36例。观察组自放疗开始每日应用核黄素磷酸钠20 mg静脉输液,直至放疗结束;对照组单纯放疗,不使用核黄素磷酸钠。观察两组患者放疗后放射性口咽黏膜炎的发生率和摄食量,分别于放疗前( D1)和放疗后( D2)采用FACT-H&N量表作为评测工具,评价放疗前后两组患者生存质量。结果观察组放射性口咽黏膜炎的发生率低于对照组,两组比较差异有统计学意义(P<0.05);观察组患者摄食量与对照组比较差异有统计学意义(P<0.05);生存质量方面,观察组在身体状况、社会家庭、情感及功能共性模块评分均高于对照组,在头颈部模块的附加条目领域得分低于对照组,两组比较差异有统计学意义(P<0.05)。结论核黄素磷酸钠可降低放射性口咽黏膜炎发生率,改善喉癌放疗患者摄食量下降,提高喉癌放疗患者生存质量,值得临床推广。%Objective Using FACT-H&N scale to evaluate the effect of riboflavin sodium phosphate on the quality of life of patients with laryngeal carcinoma who received radiotherapy. Methods Seventy-two patients with la-ryngeal carcinoma who underwent radiotherapy for the first time were randomly divided into observation group and con-trol group. Patients in observation group (n=36) accepted daily application of riboflavin sodium phosphate 20 mg in-travenous infusion throughout the course of radiotherapy. Patients in control group only received radiotherapy. The oc-currence of oropharyngeal mucositis and food intake after radiotherapy were assessed by FACT-HN scale to evaluate the quality of life of patients before (D1) and after (D2) radiotherapy. Results The incidence of oral mucositis in obser-vation group was lower than

  12. Safe and pragmatic use of sodium–glucose co-transporter 2 inhibitors in type 2 diabetes mellitus: South Asian Federation of Endocrine Societies consensus statement

    Directory of Open Access Journals (Sweden)

    Sanjay Kalra

    2017-01-01

    Full Text Available Diabetes prevalence shows a continuous increasing trend in South Asia. Although well-established treatment modalities exist for type 2 diabetes mellitus (T2DM management, they are limited by their side effect profile. Sodium–glucose co-transporter 2 inhibitors (SGLT2i with their novel insulin-independent renal action provide improved glycemic control, supplemented by reduction in weight and blood pressure, and cardiovascular safety. Based on the clinical outcomes with SGLT2i in patients with T2DM, treatment strategies that make a “good clinical sense” are desirable. Considering the peculiar lifestyle, body types, dietary patterns (long duration religious fasts, and the hot climate of the South Asian population, a unanimous decision was taken to design specific, customized guidelines for T2DM treatment strategies in these regions. The panel met for a discussion three times so as to get a consensus for the guidelines, and only unanimous consensus was included. After careful consideration of the quality and strength of the available evidence, the executive summary of this consensus statement was developed based on the American Association of Clinical Endocrinologists/American College of Endocrinology protocol.

  13. Functional role of a putative carbonic anhydrase II-binding domain in the electrogenic Na+ -HCO₃- cotransporter NBCe1 expressed in Xenopus oocytes.

    Science.gov (United States)

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

    2011-01-01

    The electrogenic Na+ -HCO₃⁻ cotransporter NBCe1 plays essential roles in the regulation of systemic and/or local pH. Homozygous inactivating mutations in NBCe1 cause proximal renal tubular acidosis associated with ocular abnormalities. We recently showed that defective membrane expression of NBCe1, caused by several mutations such as Delta65bp (S982NfsX4), is also associated with familial migraine. The Delta65bp mutant is quite unique in that it lacks a putative carbonic anhydrase (CA) II-binding domain but still shows an apparently normal transport activity in Xenopus oocytes. In this addendum, we show that the co-expression of CAII together with the wild-type NBCe1 or the Delta65bp mutant does not enhance the NBCe1 activities in oocytes. Moreover, a carbonic anhydrase inhibitor acetazolamide fails to inhibit the wild-type or the Delta65bp activities co-expressed with CAII. These results indicate that a bicarbonate transport metabolon proposed for the interaction between CAII and NBCe1 does not work at least in Xenopus oocytes.

  14. Preliminary X-ray Diffraction Analysis of the Cytoplasmic N-terminal Domain of the Na/HCO3 Cotransporter NBCe1-A

    Energy Technology Data Exchange (ETDEWEB)

    Gill,H.; Boron, W.

    2006-01-01

    The N-terminal cytoplasmic domain of the Na{sup +}-coupled HCO{sub 3}{sup -} cotransporter NBCe1-A (NtNBCe1) has been linked with proximal renal tubular acidosis. In a previous purification study of recombinant NtNBCe1, crystal growth at a suboptimal protein concentration (<1 mg ml{sup -1}) yielded small single diamond-shaped crystals that diffracted poorly. In the present study, by increasing the protein concentration 50-fold, the crystal size was doubled and robustness was also improved. Crystal annealing made the crystals suitable for X-ray diffraction. The crystals either belong to space group P3121 or P31 with pseudo P3121 symmetry, with unit-cell parameters a = 51.7, b = 51.7, c = 200.6 Angstroms, {alpha} = {beta} = 90, {gamma} = 120 deg, and diffract X-rays to 3.0 Angstroms resolution. The calculated Matthews number is 1.9 Angstroms{sup 3} Da{sup -1}, with two monomers of molecular weight {approx}83 kDa in the asymmetric unit. The molecular- replacement packing solution shows that the molecules form dimers by a domain-swapping mechanism.

  15. CD8(+) T cells stimulate Na-Cl co-transporter NCC in distal convoluted tubules leading to salt-sensitive hypertension.

    Science.gov (United States)

    Liu, Yunmeng; Rafferty, Tonya M; Rhee, Sung W; Webber, Jessica S; Song, Li; Ko, Benjamin; Hoover, Robert S; He, Beixiang; Mu, Shengyu

    2017-01-09

    Recent studies suggest a role for T lymphocytes in hypertension. However, whether T cells contribute to renal sodium retention and salt-sensitive hypertension is unknown. Here we demonstrate that T cells infiltrate into the kidney of salt-sensitive hypertensive animals. In particular, CD8(+) T cells directly contact the distal convoluted tubule (DCT) in the kidneys of DOCA-salt mice and CD8(+) T cell-injected mice, leading to up-regulation of the Na-Cl co-transporter NCC, p-NCC and the development of salt-sensitive hypertension. Co-culture with CD8(+) T cells upregulates NCC in mouse DCT cells via ROS-induced activation of Src kinase, up-regulation of the K(+) channel Kir4.1, and stimulation of the Cl(-) channel ClC-K. The last event increases chloride efflux, leading to compensatory chloride influx via NCC activation at the cost of increasing sodium retention. Collectively, these findings provide a mechanism for adaptive immunity involvement in the kidney defect in sodium handling and the pathogenesis of salt-sensitive hypertension.

  16. Generation and analysis of the thiazide-sensitive Na+ -Cl- cotransporter (Ncc/Slc12a3) Ser707X knockin mouse as a model of Gitelman syndrome.

    Science.gov (United States)

    Yang, Sung-Sen; Lo, Yi-Fen; Yu, I-Shing; Lin, Shu-Wha; Chang, Tai-Hsiang; Hsu, Yu-Juei; Chao, Tai-Kuang; Sytwu, Huey-Kang; Uchida, Shinichi; Sasaki, Sei; Lin, Shih-Hua

    2010-12-01

    Gitelman syndrome (GS) is characterized by salt-losing hypotension, hypomagnesemia, hypokalemic metabolic alkalosis, and hypocalciuria. To better model human GS caused by a specific mutation in the thiazide-sensitive Na(+) -Cl(-) cotransporter (NCC) gene SLC12A3, we generated a nonsense Ncc Ser707X knockin mouse corresponding to human p.Ser710X (c.2135C>A), a recurrent mutation with severe phenotypes in Chinese GS patients. Compared with wild-type or heterozygous littermates, homozygous (Hom) knockin mice fully recapitulated the phenotype of human GS. The markedly reduced Ncc mRNA and virtually absent Ncc protein expression in kidneys of Hom mice was primarily due to nonsense-mediated mRNA decay (NMD) surveillance mechanisms. Expression of epithelial Na(+) channel (Enac), Ca(2+) channels (Trpv5 and Trpv6), and K(+) channels (Romk1 and maxi-K) were significantly increased. Late distal convoluted tubules (DCT) volume was increased and DCT cell ultrastructure appeared intact. High K(+) intake could not correct hypokalemia but caused a further increase in maxi-K but not Romk1 expression. Renal tissue from a patient with GS also showed the enhanced TRPV5 and ROMK1 expression in distal tubules. We suggest that the upregulation of TRPV5/6 and of ROMK1 and Maxi-K may contribute to hypocalciuria and hypokalemia in Ncc Ser707X knockin mice and human GS, respectively. © 2010 Wiley-Liss, Inc.

  17. KCNJ10 determines the expression of the apical Na-Cl cotransporter (NCC) in the early distal convoluted tubule (DCT1).

    Science.gov (United States)

    Zhang, Chengbiao; Wang, Lijun; Zhang, Junhui; Su, Xiao-Tong; Lin, Dao-Hong; Scholl, Ute I; Giebisch, Gerhard; Lifton, Richard P; Wang, Wen-Hui

    2014-08-12

    The renal phenotype induced by loss-of-function mutations of inwardly rectifying potassium channel (Kir), Kcnj10 (Kir4.1), includes salt wasting, hypomagnesemia, metabolic alkalosis and hypokalemia. However, the mechanism by which Kir.4.1 mutations cause the tubulopathy is not completely understood. Here we demonstrate that Kcnj10 is a main contributor to the basolateral K conductance in the early distal convoluted tubule (DCT1) and determines the expression of the apical Na-Cl cotransporter (NCC) in the DCT. Immunostaining demonstrated Kcnj10 and Kcnj16 were expressed in the basolateral membrane of DCT, and patch-clamp studies detected a 40-pS K channel in the basolateral membrane of the DCT1 of p8/p10 wild-type Kcnj10(+/+) mice (WT). This 40-pS K channel is absent in homozygous Kcnj10(-/-) (knockout) mice. The disruption of Kcnj10 almost completely eliminated the basolateral K conductance and decreased the negativity of the cell membrane potential in DCT1. Moreover, the lack of Kcnj10 decreased the basolateral Cl conductance, inhibited the expression of Ste20-related proline-alanine-rich kinase and diminished the apical NCC expression in DCT. We conclude that Kcnj10 plays a dominant role in determining the basolateral K conductance and membrane potential of DCT1 and that the basolateral K channel activity in the DCT determines the apical NCC expression possibly through a Ste20-related proline-alanine-rich kinase-dependent mechanism.

  18. CD8+ T cells stimulate Na-Cl co-transporter NCC in distal convoluted tubules leading to salt-sensitive hypertension

    Science.gov (United States)

    Liu, Yunmeng; Rafferty, Tonya M.; Rhee, Sung W.; Webber, Jessica S.; Song, Li; Ko, Benjamin; Hoover, Robert S.; He, Beixiang; Mu, Shengyu

    2017-01-01

    Recent studies suggest a role for T lymphocytes in hypertension. However, whether T cells contribute to renal sodium retention and salt-sensitive hypertension is unknown. Here we demonstrate that T cells infiltrate into the kidney of salt-sensitive hypertensive animals. In particular, CD8+ T cells directly contact the distal convoluted tubule (DCT) in the kidneys of DOCA-salt mice and CD8+ T cell-injected mice, leading to up-regulation of the Na-Cl co-transporter NCC, p-NCC and the development of salt-sensitive hypertension. Co-culture with CD8+ T cells upregulates NCC in mouse DCT cells via ROS-induced activation of Src kinase, up-regulation of the K+ channel Kir4.1, and stimulation of the Cl− channel ClC-K. The last event increases chloride efflux, leading to compensatory chloride influx via NCC activation at the cost of increasing sodium retention. Collectively, these findings provide a mechanism for adaptive immunity involvement in the kidney defect in sodium handling and the pathogenesis of salt-sensitive hypertension. PMID:28067240

  19. 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

  20. Renale Osteopathie

    OpenAIRE

    Horn S

    2001-01-01

    Die renale Osteopathie umfaßt Erkrankungen des Knochens, die bei Patienten mit chronischen Nierenerkrankungen auftreten, wie den sekundären bzw. tertiären Hyperparathyreoidismus, die adynamische Knochenerkrankung und die Osteopathie nach Nierentransplantation. Durch die Identifikation des Kalzium-Sensing-Rezeptors bzw. des Vitamin D-Rezeptors hat sich unser Verständnis der Zusammenhänge in den letzten Jahren erheblich verbessert. Neue Medikamente versprechen effizientere Prophylaxe- und Thera...

  1. Renale Knochenerkrankungen

    Directory of Open Access Journals (Sweden)

    Mayer G

    2008-01-01

    Full Text Available Störungen des Mineral- und Knochenstoffwechsels sind bei fast allen Patienten mit chronischen Nierenerkrankungen anzutreffen. Pathogenetisch spielt eine Neigung zur Phosphatretention bei einer Reduktion der glomerulären Filtrationsrate die zentrale Rolle. Neben typischen, aber sehr variablen Veränderungen der Knochenstruktur (renale Osteopathie besteht auch eine sehr enge Assoziation zwischen diesen Störungen und dem massiv erhöhten kardiovaskulären Risiko der Patienten.

  2. Pharmacodynamic effects of canagliflozin, a sodium glucose co-transporter 2 inhibitor, from a randomized study in patients with type 2 diabetes.

    Science.gov (United States)

    Sha, Sue; Devineni, Damayanthi; Ghosh, Atalanta; Polidori, David; Hompesch, Marcus; Arnolds, Sabine; Morrow, Linda; Spitzer, Heike; Demarest, Keith; Rothenberg, Paul

    2014-01-01

    This randomized, double-blind, placebo-controlled, single and multiple ascending-dose study evaluated the pharmacodynamic effects and safety/tolerability of canagliflozin, a sodium glucose co-transporter 2 inhibitor, in patients with type 2 diabetes. Patients (N = 116) discontinued their antihyperglycemic medications 2 weeks before randomization. Patients received canagliflozin 30, 100, 200, or 400 mg once daily or 300 mg twice daily, or placebo at 2 study centers in the United States and Germany, or canagliflozin 30 mg once daily or placebo at 1 study center in Korea, while maintaining an isocaloric diet for 2 weeks. On Days -1, 1, and 16, urinary glucose excretion (UGE), plasma glucose (PG), fasting PG (FPG), and insulin were measured. The renal threshold for glucose (RTG) was calculated from UGE, PG, and estimated glomerular filtration rate. Safety was evaluated based on adverse event (AE) reports, vital signs, electrocardiograms, clinical laboratory tests, and physical examinations. Canagliflozin increased UGE dose-dependently (,80-120 g/day with canagliflozin $100 mg), with increases maintained over the 14-day dosing period with each dose. Canagliflozin dose-dependently decreased RTG, with maximal reductions to ,4-5 mM (72-90 mg/dL). Canagliflozin also reduced FPG and 24-hour mean PG; glucose reductions were seen on Day 1 and maintained over 2 weeks. Plasma insulin reductions with canagliflozin were consistent with observed PG reductions. Canagliflozin also reduced body weight. AEs were transient, mild to moderate in intensity, and balanced across groups; 1 canagliflozin-treated female reported an episode of vaginal candidiasis. Canagliflozin did not cause hypoglycemia, consistent with the RTG values remaining above the hypoglycemia threshold. At Day 16, there were no clinically meaningful changes in urine volume, urine electrolyte excretion, renal function, or routine laboratory test values. Canagliflozin increased UGE and decreased RTG, leading to reductions

  3. 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.

  4. 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

  5. Obesity and renal hemodynamics

    NARCIS (Netherlands)

    Bosma, R. J.; Krikken, J. A.; van der Heide, J. J. Homan; de Jong, P. E.; Navis, G. J.

    2006-01-01

    Obesity is a risk factor for renal damage in native kidney disease and in renal transplant recipients. Obesity is associated with several renal risk factors such as hypertension and diabetes that may convey renal risk, but obesity is also associated with an unfavorable renal hemodynamic profile inde

  6. Oligomeric structure and minimal functional unit of the electrogenic sodium bicarbonate cotransporter NBCe1-A.

    Science.gov (United States)

    Kao, Liyo; Sassani, Pakan; Azimov, Rustam; Pushkin, Alexander; Abuladze, Natalia; Peti-Peterdi, Janos; Liu, Weixin; Newman, Debra; Kurtz, Ira

    2008-09-26

    The electrogenic sodium bicarbonate cotransporter NBCe1-A mediates the basolateral absorption of sodium and bicarbonate in the proximal tubule. In this study the oligomeric state and minimal functional unit of NBCe1-A were investigated. Wild-type (wt) NBCe1-A isolated from mouse kidney or heterologously expressed in HEK293 cells was predominantly in a dimeric state as was shown using fluorescence energy transfer, pulldown, immunoprecipitation, cross-linking experiments, and nondenaturing perfluorooctanoate-PAGE. NBCe1-A monomers were found to be covalently linked by S-S bonds. When each of the 15 native cysteine residues were individually removed on a wt-NBCe1-A backbone, dimerization of the cotransporter was not affected. In experiments involving multiple native cysteine residue removal, both Cys(630) and Cys(642) in extracellular loop 3 were shown to mediate S-S bond formation between NBCe1-A monomers. When native NBCe1-A cysteine residues were individually reintroduced into a cysteineless NBCe1-A mutant backbone, the finding that a Cys(992) construct that lacked S-S bonds functioned normally indicated that stable covalent linkage of NBCe1-A monomers was not a necessary requirement for functional activity of the cotransporter. Studies using concatameric constructs of wt-NBCe1-A, whose activity is resistant to methanesulfonate reagents, and an NBCe1-A(T442C) mutant, whose activity is completely inhibited by methanesulfonate reagents, confirmed that NBCe1-A monomers are functional. Our results demonstrate that wt-NBCe1-A is predominantly a homodimer, dependent on S-S bond formation that is composed of functionally active monomers.

  7. Effect of gravity on Pseudomonas putida and kaolinite cotransport in water saturated porous media

    Science.gov (United States)

    Vasiliadou, Ioanna A.; Chrysikopoulos, Constantinos V.

    2013-04-01

    Bacterial transport in porous media can be affected by several factors, such as cell concentration, water velocity, and attachment onto the solid matrix or suspended in the aqueous phase soil particles (e.g. clays). Gravity, also may significantly influence bacterial transport behavior in the subsurface. The present study aims to determine the gravity effect on transport and cotransport of bacteria species Pseudomonas (P.) putida and kaolinite colloid particles in porous media. Transport experiments were conducted under horizontal-, up- and down-flow conditions in water saturated columns packed with glass beads. These different flow modes represent different gravity effects, namely: no-, negative- and positive-gravity effect. Initial experiments were performed with bacteria and kaolinite alone in order to evaluate the effect of gravity on their individual transport characteristics. No significant gravity effect was observed on the transport of individual bacterial cells. In contrary, each different flow mode was found to differently affect kaolinite transport. Compared to the horizontal-flow mode, the kaolinite mass recovery was decreased during the up-flow mode, and increased during the down-flow mode. Finally, P. putida and kaolinite particles were injected simultaneously into the packed column in order to investigate their cotransport behavior under different flow modes. The experimental data indicated that the kaolinite-P. putida cotransport behavior was similar to that observed for the transport of individual kaolinite particles. It was observed that the P. putida mass recovery decreased during down-flow conditions. This phenomenon may be caused by the attachment of bacteria onto kaolinite particles, which were adsorbed onto the solid matrix.

  8. Substrate specificity of human ABCC4 (MRP4)-mediated cotransport of bile acids and reduced glutathione.

    Science.gov (United States)

    Rius, Maria; Hummel-Eisenbeiss, Johanna; Hofmann, Alan F; Keppler, Dietrich

    2006-04-01

    The multidrug resistance protein ABCC4 (MRP4), a member of the ATP-binding cassette superfamily, mediates ATP-dependent unidirectional efflux of organic anions out of cells. Previous studies showed that human ABCC4 is localized to the sinusoidal membrane of hepatocytes and mediates, among other substrates, the cotransport of reduced glutathione (GSH) with bile acids. In the present study, using inside-out membrane vesicles, we demonstrated that human ABCC4 in the presence of physiological concentrations of GSH has a high affinity for the taurine and glycine conjugates of the common natural bile acids as well as the unconjugated bile acid cholate. Chenodeoxycholyltaurine and chenodeoxycholylglycine were the GSH cosubstrates with the highest affinities for ABCC4, with K(m) values of 3.6 and 5.9 microM, respectively. Ursodeoxycholyltaurine and ursodeoxycholylglycine were cotransported together with GSH by ABCC4 with K(m) values of 7.8 and 12.5 microM, respectively, but no transport of ursodeoxycholate and deoxycholate was observed. The simultaneous transport of labeled GSH and cholyltaurine or cholylglycine was demonstrated in double-labeled cotransport experiments with a bile acid-to-GSH ratio of approximately 1:22. K(m) values of the bile acids for ABCC4 were in a range similar to those reported for the canalicular bile salt export pump ABCB11. Under physiological conditions, the sinusoidal ABCC4 may compete with canalicular ABCB11 for bile acids and thereby play a key role in determining the hepatocyte concentration of bile acids. In cholestatic conditions, ABCC4 may become a key pathway for efflux of bile acids from hepatocytes into blood.

  9. Na+/HCO3- Cotransport in Normal and Cystic Fibrosis Intestine

    Directory of Open Access Journals (Sweden)

    Seidler U

    2001-07-01

    Full Text Available In a search for the HCO(3(- supply mechanisms to the enterocyte we cloned and sequenced an intestinal subtype of the Na(+HCO(3(- cotransporter isoform I (dNBC1, which turned out to be identical to the pancreatic NBC1 subtype (pNBC1. Within the intestine, we found particularly high NBC1 expression levels in the duodenum and proximal colon. Experiments with stripped rabbit duodenum in Ussing-chambers revealed that Na(+HCO(3(- cotransport (NBC and CO(2 hydration/Na(+/H(+ exchange were equally important duodenal HCO(3(- supply pathways and were both upregulated during cAMP-mediated secretion. In the proximal colon, however, HCO(3(- secretion was low but NBC1 expression even higher than in the duodenum. Ussing-chamber experiments with an NBC-specific inhibitor revealed that NBC, coupled to basolateral Cl(-/HCO(3(- exchange, was an important alternative Cl(- supply pathway to Na(+K(+2Cl(- cotransport (NKCC during cAMP-stimulated colonic Cl(- secretion. To investigate the functional integrity of anion uptake pathways in the absence of cystic fibrosis transmembrane conductance regulator (CFTR, we fluorometrically assessed NBC and NKCC transport rates and cell volume before and during forskolin-stimulation in isolated colonic crypts from normal and CFTR (-/- mice. Although forskolin stimulation decreased cell volume only in normal, not in CFTR (-/- crypts, it activated NBC and NKCC to a similar degree in both normal and CFTR (-/- crypts. We conclude that, depending on the intestinal segment, NBC1 plays an important role in basolateral HCO(3(- or Cl(- uptake. Expression and activation by cAMP is preserved in CFTR (-/- intestine.

  10. Bone effects of canagliflozin, a sodium glucose co-transporter 2 inhibitor, in patients with type 2 diabetes mellitus.

    Science.gov (United States)

    Blevins, Thomas C; Farooki, Azeez

    2017-01-01

    Canagliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor approved for the treatment of type 2 diabetes mellitus (T2DM), lowers blood glucose by inhibiting renal glucose reabsorption and increasing urinary glucose excretion. It has been reported that SGLT2 inhibitors may have potential adverse effects on bone, including increased fracture risk and decreased bone mineral density (BMD). Across clinical studies, canagliflozin was not associated with meaningful changes in serum or urine calcium, vitamin D, or parathyroid hormone. Minimal increases in serum phosphate and magnesium that were within normal limits were seen with canagliflozin versus placebo. Canagliflozin was associated with increases in serum collagen type 1 beta-carboxy telopeptide (beta-CTX), a bone resorption marker, and osteocalcin, a bone formation marker. Decreases in total hip BMD were seen with canagliflozin 100 and 300 mg versus placebo after 2 years (-1.7%, -2.1%, -0.8%; differences of -0.9% and -1.2%), but not at other skeletal sites (normal age-related bone loss, ~0.5-1.0%/year). Changes in beta-CTX and total hip BMD were significantly associated with weight loss, which is known to increase bone resorption markers and decrease BMD. Canagliflozin was associated with a higher fracture incidence in an interim analysis of the CANagliflozin cardioVascular Assessment Study (CANVAS) in patients with a history or high risk of cardiovascular disease (incidence per 100 patient-years of 1.6, 1.6, and 1.1 with canagliflozin 100 and 300 mg and placebo), but not in other clinical studies of patients with T2DM. Fractures tended to occur as early as 12 weeks after initiating treatment and were primarily located in the distal parts of the upper and lower extremities. The reason for increased fracture risk with canagliflozin treatment is unknown, but is likely not related to a direct effect of canagliflozin on bone-related biomarkers. Data from ongoing canagliflozin studies, including CANVAS, will

  11. Single-dose Pharmacokinetics and Pharmacodynamics of Canagliflozin, a Selective Inhibitor of Sodium Glucose Cotransporter 2, in Healthy Indian Participants.

    Science.gov (United States)

    Devineni, Damayanthi; Polidori, David; Curtin, Christopher; Stieltjes, Hans; Tian, Hong; Wajs, Ewa

    2016-01-01

    Canagliflozin, an orally active selective inhibitor of sodium glucose cotransporter 2, has been approved in several countries for the treatment of type 2 diabetes mellitus. This study assessed the pharmacokinetic (PK) and pharmacodynamic (PD) properties and tolerability of single-dose canagliflozin 200 or 300 mg in healthy Indian participants. In this Phase 1, single-center, open-label, 2-period crossover study, healthy adult participants were randomly assigned to receive a single dose of canagliflozin 200 mg in period 1, followed by canagliflozin 300 mg in period 2, or vice versa. The 2 periods were separated by a washout interval of 14 days. The PK and PD properties and tolerability of canagliflozin were assessed at prespecified time points. Of 15 randomized participants, 14 completed the study. After the administration of single doses of 200 and 300 mg, the mean (SD) Cmax values were 1792 (430) ng/mL and 2789 (941) ng/mL, respectively; AUC0-∞, values were 18,706 (3818) ng·h/mL and 28,207 (5901) ng·h/mL, respectively. The Tmax and t½ of canagliflozin were independent of dose (Tmax, 1.5 hours at both doses; t½, 13.0 and 12.6 hours with 200 and 300 mg). Over the first 4 hours, mean (SD) renal threshold for glucose (RTG) values were 60.8 (8.90) and 61.2 (7.04) mg/dL with the 200- and 300-mg doses, respectively. No effect on plasma glucose concentrations over 0 to 4 hours relative to baseline was observed with either dose. The only treatment-emergent adverse event (TEAE) reported in >1 participant was dizziness (2 participants with the 200-mg dose). None of the participants in the 300-mg group reported any TEAEs. No deaths, discontinuations due to TEAEs, or hypoglycemic episodes were reported. The mean plasma exposure (Cmax and AUC) to canagliflozin increased in a dose-dependent manner after the administration of single-dose oral canagliflozin 200 and 300 mg in these healthy Indian participants. The Tmax and t½ of canagliflozin appeared to be independent of

  12. Sodium-glucose cotransporter-2 inhibition and the insulin: Glucagon ratio: Unexplored dimensions

    Directory of Open Access Journals (Sweden)

    Sanjay Kalra

    2015-01-01

    Full Text Available The sodium-glucose cotransporter 2 (SGLT-2 inhibitors are a novel class of glucose-lowering drugs which act by inhibiting the reabsorption of filtered glucose from the kidneys. Their effect on insulin and glucagon levels has recently been studied but is not fully explained. This communication proposes various hypotheses: A direct effect of SGLT-2 inhibition on the alpha cell receptors, a paracrine or intra-islet mediated effect on alpha cell sensitivity to glucose, and a calorie restriction mimetic action, to explain the impact of these drugs on the insulin glucagon ratio.

  13. 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. PMID:27730088

  14. 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

    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...... 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....

  15. Regulation of the type Mb sodium-dependent phosphate cotransporter expression in the intestine

    Institute of Scientific and Technical Information of China (English)

    Bin WANG; Yulong YIN

    2009-01-01

    Phosphate (Pi) plays important roles in growth, development, bone mineralization, energy metabolism, nucleic acid synthesis, cell signaling, and acid-base regulation. The rate of intestinal absorption of Pi is a major determinant of Pi homeostasis. The type lib sodium- dependent Pi cotransporter (NaPi-Iib) is responsible for intestinal Pi absorption. Many physiological factors regulate the rate of Pi absorption via modulating the expression of NaPi-Iib in the intestine. In this review, we summarize the role of these factors in the regulation of NaPi-Iib expression in the intestine.

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

    OpenAIRE

    Awadhesh Kumar Singh

    2015-01-01

    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 com...

  17. 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.

  18. 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.

  19. 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.

  20. Angiotensin II directly stimulates macula densa Na-2Cl-K cotransport via apical AT(1) receptors.

    Science.gov (United States)

    Kovács, Gergely; Peti-Peterdi, János; Rosivall, László; Bell, P Darwin

    2002-02-01

    ANG II is a modulator of tubuloglomerular feedback (TGF); however, the site of its action remains unknown. Macula densa (MD) cells sense changes in luminal NaCl concentration ([NaCl](L)) via a Na-2Cl-K cotransporter, and these cells do possess ANG II receptors. We tested whether ANG II regulates Na-2Cl-K cotransport in MD cells. MD cell Na(+) concentration ([Na(+)](i)) was measured using sodium-binding benzofuran isophthalate with fluorescence microscopy. Resting [Na(+)](i) in MD cells was 27.7 +/- 1.05 mM (n = 138) and increased (Delta[Na(+)](i)) by 18.5 +/- 1.14 mM (n = 17) at an initial rate (Delta[Na(+)](i)/Deltat) of 5.54 +/- 0.53 x 10(-4) U/s with an increase in [NaCl](L) from 25 to 150 mM. Both Delta[Na(+)](i) and Delta[Na(+)](i)/Deltat were inhibited by 80% with 100 microM luminal furosemide. ANG II (10(-9) or 10(-12) M) added to the lumen increased MD resting [Na(+)](i) and [NaCl](L)-dependent Delta[Na(+)](i) and caused a twofold increase in Delta[Na(+)](i)/Deltat. Bath (10(-9) M) ANG II also stimulated cotransport activity, and there was no additive effect of simultaneous addition of ANG II to bath and lumen. The effects of luminal ANG II were furosemide sensitive and abolished by the AT(1) receptor blocker candesartan. ANG II at 10(-6) M failed to stimulate the cotransporter, whereas increased cotransport activity could be restored by blocking AT(2) receptors with PD-123, 319. Thus ANG II may modulate TGF responses via alterations in MD Na-2Cl-K cotransport activity.

  1. Molecular characterization of a putative K-Cl cotransporter in rat brain. A neuronal-specific isoform.

    Science.gov (United States)

    Payne, J A; Stevenson, T J; Donaldson, L F

    1996-07-05

    Using a combination of data base searching, polymerase chain reaction, and library screening, we have identified a putative K-Cl cotransporter isoform (KCC2) in rat brain that is specifically localized in neurons. A cDNA of 5566 bases was obtained from overlapping clones and encoded a protein of 1116 amino acids with a deduced molecular mass of 123.6 kDa. Over its full length, the amino acid sequence of KCC2 is 67% identical to the widely distributed K-Cl cotransporter isoform (KCC1) identified in rat brain and rabbit kidney (Gillen, C., Brill, S., Payne, J.A., and Forbush, B., III(1996) J. Biol. Chem. 271, 16237-16244) but only approximately25% identical to other members of the cation-chloride cotransporter gene family, including "loop" diuretic-sensitive Na-K-Cl cotransport and thiazide-sensitive Na-Cl cotransport. Based on analysis of the primary structure as well as homology with other cation-chloride cotransporters, we predict 12 transmembrane segments bounded by N- and C-terminal cytoplasmic regions. Four sites for N-linked glycosylation are predicted on an extracellular intermembrane loop between putative transmembrane segments 5 and 6. Northern blot analysis using a KCC2-specific cDNA probe revealed a very highly expressed approximately5.6-kilobase transcript only in brain. Reverse transcriptase-polymerase chain reaction revealed that KCC1 was present in rat primary astrocytes and rat C6 glioma cells but that KCC2 was completely absent from these cells, suggesting KCC2 was not of glial cell origin. In situ hybridization studies demonstrated that the KCC2 transcript was expressed at high levels in neurons throughout the central nervous system, including CA1-CA4 pyramidal neurons of the hippocampus, granular cells and Purkinje neurons of the cerebellum, and many groups of neurons throughout the brainstem.

  2. Bilateral Renal Mass-Renal Disorder: Tuberculosis

    Directory of Open Access Journals (Sweden)

    Ozlem Tiryaki

    2013-01-01

    Full Text Available A 30-year-old woman has presented complaining of weakness and fatigue to her primary care physician. The renal sonography is a routine step in the evaluation of new onset renal failure. When the renal masses have been discovered by sonography in this setting, the functional imaging may be critical. We reported a case about bilateral renal masses in a young female patient with tuberculosis and renal insufficiency. Magnetic resonance (MR has revealed the bilateral renal masses in patient, and this patient has been referred to our hospital for further management. The patient’s past medical and surgical history was unremarkable.

  3. Distal renal tubular acidosis

    Science.gov (United States)

    Renal tubular acidosis - distal; Renal tubular acidosis type I; Type I RTA; RTA - distal; Classical RTA ... excreting it into the urine. Distal renal tubular acidosis (Type I RTA) is caused by a defect ...

  4. Proximal renal tubular acidosis

    Science.gov (United States)

    Renal tubular acidosis - proximal; Type II RTA; RTA - proximal; Renal tubular acidosis type II ... by alkaline substances, mainly bicarbonate. Proximal renal tubular acidosis (Type II RTA) occurs when bicarbonate is not ...

  5. 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

  6. Renale Osteopathie

    Directory of Open Access Journals (Sweden)

    Horn S

    2001-01-01

    Full Text Available Die renale Osteopathie umfaßt Erkrankungen des Knochens, die bei Patienten mit chronischen Nierenerkrankungen auftreten, wie den sekundären bzw. tertiären Hyperparathyreoidismus, die adynamische Knochenerkrankung und die Osteopathie nach Nierentransplantation. Durch die Identifikation des Kalzium-Sensing-Rezeptors bzw. des Vitamin D-Rezeptors hat sich unser Verständnis der Zusammenhänge in den letzten Jahren erheblich verbessert. Neue Medikamente versprechen effizientere Prophylaxe- und Therapiemöglichkeiten. Wir beeinflussen dadurch nicht nur die Morbidität und Lebensqualität, sondern auch die Mortalität unserer Patienten.

  7. Renal disease in pregnancy.

    Science.gov (United States)

    Thorsen, Martha S; Poole, Judith H

    2002-03-01

    Anatomic and physiologic adaptations within the renal system during pregnancy are significant. Alterations are seen in renal blood flow and glomerular filtration, resulting in changes in normal renal laboratory values. When these normal renal adaptations are coupled with pregnancy-induced complications or preexisting renal dysfunction, the woman may demonstrate a reduction of renal function leading to an increased risk of perinatal morbidity and mortality. This article will review normal pregnancy adaptations of the renal system and discuss common pregnancy-related renal complications.

  8. Novel molecular variants of the Na-Cl cotransporter gene are responsible for Gitelman syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Mastroianni, N.; De Fusco, M.; Casari, G. [Univsersita` di Milano (Italy)] [and others

    1996-11-01

    A hereditary defect of the distal tubule accounts for the clinical features of Gitelman syndrome (GS), an autosomal recessive disease characterized by hypokalemia, hypomagnesemia, metabolic alkalosis, and hypocalciuria. Recently, we cloned the cDNA coding for the human Na-Cl thiazide-sensitive cotransporter (TSC; also known as {open_quotes}NCCT{close_quotes} or {open_quotes}SLC12A3{close_quotes}) as a possible candidate for GS, and Simon et al., independently, described rotation in patients with GS. Now, we show 12 additional mutations consistent with a loss of function of the Na-Cl cotransporter in GS. Two missense replacements, R09W and P349L, are common to both studies and could represent ancient mutations. The other mutations include three deletions, two insertions, and six missense mutations. When all mutations from both studies are considered, missense mutations seem to be more frequently localized within the intracellular domains of the molecule, rather than in transmembrane or extracellular domains. One family, previously reported as a GS form with dominant inheritance, has proved to be recessive, with the affected child being a compound heterozygote. A highly informative intragenic tetranucleotide marker, useful for molecular diagnostic studies, has been identified at the acceptor splice site of exon 9. 12 refs., 3 figs., 2 tabs.

  9. Sites of regulated phosphorylation that control K-Cl cotransporter activity.

    Science.gov (United States)

    Rinehart, Jesse; Maksimova, Yelena D; Tanis, Jessica E; Stone, Kathryn L; Hodson, Caleb A; Zhang, Junhui; Risinger, Mary; Pan, Weijun; Wu, Dianqing; Colangelo, Christopher M; Forbush, Biff; Joiner, Clinton H; Gulcicek, Erol E; Gallagher, Patrick G; Lifton, Richard P

    2009-08-07

    Modulation of intracellular chloride concentration ([Cl(-)](i)) plays a fundamental role in cell volume regulation and neuronal response to GABA. Cl(-) exit via K-Cl cotransporters (KCCs) is a major determinant of [Cl(-)](I); however, mechanisms governing KCC activities are poorly understood. We identified two sites in KCC3 that are rapidly dephosphorylated in hypotonic conditions in cultured cells and human red blood cells in parallel with increased transport activity. Alanine substitutions at these sites result in constitutively active cotransport. These sites are highly phosphorylated in plasma membrane KCC3 in isotonic conditions, suggesting that dephosphorylation increases KCC3's intrinsic transport activity. Reduction of WNK1 expression via RNA interference reduces phosphorylation at these sites. Homologous sites are phosphorylated in all human KCCs. KCC2 is partially phosphorylated in neonatal mouse brain and dephosphorylated in parallel with KCC2 activation. These findings provide insight into regulation of [Cl(-)](i) and have implications for control of cell volume and neuronal function.

  10. 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...

  11. RP-HPLC法测定浓维磷糖浆中咖啡因和维生素B1的含量%RP-HPLC determination of the content of caffeine and vitamine B1 in concentrated divitamins and sodium phosphate syrup

    Institute of Scientific and Technical Information of China (English)

    陈雪帆; 包瑶瑶

    2012-01-01

    目的:采用反相高效液相色谱法测定浓维磷糖浆中咖啡因和维生素B1的含量.方法:采用Diamonsil C18柱(250 mm×4.6 rnm,5μm),以甲醇-庚烷磺酸钠缓冲液为流动相(10:90),检测波长为272 nm.结果:咖啡因与维生素B1浓度分别在3.5 μg/ml ~282.6 μg/ml(r=1.0000)和0.7μg/ml ~ 54.7 μg/ml(r =0.9999)内与峰面积呈良好的线性关系(n=9),方法回收率(n=9)分别为99.2%和99.1%,RSD分别为1.8%和1.7%.结论:该方法操作简便,结果准确可靠,可以有效地控制产品质量.%Objective:To establish a method for determination of caffeine and vitamine B, in concentrated divita-mins and sodium phosphate syrup. Methods: The reversed phase HPLC system consisted of a C,, column (250 mm *4.6 mm,5 μm). The mobile phase consisted of methanol and heptanesulfonate sodium( 10:90) , and the wavelength of detector was 272 nm. Results: The linear response range of caffeine and vitamine Bl were 3. 5 μg/ml~ 282.6 μg/m\\(r = 1.0000) and 0.7 μg/ml~54.7 μg/ml (r = 0.9999), respectively(n =9). The average recovery rates (n = 9) of caffeine and vitamine B, were 99.2% (RSD = 1.8%) and 99. 1 % (RSD = 1.7%), respectively. Conclusion:This method is simple and convenient in work. It is accurate and suitable for the quality control.

  12. 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

    1979-01-01

    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 potassi

  13. 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

    1979-01-01

    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 potassi

  14. 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

    H-sensitive fluorophores, we showed that Na(+) ,HCO(3) (-) -cotransport is the predominant mechanism of acid extrusion and is inhibited 34 ± 9% by 200 µM 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid in human primary breast carcinomas. At intracellular pH (pH(i) ) levels >6.6, CO(2) /HCO(3) (-) -dependent mechanisms...

  15. Determination of the Na(+)/glucose cotransporter (SGLT1) turnover rate using the ion-trap technique.

    Science.gov (United States)

    Longpré, Jean-Philippe; Lapointe, Jean-Yves

    2011-01-05

    The Na(+)/glucose cotransporter (SGLT1) is a membrane protein that couples the transport of two Na(+) ions and one glucose molecule using the so-called alternating access mechanism. According to this principle, each cotransporter molecule can adopt either of two main conformations: one with the binding sites accessible to the extracellular solution and one with the binding sites facing the intracellular solution. The turnover rate (TOR) is the number of complete cycles that each protein performs per second. Determination of the TOR has important consequences for investigation of the cotransport mechanism, as none of the rate constants involved in mediating transport in a given direction (conformational changes and binding and unbinding reactions) can be slower than the TOR measured under the same conditions. In addition, the TOR can be used to estimate the number of cotransporter molecules involved in generating a given ensemble activity. In this study, we obtain an independent estimation of the TOR for human SGLT1 expressed in Xenopus laevis oocytes applying the ion-trap technique. This approach detects the quantity of ions released in or taken up from the restricted space existing between the oocyte plasma membrane and the tip of a large ion-selective electrode. Taking advantage of the fact that hSGLT1 in the absence of Na(+) can cotransport glucose with protons, we used a pH electrode to determine a TOR of 8.00 ± 1.3 s⁻¹ in the presence of 35 mM α-methyl-glucose at -150 mV (pH 5.5). For the same group of oocytes, a TOR of 13.3 ± 2.4 s⁻¹ was estimated under near-V(max) conditions, i.e., in the presence of 90 mM Na(+) and 5 mM α-methyl-glucose. Under these circumstances, the average cotransport current was -1.08 ± 0.61 μA (n = 14), and this activity was generated by an average of 3.6 ± 0.7 × 10¹¹ cotransporter molecules/oocyte. Copyright © 2011 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  16. Determination of the Na+/Glucose Cotransporter (SGLT1) Turnover Rate Using the Ion-Trap Technique

    Science.gov (United States)

    Longpré, Jean-Philippe; Lapointe, Jean-Yves

    2011-01-01

    The Na+/glucose cotransporter (SGLT1) is a membrane protein that couples the transport of two Na+ ions and one glucose molecule using the so-called alternating access mechanism. According to this principle, each cotransporter molecule can adopt either of two main conformations: one with the binding sites accessible to the extracellular solution and one with the binding sites facing the intracellular solution. The turnover rate (TOR) is the number of complete cycles that each protein performs per second. Determination of the TOR has important consequences for investigation of the cotransport mechanism, as none of the rate constants involved in mediating transport in a given direction (conformational changes and binding and unbinding reactions) can be slower than the TOR measured under the same conditions. In addition, the TOR can be used to estimate the number of cotransporter molecules involved in generating a given ensemble activity. In this study, we obtain an independent estimation of the TOR for human SGLT1 expressed in Xenopus laevis oocytes applying the ion-trap technique. This approach detects the quantity of ions released in or taken up from the restricted space existing between the oocyte plasma membrane and the tip of a large ion-selective electrode. Taking advantage of the fact that hSGLT1 in the absence of Na+ can cotransport glucose with protons, we used a pH electrode to determine a TOR of 8.00 ± 1.3 s−1 in the presence of 35 mM α-methyl-glucose at −150 mV (pH 5.5). For the same group of oocytes, a TOR of 13.3 ± 2.4 s−1 was estimated under near-Vmax conditions, i.e., in the presence of 90 mM Na+ and 5 mM α-methyl-glucose. Under these circumstances, the average cotransport current was −1.08 ± 0.61 μA (n = 14), and this activity was generated by an average of 3.6 ± 0.7 × 1011 cotransporter molecules/oocyte. PMID:21190656

  17. Renal actinomycosis with concomitant renal vein thrombosis.

    Science.gov (United States)

    Chang, Dong-Suk; Jang, Won Ik; Jung, Ji Yoon; Chung, Sarah; Choi, Dae Eun; Na, Ki-Ryang; Lee, Kang Wook; Shin, Yong-Tai

    2012-02-01

    Renal actinomycosis is a rare infection caused by fungi of the genus Actinomyces. A 74-year-old male was admitted to our hospital because of gross hematuria with urinary symptoms and intermittent chills. Computed tomography of the abdomen showed thrombosis in the left renal vein and diffuse, heterogeneous enlargement of the left kidney. After nephrectomy, sulfur granules with chronic suppurative inflammation were seen microscopically, and the histopathological diagnosis was renal actinomycosis. Our case is the first report of renal actinomycosis with renal vein thrombosis.

  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. Renal failure

    Institute of Scientific and Technical Information of China (English)

    1993-01-01

    930564 Dwell times affect the local host de-fence mechanism of peritoneal dialysis patients.WANG Tao(汪涛),et al.Renal Instit,SunYatsen Med Univ,Guangzhou,510080.Chin JNephrol 1993;9(2):75—77.The effect of different intraperitoneal awelltimes on the local host defence in 6 peritonealdialysis patients was studied.A significant de-crease in the number of peritoneal cells,IgG con-centration and the phagoeytosis and bactericidalactivity of macrophages was determined when thedwell time decreased from 12 to 4 hs or form 4 to0.5hs,but the peroxidase activity in macrophagesincreased significantly.All variables,except theperoxidase activity in macrophages,showed nosignificant difference between patients of high or

  20. Traumatismo renal

    OpenAIRE

    Rocha, Sofia Rosa Moura Gomes da

    2009-01-01

    Introdução: A realização deste trabalho visa a elaboração de uma revisão sistematizada subordinada à temática da traumatologia renal. Objectivos: Os principais objectivos deste trabalho são: apurar a etiologia, definir a classificação, analisar o diagnóstico e expôr o tratamento e as complicações. Desenvolvimento: Os traumatismos são a principal causa de morte antes dos 40 anos. O rim é o órgão do aparelho génito-urinário mais frequentemente atingido. Os traumatismos renais são mais fre...

  1. Using Recombinant Human Granulocyte Colony-Stimulating Factor Plus Dexamethasone Sodium Phosphate Mobilize and Apheresis Granulocyte%重组人粒细胞集落刺激因子加地塞米松磷酸钠动员单采粒细胞

    Institute of Scientific and Technical Information of China (English)

    孙琼芝

    2013-01-01

    目的 探讨采用动员剂和血细胞分离机采集粒细胞的效果.方法 选择2011年12月至2012年9月,于本血站行无偿献血的52名献血者作为研究对象.采用重组人粒细胞集落刺激因子(G-CSF)联合地塞米松磷酸钠动员献血者外周血粒细胞,用血细胞分离机采集粒细胞,分析动员剂的动员效果及影响采集效量的因素.、结果 采用动员剂动员后,献血者外周血白细胞(WBC)和中性粒细胞计数(NEUT)分别提高了4和7倍,动员前后比较,差异有统计学意义(P<0.05).本组52份粒细胞平均采集耗时为(201±83)min,处理抗凝全血为(4209±806)mL,抗凝剂枸橼酸枸橼酸钠-葡萄糖A方用量为(394±83)mL,粒细胞制品体积为(283±46)mL,制品粒细胞含量为(2.18±0.81)×1010.女性献血者粒细胞制品含量为(1.77±0.82)×1010,男性为(2.48±0.67)×1010,男性献血者粒细胞采集量高于女性献血者(t=3.331,P=0.002),单因素线形回归分析结果显示献血者采集前血细胞比容(HCT)、血红蛋白含量(Hb)、WBC计数和NEUT水平与粒细胞采集量之间呈正相关关系(P<0.05);多因素线形回归分析结果显示粒细胞采集量与献血者采集前Hb(P=0.030)和NEUT(P=0.037)相关.结论 重组人G-CSF联合地塞米松磷酸钠能有效动员献血者外周血粒细胞,采用血细胞分离机可采集足够剂量的粒细胞用于临床输注.%Objective To explore the effect of mobilization agents and blood cell separator for apheresis granulocyte.Methods From December 2011 to September 2012,52 donors who donated blood in our station were included into this study.Recombinant human granulocyte colony-stimulating factor (G-CSF) plus dexamethasone sodium phosphate were used mobilizing donors' granulocyte,and apheresis granulocyte were performed on the blood cell separator.The mobilization effective and the factors that effected product content were analyzed.Results After using mobilizing agent,the peripheral blood

  2. Ipragliflozin: A novel sodium-glucose cotransporter 2inhibitor developed in Japan

    Institute of Scientific and Technical Information of China (English)

    Tsuyoshi Ohkura

    2015-01-01

    Sodium-glucose cotransporter 2 (SGLT2) inhibitioninduces glucosuria and decreases blood glucose levelsin diabetic patients and lowers hypoglycemic risk.SGLT1 is expressed in the kidney and intestine; SGLT1inhibition causes abdominal symptoms such as diarrheaand reduces incretin secretion. Therefore, SGLT2selectivity is important. Ipragliflozin is highly selectivefor SGLT2. In type 2 diabetes mellitus (T2DM), urinaryglucose excretion increased to 90 g/24 h after 28 d oftreatment with ipragliflozin 300 mg/d. Twelve weeksof ipragliflozin 50 mg/d vs placebo reduced glycatedhemoglobin and body weight by 0.65% and 0.66kg, respectively, in Western T2DM patients, and by1.3% and 1.89 kg, respectively, in Japanese patients.Ipragliflozin (highly selective SGLT2 inhibitor) improvesglycemic control and reduces body weight andlowers hypoglycemic risk and abdominal symptoms.Ipragliflozin can be a novel anti-diabetic and antiobesityagent.

  3. Extended life-span conferred by cotransporter gene mutations in Drosophila.

    Science.gov (United States)

    Rogina, B; Reenan, R A; Nilsen, S P; Helfand, S L

    2000-12-15

    Aging is genetically determined and environmentally modulated. In a study of longevity in the adult fruit fly, Drosophila melanogaster, we found that five independent P-element insertional mutations in a single gene resulted in a near doubling of the average adult life-span without a decline in fertility or physical activity. Sequence analysis revealed that the product of this gene, named Indy (for I'm not dead yet), is most closely related to a mammalian sodium dicarboxylate cotransporter-a membrane protein that transports Krebs cycle intermediates. Indy was most abundantly expressed in the fat body, midgut, and oenocytes: the principal sites of intermediary metabolism in the fly. Excision of the P element resulted in a reversion to normal life-span. These mutations may create a metabolic state that mimics caloric restriction, which has been shown to extend life-span.

  4. 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

    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......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...... are pending. SGLT-2i are now in guidelines as a possible second-line therapy or in case of metformin intolerance....

  5. Chronic noradrenaline increases renal expression of NHE-3, NBC-1, BSC-1 and aquaporin-2.

    Science.gov (United States)

    Sonalker, Prajakta A; Tofovic, Stevan P; Bastacky, Sheldon I; Jackson, Edwin K

    2008-05-01

    1. Because chronic activation of the renal sympathetic nervous system promotes sodium and water retention, it is conceivable that long-term exposure of the kidney to the sympathetic neurotransmitter noradrenaline upregulates the expression of key renal epithelial transport systems. 2. To test this hypothesis, we used immunoblotting of renal cortical and medullary tissue to investigate the abundance of major transport systems expressed along the renal tubule in response to long-term (15 days) infusions of noradrenaline (600 ng/min) in rats. 3. Mean arterial blood pressure and heart rate were significantly elevated in rats receiving chronic infusions of noradrenaline (128 +/- 10 mmHg and 492 +/- 16 b.p.m., respectively) compared with animals treated with saline only (89 +/- 3 mmHg and 376 +/- 14 b.p.m., respectively). 4. Chronic infusions of noradrenaline also increased the protein abundance of the cortical Na(+)/H(+) exchanger isoform 3 (NHE-3; 2.5-fold; P = 0.0142), the cortical sodium-bicarbonate cotransporter NBC-1 (2.5-fold; P = 0.0067), the bumetanide-sensitive sodium-potassium-chloride cotransporter BSC-1/NKCC2 in the inner stripe of outer medulla (threefold; P = 0.0020) and aquaporin-2 in the inner medulla (twofold; P = 0.0039). 5. In contrast, noradrenaline did not significantly affect expression of the thiazide-sensitive Na(+)-Cl(-) cotransporter in the cortex, Na(+)/K(+)-ATPase-alpha(1) in the cortex and inner stripe of the outer or inner medulla, the inwardly rectifying K(+) channel (ROMK-1) in the inner stripe of the outer medulla or aquaporin-1 in the cortex or inner medulla. Noradrenaline did significantly, but modestly (less than twofold), increase aquaporin-1 in the inner stripe of the outer medulla. 6. We conclude that noradrenaline-induced increases in the expression of NHE-3, NBC-1, BSC-1 and aquaporin-2 are likely to play an important role in the regulation of salt and water transport by noradrenaline in the kidney and may explain, at least in

  6. Essential role for NHERF in cAMP-mediated inhibition of the Na+-HCO3- co-transporter in BSC-1 cells.

    Science.gov (United States)

    Weinman, E J; Evangelista, C M; Steplock, D; Liu, M Z; Shenolikar, S; Bernardo, A

    2001-11-01

    Prior studies have indicated a requirement for the PDZ domain-containing protein, Na(+)/H(+) Exchanger Regulatory Factor (NHERF), for protein kinase A (PKA)-mediated inhibition of the renal basolateral Na(+)-HCO(3)(-) co-transporter (NBC). The present studies explore the potential mechanisms by which NHERF transduces cAMP signals to inhibit NBC. In BSC-1 cells, cells that express NBC but lack NHERF, 8-bromo-cAMP (100 microm for 15 min) failed to inhibit transport until wild-type mNHERF-(1-355) was expressed. mNHERF-(116-355) containing PDZ II and C-terminal ezrin-binding sequences or a mutant unphosphorylated form of rabbit NHERF effectively transduced the cAMP signals that inhibited NBC. By contrast, mNHERF-(1-126) encompassing N-terminal PDZ I and mNHERF-(1-325), which lacks ezrin-binding, failed to support cAMP inhibition of NBC activity. NBC and NHERF did not associate with each other in yeast two-hybrid or co-immunoprecipitation assays, and confocal microscopy indicated distinct subcellular localization of the two proteins. NBC was phosphorylated in BSC-1 cells, but its phosphorylation was not increased by cAMP nor was immunoprecipitated NBC phosphorylated by PKA in vitro. Acute exposure of mNHERF-(1-355)-expressing BSC-1 cells to cAMP did not change cell surface expression of NBC. Although these results established an essential role for NHERF in cAMP-mediated inhibition of NBC in BSC-1 cells, they also suggest a novel mechanism for NHERF-mediated signal transduction distinct from that previously characterized from studies of other NHERF targets.

  7. Paradoxical activation of the sodium chloride cotransporter (NCC) without hypertension in kidney deficient in a regulatory subunit of Na,K-ATPase, FXYD2.

    Science.gov (United States)

    Arystarkhova, Elena; Ralph, Donna L; Liu, Yi Bessie; Bouley, Richard; McDonough, Alicia A; Sweadner, Kathleen J

    2014-12-01

    Na,K-ATPase generates the driving force for sodium reabsorption in the kidney. Na,K-ATPase functional properties are regulated by small proteins belonging to the FXYD family. In kidney FXYD2 is the most abundant: it is an inhibitory subunit expressed in almost every nephron segment. Its absence should increase sodium pump activity and promote Na(+) retention, however, no obvious renal phenotype was detected in mice with global deletion of FXYD2 (Arystarkhova et al. 2013). Here, increased total cortical Na,K-ATPase activity was documented in the Fxyd2(-/-) mouse, without increased α1β1 subunit expression. We tested the hypothesis that adaptations occur in distal convoluted tubule (DCT), a major site of sodium adjustments. Na,K-ATPase immunoreactivity in DCT was unchanged, and there was no DCT hypoplasia. There was a marked activation of thiazide-sensitive sodium chloride cotransporter (NCC; Slc12a3) in DCT, predicted to increase Na(+) reabsorption in this segment. Specifically, NCC total increased 30% and NCC phosphorylated at T53 and S71, associated with activation, increased 4-6 fold. The phosphorylation of the closely related thick ascending limb (TAL) apical NKCC2 (Slc12a1) increased at least twofold. Abundance of the total and cleaved (activated) forms of ENaC α-subunit was not different between genotypes. Nonetheless, no elevation of blood pressure was evident despite the fact that NCC and NKCC2 are in states permissive for Na(+) retention. Activation of NCC and NKCC2 may reflect an intracellular linkage to elevated Na,K-ATPase activity or a compensatory response to Na(+) loss proximal to the TAL and DCT. © 2014 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  8. LP-925219 maximizes urinary glucose excretion in mice by inhibiting both renal SGLT1 and SGLT2

    OpenAIRE

    Powell, David R.; Smith, Melinda G; Doree, Deon D; Harris, Angela L; Xiong, Wendy W; Mseeh, Faika; Wilson, Alan; Gopinathan, Suma; Diaz, Damaris; Goodwin, Nicole C.; Harrison, Bryce; Strobel, Eric; Rawlins, David B.; Carson, Ken; Zambrowicz, Brian

    2015-01-01

    Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a new class of oral anti-diabetic agents that improve glycemic control by inhibiting SGLT2-mediated renal glucose reabsorption. Currently available agents increase urinary glucose excretion (UGE) to 50% of filtered glucose when SGLT2 is completely inhibited. This led us to test whether LP-925219, a small molecule dual SGLT1/SGLT2 inhibitor, increases UGE to maximal values in wild-type (WT) mice. We first tested LP-925219 inhibition of gluc...

  9. 2型糖尿病治疗靶点钠-葡萄糖共转运蛋白2抑制剂研究进展%Research progress of sodium-glucose co-transporter 2 inhibitors for treatment of type 2 diabetes

    Institute of Scientific and Technical Information of China (English)

    万惠新; 沈竞康

    2012-01-01

    Sodium-glucose co-transporters are a family of glucose transporter found in the intestinal mucosa of the small intestine (SGLT-2) and the proximal tubule of the nephron (SGLT-1 and SGLT-2). They contribute to renal glucose reabsorption and most of renal glucose (about 90%) is reabsorbed by SGLT-2 located in the proximal renal tubule. Selectively inhibiting activity of SGLT-2 is an innovative therapeutic strategy for treatment of type 2 diabetes by enhancing urinary glucose excretion from the body. Therefore SGLT-2 inhibitors are considered to be potential antidiabetic drugs with an unique mechanism. This review will highlight some recent advances and structure-activity relationships in the discovery and development of SGLT-2 inhibitors including O-glycoside, C-glycoside, C, 0-spiro glycoside and non glycosides.%钠—葡萄糖共转运蛋白2 (sodium-glucose co-transporter2,SGLT-2)分布在肾脏近曲小管S1部位,负责肾脏中约90%葡萄糖的重吸收,抑制SGLT-2可以促进糖尿病患者尿糖的排出,因此SGLT-2抑制剂被认为是一种新型的具有独特作用机制的抗糖尿病药物.本文按照化合物的结构特征分类,重点介绍O-芳基糖苷类、C-芳基糖苷类、O,C-螺环芳基糖苷类、N-芳基糖苷类以及非糖苷类SGLT-2抑制剂的构效关系以及最新研究进展.

  10. Canagliflozin use in patients with renal impairment-Utility of quantitative clinical pharmacology analyses in dose optimization.

    Science.gov (United States)

    Khurana, Manoj; Vaidyanathan, Jayabharathi; Marathe, Anshu; Mehrotra, Nitin; Sahajwalla, Chandrahas G; Zineh, Issam; Jain, Lokesh

    2015-06-01

    Canagliflozin (INVOKANA™) is approved as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus (T2DM). Canagliflozin inhibits renal sodium-glucose co-transporter 2 (SGLT2), thereby, reducing reabsorption of filtered glucose and increasing urinary glucose excretion. Given the mechanism of action of SGLT2 inhibitors, we assessed the interplay between renal function, efficacy (HbA1c reduction), and safety (renal adverse reactions). The focus of this article is to highlight the FDA's quantitative clinical pharmacology analyses that were conducted to support the regulatory decision on dosing in patients with renal impairment (RI). The metrics for assessment of efficacy for T2DM drugs is standard; however, there is no standard method for evaluation of renal effects for diabetes drugs. Therefore, several analyses were conducted to assess the impact of canagliflozin on renal function (as measured by eGFR) based on available data. These analyses provided support for approval of canagliflozin in T2DM patients with baseline eGFR ≥ 45 mL/min/1.73 m(2) , highlighting a data-driven approach to dose optimization. The availability of a relatively rich safety dataset (ie, frequent and early measurements of laboratory markers) in the canagliflozin clinical development program enabled adequate assessment of benefit-risk balance in various patient subgroups based on renal function. © 2015, The American College of Clinical Pharmacology.

  11. Estradiol reduces activity of the blood-brain barrier Na-K-Cl cotransporter and decreases edema formation in permanent middle cerebral artery occlusion.

    Science.gov (United States)

    O'Donnell, Martha E; Lam, Tina I; Tran, Lien Q; Foroutan, Shahin; Anderson, Steven E

    2006-10-01

    Estrogen has been shown to protect against stroke-induced brain damage, yet the mechanism is unknown. During the early hours of stroke, cerebral edema forms as increased transport of Na and Cl from blood into brain occurs across an intact blood-brain barrier (BBB). We showed previously that a luminal BBB Na-K-Cl cotransporter is stimulated by hypoxia and arginine vasopressin (AVP), factors present during cerebral ischemia, and that inhibition of the cotransporter by intravenous bumetanide greatly reduces edema in rats subjected to permanent middle cerebral artery occlusion (MCAO). The present study was conducted to determine whether estrogen protects in stroke at least in part by reducing activity of the BBB cotransporter, thereby decreasing edema formation. Ovariectomized rats were subjected to 210 mins of permanent MCAO after 7-day or 30-min pretreatment with 17beta-estradiol and then brain swelling and 2,3,5-triphenyltetrazolium chloride staining were assessed as measures of brain edema and lesion volume, respectively. Diffusion-weighed imaging was used to monitor permanent MCAO-induced decreases in apparent diffusion coefficient (ADC) values, an index of changes in brain water distribution and mobility. Na-K-Cl cotransporter activity of cerebral microvascular endothelial cells (CMECs) was assessed as bumetanide-sensitive K influx and cotransporter abundance by Western blot analysis after estradiol treatment. Estradiol significantly decreased brain swelling and lesion volume and attenuated the decrease in ADC values during permanent MCAO. Estradiol also abolished CMEC cotransporter stimulation by chemical hypoxia or AVP and decreased cotransporter abundance. These findings support the hypothesis that estrogen attenuates stimulation of BBB Na-K-Cl cotransporter activity, reducing edema formation during stroke.

  12. Pharmacodynamic effects of canagliflozin, a sodium glucose co-transporter 2 inhibitor, from a randomized study in patients with type 2 diabetes.

    Directory of Open Access Journals (Sweden)

    Sue Sha

    Full Text Available This randomized, double-blind, placebo-controlled, single and multiple ascending-dose study evaluated the pharmacodynamic effects and safety/tolerability of canagliflozin, a sodium glucose co-transporter 2 inhibitor, in patients with type 2 diabetes.Patients (N = 116 discontinued their antihyperglycemic medications 2 weeks before randomization. Patients received canagliflozin 30, 100, 200, or 400 mg once daily or 300 mg twice daily, or placebo at 2 study centers in the United States and Germany, or canagliflozin 30 mg once daily or placebo at 1 study center in Korea, while maintaining an isocaloric diet for 2 weeks. On Days -1, 1, and 16, urinary glucose excretion (UGE, plasma glucose (PG, fasting PG (FPG, and insulin were measured. The renal threshold for glucose (RTG was calculated from UGE, PG, and estimated glomerular filtration rate. Safety was evaluated based on adverse event (AE reports, vital signs, electrocardiograms, clinical laboratory tests, and physical examinations.Canagliflozin increased UGE dose-dependently (,80-120 g/day with canagliflozin $100 mg, with increases maintained over the 14-day dosing period with each dose. Canagliflozin dose-dependently decreased RTG, with maximal reductions to ,4-5 mM (72-90 mg/dL. Canagliflozin also reduced FPG and 24-hour mean PG; glucose reductions were seen on Day 1 and maintained over 2 weeks. Plasma insulin reductions with canagliflozin were consistent with observed PG reductions. Canagliflozin also reduced body weight. AEs were transient, mild to moderate in intensity, and balanced across groups; 1 canagliflozin-treated female reported an episode of vaginal candidiasis. Canagliflozin did not cause hypoglycemia, consistent with the RTG values remaining above the hypoglycemia threshold. At Day 16, there were no clinically meaningful changes in urine volume, urine electrolyte excretion, renal function, or routine laboratory test values.Canagliflozin increased UGE and decreased RTG, leading to

  13. Pharmacodynamic effects of canagliflozin, a sodium glucose co-transporter 2 inhibitor, from a randomized study in patients with type 2 diabetes.

    Directory of Open Access Journals (Sweden)

    Sue Sha

    Full Text Available INTRODUCTION: This randomized, double-blind, placebo-controlled, single and multiple ascending-dose study evaluated the pharmacodynamic effects and safety/tolerability of canagliflozin, a sodium glucose co-transporter 2 inhibitor, in patients with type 2 diabetes. METHODS: Patients (N = 116 discontinued their antihyperglycemic medications 2 weeks before randomization. Patients received canagliflozin 30, 100, 200, or 400 mg once daily or 300 mg twice daily, or placebo at 2 study centers in the United States and Germany, or canagliflozin 30 mg once daily or placebo at 1 study center in Korea, while maintaining an isocaloric diet for 2 weeks. On Days -1, 1, and 16, urinary glucose excretion (UGE, plasma glucose (PG, fasting PG (FPG, and insulin were measured. The renal threshold for glucose (RTG was calculated from UGE, PG, and estimated glomerular filtration rate. Safety was evaluated based on adverse event (AE reports, vital signs, electrocardiograms, clinical laboratory tests, and physical examinations. RESULTS: Canagliflozin increased UGE dose-dependently (∼80-120 g/day with canagliflozin ≥100 mg, with increases maintained over the 14-day dosing period with each dose. Canagliflozin dose-dependently decreased RTG, with maximal reductions to ∼4-5 mM (72-90 mg/dL. Canagliflozin also reduced FPG and 24-hour mean PG; glucose reductions were seen on Day 1 and maintained over 2 weeks. Plasma insulin reductions with canagliflozin were consistent with observed PG reductions. Canagliflozin also reduced body weight. AEs were transient, mild to moderate in intensity, and balanced across groups; 1 canagliflozin-treated female reported an episode of vaginal candidiasis. Canagliflozin did not cause hypoglycemia, consistent with the RTG values remaining above the hypoglycemia threshold. At Day 16, there were no clinically meaningful changes in urine volume, urine electrolyte excretion, renal function, or routine laboratory test values. CONCLUSIONS

  14. Pharmacodynamic Effects of Canagliflozin, a Sodium Glucose Co-Transporter 2 Inhibitor, from a Randomized Study in Patients with Type 2 Diabetes

    Science.gov (United States)

    Sha, Sue; Devineni, Damayanthi; Ghosh, Atalanta; Polidori, David; Hompesch, Marcus; Arnolds, Sabine; Morrow, Linda; Spitzer, Heike; Demarest, Keith; Rothenberg, Paul

    2014-01-01

    Introduction This randomized, double-blind, placebo-controlled, single and multiple ascending-dose study evaluated the pharmacodynamic effects and safety/tolerability of canagliflozin, a sodium glucose co-transporter 2 inhibitor, in patients with type 2 diabetes. Methods Patients (N = 116) discontinued their antihyperglycemic medications 2 weeks before randomization. Patients received canagliflozin 30, 100, 200, or 400 mg once daily or 300 mg twice daily, or placebo at 2 study centers in the United States and Germany, or canagliflozin 30 mg once daily or placebo at 1 study center in Korea, while maintaining an isocaloric diet for 2 weeks. On Days –1, 1, and 16, urinary glucose excretion (UGE), plasma glucose (PG), fasting PG (FPG), and insulin were measured. The renal threshold for glucose (RTG) was calculated from UGE, PG, and estimated glomerular filtration rate. Safety was evaluated based on adverse event (AE) reports, vital signs, electrocardiograms, clinical laboratory tests, and physical examinations. Results Canagliflozin increased UGE dose-dependently (∼80–120 g/day with canagliflozin ≥100 mg), with increases maintained over the 14-day dosing period with each dose. Canagliflozin dose-dependently decreased RTG, with maximal reductions to ∼4–5 mM (72–90 mg/dL). Canagliflozin also reduced FPG and 24-hour mean PG; glucose reductions were seen on Day 1 and maintained over 2 weeks. Plasma insulin reductions with canagliflozin were consistent with observed PG reductions. Canagliflozin also reduced body weight. AEs were transient, mild to moderate in intensity, and balanced across groups; 1 canagliflozin-treated female reported an episode of vaginal candidiasis. Canagliflozin did not cause hypoglycemia, consistent with the RTG values remaining above the hypoglycemia threshold. At Day 16, there were no clinically meaningful changes in urine volume, urine electrolyte excretion, renal function, or routine laboratory test values. Conclusions

  15. A role for the circadian clock protein Per1 in the regulation of the NaCl co-transporter (NCC) and the with-no-lysine kinase (WNK) cascade in mouse distal convoluted tubule cells.

    Science.gov (United States)

    Richards, Jacob; Ko, Benjamin; All, Sean; Cheng, Kit-Yan; Hoover, Robert S; Gumz, Michelle L

    2014-04-25

    It has been well established that blood pressure and renal function undergo circadian fluctuations. We have demonstrated that the circadian protein Per1 regulates multiple genes involved in sodium transport in the collecting duct of the kidney. However, the role of Per1 in other parts of the nephron has not been investigated. The distal convoluted tubule (DCT) plays a critical role in renal sodium reabsorption. Sodium is reabsorbed in this segment through the actions of the NaCl co-transporter (NCC), which is regulated by the with-no-lysine kinases (WNKs). The goal of this study was to test if Per1 regulates sodium transport in the DCT through modulation of NCC and the WNK kinases, WNK1 and WNK4. Pharmacological blockade of nuclear Per1 entry resulted in decreased mRNA expression of NCC and WNK1 but increased expression of WNK4 in the renal cortex of mice. These findings were confirmed by using Per1 siRNA and pharmacological blockade of Per1 nuclear entry in mDCT15 cells, a model of the mouse distal convoluted tubule. Transcriptional regulation was demonstrated by changes in short lived heterogeneous nuclear RNA. Chromatin immunoprecipitation experiments demonstrated interaction of Per1 and CLOCK with the promoters of NCC, WNK1, and WNK4. This interaction was modulated by blockade of Per1 nuclear entry. Importantly, NCC protein expression and NCC activity, as measured by thiazide-sensitive, chloride-dependent (22)Na uptake, were decreased upon pharmacological inhibition of Per1 nuclear entry. Taken together, these data demonstrate a role for Per1 in the transcriptional regulation of NCC, WNK1, and WNK4.

  16. A Role for the Circadian Clock Protein Per1 in the Regulation of the NaCl Co-transporter (NCC) and the with-no-lysine Kinase (WNK) Cascade in Mouse Distal Convoluted Tubule Cells*

    Science.gov (United States)

    Richards, Jacob; Ko, Benjamin; All, Sean; Cheng, Kit-Yan; Hoover, Robert S.; Gumz, Michelle L.

    2014-01-01

    It has been well established that blood pressure and renal function undergo circadian fluctuations. We have demonstrated that the circadian protein Per1 regulates multiple genes involved in sodium transport in the collecting duct of the kidney. However, the role of Per1 in other parts of the nephron has not been investigated. The distal convoluted tubule (DCT) plays a critical role in renal sodium reabsorption. Sodium is reabsorbed in this segment through the actions of the NaCl co-transporter (NCC), which is regulated by the with-no-lysine kinases (WNKs). The goal of this study was to test if Per1 regulates sodium transport in the DCT through modulation of NCC and the WNK kinases, WNK1 and WNK4. Pharmacological blockade of nuclear Per1 entry resulted in decreased mRNA expression of NCC and WNK1 but increased expression of WNK4 in the renal cortex of mice. These findings were confirmed by using Per1 siRNA and pharmacological blockade of Per1 nuclear entry in mDCT15 cells, a model of the mouse distal convoluted tubule. Transcriptional regulation was demonstrated by changes in short lived heterogeneous nuclear RNA. Chromatin immunoprecipitation experiments demonstrated interaction of Per1 and CLOCK with the promoters of NCC, WNK1, and WNK4. This interaction was modulated by blockade of Per1 nuclear entry. Importantly, NCC protein expression and NCC activity, as measured by thiazide-sensitive, chloride-dependent 22Na uptake, were decreased upon pharmacological inhibition of Per1 nuclear entry. Taken together, these data demonstrate a role for Per1 in the transcriptional regulation of NCC, WNK1, and WNK4. PMID:24610784

  17. Kidney (Renal) Failure

    Science.gov (United States)

    ... How is kidney failure treated? What is kidney (renal) failure? The kidneys are designed to maintain proper fluid ... marrow and strengthen the bones. The term kidney (renal) failure describes a situation in which the kidneys have ...

  18. Renal arteries (image)

    Science.gov (United States)

    A renal angiogram is a test used to examine the blood vessels of the kidneys. The test is performed ... main vessel of the pelvis, up to the renal artery that leads into the kidney. Contrast medium ...

  19. Allodynia and hyperalgesia in diabetic rats are mediated by GABA and depletion of spinal potassium-chloride co-transporters

    OpenAIRE

    2008-01-01

    Diabetic rats show behavioral indices of painful neuropathy that may model the human condition. Hyperalgesia during the formalin test in diabetic rats is accompanied by the apparently paradoxical decrease in spinal release of excitatory neurotransmitters and increase in the inhibitory neurotransmitter GABA. Decreased expression of the potassium-chloride co-transporter, KCC2, in the spinal cord promotes excitatory properties of GABA. We therefore measured spinal KCC2 expression and explored th...

  20. Expressions of ion co-transporter genes in salicylate-induced tinnitus and treatment effects of spirulina.

    Science.gov (United States)

    Hwang, Juen-Haur; Chan, Yin-Ching

    2016-09-02

    Although the activity of tinnitus-related ion co-transporter are known, their mRNA expressions has seldom been reported. We aimed to investigate the mRNA expressions of tinnitus-related ion co-transporter genes, and treatment effects of Spirulina. The mRNA expressions of K(+)-Cl(-) co-transporter (KCC2) and Na-K-2Cl co-transporter 1 (NKCC1) genes in the cochlea and brain of mice were evaluated after tinnitus was induced by intraperitoneal injection of salicylate. The effects of spirulina water extract on these gene expressions were investigated. Compared to the control group, the tinnitus scores increased significantly, however, the salicylate-induced tinnitus could be reduced significantly by spirulina water extract. The tinnitus group had higher of borderline significance mRNA expression of KCC2 gene in the cochlear, significantly higher in the temporal lobes and in the frontal lobes. Meanwhile, compared to the tinnitus group, the spirulina group had significantly lower mRNA expression of KCC2 gene in the cochlear, temporal lobes, frontal lobes and parahippocampus/hippocampus. However, the NKCC1 mRNA expression was not significantly different between three groups in the cochlea and these brain areas. Salicylate-induced tinnitus might be associated with increased mRNA expression of KCC2 gene, but not with mRNA expressions of NKCC1 gene in the cochlear and some tinnitus-related brain areas. Spirulina reduced the expression of KCC2 genes in salicylate-induced tinnitus.

  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...... increased risk in non-serious adverse events. The analyses may overestimate the intervention benefit due bias....

  2. Determinants of Substrate and Cation Transport in the Human Na+/Dicarboxylate Cotransporter NaDC3*

    OpenAIRE

    Schlessinger, A; Sun, NN; Colas, C; Pajor, AM

    2014-01-01

    Metabolic intermediates, such as succinate and citrate, regulate important processes ranging from energy metabolism to fatty acid synthesis. Cytosolic concentrations of these metabolites are controlled, in part, by members of the SLC13 gene family. The molecular mechanism underlying Na+-coupled di- and tricarboxylate transport by this family is understood poorly. The human Na+/dicarboxylate cotransporter NaDC3 (SLC13A3) is found in various tissues, including the kidney, liver, and brain. In a...

  3. [Renal leiomyoma. Case report].

    Science.gov (United States)

    Joual, A; Guessous, H; Rabii, R; Benjelloun, M; Benlemlih, A; Skali, K; el Mrini, M; Benjelloun, S

    1999-01-01

    The authors report a case of renal leiomyoma observed in a 56-year-old man. This cyst presented in the from of loin pain. Computed tomography revealed a homogeneous renal tumor. Treatment consisted of radical nephrectomy. Histological examination of the specimen showed benign renal leiomyoma.

  4. 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...

  5. Effect of Size-Selective Retention on the Cotransport of Hydroxyapatite and Goethite Nanoparticles in Saturated Porous Media.

    Science.gov (United States)

    Wang, Dengjun; Jin, Yan; Jaisi, Deb P

    2015-07-21

    Attributable to their nanoscale size and slow phosphorus (P) release kinetics, hydroxyapatite nanoparticles (HANPs) are increasingly advocated as a promising P nanofertilizer. Additionally, HANPs have been extensively used to remediate soils, groundwater, and nuclear wastewaters contaminated with metals and radionuclides. Increasing application of HANPs for agronomic and environmental advantages will expedite their dissemination in subsurface environments. Because the biogeochemical cycling of P is intimately coupled with iron, it is anticipated that HANPs and released P from HANPs interact with iron oxides, particularly naturally occurring goethite nanoparticles (GNPs) because of their nanoscale size and high reactivity toward P. Here, we investigated the cotransport and retention of HANPs and GNPs in water-saturated sand columns under environmentally relevant transport conditions (pH and natural organic matter type and concentration). Our results indicated that the "size-selective retention", i.e., preferential retention of larger particles near the column inlet and elution of smaller particles occurred during cotransport of HANPs and GNPs, and the cotransport of both NPs is highly sensitive to solution chemistry that determines NPs dissolution, homo- and heteroaggregation, and co- and competitive-retention. These findings have important insights into application of HANPs as a promising P nanofertilizer and an in situ amendment for contaminated site remediation.

  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. Postpartum renal vein thrombosis.

    Science.gov (United States)

    Rubens, D; Sterns, R H; Segal, A J

    1985-01-01

    Renal vein thrombosis in adults is usually a complication of the nephrotic syndrome. Rarely, it has been reported in nonnephrotic women postpartum. The thrombosis may be a complication of the hypercoagulable state associated with both the nephrotic syndrome and pregnancy. Two postpartum patients with renal vein thrombosis and no prior history of renal disease are reported here. Neither patient had heavy proteinuria. In both cases, pyelonephritis was suspected clinically and the diagnosis of renal vein thrombosis was first suggested and confirmed by radiologic examination. Renal vein thrombosis should be considered in women presenting postpartum with flank pain.

  8. Renal infarction resulting from traumatic renal artery dissection.

    Science.gov (United States)

    Kang, Kyung Pyo; Lee, Sik; Kim, Won; Jin, Gong Yong; Na, Ki Ryang; Yun, Il Yong; Park, Sung Kwang

    2008-06-01

    Renal artery dissection may be caused by iatrogenic injury, trauma, underlying arterial diseases such as fibromuscular disease, atherosclerotic disease, or connective tissue disease. Radiological imaging may be helpful in detecting renal artery pathology, such as renal artery dissection. For patients with acute, isolated renal artery dissection, surgical treatment, endovascular management, or medical treatment have been considered effective measures to preserve renal function. We report a case of renal infarction that came about as a consequence of renal artery dissection.

  9. 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.

  10. 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.

  11. 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.

  12. Sodium glucose co-transporter inhibitors – A new class of old drugs

    Science.gov (United States)

    Malhotra, Aneeta; Kudyar, Surbhi; Gupta, Anil K.; Kudyar, Rattan P.; Malhotra, Pavan

    2015-01-01

    Sodium glucose co-transporter (SGLT) inhibitors are a new class of drugs which are used in the pharmacotherapy of Type-II diabetes, which happens to be a major risk factor for developing both micro as well as macro-vascular complications. These drugs inhibit the glucose reabsorption by inhibiting SGLT, which exhibits a novel and promising mechanism of action by promoting the urinary glucose excretion hence providing a basis of therapeutic intervention. Results of SGLT-II inhibitors are very encouraging as there is a significant elevation of GLP-1 level, which forms the basis of relevance in treatment of diabetes. It targets the HbA1C and keeps a check on its levels. It also exerts other positive benefits such as weight loss, reduction in blood glucose levels, reduction in blood pressure and improvement in insulin resistance and β-cell dysfunction: All contributing to effective glycemic control. SGLT inhibition will develop as effective modality as it has the capability of inhibiting reabsorption of greater percentage of filtered glucose load. PMID:26539362

  13. Blocking effect of colloids on arsenate adsorption during co-transport through saturated sand columns.

    Science.gov (United States)

    Ma, Jie; Guo, Huaming; Lei, Mei; Wan, Xiaoming; Zhang, Hanzhi; Feng, Xiaojuan; Wei, Rongfei; Tian, Liyan; Han, Xiaokun

    2016-06-01

    Transport of environmental pollutants through porous media is influenced by colloids. Co-transport of As(V) and soil colloids at different pH were systematically investigated by monitoring breakthrough curves (BTCs) in saturated sand columns. A solute transport model was applied to characterize transport and retention sites of As(V) in saturated sand in the presence of soil colloids. A colloid transport model and the DLVO theory were used to reveal the mechanism and hypothesis of soil colloid-promoted As(V) transport in the columns. Results showed that rapid transport of soil colloids, regulated by pH and ionic strength, promoted As(V) transport by blocking As(V) adsorption onto sand, although soil colloids had low adsorption for As(V). The promoted transport was more significant at higher concentrations of soil colloids (between 25 mg L(-1) and 150 mg L(-1)) due to greater blocking effect on As(V) adsorption onto the sand surfaces. The blocking effect of colloids was explained by the decreases in both instantaneous (equilibrium) As adsorption and first-order kinetic As adsorption on the sand surface sites. The discovery of this blocking effect improves our understanding of colloid-promoted As transport in saturated porous media, which provides new insights into role of colloids, especially colloids with low As adsorption capacity, in As transport and mobilization in soil-groundwater systems. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. 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.

  15. Prolactin regulates transcription of the ion uptake Na+/Cl- cotransporter (ncc) gene in zebrafish gill

    Science.gov (United States)

    Breves, Jason P.; Serizier, Sandy B.; Goffin, Vincent; McCormick, Stephen D.; Karlstrom, Rolf O.

    2013-01-01

    Prolactin (PRL) is a well-known regulator of ion and water transport within osmoregulatory tissues across vertebrate species, yet how PRL acts on some of its target tissues remains poorly understood. Using zebrafish as a model, we show that ionocytes in the gill directly respond to systemic PRL to regulate mechanisms of ion uptake. Ion-poor conditions led to increases in the expression of PRL receptor (prlra), Na+/Cl− cotransporter (ncc; slc12a10.2), Na+/H+ exchanger (nhe3b; slc9a3.2), and epithelial Ca2+ channel (ecac; trpv6) transcripts within the gill. Intraperitoneal injection of ovine PRL (oPRL) increased ncc and prlra transcripts, but did not affect nhe3b or ecac. Consistent with direct PRL action in the gill, addition of oPRL to cultured gill filaments stimulated ncc in a concentration-dependent manner, an effect blocked by a pure human PRL receptor antagonist (Δ1-9-G129R-hPRL). These results suggest that PRL signaling through PRL receptors in the gill regulates the expression of ncc, thereby linking this pituitary hormone with an effector of Cl− uptake in zebrafish for the first time.

  16. Na+-K+-2Cl- cotransporter type 2 trafficking and activity: the role of interacting proteins.

    Science.gov (United States)

    Carmosino, Monica; Procino, Giuseppe; Svelto, Maria

    2012-04-01

    The central role of Na+-K+-2Cl- cotransporter type 2 (NKCC2) in vectorial transepithelial salt reabsorption in thick ascending limb cells from Henle's loop in the kidney is evidenced by the effects of loop diuretics, the pharmacological inhibitors of NKCC2, that are amongst the most powerful antihypertensive drugs available to date. Moreover, genetic mutations of the NKCC2 encoding gene resulting in impaired apical targeting and function of NKCC2 transporter give rise to a pathological phenotype known as type I Bartter syndrome, characterised by a severe volume depletion, hypokalaemia and metabolic alkalosis with high prenatal mortality. On the contrary, excessive NKCC2 activity has been linked with inherited hypertension in humans and in rodent models. Interestingly, in animal models of hypertension, NKCC2 upregulation is achieved by post-translational mechanisms underlining the need to analyse the molecular mechanisms involved in the regulation of NKCC2 trafficking and activity to gain insights in the pathogenesis of hypertension. Copyright © 2012 Soçiété Francaise des Microscopies and Société de Biologie Cellulaire de France.

  17. Co-transport of metal complexes by the green mussel Perna viridis.

    Science.gov (United States)

    Chuang, Chia-Ying; Wang, Wen-Xiong

    2006-07-15

    We examined the uptake of ligand-bound metals (Cd and Zn) by the green mussel Perna viridis using defined artificial seawater. Different free ion concentrations (1 pM to 10 microM) in uptake solutions were created by adding different amounts of total metals (Cd 0.1 nM to 0.1 mM; Zn 0.5 nM to 0.05 mM) and ligands (EDTA, NTA, citric acid). Our results showed that Cd and Zn uptake could not be fully explained by the free Cd and Zn concentrations in the presence of different ligands, indicating that metal-ligand complexes were at least partially available for uptake by the mussels. Total Zn concentrations appeared to be a better predictor of metal uptake than the free Zn ion concentrations in the presence of different ligands. Uptake of lipophilic organic metal complexes was substantially greater than the hydrophilic metal complexes, even though the free ion concentration was comparable or lower. Moreover, the radiolabeled ligand compounds were directly accumulated by the mussels. The accumulation of metal complexes may explain the increased metal uptake with increasing ligand and total metal concentration, even though the free ion metal concentration was constant. Overall, our experimental results indicated that free metal ion cannot fully explain metal uptake since metal complex species were also available to the mussels to some extent, apparently through a co-transport process.

  18. Protein kinase C induces endocytosis of the sodium taurocholate cotransporting polypeptide.

    Science.gov (United States)

    Stross, Claudia; Helmer, Angelika; Weissenberger, Katrin; Görg, Boris; Keitel, Verena; Häussinger, Dieter; Kubitz, Ralf

    2010-08-01

    Bile salts influence signaling and metabolic pathways. In hepatocytes, the sodium taurocholate cotransporting polypeptide (Ntcp) is a major determinant of intracellular bile salt levels. Short-term downregulation of Ntcp is not well characterized to date. FLAG and enhanced green fluorescent protein (EGFP) tags were cloned to the extra- and intracellular termini of Ntcp. Endocytosis of Ntcp in transfected HepG2 cells was visualized by fluorescence of EGFP, and membrane surface expression of Ntcp was quantified by flow cytometry with fluorochrome-labeled FLAG antibodies. Activation of protein kinase C (PKC) by phorbolester or thymeleatoxin an activator of Ca(2+)-dependent conventional PKCs (cPKCs), induced endocytosis of Ntcp, whereas the Na(+)-K(+)-ATPase remained in the plasma membrane. The PKC inhibitor BIM I and the cPKC-selective inhibitor Gö6976 abolished PMA-induced endocytosis. Because of this internalization, cell surface expression of Ntcp was reduced by 36 +/- 7%, bile salt uptake was decreased by 25%, and taurolithocholate sulfate-induced cell toxicity was prevented. In conclusion, Ca(2+)-dependent PKCs induce vesicular retrieval of Ntcp, thereby reducing bile salt uptake. This mechanism may protect hepatocytes from toxic intracellular bile salt concentrations.

  19. Sodium-glucose cotransporter inhibition: therapeutic potential for the treatment of type 2 diabetes mellitus.

    Science.gov (United States)

    Raskin, Philip

    2013-07-01

    Results from randomized controlled trials have demonstrated that the risk of microvascular complications can be reduced by intensive glycaemic control in patients with type 2 diabetes mellitus (T2DM). However, only about half of patients with diagnosed diabetes achieve recommended glycaemic goals. New therapies with complementary mechanisms of action that are independent of insulin secretion or action may provide additional therapeutic options to enable patients to achieve glycaemic control. The kidney plays an important role in glucose homeostasis, primarily by the reabsorption of filtered glucose. The sodium-glucose cotransporter 2 (SGLT2), located in the proximal convoluted tubule, is responsible for the majority of glucose reabsorption by the kidney. SGLT2 inhibitors offer a novel approach to treat T2DM and reduce hyperglycaemia by increasing urinary excretion of glucose. Dapagliflozin, an SGLT2 inhibitor recently approved in Europe for the treatment of T2DM, improves glycaemic control in patients with T2DM when used as monotherapy or when added to other diabetes medications, such as metformin, sulfonylureas, pioglitazone, and insulin. As a class, SGLT2 inhibitors are well tolerated and have a low propensity to cause hypoglycaemia. An increase in signs, symptoms, and other events suggestive of genital and, in some studies, urinary tract infections has been reported with SGLT2 inhibitors. Results from ongoing and future clinical trials will help define the role for this new class of investigational compounds, with its unique mechanism of action, as a treatment option for reducing hyperglycaemia in patients with T2DM.

  20. Drosophila glia use a conserved cotransporter mechanism to regulate extracellular volume.

    Science.gov (United States)

    Leiserson, William M; Forbush, Biff; Keshishian, Haig

    2011-02-01

    The nervous system is protected by blood barriers that use multiple systems to control extracellular solute composition, osmotic pressure, and fluid volume. In the human nervous system, misregulation of the extracellular volume poses serious health threats. Here, we show that the glial cells that form the Drosophila blood-nerve barrier have a conserved molecular mechanism that regulates extracellular volume: the Serine/Threonine kinase Fray, which we previously showed is an ortholog of mammalian PASK/SPAK; and the Na-K-Cl cotransporter Ncc69, which we show is an ortholog of human NKCC1. In mammals, PASK/SPAK binds to NKCC1 and regulates its activity. In Drosophila, larvae mutant for Ncc69 develop a peripheral neuropathy, where fluid accumulates between glia and axons. The accumulation of fluid has no detectable impact on action potential conduction, suggesting that the role of Ncc69 is to maintain volume or osmotic homeostasis. Drosophila Ncc69 has kinetics similar to human NKCC1, and NKCC1 can rescue Ncc69, suggesting that they function in a conserved physiological mechanism. We show that fray and Ncc69 are coexpressed in nerve glia, interact in a yeast-two-hybrid assay, and have an essentially identical bulging nerve phenotype. We propose that normally functioning nerves generate extracellular solutes that are removed by Ncc69 under the control of Fray. This mechanism may perform a similar role in humans, given that NKCC1 is expressed at the blood-brain barrier.

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

    Science.gov (United States)

    Singh, Awadhesh Kumar

    2015-01-01

    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. PMID:26693421

  2. Euglycemic Diabetic Ketoacidosis: A Potential Complication of Treatment With Sodium–Glucose Cotransporter 2 Inhibition

    Science.gov (United States)

    Buschur, Elizabeth O.; Buse, John B.; Cohan, Pejman; Diner, Jamie C.; Hirsch, Irl B.

    2015-01-01

    OBJECTIVE Sodium–glucose cotransporter 2 (SGLT-2) inhibitors are the most recently approved antihyperglycemic medications. We sought to describe their association with euglycemic diabetic ketoacidosis (euDKA) in hopes that it will enhance recognition of this potentially life-threatening complication. RESEARCH DESIGN AND METHODS Cases identified incidentally are described. RESULTS We identified 13 episodes of SGLT-2 inhibitor–associated euDKA or ketosis in nine individuals, seven with type 1 diabetes and two with type 2 diabetes, from various practices across the U.S. The absence of significant hyperglycemia in these patients delayed recognition of the emergent nature of the problem by patients and providers. CONCLUSIONS SGLT-2 inhibitors seem to be associated with euglycemic DKA and ketosis, perhaps as a consequence of their noninsulin-dependent glucose clearance, hyperglucagonemia, and volume depletion. Patients with type 1 or type 2 diabetes who experience nausea, vomiting, or malaise or develop a metabolic acidosis in the setting of SGLT-2 inhibitor therapy should be promptly evaluated for the presence of urine and/or serum ketones. SGLT-2 inhibitors should only be used with great caution, extensive counseling, and close monitoring in the setting of type 1 diabetes. PMID:26078479

  3. Carbonic anhydrase II increases the activity of the human electrogenic Na+/HCO3- cotransporter.

    Science.gov (United States)

    Becker, Holger M; Deitmer, Joachim W

    2007-05-04

    Several acid/base-coupled membrane transporters, such as the electrogenic sodium-bicarbonate cotransporter (NBCe1), have been shown to bind to different carbonic anhydrase isoforms to create a "transport metabolon." We have expressed NBCe1 derived from human kidney in oocytes of Xenopus leavis and determined its transport activity by recording the membrane current in voltage clamp, and the cytosolic H(+) and Na(+) concentrations using ion-selective microelectrodes. When carbonic anhydrase isoform II (CAII) had been injected into oocytes, the membrane current and the rate of cytosolic Na(+) rise, indicative for NBCe1 activity, increased significantly with the amount of injected CAII (2-200 ng). The CAII inhibitor ethoxyzolamide reversed the effects of CAII on the NBCe1 activity. Co-expressing wild-type CAII or NH(2)-terminal mutant CAII together with NBCe1 provided similar results, whereas co-expressing the catalytically inactive CAII mutant V143Y had no effect on NBCe1 activity. Mass spectrometric analysis and the rate of cytosolic H(+) change following addition of CO(2)/HCO(3)(-) confirmed the catalytic activity of injected and expressed CAII in oocytes. Our results show that the transport capacity of NBCe1 is enhanced by the catalytic activity of CAII, in line with the notion that CAII forms a transport metabolon with NBCe1.

  4. The sodium chloride cotransporter (NCC) and epithelial sodium channel (ENaC) associate.

    Science.gov (United States)

    Mistry, Abinash C; Wynne, Brandi M; Yu, Ling; Tomilin, Viktor; Yue, Qiang; Zhou, Yiqun; Al-Khalili, Otor; Mallick, Rickta; Cai, Hui; Alli, Abdel A; Ko, Benjamin; Mattheyses, Alexa; Bao, Hui-Fang; Pochynyuk, Oleh; Theilig, Franziska; Eaton, Douglas C; Hoover, Robert S

    2016-10-01

    The thiazide-sensitive sodium chloride cotransporter (NCC) and the epithelial sodium channel (ENaC) are two of the most important determinants of salt balance and thus systemic blood pressure. Abnormalities in either result in profound changes in blood pressure. There is one segment of the nephron where these two sodium transporters are coexpressed, the second part of the distal convoluted tubule. This is a key part of the aldosterone-sensitive distal nephron, the final regulator of salt handling in the kidney. Aldosterone is the key hormonal regulator for both of these proteins. Despite these shared regulators and coexpression in a key nephron segment, associations between these proteins have not been investigated. After confirming apical localization of these proteins, we demonstrated the presence of functional transport proteins and native association by blue native PAGE. Extensive coimmunoprecipitation experiments demonstrated a consistent interaction of NCC with α- and γ-ENaC. Mammalian two-hybrid studies demonstrated direct binding of NCC to ENaC subunits. Fluorescence resonance energy transfer and immunogold EM studies confirmed that these transport proteins are within appropriate proximity for direct binding. Additionally, we demonstrate that there are functional consequences of this interaction, with inhibition of NCC affecting the function of ENaC. This novel finding of an association between ENaC and NCC could alter our understanding of salt transport in the distal tubule. © 2016 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

  5. Prolactin regulates transcription of the ion uptake Na+/Cl- cotransporter (ncc) gene in zebrafish gill.

    Science.gov (United States)

    Breves, Jason P; Serizier, Sandy B; Goffin, Vincent; McCormick, Stephen D; Karlstrom, Rolf O

    2013-04-30

    Prolactin (PRL) is a well-known regulator of ion and water transport within osmoregulatory tissues across vertebrate species, yet how PRL acts on some of its target tissues remains poorly understood. Using zebrafish as a model, we show that ionocytes in the gill directly respond to systemic PRL to regulate mechanisms of ion uptake. Ion-poor conditions led to increases in the expression of PRL receptor (prlra), Na(+)/Cl(-) cotransporter (ncc; slc12a10.2), Na(+)/H(+) exchanger (nhe3b; slc9a3.2), and epithelial Ca(2+) channel (ecac; trpv6) transcripts within the gill. Intraperitoneal injection of ovine PRL (oPRL) increased ncc and prlra transcripts, but did not affect nhe3b or ecac. Consistent with direct PRL action in the gill, addition of oPRL to cultured gill filaments stimulated ncc in a concentration-dependent manner, an effect blocked by a pure human PRL receptor antagonist (Δ1-9-G129R-hPRL). These results suggest that PRL signaling through PRL receptors in the gill regulates the expression of ncc, thereby linking this pituitary hormone with an effector of Cl(-) uptake in zebrafish for the first time. Copyright © 2013. Published by Elsevier Ireland Ltd.

  6. Clopidogrel attenuates lithium-induced alterations in renal water and sodium channels/transporters in mice.

    Science.gov (United States)

    Zhang, Yue; Peti-Peterdi, János; Heiney, Kristina M; Riquier-Brison, Anne; Carlson, Noel G; Müller, Christa E; Ecelbarger, Carolyn M; Kishore, Bellamkonda K

    2015-12-01

    Lithium (Li) administration causes deranged expression and function of renal aquaporins and sodium channels/transporters resulting in nephrogenic diabetes insipidus (NDI). Extracellular nucleotides (ATP/ADP/UTP), via P2 receptors, regulate these transport functions. We tested whether clopidogrel bisulfate (CLPD), an antagonist of ADP-activated P2Y(12) receptor, would affect Li-induced alterations in renal aquaporins and sodium channels/transporters. Adult mice were treated for 14 days with CLPD and/or Li and euthanized. Urine and kidneys were collected for analysis. When administered with Li, CLPD ameliorated polyuria, attenuated the rise in urine prostaglandin E2 (PGE2), and resulted in significantly higher urinary arginine vasopressin (AVP) and aldosterone levels as compared to Li treatment alone. However, urine sodium excretion remained elevated. Semi-quantitative immunoblotting revealed that CLPD alone increased renal aquaporin 2 (AQP2), Na-K-2Cl cotransporter (NKCC2), Na-Cl cotransporter (NCC), and the subunits of the epithelial Na channel (ENaC) in medulla by 25-130 %. When combined with Li, CLPD prevented downregulation of AQP2, Na-K-ATPase, and NKCC2 but was less effective against downregulation of cortical α- or γ-ENaC (70 kDa band). Thus, CLPD primarily attenuated Li-induced downregulation of proteins involved in water conservation (AVP-sensitive), with modest effects on aldosterone-sensitive proteins potentially explaining sustained natriuresis. Confocal immunofluorescence microscopy revealed strong labeling for P2Y(12)-R in proximal tubule brush border and blood vessels in the cortex and less intense labeling in medullary thick ascending limb and the collecting ducts. Therefore, there is the potential for CLPD to be directly acting at the tubule sites to mediate these effects. In conclusion, P2Y(12)-R may represent a novel therapeutic target for Li-induced NDI.

  7. Refractory anemia leading to renal hemosiderosis and renal failure

    OpenAIRE

    Sujatha Siddappa; K M Mythri; Kowsalya, R.; Ashish Parekh

    2011-01-01

    Renal hemosiderosis is a rare cause of renal failure and, as a result, may not be diagnosed unless a detailed history, careful interpretation of blood parameters and renal biopsy with special staining is done. Here, we present a rare case of renal hemosiderosis presenting with renal failure.

  8. Refractory anemia leading to renal hemosiderosis and renal failure

    Directory of Open Access Journals (Sweden)

    Sujatha Siddappa

    2011-01-01

    Full Text Available Renal hemosiderosis is a rare cause of renal failure and, as a result, may not be diagnosed unless a detailed history, careful interpretation of blood parameters and renal biopsy with special staining is done. Here, we present a rare case of renal hemosiderosis presenting with renal failure.

  9. Renal replacement therapy for acute renal failure.

    Science.gov (United States)

    Macedo, E; Bouchard, J; Mehta, R L

    2009-09-01

    Renal replacement therapy became a common clinical tool to treat patients with severe acute kidney injury (AKI) since the 1960s. During this time dialytic options have expanded considerably; biocompatible membranes, bicarbonate dialysate and dialysis machines with volumetric ultrafiltration control have improved the treatment for acute kidney injury. Along with advances in methods of intermittent hemodialysis, continuous renal replacement therapies have gained widespread acceptance in the treatment of dialysis-requiring AKI. However, many of the fundamental aspects of the renal replacement treatment such as indication, timing of dialytic intervention, and choice of dialysis modality are still controversial and may influence AKI patient's outcomes. This review outlines current concepts in the use of dialysis techniques for AKI and suggests an approach for selecting the optimal method of renal replacement therapy.

  10. Altered expression of renal NHE3, TSC, BSC-1, and ENaC subunits in potassium-depleted rats.

    Science.gov (United States)

    Elkjaer, Marie-Louise; Kwon, Tae-Hwan; Wang, Weidong; Nielsen, Jakob; Knepper, Mark A; Frøkiaer, Jørgen; Nielsen, Søren

    2002-12-01

    The purpose of this study was to examine whether hypokalemia is associated with altered abundance of major renal Na+ transporters that may contribute to the development of urinary concentrating defects. We examined the changes in the abundance of the type 3 Na+/H+ exchanger (NHE3), Na+ - K+-ATPase, the bumetanide-sensitive Na+ - K+ - 2Cl- cotransporter (BSC-1), the thiazide-sensitive Na+ - Cl- cotransporter (TSC), and epithelial sodium channel (ENaC) subunits in kidneys of hypokalemic rats. Semiquantitative immunoblotting revealed that the abundance of BSC-1 (57%) and TSC (46%) were profoundly decreased in the inner stripe of the outer medulla (ISOM) and cortex/outer stripe of the outer medulla (OSOM), respectively. These findings were confirmed by immunohistochemistry. Moreover, total kidney abundance of all ENaC subunits was significantly reduced in response to the hypokalemia: alpha-subunit (61%), beta-subunit (41%), and gamma-subunit (60%), and this was confirmed by immunohistochemistry. In contrast, the renal abundance of NHE3 in hypokalemic rats was dramatically increased in cortex/OSOM (736%) and ISOM (210%). Downregulation of BSC-1, TSC, and ENaC may contribute to the urinary concentrating defect, whereas upregulation of NHE3 may be compensatory to prevent urinary Na+ loss and/or to maintain intracellular pH levels.

  11. Renal function after renal artery stenting

    Institute of Scientific and Technical Information of China (English)

    George S. Hanzel; Mark Downes; Peter A. McCullough

    2005-01-01

    @@ Atherosclerotic renal artery stenosis (ARAS), a common clinical finding, is increasing in prevalence as the population ages. ARAS is seen in ~ 7% of persons over 65 years of age1 and in ~ 20% of patients at the time of coronary angiography.2 It is an important cause of chronic kidney disease and may result in 11-14% of cases of end stage renal disease.3

  12. Heterozygous disruption of renal outer medullary potassium channel in rats is associated with reduced blood pressure.

    Science.gov (United States)

    Zhou, Xiaoyan; Zhang, Zuo; Shin, Myung Kyun; Horwitz, Sarah Beth; Levorse, John M; Zhu, Lei; Sharif-Rodriguez, Wanda; Streltsov, Denis Y; Dajee, Maya; Hernandez, Melba; Pan, Yi; Urosevic-Price, Olga; Wang, Li; Forrest, Gail; Szeto, Daphne; Zhu, Yonghua; Cui, Yan; Michael, Bindhu; Balogh, Leslie Ann; Welling, Paul A; Wade, James B; Roy, Sophie; Sullivan, Kathleen A

    2013-08-01

    The renal outer medullary potassium channel (ROMK, KCNJ1) mediates potassium recycling and facilitates sodium reabsorption through the Na(+)/K(+)/2Cl(-) cotransporter in the loop of Henle and potassium secretion at the cortical collecting duct. Human genetic studies indicate that ROMK homozygous loss-of-function mutations cause type II Bartter syndrome, featuring polyuria, renal salt wasting, and hypotension; humans heterozygous for ROMK mutations identified in the Framingham Heart Study have reduced blood pressure. ROMK null mice recapitulate many of the features of type II Bartter syndrome. We have generated an ROMK knockout rat model in Dahl salt-sensitive background by using zinc finger nuclease technology and investigated the effects of knocking out ROMK on systemic and renal hemodynamics and kidney histology in the Dahl salt-sensitive rats. The ROMK(-/-) pups recapitulated features identified in the ROMK null mice. The ROMK(+/-) rats, when challenged with a 4% salt diet, exhibited a reduced blood pressure compared with their ROMK(+/+) littermates. More importantly, when challenged with an 8% salt diet, the Dahl salt-sensitive rats with 50% less ROMK expression showed increased protection from salt-induced blood pressure elevation and signs of protection from renal injury. Our findings in ROMK knockout Dahl salt-sensitive rats, together with the previous reports in humans and mice, underscore a critical role of ROMK in blood pressure regulation.

  13. 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.

  14. 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...

  15. Insuficiencia renal aguda.

    OpenAIRE

    Carlos Hernán Mejía

    2009-01-01

    Acute renal failure (ARF) is a clinic syndrome characterized by decline in renal function occurring over a short time period. Is a relatively common complication in hospitalized critically ill patients and is associated with high morbidity and mortality. ARF has often a multi-factorial etiology syndrome usually approached diagnostically as pre-renal, post-renal, or intrinsic ARF. Most intrinsic ARF is caused by ischemia or nephrotoxins and is classically associated with acute tubular necrosis...

  16. 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

    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...

  17. 钠葡萄糖协同转运子2抑制剂:糖尿病治疗的新选择%Sodium glucose co-transporter 2 inhibitors: A novel option for the treatment of diabetes

    Institute of Scientific and Technical Information of China (English)

    袁璐; 李倩; 高谷; 马建华

    2010-01-01

    钠葡萄糖协同转运子2(SGLT2)是几乎仅在近曲小管表达的跨膜蛋白,介导了90%滤过葡萄糖的重吸收,SGLT2抑制剂可特异性抑制肾小管对滤过葡萄糖的重吸收,增加尿糖排泄,发挥降糖作用.SGLT2抑制剂还具有促进体重下降,间接改善肥胖的作用.根皮苷作为人类最早发现的SGLT2抑制剂,研究较为局限,随着T-1095、serglilozin、dapagliflozin等新型SGLT2抑制剂的开发,SCLT2抑制剂在治疗糖尿病上的有效性和安全性得到了进一步论证,为糖尿病治疗提供了新选择.%The sodium glucose co-transporter 2 ( SGLT2 ) located in the plasma membrane of cells lining the proximal tubule mediates 90 percent of renal glucose reabsorption from the tubular fluid. Competitive inhibitors of SGLT2 that provoke the renal excretion of glucose have been discovered, which can lower the elevated blood glucose levels in patients with diabetes. The SGLT2 inhibitors also play roles in weight loss,which can improve the obesity. As the earliest SGLT2 inhibitor,the research of phlorizin are limited. With the development of novel SGLT2 inhibitors,such as T-1095, serglilozin and dapagliflozin, the efficacy and safety of SGLT2 inhibitors in the terms of treating diabetes has been further confirmed,so the SGLT2 inhibitors provide new approaches to the treatment of diabetes mellitus.

  18. Heterozygous mutations of the sodium chloride cotransporter in Chinese children: prevalence and association with blood pressure.

    Science.gov (United States)

    Hsu, Yu-Juei; Yang, Sung-Sen; Chu, Nain-Feng; Sytwu, Huey-Kang; Cheng, Chih-Jen; Lin, Shih-Hua

    2009-04-01

    Gitelman's syndrome (GS), which is caused by homozygous or compound heterozygous mutations of the thiazide-sensitive sodium chloride cotransporter (NCC), usually manifests in children and is associated with low blood pressure. However, the prevalence of heterozygous NCC mutations and their association with blood pressure in children have not yet been studied. Five hundred unrelated children from the Taipei Children Heart Study were enrolled. Genomic DNA was isolated from peripheral blood and the SLC12A3 gene was amplified by polymerase chain reaction (PCR). The 15 NCC mutations previously identified in Chinese patients with GS were evaluated using restriction fragment length polymorphism (RFLP) analysis. Blood pressure, biochemistry and urine pH were measured. The allelic frequency of heterozygous NCC mutations and their association with low blood pressure were also investigated. RFLP analysis for the 15 NCC mutations revealed heterozygous T60M in 1 child, T163M in 1, S283Y in 4, R642C in 2, W844X in 2, R928C in 9 and R959frameshift in 10 children. The overall incidence of positive heterozygous NCC mutations was approximately 2.9%. There were no significant differences in systolic or diastolic blood pressure, biochemical profiles or urine pH between children with heterozygous NCC mutations (n = 29) and non-affected controls (n = 471), except for slightly higher fasting plasma glucose concentrations in NCC-heterozygous children (91 +/- 2.3 versus 88 +/- 0.4 mg/dL, P pressures. We found a relatively high prevalence of heterozygous NCC mutations in Chinese children, suggesting that GS may not be rare in this population. Heterozygous NCC mutations were not associated with lower blood pressure in these Chinese children.

  19. 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.

  20. 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.

  1. 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

  2. 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

  3. Phosphorylation decreases ubiquitylation of the thiazide-sensitive cotransporter NCC and subsequent clathrin-mediated endocytosis.

    Science.gov (United States)

    Rosenbaek, Lena L; Kortenoeven, Marleen L A; Aroankins, Takwa S; Fenton, Robert A

    2014-05-09

    The thiazide-sensitive sodium chloride cotransporter, NCC, is the major NaCl transport protein in the distal convoluted tubule (DCT). The transport activity of NCC can be regulated by phosphorylation, but knowledge of modulation of NCC trafficking by phosphorylation is limited. In this study, we generated novel tetracycline-inducible Madin-Darby canine kidney type I (MDCKI) cell lines expressing NCC to examine the role of NCC phosphorylation and ubiquitylation on NCC endocytosis. In MDCKI-NCC cells, NCC was highly glycosylated at molecular weights consistent with NCC monomers and dimers. NCC constitutively cycles to the apical plasma membrane of MDCKI-NCC cells, with 20-30% of the membrane pool of NCC internalized within 30 min. The use of dynasore, PitStop2, methyl-β-cyclodextrin, nystatin, and filipin (specific inhibitors of either clathrin-dependent or -independent endocytosis) demonstrated that NCC is internalized via a clathrin-mediated pathway. Reduction of endocytosis resulted in greater levels of NCC in the plasma membrane. Immunogold electron microscopy confirmed the association of NCC with the clathrin-mediated internalization pathway in rat DCT cells. Compared with controls, inducing phosphorylation of NCC via low chloride treatment or mimicking phosphorylation by replacing Thr-53, Thr-58, and Ser-71 residues with Asp resulted in increased membrane abundance and reduced rates of NCC internalization. NCC ubiquitylation was lowest in the conditions with greatest NCC phosphorylation, thus providing a mechanism for the reduced endocytosis. In conclusion, our data support a model where NCC is constitutively cycled to the plasma membrane, and upon stimulation, it can be phosphorylated to both increase NCC activity and decrease NCC endocytosis, together increasing NaCl transport in the DCT.

  4. Enhanced expression of potassium-chloride cotransporter KCC2 in human temporal lobe epilepsy.

    Science.gov (United States)

    Karlócai, Mária R; Wittner, Lucia; Tóth, Kinga; Maglóczky, Zsófia; Katarova, Zoja; Rásonyi, György; Erőss, Loránd; Czirják, Sándor; Halász, Péter; Szabó, Gábor; Payne, John A; Kaila, Kai; Freund, Tamás F

    2016-09-01

    Synaptic reorganization in the epileptic hippocampus involves altered excitatory and inhibitory transmission besides the rearrangement of dendritic spines, resulting in altered excitability, ion homeostasis, and cell swelling. The potassium-chloride cotransporter-2 (KCC2) is the main chloride extruder in neurons and hence will play a prominent role in determining the polarity of GABAA receptor-mediated chloride currents. In addition, KCC2 also interacts with the actin cytoskeleton which is critical for dendritic spine morphogenesis, and for the maintenance of glutamatergic synapses and cell volume. Using immunocytochemistry, we examined the cellular and subcellular levels of KCC2 in surgically removed hippocampi of temporal lobe epilepsy (TLE) patients and compared them to control human tissue. We also studied the distribution of KCC2 in a pilocarpine mouse model of epilepsy. An overall increase in KCC2-expression was found in epilepsy and confirmed by Western blots. The cellular and subcellular distributions in control mouse and human samples were largely similar; moreover, changes affecting KCC2-expression were also alike in chronic epileptic human and mouse hippocampi. At the subcellular level, we determined the neuronal elements exhibiting enhanced KCC2 expression. In epileptic tissue, staining became more intense in the immunopositive elements detected in control tissue, and profiles with subthreshold expression of KCC2 in control samples became labelled. Positive interneuron somata and dendrites were more numerous in epileptic hippocampi, despite severe interneuron loss. Whether the elevation of KCC2-expression is ultimately a pro- or anticonvulsive change, or both-behaving differently during ictal and interictal states in a context-dependent manner-remains to be established.

  5. Phosphorylation Decreases Ubiquitylation of the Thiazide-sensitive Cotransporter NCC and Subsequent Clathrin-mediated Endocytosis*

    Science.gov (United States)

    Rosenbaek, Lena L.; Kortenoeven, Marleen L. A.; Aroankins, Takwa S.; Fenton, Robert A.

    2014-01-01

    The thiazide-sensitive sodium chloride cotransporter, NCC, is the major NaCl transport protein in the distal convoluted tubule (DCT). The transport activity of NCC can be regulated by phosphorylation, but knowledge of modulation of NCC trafficking by phosphorylation is limited. In this study, we generated novel tetracycline-inducible Madin-Darby canine kidney type I (MDCKI) cell lines expressing NCC to examine the role of NCC phosphorylation and ubiquitylation on NCC endocytosis. In MDCKI-NCC cells, NCC was highly glycosylated at molecular weights consistent with NCC monomers and dimers. NCC constitutively cycles to the apical plasma membrane of MDCKI-NCC cells, with 20–30% of the membrane pool of NCC internalized within 30 min. The use of dynasore, PitStop2, methyl-β-cyclodextrin, nystatin, and filipin (specific inhibitors of either clathrin-dependent or -independent endocytosis) demonstrated that NCC is internalized via a clathrin-mediated pathway. Reduction of endocytosis resulted in greater levels of NCC in the plasma membrane. Immunogold electron microscopy confirmed the association of NCC with the clathrin-mediated internalization pathway in rat DCT cells. Compared with controls, inducing phosphorylation of NCC via low chloride treatment or mimicking phosphorylation by replacing Thr-53, Thr-58, and Ser-71 residues with Asp resulted in increased membrane abundance and reduced rates of NCC internalization. NCC ubiquitylation was lowest in the conditions with greatest NCC phosphorylation, thus providing a mechanism for the reduced endocytosis. In conclusion, our data support a model where NCC is constitutively cycled to the plasma membrane, and upon stimulation, it can be phosphorylated to both increase NCC activity and decrease NCC endocytosis, together increasing NaCl transport in the DCT. PMID:24668812

  6. 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.

  7. Isolated Renal Hydatidosis Presenting as Renal Mass: A Diagnostic Dilemma

    Directory of Open Access Journals (Sweden)

    Datteswar Hota

    2015-07-01

    Full Text Available Hydatid disease is a parasitic infestation by larval form of Echinococcus granulosus. Isolated renal involvement is extremely rare. There are no specific signs and symptoms of renal hydatidosis. However it may present as palpable mass, flank pain, hematuria, malaise, fever, and hydatiduria or as a complication of it such as infection, abscess, hemorrhage, necrosis and pelviureteric junction obstruction, renal failure etc. Except hydatiduria, none are pathognomonic for renal hydatidosis. There is no literature on renal hydatidosis presenting as renal mass we report 2 cases of isolated renal hydatidosis, which mimicked a renal mass on imaging study.

  8. 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

    (1.1%) had complete distal renal tubular acidosis and 14 (15.5%) incomplete distal renal tubular acidosis. Our results confirm that distal renal tubular acidification defects are associated with a more severe form of stone disease and make distal renal tubular acidosis one of the most frequent...... metabolic disturbances in renal stone formers. Distal renal tubular acidosis (dRTA) was relatively more common in female stone formers and most often found in patients with bilateral stone disease (36%). Since prophylactic treatment in renal stone formers with renal acidification defects is available...

  9. 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.

  10. Hyperexcitability and epilepsy associated with disruption of the mouse neuronal-specific K-Cl cotransporter gene.

    Science.gov (United States)

    Woo, Nam-Sik; Lu, Jianming; England, Roger; McClellan, Robert; Dufour, Samuel; Mount, David B; Deutch, Ariel Y; Lovinger, David M; Delpire, Eric

    2002-01-01

    Four genes encode electroneutral, Na+-independent, K-Cl cotransporters. KCC2, is exclusively expressed in neurons where it is thought to drive intracellular Cl- to low concentrations and shift the reversal potential for Cl- conductances such as GABA(A) or glycine receptor channels, thus participating in the postnatal development of inhibitory mechanisms in the brain. Indeed, expression of the cotransporter is low at birth and increases postnatally, at a time when the intracellular Cl- concentration in neurons decreases and gamma-aminobutyric acid switches its effect from excitatory to inhibitory. To assert the significance of KCC2 in neuronal function, we disrupted the mouse gene encoding this neuronal-specific K-Cl cotransporter. We demonstrate that animals deficient in KCC2 exhibit frequent generalized seizures and die shortly after birth. We also show upregulation of Fos, the product of the immediate early gene c-fos, and the significant loss of parvalbumin-positive interneurons, both indicative of brain injury. The regions most affected are the hippocampus and temporal and entorhinal cortices. Extracellular field potential measurements in the CA1 hippocampus exhibited hyperexcitability. Application of picrotoxin, a blocker of the GABA(A) receptor, further increased hyperexcitability in homozygous hippocampal sections. Pharmacological treatment of pups showed that diazepam relieved the seizures while phenytoin prevented them between postnatal ages P4-P12. Finally, we demonstrate that adult heterozygote animals show increased susceptibility for epileptic seizure and increased resistance to the anticonvulsant effect of propofol. Taken together, these results indicate that KCC2 plays an important role in controlling CNS excitability during both postnatal development and adult life.

  11. Renal pelvis or ureter cancer

    Science.gov (United States)

    Transitional cell cancer of the renal pelvis or ureter; Kidney cancer - renal pelvis; Ureter cancer ... Cancer can grow in the urine collection system, but it is uncommon. Renal pelvis and ureter cancers ...

  12. Genital mycotic infections with canagliflozin, a sodium glucose co-transporter 2 inhibitor, in patients with type 2 diabetes mellitus: a pooled analysis of clinical studies.

    Science.gov (United States)

    Nyirjesy, Paul; Sobel, Jack D; Fung, Albert; Mayer, Cristiana; Capuano, George; Ways, Kirk; Usiskin, Keith

    2014-06-01

    To characterize genital mycotic infections with canagliflozin, a sodium glucose co-transporter 2 inhibitor, in patients with type 2 diabetes mellitus (T2DM) using pooled data from Phase 3 studies. Genital mycotic infections with canagliflozin 100 and 300 mg were evaluated in Population 1 (N = 2313; mean exposure [weeks]: canagliflozin, 24.3; placebo, 23.8), including patients from four placebo-controlled studies, and Population 2 (N = 9439; mean exposure [weeks]: canagliflozin, 68.1; control, 64.4), including patients from eight placebo/active-controlled studies (including older patients and those with renal impairment or high cardiovascular disease risk). ClinicalTrials.gov, NCT01081834; NCT01106625; NCT01106677; NCT01106690; NCT01032629; NCT01064414; NCT01106651; NCT00968812. Adverse events suggestive of genital mycotic infections were recorded, with additional information collected using supplemental electronic case report forms. In Population 1, genital mycotic infection incidence was higher with canagliflozin 100 and 300 mg than placebo (95% confidence intervals excluded zero) in females (10.4%, 11.4%, 3.2%) and males (4.2%, 3.7%, 0.6%). These were generally mild to moderate in intensity, none were serious, and few led to discontinuation. Most events with canagliflozin were treated with antifungal therapies, and median symptom duration following treatment initiation was similar across groups; few patients had >1 event (females, 2.3%; males, 0.9%). Findings with canagliflozin 100 and 300 mg versus control were similar in Population 2 (females: 14.7%, 13.9%, 3.1%; males: 7.3%, 9.3%, 1.6%); a low proportion of males underwent circumcision across groups. Most events with canagliflozin occurred within the first 4 months in females and first year in males; no consistent evidence of dose dependence was observed. Key limitations included lack of laboratory confirmation for most events and variable treatment methods. Genital mycotic infection incidences

  13. Cotransport of H+, lactate and H2O by membrane proteins in retinal pigment epithelium of bullfrog

    DEFF Research Database (Denmark)

    Zeuthen, T; Hamann, S; la Cour, M

    1996-01-01

    solution concentration and/or osmolarity. 3. Two parallel pathways for water transport were identified across the retinal membrane, an osmotic one with a hydraulic water permeability of 3.2 x 10(-4) cm s-1 (osmol l-1)-1 and one which depended on the presence of lactate. 4. Addition of sodium lactate...... the effect. The influx of water could proceed against osmotic gradients elicited by mannitol. 6. The interdependence of the fluxes of H+, lactate and H2O can be described as cotransport: the fluxes had a fixed ratio of about 109 mmol of lactic acid per litre of water, the flux of one species was able...

  14. Cotransport of hydroxyapatite nanoparticles and hematite colloids in saturated porous media: Mechanistic insights from mathematical modeling and phosphate oxygen isotope fractionation

    Science.gov (United States)

    Wang, Dengjun; Jin, Yan; Jaisi, Deb P.

    2015-11-01

    The fate and transport of individual type of engineered nanoparticles (ENPs) in porous media have been studied intensively and the corresponding mechanisms controlling ENPs transport and deposition are well-documented. However, investigations regarding the mobility of ENPs in the concurrent presence of another mobile colloidal phase such as naturally occurring colloids (colloid-mediated transport of ENPs) are largely lacking. Here, we investigated the cotransport and retention of engineered hydroxyapatite nanoparticles (HANPs) with naturally occurring hematite colloids in water-saturated sand columns under environmentally relevant transport conditions, i.e., pH, ionic strength (IS), and flow rate. Particularly, phosphate oxygen isotope fractionation of HANPs during cotransport was explored at various ISs and flow rates to examine the mechanisms controlling the isotope fractionation of HANPs in abiotic transport processes (physical transport). During cotransport, greater mobility of both HANPs and hematite occurred at higher pHs and flow rates, but at lower ISs. Intriguingly, the mobility of both HANPs and hematite was substantially lower during cotransport than the individual transport of either, attributed primarily to greater homo- and hetero-aggregation when both particles are copresent in the suspension. The shapes of breakthrough curves (BTCs) and retention profiles (RPs) during cotransport for both particles evolved from blocking to ripening with time and from flat to hyperexponential with depth, respectively, in response to decreases in pH and flow rate, and increases in IS. The blocking BTCs and RPs that are flat or hyperexponential can be well-approximated by a one-site kinetic attachment model. Conversely, a ripening model that incorporates attractive particle-particle interaction has to be employed to capture the ripening BTCs that are impacted by particle aggregation during cotransport. A small phosphate oxygen isotope fractionation (≤ 1.8

  15. [Hemorrhagic bilateral renal angiomyolipoma].

    Science.gov (United States)

    Benjelloun, Mohamed; Rabii, Redouane; Mezzour, Mohamed Hicham; Joual, Abdenbi; Bennani, Saâd; el Mrini, Mohamed

    2003-09-01

    Renal angiomyolipoma is a rare benign tumour, often associated with congenital diseases especially de Bourneville's tuberous sclerosis. Bilateral angiomyolipoma is exceptional. The authors report a case of bilateral renal angiomyolipoma in a 33-year-old patient presenting with haemorrhagic shock. In the light of this case and a review of the literature, the authors discuss the diagnostic and therapeutic aspects of this disease.

  16. FARMACOFISIOLOGÍA RENAL

    Directory of Open Access Journals (Sweden)

    Musso CG

    2014-03-01

    Full Text Available Renal physiology plays a key role in the pharmacokinetics of many drugs. Knowledge of the particularities of each nephron function (filtration, secretion, reabsorption and excretion and each of renal tubular transport mechanisms (simple diffusion, facilitated diffusion, facilitated transport, active transport, endocytosis and pinocytosis is fundamental to achieve better management of drug prescriptions.

  17. Primary renal hydatidosis

    Directory of Open Access Journals (Sweden)

    Johnsy Merla Joel

    2016-01-01

    Full Text Available Echinococcosis or hydatidosis caused by the tapeworm, Echinococcus granulosus, has the highest prevalence in endemic regions and sheep farming areas. The most common organ involved is the liver (50–75% followed by the lungs (15–20% and other organs (10–20%. Primary involvement of the kidney without the involvement of the liver and lungs, i.e., isolated renal hydatid disease is extremely rare even in endemic areas. The incidence of renal echinococcosis is 2–4%. Renal hydatid cysts usually remain asymptomatic for many years and are multiloculated. A 63-year-old male presented with left loin pain. Computed tomography scan abdomen revealed a presumptive diagnosis of renal hydatid disease. The nephrectomy specimen received in histopathology confirmed the diagnosis. We describe a rare case of primary renal hydatidosis.

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

    Directory of Open Access Journals (Sweden)

    Anthony A Portale

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

  19. Immunohistochemical localization of the Na-K-Cl co-transporter (NKCC1) in the gerbil inner ear.

    Science.gov (United States)

    Crouch, J J; Sakaguchi, N; Lytle, C; Schulte, B A

    1997-06-01

    We mapped the cellular and subcellular distribution of the Na-K-Cl co-transporter (NKCC) in the adult gerbil inner ear by immunostaining with a monoclonal antibody (MAb T4) generated against human colon NKCC. Heavy immunolabeling was seen in the basolateral plasma membrane of marginal cells in the stria vascularis and dark cells in the vestibular system. Subpopulations of fibrocytes in the cochlear spiral ligament and limbus and underlying the vestibular neurosensory epithelium also stained with moderate to strong intensity, apparently along their entire plasmalemma. Because MAb T4 recognizes both the basolateral secretory (NKCC1) and the apical absorptive (NKCC2) isoforms of the co-transporter, we employed reverse transcription and the polymerase chain reaction (RT-PCR) to explore isoform diversity in inner ear tissues. Using NKCC1 and NKCC2 isoform-specific PCR primers based on mouse and human sequences, only transcripts for NKCC1 were detected in the gerbil inner ear. The presence of abundant NKCC1 in the basolateral plasmalemma of strial marginal and vestibular dark cells confirms conclusions drawn from pharmacological and physiological data. The co-expression of NKCC1 and Na,K-ATPase in highly specialized subpopulations of cochlear and vestibular fibrocytes provides further evidence for their role in recycling K+ leaked or effluxed through hair cells into perilymph back to endolymph, as postulated in current models of inner ear ion homeostasis.

  20. The Thiazide-Sensitive Co-Transporter Promotes the Development of Sodium Retention in Mice with Diet-Induced Obesity

    Directory of Open Access Journals (Sweden)

    Matthew R P Davies

    2015-09-01

    Full Text Available Background/Aims: Intravascular volume expansion due to sodium retention is involved in the pathogenesis of obesity-related hypertension. Institution of high fat diet (HFD feeding leads to an initial state of positive sodium balance due to enhanced tubular reabsorption of sodium, but which tubular sodium transporters are responsible for this remains undefined. Methods: C57/Bl6 mice were fed control or HFD for 3 weeks. Blood pressures were recorded by tail cuff method. Sodium transporter expression and phosphorylation were determined by Western blotting. In vivo activity of NCC was determined using natriuretic responses to hydrochlorothiazide. Expression of NCC mRNA was determined using qPCR. Results: At 3 weeks HFD mice had significant weight gains compared to control mice, but blood pressures were not yet elevated. There were no changes in expression or phosphorylation of the bumetanide-sensitive cotransporter, NKCC2, or in expression of subunits of the amiloride-sensitive ion channel, ENaC. However, there were significant increases in mRNA and protein expression of the thiazide-sensitive co-transporter, NCC, in kidneys from HFD mice. Consistent with this, HFD mice had increased in vivo activity of NCC. Conclusions: Increased expression of NCC promotes the sodium loading response to institution of HFD feeding before onset of hypertension.

  1. Renal replacement therapy after cardiac surgery; renal function recovers

    DEFF Research Database (Denmark)

    Steinthorsdottir, Kristin Julia; Kandler, Kristian; Agerlin Windeløv, Nis

    2013-01-01

    To assess renal outcome in patients discharged from hospital following cardiac surgery-associated acute kidney injury (CSA-AKI) with need for renal replacement therapy.......To assess renal outcome in patients discharged from hospital following cardiac surgery-associated acute kidney injury (CSA-AKI) with need for renal replacement therapy....

  2. Erlotinib preserves renal function and prevents salt retention in doxorubicin treated nephrotic rats.

    Directory of Open Access Journals (Sweden)

    Raed N Bou Matar

    Full Text Available Nephrotic syndrome is associated with up-regulation of the heparin-binding epidermal growth factor (HB-EGF. Erlotinib blocks the activation of the epidermal growth factor receptor (EGFR in response to HB-EGF. This study investigates the effect of Erlotinib on the progression of proteinuria, renal dysfunction, and salt retention in doxorubicin treated nephrotic rats. Male rats were divided into 3 pair-fed groups (n = 13/group as follows: Control rats (Ctrl; rats receiving intravenous doxorubicin (Dox; and rats receiving intravenous doxorubicin followed by daily oral Erlotinib (Dox + Erl. Upon establishment of high grade proteinuria, urine sodium and creatinine clearance were measured. Kidney tissue was dissected and analyzed for γ-epithelial sodium channel (γENaC, sodium-potassium -chloride co-transporter 2 (NKCC2, sodium chloride co-transporter (NCC, aquaporin 2 (AQP2, and EGFR abundances using western blot. Creatinine clearance was preserved in the Dox + Erl rats as compared to the Dox group (in ml/min: Ctrl: 5.2±.5, Dox: 1.9±0.3, Dox + Erl: 3.6±0.5. Despite a minimal effect on the degree of proteinuria, Erlotinib prevented salt retention (Urinary Na in mEq/d: Ctrl: 2.2±0.2, Dox: 1.8±0.3, Dox + Erl: 2.2±0.2. The cleaved/uncleaved γENaC ratio was increased by 41±16% in the Dox group but unchanged in the Dox + Erl group when compared to Ctrl. The phosphorylated EGFR/total EGFR ratio was reduced by 74±7% in the Dox group and by 77±4% in the Dox + Erl group. In conclusion, Erlotinib preserved renal function and prevented salt retention in nephrotic rats. The observed effects do not appear to be mediated by direct blockade of EGFR.

  3. Renal neuroendocrine tumors

    Directory of Open Access Journals (Sweden)

    Brian R Lane

    2009-01-01

    Full Text Available Objectives: Neuroendocrine tumors (NETs are uncommon tumors that exhibit a wide range of neuroendocrine differentiation and biological behavior. Primary NETs of the kidney, including carcinoid tumor, small cell carcinoma (SCC, and large cell neuroendocrine carcinoma (LCNEC are exceedingly rare. Materials and Methods: The clinicopathologic features of renal NETs diagnosed at a single institution were reviewed along with all reported cases in the worldwide literature. Results: Eighty renal NETs have been described, including nine from our institution. Differentiation between renal NETs and the more common renal neoplasms (renal cell carcinoma, transitional cell carcinoma can be difficult since clinical, radiographic, and histopathologic features overlap. Immunohistochemical staining for neuroendocrine markers, such as synaptophysin and chromogranin, can be particularly helpful in this regard. Renal carcinoids are typically slow-growing, may secrete hormones, and pursue a variable clinical course. In contrast, SCC and LCNEC often present with locally advanced or metastatic disease and carry a poor prognosis. Nephrectomy can be curative for clinically localized NETs, but multimodality treatment is indicated for advanced disease. Conclusions: A spectrum of NETs can rarely occur in the kidney. Renal carcinoids have a variable clinical course; SCC and LCNEC are associated with poor clinical outcomes. Diagnosis of NETs, especially LCNEC, requires awareness of their rare occurrence and prudent use of immunohistochemical neuroendocrine markers.

  4. Pregnancy and renal transplantation.

    Science.gov (United States)

    Başaran, O; Emiroğlu, R; Seçme, S; Moray, G; Haberal, M

    2004-01-01

    Ovarian dysfunction, anovulatory vaginal bleeding, amenorrhea, high prolactin levels, and loss of libido are the causes of infertility in women with chronic renal failure. After renal transplantation, endocrine function generally improves after recovery of renal function. In this study we retrospectively evaluated the prepregnancy and postdelivery renal function, outcome of gestation, as well as maternal and fetal complications for eight pregnancies in eight renal transplant recipients between November 1975 and March 2003 of 1095 among 1425. Eight planned pregnancies occurred at a mean of 3.6 years posttransplant. Spontaneous abortion occured in the first trimester in one case. One intrauterine growth retardation was observed with a full-term pregnancy; one intrauterine growth retardation and preterm delivery; one preeclampsia with preterm delivery and urinary tract infection; and one preeclampsia with preterm delivery and oligohydramnios. The mean gestation period was 35.5 +/- 3.0 weeks (31.2 to 38.0). Pregnancy had no negative impact on renal function during a 2-year follow-up. No significant proteinuria or acute rejection episodes were observed. Among the seven deliveries, no congenital anomaly was documented and no postpartum problems for the child and the mother were observed. Our study suggests that successful pregnancy is possible in renal transplant recipients. In cases with good graft function and absence of severe proteinuria or hypertension, pregnancy does not affect graft function or patient survival; however, fetal problems are encountered such as intrauterine growth retardation, low birth weight, and preeclampsia.

  5. Renal autotransplantation: current perspectives.

    Science.gov (United States)

    Stewart, B H; Banowsky, L H; Hewitt, C B; Straffon, R A

    1976-01-01

    Autotransplantation, with or without an extracorporeal renal operation, has been done 39 times in 37 patients. Indications for the procedure included severe ureteral injury in 4 patients, failed supravesical diversion in 2, renal carcinoma in a solitary kidney in 1, renovascular hypertension in 1 and donor arterial reconstruction before renal transplantation in 29. Success was obtained in all but 2 procedures, both of which involved previously operated kidneys with severe inflammation and adhesions involving the renal pelvis and pedicle. Based on our experience and a review of currently available literature we believe that renal autotransplantation and extracorporeal reconstruction can provide the best solution for patients with severe renovascular and ureteral disease not correctable by conventional operative techniques. The technique can be of particular value in removing centrally located tumors in solitary kidneys and in preparing donor kidneys with abnormal arteries for renal transplantation. The role of autotransplantation in the management of advanced renal trauma and calculus disease is less clear. A long-term comparison of patients treated by extracorporeal nephrolithotomy versus conventional lithotomy techniques will be necessary before a conclusion is reached in these disease categories.

  6. 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.

  7. Midterm renal functions following acute renal infarction

    Directory of Open Access Journals (Sweden)

    Sakir Ongun

    2015-10-01

    Full Text Available The aim of this study was to explore clinical features of renal infarction (RI that may have a role in diagnosis and treatment in our patient cohort and provide data on midterm renal functions. Medical records of patients with diagnosis of acute RI, established by contrast enhanced computed tomography (CT and at least 1 year follow-up data, who were hospitalized in our clinic between 1998 and 2012 were retrospectively reviewed; including descriptive data, clinical signs and symptoms, etiologic factors, laboratory findings, and prescribed treatments. Patients with solitary infarct were treated with acetylsalicylic acid (ASA only, whereas patients with atrial fibrillation (AF or multiple or global infarct were treated with anticoagulants. Estimated Glomerular Filtration Rate (eGFR referring to renal functions was determined by the Modification of Diet in Renal Disease (MDRD formula. Twenty-seven renal units of 23 patients with acute RI were identified. The mean age was 59.7 ± 15.7 years. Fourteen patients (60.8% with RI had atrial fibrillation (AF as an etiologic factor of which four had concomitant mesenteric ischemia at diagnosis. At presentation, 20 patients (86.9% had elevated serum lactate dehydrogenase (LDH, 18 patients (78.2% had leukocytosis, and 16 patients (69.5% had microscopic hematuria. Two patients with concomitant mesenteric ischemia and AF passed away during follow up. Mean eGFR was 70.8 ± 23.2 mL/min/1.73 m2 at admission and increased to 82.3 ± 23.4 mL/min/1.73 m2 at 1 year follow up. RI should be considered in patients with persistent flank or abdominal pain, particularly if they are at high risk of thromboembolism. Antiplatelet and/or anticoagulant drugs are both effective treatment options according to the amplitude of the infarct for preserving kidney functions.

  8. Midterm renal functions following acute renal infarction.

    Science.gov (United States)

    Ongun, Sakir; Bozkurt, Ozan; Demir, Omer; Cimen, Sertac; Aslan, Guven

    2015-10-01

    The aim of this study was to explore clinical features of renal infarction (RI) that may have a role in diagnosis and treatment in our patient cohort and provide data on midterm renal functions. Medical records of patients with diagnosis of acute RI, established by contrast enhanced computed tomography (CT) and at least 1 year follow-up data, who were hospitalized in our clinic between 1998 and 2012 were retrospectively reviewed; including descriptive data, clinical signs and symptoms, etiologic factors, laboratory findings, and prescribed treatments. Patients with solitary infarct were treated with acetylsalicylic acid (ASA) only, whereas patients with atrial fibrillation (AF) or multiple or global infarct were treated with anticoagulants. Estimated Glomerular Filtration Rate (eGFR) referring to renal functions was determined by the Modification of Diet in Renal Disease (MDRD) formula. Twenty-seven renal units of 23 patients with acute RI were identified. The mean age was 59.7 ± 15.7 years. Fourteen patients (60.8%) with RI had atrial fibrillation (AF) as an etiologic factor of which four had concomitant mesenteric ischemia at diagnosis. At presentation, 20 patients (86.9%) had elevated serum lactate dehydrogenase (LDH), 18 patients (78.2%) had leukocytosis, and 16 patients (69.5%) had microscopic hematuria. Two patients with concomitant mesenteric ischemia and AF passed away during follow up. Mean eGFR was 70.8 ± 23.2 mL/min/1.73 m(2) at admission and increased to 82.3 ± 23.4 mL/min/1.73 m(2) at 1 year follow up. RI should be considered in patients with persistent flank or abdominal pain, particularly if they are at high risk of thromboembolism. Antiplatelet and/or anticoagulant drugs are both effective treatment options according to the amplitude of the infarct for preserving kidney functions.

  9. Effects of hydrochlorothiazide on the pharmacokinetics, pharmacodynamics, and tolerability of canagliflozin, a sodium glucose co-transporter 2 inhibitor, in healthy participants.

    Science.gov (United States)

    Devineni, Damayanthi; Vaccaro, Nicole; Polidori, David; Rusch, Sarah; Wajs, Ewa

    2014-05-01

    Many patients with type 2 diabetes mellitus (T2DM) also have hypertension, which is commonly treated with thiazide diuretics, including hydrochlorothiazide (HCTZ). Canagliflozin, a sodium glucose cotransporter 2 inhibitor developed for the treatment of T2DM, lowers plasma glucose by inhibiting renal glucose reabsorption, thereby increasing urinary glucose excretion and mild osmotic diuresis. Because patients with T2DM are likely to receive concurrent canagliflozin and HCTZ, potential interactions were evaluated. This study evaluated the effects of HCTZ on the pharmacokinetic and pharmacodynamic properties and tolerability of canagliflozin in healthy participants. This Phase I, single-center, open-label, fixed-sequence, 2-period study was conducted in healthy participants. During period 1, participants received canagliflozin 300 mg once daily for 7 days, followed by a 14-day washout period. During period 2, participants received HCTZ 25 mg once daily for 28 days, followed by canagliflozin 300 mg + HCTZ 25 mg once daily for 7 days. Blood samples were taken before and several times after administration on day 7 of period 1 and on days 28 and 35 of period 2 for canagliflozin and HCTZ pharmacokinetic analyses using LC-MS/MS. Blood and urine samples were collected for up to 24 hours after canagliflozin administration on day 1 of period 1 and day 35 of period 2 for pharmacodynamic glucose assessment. Tolerability was also evaluated. Thirty participants were enrolled (16 men, 14 women; all white; mean age, 43.7 years). Canagliflozin AUC during a dosing interval (T) at steady state (AUCτ,ss) and Cmax at steady state (Cmax,ss) were increased when canagliflozin was coadministered with HCTZ, with geometric mean ratios (90% CI) of 1.12 (1.08-1.17) and 1.15 (1.06-1.25), respectively. AUCτ,ss and Cmax,ss for HCTZ were similar with and without canagliflozin coadministration. The 24-hour mean renal threshold for glucose and mean plasma glucose were comparable for canagliflozin

  10. Diferentes vias de administração da solução de fosfato monobásico e dibásico de sódio no preparo do cólon para colonoscopia rígida em cães Different routes in administration of sodium phosphate monobasic and dibasic solution in bowel preparation for rigid colonoscopy in dogs

    Directory of Open Access Journals (Sweden)

    A.B. Trindade

    2009-08-01

    Full Text Available Foram comparadas duas vias de administração, oral e retal, com a solução de fosfato monobásico e dibásico de sódio (NaP, juntamente com bisacodil via oral, no preparo do cólon para colonoscopia rígida em cães, para avaliar parâmetros clínicos, qualidade do preparo e variações dos eletrólitos fósforo, cálcio, potássio (K+ sódio (Na+ e magnésio (Mg+, além da creatinina, albumina e hemograma. Todos os eletrólitos apresentaram alterações, sendo significativa a queda nos níveis de K+ e Mg+. Não houve alterações eletrocardiográficas, e a redução da microbiota bacteriana foi confirmada nos dois grupos de administração da solução. Os resultados foram similares quanto à incidência de efeitos colaterais, porém a via retal apresentou facilidade na administração, menor retenção fecal no cólon, maior rapidez para realização da colonoscopia, com menor desperdício de tempo na lavagem e na aspiração do conteúdo fecal. O preparo intestinal com bisacodil oral e solução de NaP por via retal foi mais eficaz, podendo ser recomendado em cães que serão submetidos à colonoscopia.The efficacy of oral and rectal administration of sodium phosphate monobasic and dibasic solution (NaP combined with bisacodil per oral, as drugs to prepare the colon for rigid colonoscopy in dogs was compa1ed. Clinical parameters; colonic cleaning, plasma concentration of calcium, potassium (K+, sodium (Na+, magnesium (Mg+, creatinine, and albumin, and complete blood count were evaluated. In both groups, all electrolytes presented alterations, with significant reduction of the levels of K+ and Mg+, but there were no electrocardiographic alterations. No difference in the reduction of bacterial population was observed between the two groups. The results were similar regarding the incidence of side effects; however, the rectal route presented less fecal retention in colon and could get patients ready for the procedure faster. The preparation

  11. Lactulose and renal failure.

    Science.gov (United States)

    Vogt, B; Frey, F J

    1997-01-01

    The introduction of lactulose as a new therapeutic agent for treatment of hepatic encephalopathy was a major breakthrough in this field. It was hypothesized that lactulose might prevent postoperative renal impairment after biliary surgery in patients with obstructive jaundice. The presumable mechanism purported was the diminished endotoxinemia by lactulose. Unfortunately, such a reno-protective effect has not been shown conclusively until now in clinical studies. In chronic renal failure lactulose is known to promote fecal excretion of water, sodium, potassium, amonium, urea, creatinine and protons. Thus, lactulose could be useful for the treatment of chronic renal failure. However, compliance to the therapy represents a major problem.

  12. Renal tubule cell repair following acute renal injury.

    Science.gov (United States)

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

    1995-01-01

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

  13. Efficacy and Safety of Canagliflozin, an Inhibitor of Sodium-Glucose Cotransporter 2, When Used in Conjunction With Insulin Therapy in Patients With Type 2 Diabetes

    NARCIS (Netherlands)

    Neal, Bruce; Perkovic, Vlado; de Zeeuw, Dick; Mahaffey, Kenneth W.; Fulcher, Greg; Ways, Kirk; Desai, Mehul; Shaw, Wayne; Capuano, George; Alba, Maria; Jiang, Joel; Vercruysse, Frank; Meininger, Gary; Matthews, David

    OBJECTIVE There are limited data about the effects of sodium-glucose cotransporter 2 inhibitors when used with insulin. We report the efficacy and safety of canagliflozin in patients with type 2 diabetes using insulin. RESEARCH DESIGN AND METHODS The CANagliflozin CardioVascular Assessment Study is

  14. 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....

  15. Relative contributions of Na+/H+ exchange and Na+/HCO3- cotransport to ischemic Na-i(+) overload in isolated rat hearts

    NARCIS (Netherlands)

    Ten Hove, M; Nederhoff, MGJ; Van Echteld, CJA

    2005-01-01

    The Na+/H+ exchanger (NHE) and/or the Na+/HCO3- cotransporter (NBC) were blocked during ischemia in isolated rat hearts. Intracellular Na+ concentration ([Na+](i)), intracellular pH (pH(i)), and energy-related phosphates were measured by using simultaneous Na-23 and P-31 NMR spectroscopy. Hearts wer

  16. Efficacy and Safety of Canagliflozin, an Inhibitor of Sodium-Glucose Cotransporter 2, When Used in Conjunction With Insulin Therapy in Patients With Type 2 Diabetes

    NARCIS (Netherlands)

    Neal, Bruce; Perkovic, Vlado; de Zeeuw, Dick; Mahaffey, Kenneth W.; Fulcher, Greg; Ways, Kirk; Desai, Mehul; Shaw, Wayne; Capuano, George; Alba, Maria; Jiang, Joel; Vercruysse, Frank; Meininger, Gary; Matthews, David

    2015-01-01

    OBJECTIVE There are limited data about the effects of sodium-glucose cotransporter 2 inhibitors when used with insulin. We report the efficacy and safety of canagliflozin in patients with type 2 diabetes using insulin. RESEARCH DESIGN AND METHODS The CANagliflozin CardioVascular Assessment Study is

  17. Renal scintigraphy in veterinary medicine.

    Science.gov (United States)

    Tyson, Reid; Daniel, Gregory B

    2014-01-01

    Renal scintigraphy is performed commonly in dogs and cats and has been used in a variety of other species. In a 2012 survey of the members of the Society of Veterinary Nuclear Medicine, 95% of the respondents indicated they perform renal scintigraphy in their practice. Renal scintigraphy is primarily used to assess renal function and to evaluate postrenal obstruction. This article reviews how renal scintigraphy is used in veterinary medicine and describes the methods of analysis. Species variation is also discussed.

  18. 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...

  19. 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.

  20. 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......-stage renal disease in the Western world and accounts for more than a quarter of all end-stage renal diseases. Diabetic nephropathy is a major cause of increased morbidity and mortality in diabetic patients. Increased arterial blood pressure is an early and common phenomenon in incipient and overt diabetic...... nephropathy. The relationship between arterial blood pressure and diabetic nephropathy is a complex one, with diabetic nephropathy increasing blood pressure and blood pressure accelerating the course of nephropathy. OVERVIEW: Calcium antagonists antagonize preglomerular vasoconstriction. Additional putative...

  1. Renal primitive neuroectodermal tumors.

    Science.gov (United States)

    Bartholow, Tanner; Parwani, Anil

    2012-06-01

    Primitive neuroectodermal tumors exist as a part of the Ewing sarcoma/primitive neuroectodermal tumor family. These tumors most commonly arise in the chest wall and paraspinal regions; cases with a renal origin are rare entities, but have become increasingly reported in recent years. Although such cases occur across a wide age distribution, the average age for a patient with a renal primitive neuroectodermal tumor is the mid- to late 20s, with both males and females susceptible. Histologically, these tumors are characterized by pseudorosettes. Immunohistochemically, CD99 is an important diagnostic marker. Clinically, these are aggressive tumors, with an average 5-year disease-free survival rate of only 45% to 55%. Given that renal primitive neuroectodermal tumor bears many similarities to other renal tumors, it is important to review the histologic features, immunostaining profile, and genetic abnormalities that can be used for its correct diagnosis.

  2. Renal vein thrombosis

    Science.gov (United States)

    ... Saunders; 2012:chap 34. Read More Acute kidney failure Arteriogram Blood clots Dehydration Nephrotic syndrome Pulmonary embolus Renal Tumor Review Date 5/19/2015 Updated by: Charles Silberberg, ...

  3. 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......Based on the SYMPLICITY studies and CE (Conformité Européenne) certification, renal denervation is currently applied as a novel treatment of resistant hypertension in Europe. However, information on the proportion of patients with resistant hypertension qualifying for renal denervation after...... 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...

  4. Complete renal recovery from severe acute renal failure after thrombolysis of bilateral renal vein thrombosis.

    Science.gov (United States)

    Ramadoss, Suresh; Jones, Robert G; Foggensteiner, Lukas; Willis, Andrew P; Duddy, Martin J

    2012-10-01

    A previously healthy young man presented with acute renal failure due to extensive spontaneous deep vein thrombosis, including the inferior vena cava (IVC) and both renal veins. The patient was treated with selectively delivered thrombolytic therapy over a 7-day-period, which resulted in renal vein patency and complete recovery of renal function. A stent was placed over a segment stenosis of the IVC. No thrombophilic factors were identified. Bilateral renal vein thrombosis in young fit individuals is an unusual cause of acute renal failure. Thrombolytic therapy, even with delay, can completely restore renal function.

  5. 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

  6. Renal papillary necrosis

    Directory of Open Access Journals (Sweden)

    Stephen A. Geller

    2013-12-01

    Full Text Available In 1877, Dr. Nikolaus Friedreich (1825-1882; student of Virchow who became Professor of Pathology at Heidelberg and who also described Friedreich’s ataxia first described renal papillary necrosis (RPN in patients with prostatic hypertrophy and secondary hydronephrosis. Thereafter in 1937, Froboese and Günther emphasized the association of this entity with diabetes mellitus. These authors also observed renal papillary necrosis in cases of urinary tract obstruction even in the absence of diabetes mellitus.

  7. [Hyperuricemia and renal risk].

    Science.gov (United States)

    Viazzi, Francesca; Bonino, Barbara; Ratto, Elena; Desideri, Giovambattista; Pontremoli, Roberto

    2015-01-01

    Recent studies have revealed an association between elevated levels of uric acid and conditions correlated to chronic kidney diseases such as hypertension, cardiovascular and cerebral disease, insulin resistance. Several pathogenetic mechanisms at cellular and tissue levels could justify a direct correlation between serum uric acid levels and renal damage. Growing evidence indicating a correlation between urate lowering therapy and renal morbidity could encourage the use of urate lowering therapy in primary or secondary prevention in chronic kidney disease.

  8. Mecanismos de modulación del cotransporte sodio-cloruro por la angiotensina

    OpenAIRE

    Manucha, Walter Ariel Fernando

    2015-01-01

    Nuevas evidencias relacionadas con la regulación que, independiente de la aldosterona (Aldo), ejercen la angiotensina II (Ang II) sobre el cotransportador sodio/cloro sensible a la tiazida (NCC), así como los mecanismos celulares comprometidos. El sistema renina-angiotensina-aldosterona es un importante modulador de la excreción renal de sal como de la presión arterial. Fil: Manucha, Walter Ariel Fernando. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Departamento de Patologí...

  9. Laparoscopic Renal Cryoablation

    Science.gov (United States)

    Schiffman, Marc; Moshfegh, Amiel; Talenfeld, Adam; Del Pizzo, Joseph J.

    2014-01-01

    In light of evidence linking radical nephrectomy and consequent suboptimal renal function to adverse cardiovascular events and increased mortality, research into nephron-sparing techniques for renal masses widely expanded in the past two decades. The American Urological Association (AUA) guidelines now explicitly list partial nephrectomy as the standard of care for the management of T1a renal tumors. Because of the increasing utilization of cross-sectional imaging, up to 70% of newly detected renal masses are stage T1a, making them more amenable to minimally invasive nephron-sparing therapies including laparoscopic and robotic partial nephrectomy and ablative therapies. Cryosurgery has emerged as a leading option for renal ablation, and compared with surgical techniques it offers benefits in preserving renal function with fewer complications, shorter hospitalization times, and allows for quicker convalescence. A mature dataset exists at this time, with intermediate and long-term follow-up data available. Cryosurgical recommendations as a first-line therapy are made at this time in limited populations, including elderly patients, patients with multiple comorbidities, and those with a solitary kidney. As more data emerge on oncologic efficacy, and technical experience and the technology continue to improve, the application of this modality will likely be extended in future treatment guidelines. PMID:24596441

  10. Neonatal renal vein thrombosis.

    Science.gov (United States)

    Brandão, Leonardo R; Simpson, Ewurabena A; Lau, Keith K

    2011-12-01

    Neonatal renal vein thrombosis (RVT) continues to pose significant challenges for pediatric hematologists and nephrologists. The precise mechanism for the onset and propagation of renal thrombosis within the neonatal population is unclear, but there is suggestion that acquired and/or inherited thrombophilia traits may increase the risk for renal thromboembolic disease during the newborn period. This review summarizes the most recent studies of neonatal RVT, examining its most common features, the prevalence of acquired and inherited prothrombotic risk factors among these patients, and evaluates their short and long term renal and thrombotic outcomes as they may relate to these risk factors. Although there is some consensus regarding the management of neonatal RVT, the most recent antithrombotic therapy guidelines for the management of childhood thrombosis do not provide a risk-based algorithm for the acute management of RVT among newborns with hereditary prothrombotic disorders. Whereas neonatal RVT is not a condition associated with a high mortality rate, it is associated with significant morbidity due to renal impairment. Recent evidence to evaluate the effects of heparin-based anticoagulation and thrombolytic therapy on the long term renal function of these patients has yielded conflicting results. Long term cohort studies and randomized trials may be helpful to clarify the impact of acute versus prolonged antithrombotic therapy for reducing the morbidity that is associated with neonatal RVT.

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

    OpenAIRE

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

    2016-01-01

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

  12. 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.

  13. Renal and hepatic transporter expression in type 2 diabetic rats.

    Science.gov (United States)

    Nowicki, Michael T; Aleksunes, Lauren M; Sawant, Sharmilee P; Dnyanmote, Ankur V; Mehendale, Harihara M; Manautou, José E

    2008-01-01

    Membrane transporters are critical for the uptake as well as elimination of chemicals and by-products of metabolism from the liver and kidneys. Since these proteins are important determinants of chemical disposition, changes in their expression in different disease states can modulate drug pharmacokinetics. The present study investigated alterations in the renal and hepatic expression of organic anion and cation transporters (Oats/Octs), multidrug resistance-associated proteins (Mrps), breast cancer resistance protein (Bcrp), P-glycoprotein (Pgp), and hepatic Na(+)-taurocholate cotransporting polypeptide (Ntcp) in type 2 diabetic rats. For this purpose, type 2 diabetes was induced by feeding male Sprague-Dawley rats a high fat diet followed by a single dose of streptozotocin (45 mg/kg, i.p., in 0.01 M citrate buffer pH 4.3) on day 14. Controls received normal diet and vehicle. Kidney and liver samples were collected on day 24 for generation of crude plasma membrane fractions and Western blot analysis of Oat, Oct, Mrp, Bcrp, Pgp, and Ntcp proteins. With regards to renal uptake transporters, type 2 diabetes increased levels of Oat2 (2.3-fold) and decreased levels of Oct2 to 50% of control kidneys. Conversely, efflux transporters Mrp2, Mrp4, and Bcrp were increased 5.4-fold, 2-fold, and 1.6-fold, respectively in type 2 diabetic kidneys with no change in levels of Mrp1, Mrp5, or Pgp. Studies of hepatic transporters in type 2 diabetic rats reveal that the protein level of Mrp5 was reduced to 4% of control livers with no change in levels of Bcrp, Mrp1, Mrp2, Mrp4, Ntcp, or Pgp. The changes reported in this study may have implications in type 2 diabetic patients.

  14. Disrupting Na+,HCO3--cotransporter NBCn1 (Slc4a7) delays murine breast cancer development

    DEFF Research Database (Denmark)

    Lee, S.; Axelsen, T. V.; Andersen, Anne Poder

    2016-01-01

    ) mice. Breast cancer histopathology in NBCn1 KO mice differed from that in WT mice and included less aggressive tumor types. The extracellular tumor microenvironment in NBCn1 KO mice contained higher concentrations of glucose and lower concentrations of lactate than that in WT mice. Independently......Increased metabolism and insufficient blood supply cause acidic waste product accumulation in solid cancers. During carcinogenesis, cellular acid extrusion is upregulated but the underlying molecular mechanisms and their consequences for cancer growth and progression have not been established....... Genome-wide association studies have indicated a possible link between the Na(+),HCO3(-)-cotransporter NBCn1 (SLC4A7) and breast cancer. We tested the functional consequences of NBCn1 knockout (KO) for breast cancer development. NBCn1 protein expression increased 2.5-fold during breast carcinogenesis...

  15. Mutation of the Na-K-Cl co-transporter gene Slc12a2 results in deafness in mice.

    Science.gov (United States)

    Dixon, M J; Gazzard, J; Chaudhry, S S; Sampson, N; Schulte, B A; Steel, K P

    1999-08-01

    Hearing impairment is a common human condition, but we know little about the molecular basis of cochlear function. Shaker-with-syndactylism (sy) is a classic deaf mouse mutant and we show here that a second allele, sy(ns), is associated with abnormal production of endolymph, the fluid bathing sensory hair cells. Using a positional candidate approach, we demonstrate that mutations in the gene encoding the basolateral Na-K-Cl co-transporter Slc12a2 (Nkcc1, mBSC2) cause the deafness observed in sy and sy(ns) mice. This finding provides the molecular basis of another link in the chain of K+recycling in the cochlea, a process essential for normal cochlear function.

  16. 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.

  17. ¬Immunolocalization of cation-chloride cotransporters in the developing and mature spinal cord of opossums, Monodelphis domestica

    Directory of Open Access Journals (Sweden)

    Ha-Loan ePhan

    2013-05-01

    Full Text Available Spinal inhibition is required to generate coordinated outputs between antagonistic muscles during locomotion. It relies on low neuronal chloride concentration set by two cation-chloride cotransporters, NKCC1 and KCC2 which, respectively, pumps Cl- in or out of neurons. It is generally accepted that NKCC1 is gradually inactivated during development, while KCC2 is upregulated and activated, resulting in low intracellular [Cl-]. Newborn opossums are very immature but perform rhythmic and alternate movements of the forelimbs to crawl on the mother’s belly and attach to a teat. Their hindlimbs are immobile. The alternation of the forelimbs suggests that mechanisms allowing spinal inhibition are present at birth. We studied the anatomical basis of inhibition in the spinal enlargements of postnatal opossums by immunolocalizing NKCC1 and KCC2. In some specimens, motoneurons and sensory afferents were labeled with TRDA prior to immunolabeling. At birth, both NKCC1 and KCC2 are detected in the presumptive grey and white matter of the ventral and the intermediolateral cord of both enlargements, but are sparse in the dorsal horn, where KCC2 is mostly seen on a small bundle of dendrites along primary afferents. KCC2 labeling is bright and has a mesh-like appearance in the grey matter and a radial appearance in the white matter, whereas NKCC1 is pale and diffuse. The subsequent expression of the cotransporters follows general ventrodorsal and mediolateral gradients, with the lumbar segments slightly lagging the cervical segments, until the mature pattern is observed around the 5th week. At all ages studied, KCC2 labeling is strong in the periphery of neurons. NKCC1 labeling decreases and becomes more uniformly distributed in the cells with age. Despite the significant anatomical and motor differences between the forelimbs and the hindlimbs of neonatal opossums, the maturation of KCC2 and NKCC1 is quite similar in both enlargements.

  18. PSD-95 interacts with NBCn1 and enhances channel-like activity without affecting Na/HCO(3) cotransport.

    Science.gov (United States)

    Lee, Soojung; Yang, Han Soo; Kim, Eunjin; Ju, Eun Ji; Kwon, Min Hyung; Dudley, R Kyle; Smith, Yoland; Yun, C Chris; Choi, Inyeong

    2012-01-01

    The sodium/bicarbonate transporter NBCn1 plays an essential role in intracellular pH regulation and transepithelial HCO(3)(-) movement in the body. NBCn1 also has sodium channel-like activity uncoupled to Na/HCO(3) cotransport. We previously reported that NBCn1 interacts with the postsynaptic density protein PSD-95 in the brain. Here, we elucidated the structural determinant and functional consequence of NBCn1/PSD-95 interaction. In rat hippocampal CA3 neurons, NBCn1 was localized to the postsynaptic membranes of both dendritic shafts and spines and occasionally to the presynaptic membranes. A GST/NBCn1 fusion protein containing the C-terminal 131 amino acids of NBCn1 pulled down PSD-95 from rat brain lysates, whereas GST/NBCn1-ΔETSL (deletion of the last four amino acids) and GST/NBCn2 (NCBE) lacking the same ETSL did not. NBCn1 and PSD-95 were coimmunoprecipitated in HEK 293 cells, and their interaction did not affect the efficacy of PSD-95 to bind to the NMDA receptor NR2A. PSD-95 has negligible effects on intracellular pH changes mediated by NBCn1 in HEK 293 cells and Xenopus oocytes. However, PSD-95 increased an ionic conductance produced by NBCn1 channel-like activity. This increase was abolished by NBCn1-ΔETSL or by the peptide containing the last 15 amino acids of NBCn1. Our data suggest that PSD-95 interacts with NBCn1 and increases its channel-like activity while negligibly affecting Na/HCO(3) cotransport. The possibility that the channel-like activity occurs via an intermolecular cavity of multimeric NBCn1 proteins is discussed. Copyright © 2012 S. Karger AG, Basel.

  19. PSD-95 Interacts with NBCn1 and Enhances Channel-like Activity without Affecting Na/HCO3 Cotransport

    Science.gov (United States)

    Lee, Soojung; Yang, Han Soo; Kim, Eunjin; Ju, Eun Ji; Kwon, Min Hyung; Dudley, R. Kyle; Smith, Yoland; Yun, C. Chris; Choi, Inyeong

    2013-01-01

    Background/Aims The sodium/bicarbonate transporter NBCn1 plays an essential role in intracellular pH regulation and transepithelial HCO3− movement in the body. NBCn1 also has sodium channel-like activity uncoupled to Na/HCO3 cotransport. We previously reported that NBCn1 interacts with the postsynaptic density protein PSD-95 in the brain. Here, we elucidated the structural determinant and functional consequence of NBCn1/PSD-95 interaction. Methods: Results In rat hippocampal CA3 neurons, NBCn1 was localized to the postsynaptic membranes of both dendritic shafts and spines and occasionally to the presynaptic membranes. A GST/NBCn1 fusion protein containing the C-terminal 131 amino acids of NBCn1 pulled down PSD-95 from rat brain lysates, whereas GST/NBCn1-ΔETSL (deletion of the last four amino acids) and GST/NBCn2 (NCBE) lacking the same ETSL did not. NBCn1 and PSD-95 were coimmunoprecipitated in HEK 293 cells, and their interaction did not affect the efficacy of PSD-95 to bind to the NMDA receptor NR2A. PSD-95 has negligible effects on intracellular pH changes mediated by NBCn1 in HEK 293 cells and Xenopus oocytes. However, PSD-95 increased an ionic conductance produced by NBCn1 channel-like activity. This increase was abolished by NBCn1-ΔETSL or by the peptide containing the last 15 amino acids of NBCn1. Conclusion Our data suggest that PSD-95 interacts with NBCn1 and increases its channel-like activity while negligibly affecting Na/HCO3 cotransport. The possibility that the channel-like activity occurs via an intermolecular cavity of multimeric NBCn1 proteins is discussed. PMID:23183381

  20. Malignant renal tumors in children

    Directory of Open Access Journals (Sweden)

    Justin Scott Lee

    2015-05-01

    Full Text Available Renal malignancies are common in children. While the majority of malignant renal masses are secondary to Wilms tumor, it can be challenging to distinguish from more aggressive renal masses. For suspicious renal lesions, it is crucial to ensure prompt diagnosis in order to select the appropriate surgical procedure and treatment. This review article will discuss the common differential diagnosis that can be encountered when evaluating a suspicious renal mass in the pediatric population. This includes clear cell sarcoma of the kidney, malignant rhabdoid tumor, renal medullary carcinoma and lymphoma. 

  1. Rescue of the temperature-sensitive, autosomal-recessive mutation R298S in the sodium-bicarbonate cotransporter NBCe1-A characterized by a weakened dimer and abnormal aggregation

    Science.gov (United States)

    Gill, Harindarpal S.; Choi, Kun-Young; Kammili, Lakshmi; Popratiloff, Anastas

    2015-01-01

    Background Band keratopathy, an ocular disease that is characterized by hypercalcemia and opaque bands across the cornea, has been associated with kidney disease. Type-II renal tubular acidosis (RTA), a condition in which the kidneys fail to recover bicarbonate (HCO3−) in the proximal tubule of the nephron, results in HCO3− wastage in the urine and low blood pH. The development of these diseases is associated with autosomal-recessive mutations in the Na+-coupled HCO3− cotransporter NBCe1-A located at the basolateral membranes of either cell type. Methods We provide insight into the devastating R298S mutation found in type-II RTA-afflicted individuals using confocal-microscopy imaging of fluorescently-tagged NBCe1-A and NBCe1-A-R298S molecules expressed in human corneal endothelial and proximal tubule cells and from in-depth biophysical studies of their cytoplasmic N-terminal domains (Nt and Nt-R298S), including Nt crystal structure, melting-temperature, and homodimer dissociation constant (KD) analyses. Results We illuminate and rescue trafficking defects of the R298S mutation of NBCe1-A. The KD for Nt monomer-dimer equilibrium is established. The KD for Nt-R298S is significantly higher, but immeasurable due to environmental factors (pH, temperature, concentration) that result in dimer instability leading to precipitation. The crystal structure of Nt-dimer shows that R298 is part of a putative substrate conduit and resides near the dimer interface held together by hydrogen-bond networks. Conclusions The R298S is a temperature-sensitive mutation in Nt that results in instability of the colloidal system leading to abnormal aggregation. General significance Our findings provide new perspectives to the aberrant mechanism of certain ocular pathologies and type-II RTA associated with the R298S mutation. PMID:25743102

  2. Percutaneous renal tumour biopsy.

    Science.gov (United States)

    Delahunt, Brett; Samaratunga, Hemamali; Martignoni, Guido; Srigley, John R; Evans, Andrew J; Brunelli, Matteo

    2014-09-01

    The use of percutaneous renal tumour biopsy (RTB) as a diagnostic tool for the histological characterization of renal masses has increased dramatically within the last 30 years. This increased utilization has paralleled advances in imaging techniques and an evolving knowledge of the clinical value of nephron sparing surgery. Improved biopsy techniques using image guidance, coupled with the use of smaller gauge needles has led to a decrease in complication rates. Reports from series containing a large number of cases have shown the non-diagnostic rate of RTB to range from 4% to 21%. Re-biopsy has been shown to reduce this rate, while the use of molecular markers further improves diagnostic sensitivity. In parallel with refinements of the biopsy procedure, there has been a rapid expansion in our understanding of the complexity of renal cell neoplasia. The 2013 Vancouver Classification is the current classification for renal tumours, and contains five additional entities recognized as novel forms of renal malignancy. The diagnosis of tumour morphotype on RTB is usually achievable on routine histology; however, immunohistochemical studies may be of assistance in difficult cases. The morphology of the main tumour subtypes, based upon the Vancouver Classification, is described and differentiating features are discussed.

  3. Can renal infarction occur after renal cyst aspiration? Case report.

    Science.gov (United States)

    Emre, Habib; Soyoral, Yasemin Usul; Tanik, Serhat; Gecit, Ilhan; Begenik, Huseyin; Pirincci, Necip; Erkoc, Reha

    2011-01-01

    Renal infarction (RI) is a rarely seen disorder, and the diagnosis is often missed. The two major causes of RI are thromboemboli originhating from a thrombus in the heart or aorta, and in-situ thrombosis of a renal artery. We report a case of RI that developed due to renal artery and vein thrombosis, as confirmed by pathological evaluation of the nephrectomy material, three weeks after renal cyst aspiration.

  4. Inhibition by mercuric chloride of Na-K-2Cl cotransport activity in rectal gland plasma membrane vesicles isolated from Squalus acanthias.

    Science.gov (United States)

    Kinne-Saffran, E; Kinne, R K

    2001-02-09

    The rectal gland of the dogfish shark is a model system for active transepithelial transport of chloride. It has been shown previously that mercuric chloride, one of the toxic environmental pollutants, inhibits chloride secretion in this organ. In order to investigate the mechanism of action of HgCl(2) at a membrane-molecular level, plasma membrane vesicles were isolated from the rectal gland and the effect of mercury on the activity of the Na-K-2Cl cotransporter was investigated in isotope flux studies. During a 30 s exposure HgCl(2) inhibited cotransport activity in a dose-dependent manner with an apparent K(i) of approx. 50 microM. The inhibition was complete after 15 s, partly reversible by dilution of the incubation medium and completely attenuated upon addition of reduced glutathione. The extent of inhibition by mercury depended on the ionic composition of the medium. The sensitivity of the cotransporter was highest when only the high affinity binding sites for sodium and chloride were saturated. Organic mercurials such as p-chloromercuribenzoic acid and p-chloromercuriphenylsulfonic acid at 100 microM did not inhibit the cotransporter, similarly exposure of the vesicles to 10 mM H(2)O(2) or 1 mM dithiothreitol for 30 min at 15 degrees C did not change cotransport activity. Transport activity was, however, reduced by 45.9+/-2.5% after an incubation with 3 mM N-ethylmaleimide for 20 min. Blocking free amino groups by N-hydroxysuccinimide or biotinamidocapronate-N-hydroxysulfosuccinimide had no effect. Investigations on the sidedness of the plasma membrane vesicles, employing the asymmetry of the (Na+K)-ATPase, demonstrated a right-side-out orientation in which the former extracellular face of the membrane is exposed to the incubation medium. In addition, extracellular mercury (5x10(-5) M) inhibited bumetanide-sensitive rubidium uptake into T84 cells by 48.5+/-7.1% after a 2 min incubation period. This inhibition was reversible in a manner similar to that

  5. Imaging chronic renal disease and renal transplant in children

    Energy Technology Data Exchange (ETDEWEB)

    Carmichael, Jim; Easty, Marina [Great Ormond Street Hospital, Radiology Department, London (United Kingdom)

    2010-06-15

    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.)

  6. 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.

  7. 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...

  8. Bumetanide, an Inhibitor of NKCC1 (Na-K-2Cl Cotransporter Isoform 1), Enhances Propofol-Induced Loss of Righting Reflex but Not Its Immobilizing Actions in Neonatal Rats

    OpenAIRE

    Koyama, Yukihide; Andoh, Tomio; Kamiya, Yoshinori; Miyazaki, Tomoyuki; Maruyama, Koichi; Kariya, Takayuki; Goto, Takahisa

    2016-01-01

    Gamma-aminobutyric acid (GABA) has been shown to induce excitation on immature neurons due to increased expression of Na+-K+-2Cl- co-transporter isoform 1 (NKCC1), and the transition of GABAergic signaling from excitatory to inhibitory occurs before birth in the rat spinal cord and spreads rostrally according to the developmental changes in cation-chloride co-transporter expression. We previously showed that midazolam activates the hippocampal CA3 area and induces less sedation in neonatal ra...

  9. Renal Tumor Biopsy Technique

    Institute of Scientific and Technical Information of China (English)

    Lei Zhang; Xue-Song Li; Li-Qun Zhou

    2016-01-01

    Objective:To review hot issues and future direction of renal tumor biopsy (RTB) technique.Data Sources:The literature concerning or including RTB technique in English was collected from PubMed published from 1990 to 2015.Study Selection:We included all the relevant articles on RTB technique in English,with no limitation of study design.Results:Computed tomography and ultrasound were usually used for guiding RTB with respective advantages.Core biopsy is more preferred over fine needle aspiration because of superior accuracy.A minimum of two good-quality cores for a single renal tumor is generally accepted.The use of coaxial guide is recommended.For biopsy location,sampling different regions including central and peripheral biopsies are recommended.Conclusion:In spite of some limitations,RTB technique is relatively mature to help optimize the treatment of renal tumors.

  10. Dyslipoproteinemia in renal transplantation.

    Directory of Open Access Journals (Sweden)

    Gunjotikar R

    1994-01-01

    Full Text Available Twenty-seven live related donor renal allograft recipients were evaluated for dyslipoproteinemia. Twenty-two patients received dual immunosuppression with prednisolone and azathioprine. Five patients received cyclosporin as well. Total cholesterol (Tch, triglycerides (TG, HDL cholesterol (HDLch, LDL cholesterol (LDLch and VLDL cholesterol (VLDLch levels were estimated. Fifteen (56% patients showed significant lipoprotein abnormalities. Renal allograft recipients showed significantly lower levels of Tch (p < 0.05 and LDLch (p < 0.05 and higher levels of TG (p < 0.005 and HDLch (p < 0.05. Diet and beta blockers did not influence lipoprotein levels. A significant negative correlation was noted between post-transplant duration and Tch, TG and VLDLch levels. Increased TG levels were associated with increase in weight and higher daily prednisolone dosage at the time of evaluation. The study confirms the existence of dyslipoproteinemia in renal allograft recipients.

  11. Renal (Kidney) Manifestations in TSC

    Science.gov (United States)

    ... International TSC Research Conference Text Size Get Involved RENAL (KIDNEY) MANIFESTATIONS IN TSC Download a PDF of ... sclerosis complex (TSC) will develop some form of renal (kidney) disease during their lifetime. There are three ...

  12. Renal involvement in antiphospholipid syndrome.

    Science.gov (United States)

    Pons-Estel, Guillermo J; Cervera, Ricard

    2014-02-01

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

  13. [Renal transplantation and urinary lithiasis].

    Science.gov (United States)

    Lechevallier, E; Saussine, C; Traxer, O

    2008-12-01

    Renal lithiasis in renal donors is rare. A renal stone in a donor, or in a renal transplant, is not a contraindication for harvesting nor transplantation. If possible, the stone must be removed at the time of the transplantation. The risk of lithiasis is increased in the renal transplant recipient, with a frequency of 2-6%. Metabolic abnormalities for lithiasis are frequent and can be induced by the immunosuppressive treatment, anticalcineurins. Lithiasis can have a poor prognosis in the renal recipient with a risk for infection or renal dysfunction. Small (renal transplant can be followed-up. Stones of 0.5-1.5cm need an extracorporeal lithotripsy with a previous safety JJ stent. Stones greater than 1.5cm can be treated by ureteroscopy or percutaneous surgery.

  14. 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

  15. Renal Artery Stent Outcomes

    Science.gov (United States)

    Murphy, Timothy P.; Cooper, Christopher J.; Matsumoto, Alan H.; Cutlip, Donald E.; Pencina, Karol M.; Jamerson, Kenneth; Tuttle, Katherine R.; Shapiro, Joseph I.; D’Agostino, Ralph; Massaro, Joseph; Henrich, William; Dworkin, Lance D.

    2016-01-01

    BACKGROUND Multiple randomized clinical trials comparing renal artery stent placement plus medical therapy with medical therapy alone have not shown any benefit of stent placement. However, debate continues whether patients with extreme pressure gradients, stenosis severity, or baseline blood pressure benefit from stent revascularization. OBJECTIVES The study sought to test the hypothesis that pressure gradients, stenosis severity, and/or baseline blood pressure affects outcomes after renal artery stent placement. METHODS Using data from 947 patients with a history of hypertension or chronic kidney disease from the largest randomized trial of renal artery stent placement, the CORAL (Cardiovascular Outcomes in Renal Atherosclerotic Lesions) study, we performed exploratory analyses to determine if subsets of patients experienced better outcomes after stent placement than the overall cohort. We examined baseline stenosis severity, systolic blood pressure, and translesion pressure gradient (peak systolic and mean) and performed interaction tests and Cox proportional hazards analyses for the occurrence of the primary endpoint through all follow-up, to examine the effect of these variables on outcomes by treatment group. RESULTS There were no statistically significant differences in outcomes based on the examined variables nor were there any consistent nonsignificant trends. CONCLUSIONS Based on data from the CORAL randomized trial, there is no evidence of a significant treatment effect of the renal artery stent procedure compared with medical therapy alone based on stenosis severity, level of systolic blood pressure elevation, or according to the magnitude of the transstenotic pressure gradient. (Benefits of Medical Therapy Plus Stenting for Renal Atherosclerotic Lesions [CORAL]; NCT00081731) PMID:26653621

  16. Renal Failure in Pregnancy.

    Science.gov (United States)

    Balofsky, Ari; Fedarau, Maksim

    2016-01-01

    Renal failure during pregnancy affects both mother and fetus, and may be related to preexisting disease or develop secondary to diseases of pregnancy. Causes include hypovolemia, sepsis, shock, preeclampsia, thrombotic microangiopathies, and renal obstruction. Treatment focuses on supportive measures, while pharmacologic treatment is viewed as second-line therapy, and is more useful in mitigating harmful effects than treating the underlying cause. When supportive measures and pharmacotherapy prove inadequate, dialysis may be required, with the goal being to prolong pregnancy until delivery is feasible. Outcomes and recommendations depend primarily on the underlying cause.

  17. Renal lithiasis and nutrition.

    Science.gov (United States)

    Grases, Felix; Costa-Bauza, Antonia; Prieto, Rafel M

    2006-09-06

    Renal lithiasis is a multifactorial disease. An important number of etiologic factors can be adequately modified through 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. Pediatric Renal Neoplasms.

    Science.gov (United States)

    Ranganathan, Sarangarajan

    2009-03-01

    Renal tumors in childhood consist of a diverse group of tumors ranging from the most common Wilms' tumor, to the uncommon and often fatal rhabdoid tumor. Diagnosis is based on morphologic features and aided by ancillary techniques such as immunohistochemistry and cytogenetics. Molecular techniques have helped identify a group of pediatric renal cell carcinomas that have specific translocations, called translocation-associated carcinomas. Differential diagnosis of the various tumors is discussed. Pathogenesis and nephroblastomatosis, the precursor lesions of Wilms tumor, also are discussed briefly, as are the handling of these tumor specimens and prognostic factors. Copyright © 2009 Elsevier Inc. All rights reserved.

  19. Gravidez e transplante renal

    OpenAIRE

    Andrade, Joana Rita Ferreira

    2014-01-01

    Enquadramento: A gravidez é rara em mulheres com Doença Renal Crónica, sobretudo em estadio avançado, em virtude de várias condicionantes como a disfunção ovárica, hemorragias vaginais anovulatórias e amenorreia. Contudo, após transplante renal é possível alimentar o sonho de constituir família, mas é preciso considerar os riscos aumentados para o enxerto e a maior susceptibilidade para complicações da gravidez. Objectivo: Avaliar os riscos e identificar as variáveis que influenciam o suce...

  20. 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.

  1. Branchio-oto-renal syndrome.

    Science.gov (United States)

    Jalil, Jawad; Basheer, Faisal; Shafique, Mobeen

    2014-05-01

    The association of branchial arch anomalies (branchial cysts, branchial fistulas), hearing loss and renal anomalies constitutes the branchio-oto-renal (BOR) syndrome also known as Melnick Fraser syndrome. We present a case of this rare disorder in a girl child who presented with profound deafness, preauricular pits, branchial sinuses and renal hypoplasia.

  2. Drug-induced renal disease.

    Science.gov (United States)

    Curtis, J R

    1979-11-01

    The clinical manifestations of drug-induced renal disease may include all the manifestations attributed to natural or spontaneous renal diseases such as acute renal failure, chronic renal failure, acute nephritic syndrome, renal colic, haematuria, selective tubular defects, obstructive nephropathy, etc. It is therefore vital in any patient with renal disease whatever the clinical manifestations might be, to obtain a meticulous drug and toxin inventory. Withdrawal of the offending drug may result in amelioration or cure of the renal disorder although in the case of severe renal failure it may be necessary to utilise haemodialysis or peritoneal dialysis to tide the patient over the period of acute renal failure. Analgesic nephropathy is an important cause of terminal chronic renal failure and it is therefore vital to make the diagnosis as early as possible. The pathogenesis of some drug-induced renal disorders appears to be immunologically mediated. There are many other pathogenetic mechanisms involved in drug-induced renal disorders and some drugs may under appropriate circumstances be responsible for a variety of different nephrotoxic effects. For example, the sulphonamides have been incriminated in examples of crystalluria, acute interstitial nephritis, acute tubular necrosis, generalised hypersensitivity reactions, polyarteritis nodosa and drug-induced lupus erythematosus.

  3. 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

  4. Regulation of blood pressure and renal function by NCC and ENaC: lessons from genetically engineered mice.

    Science.gov (United States)

    Verouti, Sophia N; Boscardin, Emilie; Hummler, Edith; Frateschi, Simona

    2015-04-01

    The activity of the thiazide-sensitive Na(+)/Cl(-) cotransporter (NCC) and of the amiloride-sensitive epithelial Na(+) channel (ENaC) is pivotal for blood pressure regulation. NCC is responsible for Na(+) reabsorption in the distal convoluted tubule (DCT) of the nephron, while ENaC reabsorbs the filtered Na(+) in the late DCT and in the cortical collecting ducts (CCD) providing the final renal adjustment to Na(+) balance. Here, we aim to highlight the recent advances made using transgenic mouse models towards the understanding of the regulation of NCC and ENaC function relevant to the control of sodium balance and blood pressure. We thus like to pave the way for common mechanisms regulating these two sodium-transporting proteins and their potential implication in structural remodeling of the nephron segments and Na(+) and Cl(-) reabsorption. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Characterization of the isoforms of type IIb sodium-dependent phosphate cotransporter (Slc34a2) in yellow catfish, Pelteobagrus fulvidraco, and their vitamin D3-regulated expression under low-phosphate conditions.

    Science.gov (United States)

    Chen, Pei; Huang, Yanqing; Bayir, Abdulkadir; Wang, Chunfang

    2017-02-01

    In this study, two isoforms slc34a2 genes (type IIb sodium-dependent phosphate cotransporter), slc34a2a2 and slc34a2b, were cloned from intestine and kidney of yellow catfish (Pelteobagrus fulvidraco), with rapid amplification of cDNA ends. The structure differences and the regulation effects of dietary VD3 under low phosphorus were compared among three isoforms of slc34a2 in yellow catfish. The predicted Slc34a2a2 and Slc34a2b proteins match 65 % and 53.8 % sequence identity, with Slc34a2a1, respectively. The membrane-spanning domains were different among these three isoforms. Intestinal Slc34a2a1 and Slc34a2a2 proteins had eight and eleven transmembrane domains, while renal Slc34a2b protein had nine. The tissue distribution study showed that same as slc34a2a1, slc34a2a2 mRNA was mainly distributed in intestine and slc34a2b mRNA in kidney. The effect of vitamin D3 (VD3) level on slc34a2 subfamily expression under low-phosphate conditions, induced by the addition of 0 (VD0), 324 (VD1), 1243 (VD2), 3621 (VD3), 8040 (VD4), or 22700 (VD5) IU VD3/kg feed, was assessed by qPCR. The dose-responsive expression of intestinal slc34a2a2 and high expression of intestinal slc34a2a2 in VD5 together with peak expression of kidney slc34a2b in VD3 coincided with the accumulation of body phosphate content. These data suggested that appropriate level of dietary VD3 up-regulated slc34a2a1, slc34a2a2, and slc34a2b mRNA levels, which increased phosphate retention. In conclusion, the current study provided another possible approach to improve dietary phosphate utilization by adding appropriate level of VD3 to a low-phosphate diet to regulate intestinal and renal slc34a2 gene expression and thus minimize the excretion of phosphorus in yellow catfish.

  6. Pharmacodynamic Effects of Canagliflozin, a Sodium Glucose Co-Transporter 2 Inhibitor, from a Randomized Study in Patients with Type 2 Diabetes

    OpenAIRE

    Sue Sha; Damayanthi Devineni; Atalanta Ghosh; David Polidori; Marcus Hompesch; Sabine Arnolds; Linda Morrow; Heike Spitzer; Keith Demarest; Paul Rothenberg

    2014-01-01

    INTRODUCTION: This randomized, double-blind, placebo-controlled, single and multiple ascending-dose study evaluated the pharmacodynamic effects and safety/tolerability of canagliflozin, a sodium glucose co-transporter 2 inhibitor, in patients with type 2 diabetes. METHODS: Patients (N = 116) discontinued their antihyperglycemic medications 2 weeks before randomization. Patients received canagliflozin 30, 100, 200, or 400 mg once daily or 300 mg twice daily, or placebo at 2 study centers in th...

  7. Euglycemic Diabetic Ketoacidosis in a 27 year-old female patient with type-1-Diabetes treated with sodium-glucose cotransporter-2 (SGLT2) inhibitor Canagliflozin

    OpenAIRE

    Bader, Nimrah; Mirza, Lubna

    2016-01-01

    We are reporting a timely case of atypical euglycemic diabetic ketoacidosis in a type 1 diabetic patient treated with sodium-glucose cotransporter-2 (SGLT-2) inhibitor canagliflozin. The clinical history, physical examination findings and laboratory values are described. Other causes of acidosis such as salicylate toxicity or alcohol intoxication were excluded. Ketoacidosis resolved after increasing dextrose and insulin doses supporting the hypothesis that SGLT-2 inhibitors may lead to hypoin...

  8. [Hypertension and renal disease

    DEFF Research Database (Denmark)

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

    2009-01-01

    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...

  9. Insuficiencia renal aguda.

    Directory of Open Access Journals (Sweden)

    Carlos Hernán Mejía

    2009-10-01

    Full Text Available La insuficiencia renal aguda se diagnostica aproximadamente en 5% de los pacientes hospitalizados. Sus principales causas se relacionan con la alteración del flujo sanguíneo renal, sea por depleción de volumen, baja perfusión renal o por distribución intrarrenal inadecuada y obstrucción del árbol urinario. El diagnóstico parte de la historia clínica y un buen examen físico que corrobore el estado de volemia del paciente y se complementa con el uso adecuado de los índices urinarios (excreción de sodio y osmolaridad, el uroanálisis y la ecografía renal. Su tratamiento consiste en una adecuada recuperación del volumen, manejo de los diuréticos, soporte nutricional, conservación del equilibrio hidroelectrolítico y brindar terapia de diálisis si hay toxicidad urémica, hipercaliemia severa (>6.5 mEq/l, acidosis metabólica o sobrecarga severa de volumen.

  10. Management of Renal Cysts

    Science.gov (United States)

    Nalbant, Ismail; Can Sener, Nevzat; Firat, Hacer; Yeşil, Süleyman; Zengin, Kürşad; Yalcınkaya, Fatih; Imamoglu, Abdurrahim

    2015-01-01

    Background and Objectives: Renal cysts have a high prevalence in the general population, and their estimated incidence increases with age. Renal cyst aspiration (usually with sclerotherapy) or open/laparoscopic decortication is a generally effective and safe method in the treatment of symptomatic simple renal cysts. The success rates of laparoscopic decortication and percutaneous aspiration-sclerotherapy were compared to assist in the decision making for the procedure. Methods: A total of 184 patients with symptomatic simple renal cysts were treated with either laparoscopic decortication in 149 cases or percutaneous aspiration-sclerotherapy in 35 cases. The follow-up period was approximately 35 months, and the symptomatic and radiologic success rates of the 2 techniques were compared retrospectively. Results: Laparoscopic decortication was found to have high success rates, a low recurrence rate, and minimal morbidity. Percutaneous aspiration-sclerotherapy is an outpatient procedure with a minimally higher recurrence rate. Conclusion: When a symptomatic cyst is encountered and treatment of the cyst is indicated, laparoscopic decortication is a more efficient method that offers better results than percutaneous aspiration-sclerotherapy. PMID:25848184

  11. Rupture of Renal Transplant

    Directory of Open Access Journals (Sweden)

    Shona Baker

    2015-01-01

    Full Text Available Background. Rupture of renal allograft is a rare and serious complication of transplantation that is usually attributed to acute rejection, acute tubular necrosis, or renal vein thrombosis. Case Presentation. LD, a 26-year-old male with established renal failure, underwent deceased donor transplantation using kidney from a 50-year-old donor with acute kidney injury (Cr 430 mmol/L. LD had a stormy posttransplant recovery and required exploration immediately for significant bleeding. On day three after transplant, he developed pain/graft swelling and another significant haemorrhage with cardiovascular compromise which did not respond to aggressive resuscitation. At reexploration, the renal allograft was found to have a longitudinal rupture and was removed. Histology showed features of type IIa Banff 97 acute vascular rejection, moderate arteriosclerosis, and acute tubular necrosis. Conclusion. Possible ways of avoiding allograft rupture include use of well-matched, good quality kidneys; reducing or managing risk factors that would predispose to delayed graft function; ensuring a technically satisfactory transplant procedure with short cold and warm ischemia times; and avoiding large donor-recipient age gradients.

  12. Primary renal graft thrombosis

    NARCIS (Netherlands)

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

    1996-01-01

    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 an

  13. Effects of Sodium Glucose Cotransporter-2 Inhibitors on Serum Uric Acid in Type 2 Diabetes Mellitus.

    Science.gov (United States)

    Ahmadieh, Hala; Azar, Sami

    2017-07-27

    Hyperuricemia has been linked to metabolic syndrome, cardiovascular disease, and chronic kidney disease. Hyperuricemia and type 2 diabetes mellitus were inter-related, type 2 diabetes mellitus was more at risk of having a higher serum uric acid level, and also individuals with higher serum uric acid had higher risk of developing type 2 diabetes in the future. Insulin resistance seems to play an important role in the causal relationship between metabolic syndrome, type 2 diabetes, and hyperuricemia. Oral diabetic drugs that would have additional beneficial effects on reducing serum uric acid levels are of importance. Selective SGLT2 inhibitors were extensively studied in type 2 diabetes mellitus and were found to have improvement of glycemic control, in addition to their proven metabolic effects on weight and blood pressure. Additional beneficial effect of SGLT2 inhibitors on serum uric acid level reduction is investigated. Recently, data have been accumulating showing that they have additional beneficial effects on serum uric acid reduction. As for the postulated mechanism, serum uric acid decreased in SGLT2 inhibitor users as a result of the increase in the urinary excretion rate of uric acid, due to the inhibition of uric acid reabsorption mediated by the effect of the drug on the GLUT9 isoform 2, located at the collecting duct of the renal tubule.

  14. ``Aggressive`` renal angiomyolipoma

    Energy Technology Data Exchange (ETDEWEB)

    Cittadini, G. Jr. [Univ. of Genoa (Italy). Dept. of Radiology; Pozzi Mucelli, F. [Univ. of Trieste (Italy). Dept. of Radiology; Danza, F.M. [Catholic Sacro Cuore Univ., Rome (Italy). Dept. of Radiology; Derchi, L.E. [Univ. of Genoa (Italy). Dept. of Radiology; Pozzi Mucelli, R.S. [Univ. of Trieste (Italy). Dept. of Radiology

    1996-11-01

    We describe the US and CT examinations of 4 patients with renal angiomyolipoma with an `aggressive` appearance, and review the literature. The imaging findings in 4 patients with benign renal angiomyolipomas associated with thrombosis of the renal vein and/or inferior vena cava are presented. CT demonstrated fat densities within both tumor and thrombus. In one patient, small lymph nodes with low density internal areas were detected in the para-aortic region. When considering our patients together with those reported in the literature, we found that most angiomyolipomas with venous invasion were large and centrally located within the kidney. Venous thrombosis was observed in 9 lesions of the right kidney, and in only 4 of the left one. One patient only had symptoms due to the thrombus; 10 had problems due to the tumor; and 3 were asymptomatic. Only 4 patients with pararenal enlarged lymph nodes have been reported on in the imaging literature. Fat-containing nodes were detected by CT in one case only; the others had enlarged nodes of soft-tissue density. In one patient the diagnosis of hamartomatous lymph node invasion was established by angiography. In patients with renal angiomyolipoma, demonstration of both fatty thrombus and the fatty infiltration of lymph nodes of the renal hilum cannot be regarded as an indication of malignancy, but only of local aggessive behavior. Conservative treatment seems possible. Detection of enlarged lymph nodes of soft tissue density may cause difficult diagnostic problems, with the diagnosis addressed only by the presence of associated lesions. (orig./MG).

  15. Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes.

    Science.gov (United States)

    Neal, Bruce; Perkovic, Vlado; Mahaffey, Kenneth W; de Zeeuw, Dick; Fulcher, Greg; Erondu, Ngozi; Shaw, Wayne; Law, Gordon; Desai, Mehul; Matthews, David R

    2017-08-17

    Background Canagliflozin is a sodium-glucose cotransporter 2 inhibitor that reduces glycemia as well as blood pressure, body weight, and albuminuria in people with diabetes. We report the effects of treatment with canagliflozin on cardiovascular, renal, and safety outcomes. Methods The CANVAS Program integrated data from two trials involving a total of 10,142 participants with type 2 diabetes and high cardiovascular risk. Participants in each trial were randomly assigned to receive canagliflozin or placebo and were followed for a mean of 188.2 weeks. The primary outcome was a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. Results The mean age of the participants was 63.3 years, 35.8% were women, the mean duration of diabetes was 13.5 years, and 65.6% had a history of cardiovascular disease. The rate of the primary outcome was lower with canagliflozin than with placebo (occurring in 26.9 vs. 31.5 participants per 1000 patient-years; hazard ratio, 0.86; 95% confidence interval [CI], 0.75 to 0.97; Pcanagliflozin with respect to the progression of albuminuria (hazard ratio, 0.73; 95% CI, 0.67 to 0.79) and the composite outcome of a sustained 40% reduction in the estimated glomerular filtration rate, the need for renal-replacement therapy, or death from renal causes (hazard ratio, 0.60; 95% CI, 0.47 to 0.77). Adverse reactions were consistent with the previously reported risks associated with canagliflozin except for an increased risk of amputation (6.3 vs. 3.4 participants per 1000 patient-years; hazard ratio, 1.97; 95% CI, 1.41 to 2.75); amputations were primarily at the level of the toe or metatarsal. Conclusions In two trials involving patients with type 2 diabetes and an elevated risk of cardiovascular disease, patients treated with canagliflozin had a lower risk of cardiovascular events than those who received placebo but a greater risk of amputation, primarily at the level of the toe or metatarsal. (Funded by

  16. Chronic renal disease in pregnancy.

    Science.gov (United States)

    Ramin, Susan M; Vidaeff, Alex C; Yeomans, Edward R; Gilstrap, Larry C

    2006-12-01

    The purpose of this review was to examine the impact of varying degrees of renal insufficiency on pregnancy outcome in women with chronic renal disease. Our search of the literature did not reveal any randomized clinical trials or meta-analyses. The available information is derived from opinion, reviews, retrospective series, and limited observational series. It appears that chronic renal disease in pregnancy is uncommon, occurring in 0.03-0.12% of all pregnancies from two U.S. population-based and registry studies. Maternal complications associated with chronic renal disease include preeclampsia, worsening renal function, preterm delivery, anemia, chronic hypertension, and cesarean delivery. The live birth rate in women with chronic renal disease ranges between 64% and 98% depending on the severity of renal insufficiency and presence of hypertension. Significant proteinuria may be an indicator of underlying renal insufficiency. Management of pregnant women with underlying renal disease should ideally entail a multidisciplinary approach at a tertiary center and include a maternal-fetal medicine specialist and a nephrologist. Such women should receive counseling regarding the pregnancy outcomes in association with maternal chronic renal disease and the effect of pregnancy on renal function, especially within the ensuing 5 years postpartum. These women will require frequent visits and monitoring of renal function during pregnancy. Women whose renal disease is further complicated by hypertension should be counseled regarding the increased risk of adverse outcome and need for blood pressure control. Some antihypertensives, especially angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers, should be avoided during pregnancy, if possible, because of the potential for both teratogenic (hypocalvaria) and fetal effects (renal failure, oliguria, and demise).

  17. CUTANEOUS MANIFESTATIONS OF CHRONIC RENAL FAILURE AND RENAL TRANSPLANTATION

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    R. Suganya Gnanadeepam

    2017-07-01

    Full Text Available 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 Hospital, Trichy. During this period, 100 patients who had the presence of skin manifestations were selected and studied (80 renal failure patients and 20 renal transplantation patients. RESULTS Most of the specific cutaneous manifestations of chronic renal failure and renal transplantation were noted in this study. Pruritus and xerosis were the most common manifestations noted in chronic renal failure while infections was commonly noted in renal transplantation patients. CONCLUSION Pruritus and xerosis were the most common among the specific cutaneous manifestations in chronic renal failure followed by nail abnormalities and pigmentary changes. Cutaneous manifestations of renal transplantation were mostly due to infections of which fungal infection is the most common followed by viral infection.

  18. Transarterial embolization for serious renal hemorrhage following renal biopsy.

    Science.gov (United States)

    Zeng, Dan; Liu, Guihua; Sun, Xiangzhou; Zhuang, Wenquan; Zhang, Yuanyuan; Guo, Wenbo; Yang, Jianyong; Chen, Wei

    2013-01-01

    The goal of this study is to evaluate the feasibility and efficacy of percutaneous transarterial embolization for the treatment of serious renal hemorrhage after renal biopsy. Nine patients with renal hemorrhage had frank pain and gross hematuria as main symptoms after renal biopsy. Intrarenal arterial injuries and perinephric hematoma were confirmed by angiography in all cases. The arterial injuries led to two types of renal hemorrhage, Type I: severe renal injure or intrarenal renal artery rupture (n=5), with contrast medium spilling out of the artery and spreading into renal pelvis or kidney capsule in angiography; Type II, pseudo aneurysm or potential risk of intrarenal artery injure (n=4), where contrast medium that spilled out of intraartery was retained in the parenchyma as little spots less than 5 mm in diameter in angiography. Transcatheter superselective intrarenal artery embolization was performed with coils or microcoils (Type I intrarenal artery injure) and polyvinyl alcohol particles (Type II injure). The intrarenal arterial injuries were occluded successfully in all patients. Light or mild back or abdominal pain in the side of the embolized kidney was found in three patients following embolization procedures and disappeared 3 days later. Serum creatinine and perinephric hematoma were stable, and gross hematuresis stopped immediately (n=4) or 3-5 days (n=3) after embolization. In conclusions, transcatheter superselective intrarenal artery embolization as a minimally invasive therapy is safe and effective for treatment of serious renal hemorrhage following percutaneous renal biopsy.

  19. Problemas renales de la cirrosis Renal problems of cirrhosis

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    Alvaro García

    1992-02-01

    Full Text Available Presentamos una revisión actualizada y condensada acerca de los problemas renales más relevantes que ocurren en la cirrosis tales como las alteraciones en el manejo del sodio y del agua, el tratamiento de la ascitis y el edema y el enfoque de la falla renal que ocurre en esta enfermedad, es decir síndrome hepato-renal y necrosis tubular aguda.

    We present a condensed and updated review on the most common renal problems occurring in cirrhosis such as the handling of sodium and water, the treatment of ascites and edema and the approach to the renal failure that frequently takes place in this disease, namely hepato-renal syndrome and acute tubular necrosis.

  20. MR imaging findings of renal infarction induced by renal artery

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jun Woo; Kim, Suck; Kim, Yong Woo; Hu, Jin Sam; Choi, Sang Yoel; Moon, Tae Yong; Lee, Suck Hong; Kim, Byung Su; Lee, Chang Hun [Pusan National Univ., Pusan (Korea, Repulic of). Coll. of Medicine

    1998-02-01

    To assess the usefulness of diffusion-weighted imaging (DWI) in evaluating serial parenchymal changes in renal infarction induced by renal artery ligation, by comparing this with the conventional spin echo technique and correlating the results with the histopathological findings. In 22 rabbits, renal infarction was induced by ligation of the renal artery. Spin-echo T1-weighted imaging (T1WI), turbo spin-echo (TSE) T2-weighted imaging (T2WI), and DWI were performed, using a 1.5-T superconductive unit, at 30 minutes, 1 hour, 2,3,6, 12 and 24 hours, and 2, 3, 7 and 20 days after left renal artery ligation. Changes in signal intensity on T1WI, T2WI, and DWI were correlated with histopathologic findings. Diffusion-weighted imaging is useful for the detection of hyperacute renal infarction, and the apparent diffusion coefficient may provide additional information concerning its evolution. (author). 21 refs., 9 figs.

  1. 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.

  2. The Na+/Glucose Cotransporter Inhibitor Canagliflozin Activates AMPK by Inhibiting Mitochondrial Function and Increasing Cellular AMP Levels.

    Science.gov (United States)

    Hawley, Simon A; Ford, Rebecca J; Smith, Brennan K; Gowans, Graeme J; Mancini, Sarah J; Pitt, Ryan D; Day, Emily A; Salt, Ian P; Steinberg, Gregory R; Hardie, D Grahame

    2016-09-01

    Canagliflozin, dapagliflozin, and empagliflozin, all recently approved for treatment of type 2 diabetes, were derived from the natural product phlorizin. They reduce hyperglycemia by inhibiting glucose reuptake by sodium/glucose cotransporter (SGLT) 2 in the kidney, without affecting intestinal glucose uptake by SGLT1. We now report that canagliflozin also activates AMPK, an effect also seen with phloretin (the aglycone breakdown product of phlorizin), but not to any significant extent with dapagliflozin, empagliflozin, or phlorizin. AMPK activation occurred at canagliflozin concentrations measured in human plasma in clinical trials and was caused by inhibition of Complex I of the respiratory chain, leading to increases in cellular AMP or ADP. Although canagliflozin also inhibited cellular glucose uptake independently of SGLT2, this did not account for AMPK activation. Canagliflozin also inhibited lipid synthesis, an effect that was absent in AMPK knockout cells and that required phosphorylation of acetyl-CoA carboxylase (ACC) 1 and/or ACC2 at the AMPK sites. Oral administration of canagliflozin activated AMPK in mouse liver, although not in muscle, adipose tissue, or spleen. Because phosphorylation of ACC by AMPK is known to lower liver lipid content, these data suggest a potential additional benefit of canagliflozin therapy compared with other SGLT2 inhibitors. © 2016 by the American Diabetes Association.

  3. Antioxidants and NOS inhibitors selectively targets manganese-induced cell volume via Na-K-Cl cotransporter-1 in astrocytes.

    Science.gov (United States)

    Alahmari, Khalid A; Prabhakaran, Harini; Prabhakaran, Krishnan; Chandramoorthy, Harish C; Ramugounder, Ramakrishnan

    2015-06-12

    Manganese has shown to be involved in astrocyte swelling. Several factors such as transporters, exchangers and ion channels are attributed to astrocyte swelling as a result in the deregulation of cell volume. Products of oxidation and nitration have been implied to be involved in the pathophysiology of swelling; however, the direct link and mechanism of manganese induced astrocyte swelling has not been fully elucidated. In the current study, we used rat primary astrocyte cultures to investigate the activation of Na-K-Cl cotransporter-1 (NKCC1) a downstream mechanism for free radical induced astrocyte swelling as a result of manganese toxicity. Our results showed manganese, oxidants and NO donors as potent inducer of oxidation and nitration of NKCC1. Our results further confirmed that manganese (50 μM) increased the total protein, phosphorylation and activity of NKCC1 as well as cell volume (p manganese or oxidants and NO induced activation, oxidation/nitration of NKCC1 play an important role in the astrocyte swelling. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Role of the neuronal K-Cl co-transporter KCC2 in inhibitory and excitatory neurotransmission

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    Ingrid eChamma

    2012-02-01

    Full Text Available The K-Cl co-transporter KCC2 plays multiple roles in the physiology of central neurons and alterations of its function and/or expression are associated with several neurological conditions. By regulating intraneuronal chloride homeostasis, KCC2 strongly influences the efficacy and polarity of the chloride-permeable -aminobutyric acid (GABA type A and glycine receptor (GlyR mediated synaptic transmission. This appears particularly critical for the development of neuronal circuits as well as for the dynamic control of GABA and glycine signaling in mature networks. The activity of the transporter is also associated with transmembrane water fluxes which compensate solute fluxes associated with synaptic activity. Finally, KCC2 interaction with the actin cytoskeleton appears critical both for dendritic spine morphogenesis and the maintenance of glutamatergic synapses. In light of the pivotal role of KCC2 in the maturation and function of central synapses, it is of particular importance to understand the cellular and molecular mechanisms underlying its regulation. These include development- and activity-dependent modifications both at the transcriptional and post-translational levels. We emphasize the importance of post-translational mechanisms such as phosphorylation and dephosphorylation, oligomerization, cell surface stability, clustering and membrane diffusion for the rapid and dynamic regulation of KCC2 function.

  5. Allodynia and hyperalgesia in diabetic rats are mediated by GABA and depletion of spinal potassium-chloride co-transporters

    Science.gov (United States)

    Jolivalt, Corinne G.; Lee, Corinne A.; Ramos, Khara M.; Calcutt, Nigel A.

    2008-01-01

    Diabetic rats show behavioral indices of painful neuropathy that may model the human condition. Hyperalgesia during the formalin test in diabetic rats is accompanied by the apparently paradoxical decrease in spinal release of excitatory neurotransmitters and increase in the inhibitory neurotransmitter GABA. Decreased expression of the potassium-chloride co-transporter, KCC2, in the spinal cord promotes excitatory properties of GABA. We therefore measured spinal KCC2 expression and explored the role of the GABAA receptor in rats with painful diabetic neuropathy. KCC2 protein levels were significantly reduced in the spinal cord of diabetic rats while levels of NKCC1 and the GABAA receptor were unchanged. Spinal delivery of the GABAA receptor antagonist bicuculline reduced formalin-evoked flinching in diabetic rats and also dose-dependently alleviated tactile allodynia. GABAA receptor-mediated rate-dependent depression of the spinal H reflex was absent in the spinal cord of diabetic rats. Control rats treated with the KCC2 blocker DIOA, mimicked diabetes by showing increased formalin-evoked flinching and diminished rate dependent depression. The ability of bicuculline to alleviate allodynia and formalin-evoked hyperalgesia in diabetic rats is consistent with a reversal of the properties of GABA predicted by reduced spinal KCC2 and suggests that reduced KCC2 expression and increased GABA release contribute to spinally-mediated hyperalgesia in diabetes. PMID:18755547

  6. Allodynia and hyperalgesia in diabetic rats are mediated by GABA and depletion of spinal potassium-chloride co-transporters.

    Science.gov (United States)

    Jolivalt, Corinne G; Lee, Corinne A; Ramos, Khara M; Calcutt, Nigel A

    2008-11-15

    Diabetic rats show behavioral indices of painful neuropathy that may model the human condition. Hyperalgesia during the formalin test in diabetic rats is accompanied by the apparently paradoxical decrease in spinal release of excitatory neurotransmitters and increase in the inhibitory neurotransmitter GABA. Decreased expression of the potassium-chloride co-transporter, KCC2, in the spinal cord promotes excitatory properties of GABA. We therefore measured spinal KCC2 expression and explored the role of the GABA(A) receptor in rats with painful diabetic neuropathy. KCC2 protein levels were significantly reduced in the spinal cord of diabetic rats, while levels of NKCC1 and the GABA(A) receptor were unchanged. Spinal delivery of the GABA(A) receptor antagonist bicuculline reduced formalin-evoked flinching in diabetic rats and also dose-dependently alleviated tactile allodynia. GABA(A) receptor-mediated rate-dependent depression of the spinal H reflex was absent in the spinal cord of diabetic rats. Control rats treated with the KCC2 blocker DIOA, mimicked diabetes by showing increased formalin-evoked flinching and diminished rate- dependent depression. The ability of bicuculline to alleviate allodynia and formalin-evoked hyperalgesia in diabetic rats is consistent with a reversal of the properties of GABA predicted by reduced spinal KCC2 and suggests that reduced KCC2 expression and increased GABA release contribute to spinally mediated hyperalgesia in diabetes.

  7. Co-transport of polycyclic aromatic hydrocarbons by motile microorganisms leads to enhanced mass transfer under diffusive conditions.

    Science.gov (United States)

    Gilbert, Dorothea; Jakobsen, Hans H; Winding, Anne; Mayer, Philipp

    2014-04-15

    The environmental chemodynamics of hydrophobic organic chemicals (HOCs) are often rate-limited by diffusion in stagnant boundary layers. This study investigated whether motile microorganisms can act as microbial carriers that enhance mass transfer of HOCs through diffusive boundary layers. A new experimental system was developed that allows (1) generation of concentration gradients of HOCs under the microscope, (2) exposure and direct observation of microorganisms in such gradients, and (3) quantification of HOC mass transfer. Silicone O-rings were integrated into a Dunn chemotaxis chamber to serve as sink and source for polycyclic aromatic hydrocarbons (PAHs). This resulted in stable concentration gradients in water (>24 h). Adding the model organism Tetrahymena pyriformis to the experimental system enhanced PAH mass transfer up to hundred-fold (benzo[a]pyrene). Increasing mass transfer enhancement with hydrophobicity indicated PAH co-transport with the motile organisms. Fluorescence microscopy confirmed such transport. The effective diffusivity of T. pyriformis, determined by video imaging microscopy, was found to exceed molecular diffusivities of the PAHs up to four-fold. Cell-bound PAH fractions were determined to range from 28% (naphthalene) to 92% (pyrene). Motile microorganisms can therefore function as effective carriers for HOCs under diffusive conditions and might significantly enhance mobility and availability of HOCs.

  8. Review. The mammalian proton-coupled peptide cotransporter PepT1: sitting on the transporter-channel fence?

    Science.gov (United States)

    Meredith, David

    2009-01-27

    The proton-coupled di- and tripeptide transporter PepT1 (SLC15a1) is the major route by which dietary nitrogen is taken up from the small intestine, as well as being the route of entry for important therapeutic (pro)drugs such as the beta-lactam antibiotics, angiotensin-converting enzyme inhibitors and antiviral and anti-cancer agents. PepT1 is a member of the major facilitator superfamily of 12 transmembrane domain transporter proteins. Expression studies in Xenopus laevis on rabbit PepT1 that had undergone site-directed mutagenesis of a conserved arginine residue (arginine282 in transmembrane domain 7) to a glutamate revealed that this residue played a role in the coupling of proton and peptide transport and prevented the movement of non-coupled ions during the transporter cycle. Mutations of arginine282 to other non-positive residues did not uncouple proton-peptide cotransport, but did allow additional ion movements when substrate was added. By contrast, mutations to positive residues appeared to function the same as wild-type. These findings are discussed in relation to the functional role that arginine282 may play in the way PepT1 operates, together with structural information from the homology model of PepT1 based on the Escherichia coli lactose permease crystal structure.

  9. A dileucine motif is involved in plasma membrane expression and endocytosis of rat sodium taurocholate cotransporting polypeptide (Ntcp).

    Science.gov (United States)

    Stross, Claudia; Kluge, Stefanie; Weissenberger, Katrin; Winands, Elisabeth; Häussinger, Dieter; Kubitz, Ralf

    2013-11-15

    The sodium taurocholate cotransporting polypeptide (Ntcp) is the major uptake transporter for bile salts into liver parenchymal cells, and PKC-mediated endocytosis was shown to regulate the number of Ntcp molecules at the plasma membrane. In this study, mechanisms of Ntcp internalization were analyzed by flow cytometry, immunofluorescence, and Western blot analyses in HepG2 cells. PKC activation induced endocytosis of Ntcp from the plasma membrane by ~30%. Endocytosis of Ntcp was clathrin dependent and was followed by lysosomal degradation. A dileucine motif located in the third intracellular loop of Ntcp was essential for endocytosis but also for processing and plasma membrane targeting, suggesting a dual function of this motif for intracellular trafficking of Ntcp. Mutation of two of five potential phosphorylation sites surrounding the dileucine motif (Thr225 and Ser226) inhibited PKC-mediated endocytosis. In conclusion, we could identify a motif, which is critical for Ntcp plasma membrane localization. Endocytic retrieval protects hepatocytes from elevated bile salt concentrations and is of special interest, because NTCP has been identified as a receptor for the hepatitis B and D virus.

  10. Dietary salt regulates the phosphorylation of OSR1/SPAK kinases and the sodium chloride cotransporter through aldosterone.

    Science.gov (United States)

    Chiga, Motoko; Rai, Tatemitsu; Yang, Sung-Sen; Ohta, Akihito; Takizawa, Toichiro; Sasaki, Sei; Uchida, Shinichi

    2008-12-01

    Pseudohypoaldosteronism type II (PHAII) is caused by mutations in the WNK1 and WNK4 genes (WNK with-no-lysine kinase). In a mouse model of this disease where a mutant of Wnk4 D561A was knocked in, increased phosphorylation of the sodium chloride cotransporter (NCC) was found and the transporter was concentrated on the apical membrane of the distal tubules. In addition, we recently found that other kinases, such as the oxidative stress response kinase-1/STE20/SPS1-related proline alanine-rich kinase (OSR1/SPAK), also showed increased phosphorylation in these mice. Here we determined whether this kinase cascade is regulated by dietary salt intake. We found that the phosphorylation states of NCC and OSR1/SPAK were increased by low-salt diets and decreased by high-salt diets; a regulation completely lost in the knock-in mice. Increased phosphorylation was reversed by spironolactone and this decreased phosphorylation was reversed by administration of exogenous aldosterone. These studies suggest that that the WNK-OSR1/SPAK-NCC cascade may be a novel effector system of aldosterone action in the kidney.

  11. The K–Cl Cotransporter KCC3 as an Independent Prognostic Factor in Human Esophageal Squamous Cell Carcinoma

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    Atsushi Shiozaki

    2014-01-01

    Full Text Available The objectives of the present study were to investigate the role of K–Cl cotransporter 3 (KCC3 in the regulation of cellular invasion and the clinicopathological significance of its expression in esophageal squamous cell carcinoma (ESCC. Immunohistochemical analysis performed on 70 primary tumor samples obtained from ESCC patients showed that KCC3 was primarily found in the cytoplasm of carcinoma cells. Although the expression of KCC3 in the main tumor (MT was related to several clinicopathological features, such as the pT and pN categories, it had no prognostic impact. KCC3 expression scores were compared between the MT and cancer nest (CN, and the survival rate of patients with a CN>MT score was lower than that of patients with a CN≤MT score. In addition, the survival rate of patients in whom KCC3 was expressed in the invasive front of tumor was lower than that of the patients without it. Furthermore, multivariate analysis demonstrated that the expression of KCC3 in the invasive front was one of the most important independent prognostic factors. The depletion of KCC3 using siRNAs inhibited cell migration and invasion in human ESCC cell lines. These results suggest that the expression of KCC3 in ESCC may affect cellular invasion and be related to a worse prognosis in patients with ESCC.

  12. Renal subcapsular haematoma: an unusual complication of renal artery stenting

    Institute of Scientific and Technical Information of China (English)

    XIA Dan; CHEN Shan-wen; ZHANG Hong-kun; WANG Shuo

    2011-01-01

    After successful renal artery angioplasty and stent placement, a patient in a fully anticoagulated state developed hypotension and flank pain. Computed tomography (CT) of the abdomen revealed a large renal subcapsular haematoma which was successfully managed conservatively without embolotherapy and surgical intervention. To prevent hemorrhage after renal artery stenting, it is necessary to underscore the importance of reducing the contrast volume and pressure of angiography, controlling systemic blood pressure, and monitoring guide wire position at all times.

  13. Dopamins renale virkninger

    DEFF Research Database (Denmark)

    Olsen, Niels Vidiendal

    1990-01-01

    Dopamine is an endogenic catecholamine which, in addition to being the direct precursor of noradrenaline, has also an effect on peripheral dopaminergic receptors. These are localized mainly in the heart, splanchnic nerves and the kidneys. Dopamine is produced in the kidneys and the renal metaboli...... dialysis unnecessary in a number of patients on account of increased diuresis and natriuresis. The effect of GFR and the significance for the prognosis are not known....

  14. Renal lithiasis and nutrition

    OpenAIRE

    Prieto Rafel M; Costa-Bauza Antonia; Grases Felix

    2006-01-01

    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...

  15. Nutrition and renal disease.

    Directory of Open Access Journals (Sweden)

    Iris de Castaño

    2009-11-01

    Full Text Available Kidney plays an important roll in body homeostasis through excretory, metabolic and endocrine functions. Kidneys filter fluids and solutes and reabsorbed water , electrolytes an minerals. Urine volume and solute excretion are adjusted to keep composition of the extracellular space, serum osmolarity and intravascular volume in constant balance. Kidneys also regulate acid base equilibrium, hormone metabolism and excretion and amino acid concentration. Vitamin D hydroxylation takes place in the kidney, this is the active form of this vitamin, which inhibits PTH. In addition they produce erythropoietin which control hemoglobin concentration in erythrocytes. When renal insufficiency develops, and glormerular filtration rate is between 50 to 75% of normal, this functions are decreased .When renal function is less than 10%, this functions ceased. In children small changes in water, solute, acid base, calcium and phosphorus can alter normal growth and development. If kidneys can not maintain internal equilibrium, specific nutrients should be used. Compensation should be done according to age, type or renal disease and level of glomerular filtration rate.

  16. Renal artery aneurysm mimicking renal calculus with hydronephrosis.

    Science.gov (United States)

    Chen, Shanwen; Meng, Hongzhou; Cao, Min; Shen, Baihua

    2013-06-01

    A 51-year-old woman was found to have a left renal calculus with hydronephrosis. She underwent unsuccessful extracorporeal shock wave lithotripsy, leading to the recommendation that percutaneous lithotomy was necessary to remove the renal calculus. In view of the unusual shape of the calculus and absence of abnormalities in urine sediment, preoperative computed tomography and renal angiography were performed, which instead showed a calcified left renal artery aneurysm. Subsequent efforts to perform an aneurysmectomy also failed, eventually necessitating left nephrectomy. This case illustrates the pitfalls in the diagnosis of a renal artery aneurysm, which is a relatively common condition that may have unusual presentations. Hence, it is suggested that the possibility of a renal artery aneurysm be considered in the differential diagnosis when one detects a renal calculus with an unusual appearance. In addition, we propose that 3-dimensional reconstruction computed tomography be performed before considering surgical options for such renal calculi to rule out the possibility of a renal artery aneurysm.

  17. Renal scintigraphy in infants with antenatally diagnosed renal pelvis dilatation

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    Ajdinović Boris

    2008-01-01

    Full Text Available Background/Aim. Ureteropelvic junction obstruction and vesicoureteral reflux are the most frequent entities identified on the basis of antenatal hydronephrosis. The aim of this study was to determine the incidence and pattern of abnormal renal scintigraphy findings in postnatal investigation of children with antenatal hydronephrosis. Methods. Twenty four infants (19 boys and five girls presented with antenatal hydronephrosis and mild to moderate hydronephrosis on ultrasound in newborn period were referred for renal scintigraphy. Ten patients with vesicoureteral reflux documented on micturating cystoureterography underwent 99mTc-DMSA renal scintigraphy and 14 patients were subjected to 99mTc-DTPA scintigraphy. Results. Anteroposterior pelvic diameter on ultrasound ranged from 11 to 24 mm. Renal DMSA scans identified congenital scars in two boys with bilateral reflux of grade V and unilateral reflux of grade III. Relative kidney uptake (RKU less than 40% was found in three, and poor kidney function (RKU less than 10% in two patients. Significant obstruction was shown on DTPA diuretic renal scintigraphy in 6/14 patients. Some slowing in dranaige (T1/2 greater than 10 minutes with no reduction in differential renal function was identified in three patients. Differential renal function less than 10% was obtained in one case. Conclusion. A high percent of abnormal renal scintigraphy findings was obtained. Renal scintigraphy was useful in determination of underlying cause of antenatally detected hydronephrosis.

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

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Young Jae; Choi, Chul Soon; Min, Seon Jeong; Lee, Gyung Kyu; Lee, Eil Seong; Kang, Ik Won; Bae, Sang Hoon [Hallym University College of Medicine, Chuncheon (Korea, Republic of)

    2003-12-15

    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.

  19. Trasplante renal Kidney transplant

    Directory of Open Access Journals (Sweden)

    P. Martín

    2006-08-01

    Full Text Available El trasplante renal es la terapia de elección para la mayoría de las causas de insuficiencia renal crónica terminal porque mejora la calidad de vida y la supervivencia frente a la diálisis. El trasplante renal de donante vivo es una excelente alternativa para el paciente joven en situación de prediálisis porque ofrece mejores resultados. El tratamiento inmunosupresor debe ser individualizado buscando la sinergia inmunosupresora y el mejor perfil de seguridad, y debe adaptarse a las diferentes etapas del trasplante renal. En el seguimiento del trasplante renal hay que tener muy en cuenta los factores de riesgo cardiovascular y los tumores puesto que la muerte del paciente con injerto funcionante es la segunda causa de pérdida del injerto tras el primer año del trasplante. La función alterada del injerto es un factor de mortalidad cardiovascular independiente que requerirá seguimiento y control de todas sus complicaciones para retrasar la entrada en diálisis.The kidney transplant is the therapy of choice for the majority of the causes of chronic terminal kidney insufficiency, because it improves the quality of life and survival in comparison with dialysis. A kidney transplant from a live donor is an excellent alternative for the young patient in a state of pre-dialysis because it offers the best results. Immunosuppressive treatment must be individualised, seeking immunosuppressive synergy and the best safety profile, and must be adapted to the different stages of the kidney transplant. In the follow-up to the kidney transplant, cardiovascular risk factors and tumours must be especially taken into account, given that the death of the patient with a working graft is the second cause of loss of the graft following the first year of the transplant. The altered function of the graft is a factor of independent cardiovascular mortality that will require follow-up and the control of all its complications to postpone the entrance in dialysis.

  20. Haemostatic aspects of renal transplantation.

    Science.gov (United States)

    Sørensen, P J; Schmidt, E B; Knudsen, F; Nielsen, A H; Kristensen, S D; Dyerberg, J; Kornerup, H J

    1988-01-01

    Platelet function and protein C activity and antigen level was studied in 31 renal transplant recipients and 10 healthy controls. The patients were divided into three groups: (I) cyclosporin treated, (II) azathioprine treated, and (III) azathioprine treated patients with chronic rejection. The platelet function in the renal transplant patients was normal and there was no difference between groups I and II. The specific activity of protein C was decreased in patients after renal transplantation and decreasing protein C activity and progressive renal failure was found to be positively correlated in the azathioprine treated groups.

  1. Renal replacement therapy in ICU

    Directory of Open Access Journals (Sweden)

    C Deepa

    2012-01-01

    Full Text Available Diagnosing and managing critically ill patients with renal dysfunction is a part of the daily routine of an intensivist. Acute kidney insufficiency substantially contributes to the morbidity and mortality of critically ill patients. Renal replacement therapy (RRT not only does play a significant role in the treatment of patients with renal failure, acute as well as chronic, but also has spread its domains to the treatment of many other disease conditions such as myaesthenia gravis, septic shock and acute on chronic liver failure. This article briefly outlines the role of renal replacement therapy in ICU.

  2. 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.

  3. 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.

  4. CT features of renal infarction

    Energy Technology Data Exchange (ETDEWEB)

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

    2002-10-01

    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.

  5. Hemorrhagic Fever with Renal Syndrome (HFRS)

    Science.gov (United States)

    ... this page: About CDC.gov . Share Compartir Hemorrhagic Fever with Renal Syndrome (HFRS) On this Page What ... is HFRS prevented? Suggested Reading What is hemorrhagic fever with renal syndrome? Hemorrhagic fever with renal syndrome ( ...

  6. Renal cirsoid arteriovenous malformation masquerading as neoplasia.

    Science.gov (United States)

    Silverthorn, K; George, D

    1988-12-01

    A woman with renal colic and microscopic hematuria had filling defects in the left renal collecting system detected on excretory urography. A nephrectomy, performed because of suspected malignancy, might have been averted by renal angiography.

  7. 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.

  8. Functional coupling of renal K+ and Na+ handling causes high blood pressure in Na+ replete mice.

    Science.gov (United States)

    Vitzthum, Helga; Seniuk, Anika; Schulte, Laura Helene; Müller, Maxie Luise; Hetz, Hannah; Ehmke, Heimo

    2014-03-01

    A network of kinases, including WNKs, SPAK and Sgk1, is critical for the independent regulation of K+ and Na+ transport in the distal nephron. Angiotensin II is thought to act as a key hormone in orchestrating these kinases to switch from K+ secretion during hyperkalaemia to Na+ reabsorption during intravascular volume depletion, thus keeping disturbances in electrolyte and blood pressure homeostasis at a minimum. It remains unclear, however, how K+ and Na+ transport are regulated during a high Na+ intake, which is associated with suppressed angiotensin II levels and a high distal tubular Na+ load. We therefore investigated the integrated blood pressure, renal, hormonal and gene and protein expression responses to large changes of K+ intake in Na+ replete mice. Both low and high K+ intake increased blood pressure and caused Na+ retention. Low K+ intake was accompanied by an upregulation of the sodium-chloride cotransporter (NCC) and its activating kinase SPAK, and inhibition of NCC normalized blood pressure. Renal responses were unaffected by angiotensin AT1 receptor antagonism, indicating that low K+ intake activates the distal nephron by an angiotensin-independent mode of action. High K+ intake was associated with elevated plasma aldosterone concentrations and an upregulation of the epithelial sodium channel (ENaC) and its activating kinase Sgk1. Surprisingly, high K+ intake increased blood pressure even during ENaC or mineralocorticoid receptor antagonism, suggesting the contribution of aldosterone-independent mechanisms. These findings show that in a Na+ replete state, changes in K+ intake induce specific molecular and functional adaptations in the distal nephron that cause a functional coupling of renal K+ and Na+ handling, resulting in Na+ retention and high blood pressure when K+ intake is either restricted or excessively increased.

  9. Sex differences in renal and metabolic responses to a high-fructose diet in mice

    Science.gov (United States)

    Sharma, Nikhil; Li, Lijun

    2014-01-01

    High fructose intake has been associated with increased incidences of renal disease and hypertension, among other pathologies. Most fructose is cleared by the portal system and metabolized in the liver; however, systemic levels of fructose can rise with increased consumption. We tested whether there were sex differences in the renal responses to a high-fructose diet in mice. Two-month-old male and female C57BL6/129/SV mice (n = 6 mice per sex per treatment) were randomized to receive control or high-fructose (65% by weight) diets as pelleted chow ad libitum for 3 mo. Fructose feeding did not significantly affect body weight but led to a 19% and 10% increase in kidney weight in male and female mice, respectively. In male mice, fructose increased the expression (∼50%) of renal cortical proteins involved in metabolism, including glucose transporter 5 (facilitative fructose transporter), ketohexokinase, and the insulin receptor (β-subunit). Female mice had lower basal levels of glucose transporter 5, which were unresponsive to fructose. However, female mice had increased urine volume and plasma K+ and decreased plasma Na+ with fructose, whereas male mice were less affected. Likewise, female mice showed a two- to threefold reduction in the expression Na+-K+-2Cl− cotransporter 2 in the thick ascending limb and aquaporin-2 in the collecting duct with fructose relative to female control mice, whereas male mice had no change. Overall, our results support greater proximal metabolism of fructose in male animals and greater distal tubule/collecting duct (electrolyte homeostasis) alterations in female animals. These sex differences may be important determinants of the specific nature of pathologies that develop in association with high fructose consumption. PMID:25537743

  10. Renal tubular NEDD4-2 deficiency causes NCC-mediated salt-dependent hypertension.

    Science.gov (United States)

    Ronzaud, Caroline; Loffing-Cueni, Dominique; Hausel, Pierrette; Debonneville, Anne; Malsure, Sumedha Ram; Fowler-Jaeger, Nicole; Boase, Natasha A; Perrier, Romain; Maillard, Marc; Yang, Baoli; Stokes, John B; Koesters, Robert; Kumar, Sharad; Hummler, Edith; Loffing, Johannes; Staub, Olivier

    2013-02-01

    The E3 ubiquitin ligase NEDD4-2 (encoded by the Nedd4L gene) regulates the amiloride-sensitive epithelial Na+ channel (ENaC/SCNN1) to mediate Na+ homeostasis. Mutations in the human β/γENaC subunits that block NEDD4-2 binding or constitutive ablation of exons 6-8 of Nedd4L in mice both result in salt-sensitive hypertension and elevated ENaC activity (Liddle syndrome). To determine the role of renal tubular NEDD4-2 in adult mice, we generated tetracycline-inducible, nephron-specific Nedd4L KO mice. Under standard and high-Na+ diets, conditional KO mice displayed decreased plasma aldosterone but normal Na+/K+ balance. Under a high-Na+ diet, KO mice exhibited hypercalciuria and increased blood pressure, which were reversed by thiazide treatment. Protein expression of βENaC, γENaC, the renal outer medullary K+ channel (ROMK), and total and phosphorylated thiazide-sensitive Na+Cl- cotransporter (NCC) levels were increased in KO kidneys. Unexpectedly, Scnn1a mRNA, which encodes the αENaC subunit, was reduced and proteolytic cleavage of αENaC decreased. Taken together, these results demonstrate that loss of NEDD4-2 in adult renal tubules causes a new form of mild, salt-sensitive hypertension without hyperkalemia that is characterized by upregulation of NCC, elevation of β/γENaC, but not αENaC, and a normal Na+/K+ balance maintained by downregulation of ENaC activity and upregulation of ROMK.

  11. Tumor Seeding With Renal Cell Carcinoma After Renal Biopsy

    OpenAIRE

    M.F.B. Andersen; Norus, T.P.

    2016-01-01

    Tumor seeding following biopsy of renal cell carcinoma is extremely rare with an incidence of 1:10.000. In this paper two cases with multiple recurrent RRC metastasis in the biopsy tract following biopsy of renal tumor is presented and the current literature is shortly discussed.

  12. Renal blood flow in experimental septic acute renal failure

    NARCIS (Netherlands)

    Langenberg, C.; Wan, L.; Egi, M.; May, C. N.; Bellomo, R.

    2006-01-01

    Reduced renal blood flow (RBF) is considered central to the pathogenesis of septic acute renal failure (ARF). However, no controlled experimental studies have continuously assessed RBF during the development of severe septic ARF. We conducted a sequential animal study in seven female Merino sheep. F

  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...

  14. The renal scan in pregnant renal transplant patients

    Energy Technology Data Exchange (ETDEWEB)

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

    1985-05-01

    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.

  15. 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

  16. [Renal abnormalities in ankylosing spondylitis].

    Science.gov (United States)

    Samia, Barbouch; Hazgui, Faiçal; Abdelghani, Khaoula Ben; Hamida, Fethi Ben; Goucha, Rym; Hedri, Hafedh; Taarit, Chokri Ben; Maiz, Hedi Ben; Kheder, Adel

    2012-07-01

    We will study the epidemiologic, clinical, biological, therapeutic, prognostic characteristics and predictive factors of development of nephropathy in ankylosing spondylitis patients. We retrospectively reviewed the medical record of 32 cases with renal involvement among 212 cases of ankylosing spondylitis followed in our service during the period spread out between 1978 and 2006. The renal involvement occurred in all patients a mean of 12 years after the clinical onset of the rheumatic disease. Thirty-two patients presented one or more signs of renal involvement: microscopic hematuria in 22 patients, proteinuria in 23 patients, nephrotic syndrome in 11 patients and decreased renal function in 24 patients (75%). Secondary renal amyloidosis (13 patients), which corresponds to a prevalence of 6,1% and tubulointerstitial nephropathy (7 patients) were the most common cause of renal involvement in ankylosing spondylitis followed by IgA nephropathy (4 patients). Seventeen patients evolved to the end stage renal disease after an average time of 29.8 ± 46 months. The average follow-up of the patients was 4,4 years. By comparing the 32 patients presenting a SPA and renal disease to 88 with SPA and without nephropathy, we detected the predictive factors of occurred of nephropathy: tobacco, intense inflammatory syndrome, sacroileite stage 3 or 4 and presence of column bamboo. The finding of 75% of the patients presented a renal failure at the time of the diagnosis of renal involvement suggests that evidence of renal abnormality involvement should be actively sought in this disease. Copyright © 2011 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

  17. Renal metabolism of calcitonin

    Energy Technology Data Exchange (ETDEWEB)

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

    1988-04-01

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

  18. 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.

  19. Renal calculus disease.

    Science.gov (United States)

    Schulsinger, D A; Sosa, R E

    1998-03-01

    We have seen an explosion in technical innovations for the management of urolithiasis. Today, the endourologist possesses an assortment of minimally invasive tools to treat renal stones. Most patients receive fast, safe and effective treatment in the outpatient setting. Despite the many technical advances, however, anatomical malformations and complex stones still provide significant challenges in diagnosis, access to a targeted stone, fragmentation, and clearance of the resulting fragments. This review examines a variety of urinary stone presentations and treatment strategies for cost-effective management.

  20. [Pulmonary-renal syndrome].

    Science.gov (United States)

    Risso, Jorge A; Mazzocchi, Octavio; De All, Jorge; Gnocchi, César A

    2009-01-01

    The pulmonary-renal syndrome is defined as a combination of diffuse alveolar hemorrhage and glomerulonephritis. The coexistence of these two clinical conditions is due to diseases with different pathogenic mechanisms. Primary systemic vasculitis and Goodpasture syndrome are the most frequent etiologies. Systemic lupus erythematosus, connective tissue diseases, negative anti neutrophil cytoplasmic antibody vasculitis and those secondary to drugs are far less common causes. An early diagnosis based on clinical, radiologic, laboratory and histologic criteria enables early treatment, thus diminishing its high morbidity-mortality rate. Therapy is based on high doses of corticosteroids, immunosuppressants, tumor necrosis factor inhibitors and plasmapheresis.