21 CFR 182.1781 - Sodium aluminum phosphate.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Sodium aluminum phosphate. 182.1781 Section 182.1781 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Food Substances § 182.1781 Sodium aluminum phosphate. (a) Product. Sodium aluminum phosphate. (b...

Nanomaterials-Based Approaches for the Modulation of Sodium Bicarbonate Cotransporters

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Jeong Hee Hong

2015-01-01

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

Modulation of small intestinal phosphate transporter by dietary supplements of mineral phosphorus and phytase in broilers.

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Huber, Korinna; Zeller, Ellen; Rodehutscord, Markus

2015-05-01

Dietary phosphorus (P) is known as a main modulator of phosphate (Pi) transporter expression. The effect of supplemented mineral P with or without phytase on protein expression of two sodium-dependent Pi (NaPi) transporters and a calcium channel was studied in the small intestine of broilers. Thirty-six broilers were randomly assigned to six different diets at 15 days of age. Two levels of total P (tP, adjusted by monocalcium phosphate (MCP) supplementation), 0.39% (BD-) and 0.47% (BD+) were fed until day 25; and at each tP level, three levels of phytase were used with 0, 500, and 12,500 FTU/kg of an E. coli phytase. Mucosa samples from jejunum and ileum were taken and apical membranes were isolated by MgCl2 precipitation. Protein expression of NaPi IIb, NaPi type III (PiT1) and the calcium channel TRPV6 were semiquantitatively measured by Western blotting and jejunal mucosal phytase activity by measurement of Pi release. The jejunal NaPi IIb transporter was expressed with two distinct bands, which were modulated differently by diet. NaPi IIb Band1 increased (P phytase supplementation but was not affected by MCP supplementation. This inverse modulation of Band1 and Band2 was significantly related to the amount of net absorbed P with higher expression of Band1 at higher amounts of net absorbed P. In addition, a second Pi transporter, PiT1, was detected in which ileal expression decreased (P phytase supplementation. The expression of the calcium channel TRPV6 was increased in BD+ groups. A trend for an interaction between MCP and phytase supplementation on mucosal phytase activity was observed (P = 0.079) with a decrease in activity when BD+ with 12,500 FTU/kg phytase was fed. Chicken intestinal epithelial cells responded to dietary supplemented phytase and MCP by changing the Pi transporter expression in apical membranes. In conclusion, availability of Pi is most likely the key modulator of transporter protein expression. However, a contribution of lower inositol

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

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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.

Phosphate Framework Electrode Materials for Sodium Ion Batteries.

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Fang, Yongjin; Zhang, Jiexin; Xiao, Lifen; Ai, Xinping; Cao, Yuliang; Yang, Hanxi

2017-05-01

Sodium ion batteries (SIBs) have been considered as a promising alternative for the next generation of electric storage systems due to their similar electrochemistry to Li-ion batteries and the low cost of sodium resources. Exploring appropriate electrode materials with decent electrochemical performance is the key issue for development of sodium ion batteries. Due to the high structural stability, facile reaction mechanism and rich structural diversity, phosphate framework materials have attracted increasing attention as promising electrode materials for sodium ion batteries. Herein, we review the latest advances and progresses in the exploration of phosphate framework materials especially related to single-phosphates, pyrophosphates and mixed-phosphates. We provide the detailed and comprehensive understanding of structure-composition-performance relationship of materials and try to show the advantages and disadvantages of the materials for use in SIBs. In addition, some new perspectives about phosphate framework materials for SIBs are also discussed. Phosphate framework materials will be a competitive and attractive choice for use as electrodes in the next-generation of energy storage devices.

21 CFR 184.1697 - Riboflavin-5′-phosphate (sodium).

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Riboflavin-5â²-phosphate (sodium). 184.1697 Section... SAFE Listing of Specific Substances Affirmed as GRAS § 184.1697 Riboflavin-5′-phosphate (sodium). (a) Riboflavin-5′-phosphate (sodium) (C17H20N4O9PNa·2H2O, CAS Reg. No 130-40-5) occurs as the dihydrate in yellow...

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

DEFF Research Database (Denmark)

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

2014-01-01

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

Prevention and Therapeutic Effects and Mechanisms of Tanshinone IIA Sodium Sulfonate on Acute Liver Injury Mice Model

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Lunjie Lu

2016-01-01

Full Text Available Tanshinone IIA sodium sulfonate (TSS is a water-soluble derivative of tanshinone IIA, which is the main pharmacologically active component of Salvia miltiorrhiza. This study aimed to verify the preventive and therapeutic effects of TSS and its combined therapeutic effects with magnesium isoglycyrrhizinate (MI in D-galactosamine- (D-Gal- induced acute liver injury (ALI in mice. The potential regulatory mechanisms of TSS on ALI were also examined. Our results may provide a basis for the development of novel therapeutics for ALI.

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

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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.

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.

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

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

International Nuclear Information System (INIS)

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

2004-01-01

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

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

Science.gov (United States)

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

2015-12-01

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

Allergic contact dermatitis from sodium dihydroxycetyl phosphate, a new cosmetic allergen?

DEFF Research Database (Denmark)

Lomholt, H; Rastogi, S C; Andersen, Klaus Ejner

2001-01-01

Sodium dihydroxycetyl phosphate (trade name Dragophos S 2/918501) was identified as a contact allergen in a herbal moisturizing cream causing severe acute contact dermatitis on the hands and face of a 41-year-old woman. Sodium dihydroxycetyl phosphate is a complex mixture of phosphate esters of d...

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

Science.gov (United States)

Curran, Monique P; Plosker, Greg L

2004-01-01

Oral sodium phosphate solution (Fleet Phospho-soda, Casen-Fleet Fosfosoda is a low-volume, hyperosmotic agent used as part of a colorectal-cleansing preparation for surgery, x-ray or endoscopic examination. The efficacy and tolerability of oral sodium phosphate solution was generally similar to, or significantly better than, that of polyethylene glycol (PEG) or other colorectal cleansing regimens in patients preparing for colonoscopy, colorectal surgery or other colorectal-related procedures. Generally, oral sodium phosphate solution was significantly more acceptable to patients than PEG or other regimens. The use of this solution should be considered in most patients (with the exception of those with contraindications) requiring colorectal cleansing. PHARMACOLOGICAL PROPERTIES: After the first and second 45 mL dose of oral sodium phosphate solution, the mean time to onset of bowel activity was 1.7 and 0.7 hours and the mean duration of activity was 4.6 and 2.9 hours. Bowel activity ceased within 4 hours of administration of the second dose in 83% of patients. Elevations in serum phosphorus and falls in serum total and ionised calcium from baseline occurred during the 24 hours after administration of oral sodium phosphate solution in seven healthy volunteers. These changes were not associated with significant changes in clinical assessments. The decrease in serum potassium levels after administration of oral sodium phosphate solution was negatively correlated with baseline intracellular potassium levels. A regimen that administered the first dose of sodium phosphate on the previous evening and a second dose on the morning of the procedure (10-12 hours apart) was significantly more effective than PEG-based regimens for colorectal cleansing in preparation for colonoscopy, sigmoidoscopy or colorectal surgery. A regimen that administered both doses of oral sodium phosphate on the day prior to the procedure offered no colorectal cleansing advantage over PEG

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

DEFF Research Database (Denmark)

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

2016-01-01

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

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

DEFF Research Database (Denmark)

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

2016-01-01

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

Metal Oxide Decomposition In Hydrothermal Alkaline Sodium Phosphate Solutions

Energy Technology Data Exchange (ETDEWEB)

S.E. Ziemniak

2003-09-24

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

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

International Nuclear Information System (INIS)

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

1987-01-01

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

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...

UV reflectance is associated with environmental conditions in Palaearctic Pieris napi (Lepidoptera: Pieridae).

Science.gov (United States)

Stella, David; Pecháček, Pavel; Meyer-Rochow, Victor Benno; Kleisner, Karel

2018-06-01

The subject of our investigation was the visual features of wing color with special focus on the UV reflectance in the green-veined white butterfly (Pieris napi). Previous studies had concluded that UV reflectance on dorsal wing surfaces is found only in the female P. napi. Based on UV sensitive photography, we analyzed a correlation between 12 geographic and environmental factors and UV reflectance patterns on 3 patches on the forewings of 407 P. napi specimens from the Palaearctic region. Results had shown that females significantly differ from males: they exhibit a 25% higher UV reflectance. To investigate whether and how UV reflectance levels on the forewings and hindwings of both sexes are influenced by the environment, we performed a principal component analysis (PCA) with several environmental variables. For several variables (in particular, latitude and longitude, mean annual temperature and precipitation, and temperature annual range and altitude), the generalized linear model (GLM) model revealed a significant correlation in both sexes. This suggests a link between UV reflectance levels and the environment and distribution of P. napi. We found that stronger UV reflectance is associated with generally more hostile environments and concluded that large-scale environmental factors influence the UV reflectance on the forewings of both male and female green-veined white butterflies. © 2016 Institute of Zoology, Chinese Academy of Sciences.

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

Science.gov (United States)

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

2015-01-01

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

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.

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

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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.

Effects of Inulin and Sodium Carbonate in Phosphate-Free Restructured Poultry Steaks

Science.gov (United States)

Öztürk, B.; Serdaroğlu, M.

2017-09-01

Recently inorganic phosphates used in meat product formulations have caused negative impact on consumers due to their potential health risks. Therefore, utilization of natural ingredients as phosphate replacers has come into prominence as a novel research topic to meet consumer demands for clean-label trends. In this study, we objected to investigate the effects of inulin utilization either in the powder or gelled form, alone or in combination with sodium carbonate on quality of phosphate-free restructured chicken steaks. Total moisture, protein, lipid and ash values of the trial groups were in the range of 71.54-75.46%, 22.60-24.31%, 0.94-1.70% and 1.45-2.13%, respectively. pH of the samples was between 6.18-6.39, significant increments were recorded in samples containing inulin with sodium carbonate. L*, a* and b* values were recorded as 78.92-81.05, 1.76-3.05 and 10.80-11.94, respectively, where use of gelled inulin resulted in changes of L* and a* values. Utilization of inulin in combination with sodium carbonate decreased cook loss and enhanced product yield. Sensory scores in control group with phosphate showed a similar pattern to sensory scores in groups with inulin and sodium carbonate. During storage, purge loss and lipid oxidation rate were similar in control and inulin + sodium carbonate samples. The results showed that use of inulin in combination with sodium carbonate provided equivalent physical, chemical and sensory quality to phosphates in restructured chicken steaks.

Reversed electrogenic sodium bicarbonate cotransporter 1 is the major acid loader during recovery from cytosolic alkalosis in mouse cortical astrocytes.

Science.gov (United States)

Theparambil, Shefeeq M; Naoshin, Zinnia; Thyssen, Anne; Deitmer, Joachim W

2015-08-15

The regulation of H(+) i from cytosolic alkalosis has generally been attributed to the activity of Cl(-) -coupled acid loaders/base extruders in most cell types, including brain cells. The present study demonstrates that outwardly-directed sodium bicarbonate cotransport via electrogenic sodium bicarbonate cotransporter 1 (NBCe1) mediates the major fraction of H(+) i regulation from cytosolic alkalosis in mouse cortical astrocytes. Cl(-) -coupled acid-loading transporters play only a minor role in the regulation of H(+) i from alkalosis in mouse cortical astrocytes. NBCe1-mediated H(+) i regulation from alkalosis was dominant, with the support of intracellular carbonic anhydrase II, even when the intra- and extracellular [HCO3 (-) ] was very low (sodium bicarbonate cotransporter 1 (NBCe1) and for carbonic anhydrase (CA) isoform II. An acute cytosolic alkalosis was induced by the removal of either CO2 /HCO3 (-) or butyric acid, and the subsequent acid loading was analysed by monitoring changes in cytosolic H(+) or Na(+) using ion-sensitive fluorescent dyes. We have identified that NBCe1 reverses during alkalosis and contributes more than 70% to the rate of recovery from alkalosis by extruding Na(+) and HCO3 (-) . After CA inhibition or in CAII-knockout (KO) cells, the rate of recovery was reduced by 40%, and even by 70% in the nominal absence of CO2 /HCO3 (-) . Increasing the extracellular K(+) concentration modulated the rate of acid loading in wild-type cells, but not in NBCe1-KO cells. Removing chloride had only a minor effect on the recovery from alkalosis. Reversal of NBCe1 by reducing pH/[HCO3 (-) ] was demonstrated in astrocytes and in Xenopus oocytes, in which human NBCe1 was heterologously expressed. The results obtained suggest that reversed NBCe1, supported by CAII activity, plays a major role in acid-loading cortical astrocytes to support recovery from cytosolic alkalosis. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

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

Science.gov (United States)

Abdul-Ghani, Muhammad A; DeFronzo, Ralph A

2017-01-01

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

Comparison of the postoperative analgesic effects of naproxen sodium and naproxen sodium-codeine phosphate for arthroscopic meniscus surgery

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Cagla Bali

2016-04-01

Full Text Available ABSTRACT BACKGROUND AND OBJECTIVES: Nonsteroidal anti-inflammatory drugs (NSAIDs are frequently used to control arthroscopic pain. Addition of oral effective opioid "codeine" to NSAIDs may be more effective and decrease parenteral opioid consumption in the postoperative period. The aim of this study was to compare the efficacy and side effects of naproxen sodium and a new preparation naproxen sodium-codeine phosphate when administered preemptively for arthroscopic meniscectomy. METHODS: Sixty-one patients were randomized into two groups to receive either oral naproxen sodium (Group N or naproxen sodium-codeine phosphate (Group NC before surgery. The surgery was carried out under general anesthesia. Intravenous meperidine was initiated by patient-controlled analgesia (PCA for all patients. The primary outcome measure was pain score at the first postoperative hour assessed by the Visual Analogue Scale (VAS. Sedation assessed by Ramsey Sedation Scale, first demand time of PCA, postoperative meperidine consumption, side effects and hemodynamic data were also recorded. RESULTS: The groups were demographically comparable. Median VAS scores both at rest and on movement were significantly lower in Group NC compared with Group N, except 18th hour on movement (p 0.05. CONCLUSIONS: The combination of naproxen sodium-codeine phosphate provided more effective analgesia than naproxen sodium and did not increase side effects.

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

Directory of Open Access Journals (Sweden)

Prakash Katakam

2012-01-01

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

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

International Nuclear Information System (INIS)

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

2013-01-01

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

EFFECT OF SODIUM PHOSPHATES ON SELECTED FOOD GRADE BACTERIA

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Stanislav Kráčmar

2011-04-01

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

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

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Jabbour, S A; Goldstein, B J

2008-08-01

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

Synergy between scientific advancement and technological innovation, illustrated by a mechanism-based model characterizing sodium-glucose cotransporter-2 inhibition.

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Zhang, Liping; Ng, Chee M; List, James F; Pfister, Marc

2010-09-01

Advances in experimental medicine and technological innovation during the past century have brought tremendous progress in modern medicine and generated an ever-increasing amount of data from bench and bedside. The desire to extend scientific knowledge motivates effective data integration. Technological innovation makes this possible, which in turn accelerates the advancement in science. This mutually beneficial interaction is illustrated by the development of an expanded mechanism-based model for understanding a novel mechanism, sodium-glucose cotransporter-2 SGLT2 inhibition for potential treatment of type 2 diabetes mellitus.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors and fracture risk in patients with type 2 diabetes mellitus: A meta-analysis.

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Ruanpeng, Darin; Ungprasert, Patompong; Sangtian, Jutarat; Harindhanavudhi, Tasma

2017-09-01

Sodium-glucose cotransporter 2 (SGLT2) inhibitors could potentially alter calcium and phosphate homeostasis and may increase the risk of bone fracture. The current meta-analysis was conducted to investigate the fracture risk among patients with type 2 diabetes mellitus treated with SGLT2 inhibitors. Randomized controlled trials that compared the efficacy of SGLT2 inhibitors to placebo were identified. The risk ratios of fracture among patients who received SGLT2 inhibitors versus placebo were extracted from each study. Pooled risk ratios and 95% confidence intervals were calculated using a random-effect, Mantel-Haenszel analysis. A total of 20 studies with 8286 patients treated with SGLT2 inhibitors were included. The pooled risk ratio of bone fracture in patients receiving SGLT2 inhibitors versus placebo was 0.67 (95% confidence interval, 0.42-1.07). The pooled risk ratio for canagliflozin, dapagliflozin, and empagliflozin was 0.66 (95% confidence interval, 0.37-1.19), 0.84 (95% confidence interval, 0.22-3.18), and 0.57 (95% confidence interval, 0.20-1.59), respectively. Increased risk of bone fracture among patients with type 2 diabetes mellitus treated with SGLT2 inhibitors compared with placebo was not observed in this meta-analysis. However, the results were limited by short duration of treatment/follow-up and low incidence of the event of interest. Copyright © 2017 John Wiley & Sons, Ltd.

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

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

2014-12-01

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

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

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Washburn, William N

2012-05-01

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

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

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

2005-01-01

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

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

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Trissel, Lawrence A; Zhang, Yanping

2004-01-01

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

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

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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.

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

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

2016-01-15

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

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

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

2003-09-16

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

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.

Cotransport of sodium and chloride by the adult mammalian choroid plexus

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

1990-02-01

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

Sodium-glucose cotransporter 2 inhibitors combined with dipeptidyl peptidase-4 inhibitors in the management of type 2 diabetes: a review of current clinical evidence and rationale

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Yassin SA

2017-03-01

Full Text Available Sayf A Yassin,1 Vanita R Aroda2 1MedStar Union Memorial Hospital, Baltimore, 2MedStar Health Research Institute, Hyattsville, MD, USA Abstract: Type 2 diabetes mellitus (T2DM is a progressive and multifactorial cardiometabolic disorder. Almost half of adults with diabetes fail to achieve their recommended glucose control target. This has prompted some clinicians to advocate the use of more intensive initial therapy, including the use of combination therapy to target multiple physiologic defects in diabetes with the goal of achieving and sustaining glucose control. Numerous options exist for combining the various classes of glucose-lowering agents in the treatment of T2DM. This report reviews the mechanism, rationale, and evidence from clinical trials for combining two of the newer drug classes, namely, dipeptidyl peptidase-4 inhibitors and sodium-glucose cotransporter 2 inhibitors, and considers the possible role of such dual therapy in the management of T2DM. Keywords: sodium-glucose cotransporter 2 inhibitors, dipeptidyl peptidase-4 inhibitors, type 2 diabetes mellitus, combination therapy

Tanshinone IIA ameliorates dextran sulfate sodium-induced inflammatory bowel disease via the pregnane X receptor

Science.gov (United States)

Zhang, Xianxie; Wang, Yuguang; Ma, Zengchun; Liang, Qiande; Tang, Xianglin; Hu, Donghua; Tan, Hongling; Xiao, Chengrong; Gao, Yue

2015-01-01

Tanshinone IIA (Tan IIA) (C19H18O3) is one of the major active lipophilic components in a conventional Chinese medicine called danshen, and it has long been used in the People’s Republic of China and other neighboring countries to treat patients suffering from inflammatory bowel disease (IBD). Previous experiments by many teams determined which mechanism of Tan IIA is relevant to the treatment of IBD associated with inflammation and the pregnane X receptor (PXR). The current study demonstrated that Tan IIA is an efficacious PXR agonist and its ability to induce CYP3A4 mRNA and protein expression was mediated by the transactivation of PXR, a known target of abrogating inflammation in IBD. Clinical symptoms in mice and histological assessment data suggested that administration of Tan IIA in mice demonstrated significant protection and showed that in DSS-induced IBD it acts in a concentration-dependent manner. PXR-silenced mice treated with Tan IIA demonstrated low protection against DSS-induced mouse IBD and exacerbated the severity of IBD compared with wild-type mice; PXR-silenced mice demonstrated the necessity for PXR in Tan IIA-mediated upregulation of xenobiotic metabolism genes. The IBD treatment effects of Tan IIA are partially due to PXR-mediated upregulation of xenobiotic metabolism and downregulation of inflammatory mediators. The novel findings reported here may contribute to the effective utilization of Tan IIA and its derivatives as a PXR ligand in the treatment of human IBD. This suggests that Tan IIA may have considerable clinical utility. PMID:26674743

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

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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

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

Science.gov (United States)

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

2017-08-01

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

Sulfotanshinone IIA Sodium Ameliorates Glucose Peritoneal Dialysis Solution-Induced Human Peritoneal Mesothelial Cell Injury via Suppression of ASK1-P38-mediated Oxidative Stress

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Yao Zhou

2018-05-01

Full Text Available Background/Aims: Long-term use of high-glucose peritoneal dialysis solution (PDS induces peritoneal mesothelial cell (PMC injury, peritoneal dysfunction, and peritoneal dialysis (PD failure in patients with end-stage renal disease. How to preserve PMCs in PD is a major challenge for nephrologists worldwide. In this study, we aimed to elucidate the efficacy and mechanisms of sulfotanshinone IIA sodium (Tan IIa in ameliorating high-glucose PDS-induced human PMC injury. Methods: The human PMC line HMrSV5 was incubated with 4.25% PDS in vitro to mimic the high-glucose conditions in PD. Cellular viability was measured by Cell Counting Kit 8. Generation of superoxide and reactive oxygen species (ROS was assessed using a Total ROS/Superoxide Detection Kit. Oxidative modification of protein was evaluated by OxyBlot Protein Oxidation Detection Kit. TUNEL (dT-mediated dUTP nick end labeling assay and DAPI (4,6-diamidino-2-phenylindole staining were used to evaluate apoptosis. Western blot analysis was performed to evaluate the efficacy and mechanisms of Tan IIa. Results: Tan IIa protected PMCs against PDS-induced injury as evidenced by alleviating changes in morphology and loss of cell viability. Consistent with their antioxidant properties, N-acetyl-L-cysteine (NAC and Tan IIa suppressed superoxide and ROS production, protein oxidation, and apoptosis elicited by PDS. Apoptosis signal-regulating kinase 1 (ASK1-p38 signaling was activated by PDS. Both Tan IIa and NAC suppressed ASK1 and p38 phosphorylation elicited by PDS. Moreover, genetic downregulation of ASK1 ameliorated cell injury and inhibited the phosphorylation of p38 and activation of caspase 3. Conclusion: Tan IIa protects PMCs against PDS-induced oxidative injury through suppression of ASK1-p38 signaling.

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

DEFF Research Database (Denmark)

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

2014-01-01

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

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

Science.gov (United States)

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

2009-02-01

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

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

Science.gov (United States)

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

2018-01-01

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

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

International Nuclear Information System (INIS)

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

1987-01-01

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

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.

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

Science.gov (United States)

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

2016-10-10

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

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

Science.gov (United States)

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

2014-01-01

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

Characterizing and evaluating the expression of the type IIb sodium-dependent phosphate cotransporter (slc34a2) gene and its potential influence on phosphorus utilization efficiency in yellow catfish (Pelteobagrus fulvidraco).

Science.gov (United States)

Chen, Pei; Tang, Qin; Wang, Chunfang

2016-02-01

A sodium-dependent phosphate cotransporter gene, NaPi-IIb (slc34a2), was isolated from yellow catfish (Pelteobagrus fulvidraco) intestine through homology cloning and the rapid amplification of cDNA ends. The full-length cDNA of slc34a2 consisted of 2326 bp with an open reading frame encoding 621 amino acids, a 160-bp 5' untranslated region, and a 300-bp 3' untranslated region. The deduced amino acid sequence showed 79.0 and 70.9% sequence identity to Astyanax mexicanus and Pundamilia nyererei, respectively. The membrane-spanning domains based on the hydrophilic and hydrophobic properties of the deduced amino acids were predicted, and results showed that the putative protein had eight transmembrane domains, with the intracellular NH2 and COOH termini. Two functional regions including first intracellular loop and third extracellular loop as well as the six N-glycosylation sites in second extracellular loop were found. The slc34a2 mRNA in the tested tissues was examined through semiquantitative reverse transcription polymerase chain reaction and quantitative real-time PCR, with the highest level found in the anterior intestine, followed by the posterior and middle intestines. The slc34a2 mRNA expression in the whole intestine under different dietary phosphorus (P) treatments was detected using qPCR. The results showed that the slc34a2 expression levels in the low-P groups (0.33 and 0.56%) were significantly higher (p < 0.05) than levels in the sufficient-P (0.81%) and high-P (1.15, 1.31, and 1.57%) groups. High expression of slc34a2 mRNA in low-P groups stimulated P utilization efficiency, indicating the close relationship between genotype and phenotype in yellow catfish. In contrast with conventional strategies (formula and feeding strategies), this study provided another possible approach by using molecular techniques to increase the P utilization in yellow catfish.

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

The corrosion properties of phosphate coating on AZ31 magnesium alloy: The effect of sodium dodecyl sulfate (SDS) as an eco-friendly accelerating agent

Energy Technology Data Exchange (ETDEWEB)

Amini, R. [Department of Polymer Engineering and Color Technology, AmirKabir University of Technology, P.O. Box 15875-4413, Tehran (Iran, Islamic Republic of); Sarabi, A.A., E-mail: sarabi@aut.ac.ir [Department of Polymer Engineering and Color Technology, AmirKabir University of Technology, P.O. Box 15875-4413, Tehran (Iran, Islamic Republic of)

2011-06-01

Sodium nitrite has been used as an accelerating agent in phosphating bath to improve its properties. However, it is well known that sodium nitrite is a carcinogenic component in phosphating sludge. In this study, it has been aimed to replace sodium nitrite by an environmentally friendly accelerating agent. To this end, sodium dodecyl sulfate (SDS) was used in phosphating bath to improve the phosphate coating formation on an AZ31 magnesium alloy. The effect of SDS/sodium nitrite ratio on the phosphated samples properties was also studied. Using field emission scanning electron microscope (FE-SEM), X-ray diffraction (XRD), direct current (DC) polarization and electrochemical impedance spectroscopy (EIS) the properties of phosphated magnesium samples were studied. Results showed uniform phosphate coating formation on the magnesium sample mostly in hopeite phase composition. In addition, a denser and less permeable coating can be obtained at these conditions. The corrosion resistance of the phosphated samples was superiorly improved using higher SDS concentration in the phosphating bath.

The corrosion properties of phosphate coating on AZ31 magnesium alloy: The effect of sodium dodecyl sulfate (SDS) as an eco-friendly accelerating agent

International Nuclear Information System (INIS)

Amini, R.; Sarabi, A.A.

2011-01-01

Sodium nitrite has been used as an accelerating agent in phosphating bath to improve its properties. However, it is well known that sodium nitrite is a carcinogenic component in phosphating sludge. In this study, it has been aimed to replace sodium nitrite by an environmentally friendly accelerating agent. To this end, sodium dodecyl sulfate (SDS) was used in phosphating bath to improve the phosphate coating formation on an AZ31 magnesium alloy. The effect of SDS/sodium nitrite ratio on the phosphated samples properties was also studied. Using field emission scanning electron microscope (FE-SEM), X-ray diffraction (XRD), direct current (DC) polarization and electrochemical impedance spectroscopy (EIS) the properties of phosphated magnesium samples were studied. Results showed uniform phosphate coating formation on the magnesium sample mostly in hopeite phase composition. In addition, a denser and less permeable coating can be obtained at these conditions. The corrosion resistance of the phosphated samples was superiorly improved using higher SDS concentration in the phosphating bath.

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

International Nuclear Information System (INIS)

Sadeghi, Rahmat; Hosseini, Rahim; Jamehbozorg, Bahman

2008-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2008-09-15

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

Audiological findings in Usher syndrome types IIa and II (non-IIa).

Science.gov (United States)

Sadeghi, Mehdi; Cohn, Edward S; Kelly, William J; Kimberling, William J; Tranebjoerg, Lisbeth; Möller, Claes

2004-03-01

The aim was to define the natural history of hearing loss in Usher syndrome type IIa compared to non-IIa. People with Usher syndrome type II show moderate-to-severe hearing loss, normal balance and retinitis pigmentosa. Several genes cause Usher syndrome type II. Our subjects formed two genetic groups: (1) subjects with Usher syndrome type IIa with a mutation and/or linkage to the Usher IIa gene; (2) subjects with the Usher II phenotype with no mutation and/or linkage to the Usher IIa gene. Four hundred and two audiograms of 80 Usher IIa subjects were compared with 435 audiograms of 87 non-IIa subjects. Serial audiograms with intervals of > or = 5 years were examined for progression in 109 individuals Those with Usher syndrome type IIa had significantly worse hearing thresholds than those with non-IIa Usher syndrome after the second decade. The hearing loss in Usher syndrome type IIa was found to be more progressive, and the progression started earlier than in non-IIa Usher syndrome. This suggests an auditory phenotype for Usher syndrome type IIa that is different from that of other types of Usher syndrome II. Thus, this is to our knowledge one of the first studies showing a genotype-phenotype auditory correlation.

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

Energy Technology Data Exchange (ETDEWEB)

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

2002-07-01

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

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

International Nuclear Information System (INIS)

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

2002-01-01

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

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

DEFF Research Database (Denmark)

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

2016-01-01

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

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

International Nuclear Information System (INIS)

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

2011-01-01

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

Optical detection of sodium salts of fluoride, acetate and phosphate

Indian Academy of Sciences (India)

Optical detection of sodium salts of fluoride, acetate and phosphate by a diacylhydrazine ligand by the formation of a colour alkali metal complex. Purnandhu Bose Ranjan Dutta I ... Department of Inorganic Chemistry, Indian Association for the Cultivation of Science, 2A and 2B Raja S C Mullick Road, Kolkata 700032, India ...

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

OpenAIRE

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

2014-01-01

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

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

Science.gov (United States)

Zhang, An-yang; Fan, Tian-yuan

2009-12-18

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

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

International Nuclear Information System (INIS)

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

1992-01-01

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

Sodium glucose co-transporter inhibitors for the management of diabetes mellitus: an opinion paper from the Endocrine and Metabolism Practice and Research Network of the American College of Clinical Pharmacy.

Science.gov (United States)

Clements, Jennifer N; Whitley, Heather P; D'Souza, Jennifer J; Gross, Benjamin; Hess, Rick; Reece, Sara; Gentry, Chad; Shealy, Kayce

2015-01-01

Type 2 diabetes mellitus (T2DM) carries a high prevalence in the United States and worldwide. Therefore, the number of medication classes being developed and studied has grown. The individualized management of diabetes is accomplished by evaluating a medication's efficacy, safety, and cost, along with the patient's preference and tolerance to the medication. Sodium glucose co-transporter 2 inhibitors are a new therapeutic class indicated for the treatment of diabetes and have a unique mechanism of action, independent of beta-cell function. The first agent approved by the Food and Drug Administration (FDA) was canagliflozin in March 2013. Two agents - dapagliflozin and empagliflozin - were FDA-approved in January and July 2014, respectively. A clear understanding of the new class is needed to identify its appropriate use in clinical practice. Members of the American College of Clinical Pharmacy Endocrine and Metabolism Practice and Research Network reviewed available literature regarding this therapeutic class. The article addresses the advantages, disadvantages, emerging role, and patient education for sodium glucose co-transporter 2 inhibitors. Key limitations for this article include limited access to clinical trial data not published by the pharmaceutical company and limited data on products produced outside the United States.

The vascular effects of sodium tanshinone IIA sulphonate in rodent and human pregnancy.

Directory of Open Access Journals (Sweden)

Jude S Morton

Full Text Available Danshen, in particular its derivative tanshinone IIA (TS, is a promising compound in the treatment of cardiovascular diseases and has been used for many years in traditional Chinese medicine. Although many actions of TS have been researched, its vasodilator effects in pregnancy remain unknown. There have been a few studies that have shown the ability of TS to reduce blood pressure in women with hypertensive pregnancies; however, there are no studies which have examined the vascular effects of TS in the pregnant state in either normal or complicated pregnancies. Our aim was to determine the vasoactive role of TS in multiple arteries during pregnancy including: rat resistance (mesenteric and uterine and conduit (carotid arteries. Further, we aimed to assess the ability of TS to improve uterine blood flow in a rodent model of intrauterine growth restriction. Wire myography was used to assess vascular responses to the water-soluble derivative, sodium tanshinone IIA sulphonate (STS or to the endothelium-dependent vasodilator, methylcholine. At mid-pregnancy, STS caused direct vasodilation of rat resistance (pEC50 mesenteric: 4.47±0.05 and uterine: 3.65±0.10 but not conduit (carotid arteries. In late pregnancy, human myometrial arteries responded with a similar sensitivity to STS (pEC50 myometrial: 3.26±0.13. STS treatment for the last third of pregnancy in eNOS-/- mice increased uterine artery responses to methylcholine (Emax eNOS-/-: 55.2±9.2% vs. eNOS-/- treated: 75.7±8.9%, p<0.0001. The promising vascular effects, however, did not lead to improved uterine or umbilical blood flow in vivo, nor to improved fetal biometrics; body weight and crown-rump length. Further, STS treatment increased the uterine artery resistance index and decreased offspring body weight in control mice. Further research would be required to determine the safety and efficacy of use of STS in pregnancy.

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.

In vitro characterization of luseogliflozin, a potent and competitive sodium glucose co-transporter 2 inhibitor: Inhibition kinetics and binding studies

Directory of Open Access Journals (Sweden)

Saeko Uchida

2015-05-01

Full Text Available In this study, we evaluated an inhibition model of luseogliflozin on sodium glucose co-transporter 2 (SGLT2. We also analyzed the binding kinetics of the drug to SGLT2 protein using [3H]-luseogliflozin. Luseogliflozin competitively inhibited human SGLT2 (hSGLT2-mediated glucose uptake with a Ki value of 1.10 nM. In the absence of glucose, [3H]-luseogliflozin exhibited a high affinity for hSGLT2 with a Kd value of 1.3 nM. The dissociation half-time was 7 h, suggesting that luseogliflozin dissociates rather slowly from hSGLT2. These profiles of luseogliflozin might contribute to the long duration of action of this drug.

Isolation and Characterization of Plantaricin Produced by Lactobacillus plantarum Strains (IIA-1A5, IIA-1B1, IIA-2B2

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I. I. Arief

2013-08-01

Full Text Available Bacteriocins produced by Indonesian lactic acid bacteria Lactobacillus plantarum IIA-1A5, IIA-1B1, IIA-2B2 were purified and characterized. Plantaricin W gene had been successfully amplified from all strains. This amplicon showed the expected 200 bp size of plantaricin W gene. This bacteriocins purified from L. plantarum IIA-1A5, IIA-1B1, and IIA-2B2 were named plantaricin IIA-1A5, IIA-1B1, and IIA-2B2. Purification by cation exchange chromatography increased the purity (fold and activity of plantaricins. Purity of plantaricin IIA-1A5 was increased by 3.13 fold with specific activity 13.40 AU/mg. Plantaricin IIA-1B1 had 2.98 fold purity with specific activity 5.12 AU/mg, while purity of plantaricin IIA-2B2 was 1.37 fold with specific activity 7.70 AU/mg. All plantaricins could inhibit the growth of pathogenic bacteria, such as Escherichia coli, Salmonella typhimurium, Bacillus cereus, and Staphylococcus aureus. Plantaricins could be digested by trypsin. Stability of plantaricins at 80 oC for 30 min and at 121 oC for 15 min were affected by type of plantaricin and species of pathogenic bacteria. Generally, plantaricin IIA-1A5 was better as antimicrobial agent than plantaricin IIA-1B1 and plantaricin IIA-2B2.

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

International Nuclear Information System (INIS)

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

2004-01-01

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

Sodium isotopic exchange rate between crystalline zirconium phosphate and molten NaNO/sub 3/

Energy Technology Data Exchange (ETDEWEB)

Inoue, Y; Yamada, Y [Tohoku Univ., Sendai (Japan). Faculty of Engineering

1975-12-01

The isotopic exchange rate of sodium ion between crystalline zirconium phosphate and molten NaNO/sub 3/ has been measured at 312/sup 0/C and 362/sup 0/C by batch method. The equilibrium was reached within 20 minutes at either temperature, and the rate was very rapid as compared with that of sodium-potassium ion exchange.

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

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Christina Schueler

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

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

Science.gov (United States)

Mauricio, Dídac

2013-09-01

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

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

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Choi, Chang-Ik

2016-08-27

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

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

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Abdul-Ghani, Muhammad A.; Norton, Luke

2015-01-01

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

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

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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.

τ - hydrogen phosphate of zirconia in sodium salt form and some of its properties

International Nuclear Information System (INIS)

Fernandez V, S.M.; Ordonez R, E.

2004-01-01

It is reported the obtaining and characterization in the sodium salt form of the τ-hydrogen phosphate of zirconium in sodium form, this compound it was synthesized, for a new technique developed in the laboratory of Dept. of Chemistry of the ININ. The characterization was carried out for XRD, IR, Sem and EDS the thermal gravimetric analysis is also reported. (Author)

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

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

2013-04-01

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

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

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Blaschek, Wolfgang

2017-08-01

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

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

Science.gov (United States)

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

2013-07-01

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

Application of l-ascorbic acid and its derivatives (sodium ascorbyl phosphate and magnesium ascorbyl phosphate) in topical cosmetic formulations: stability studies

International Nuclear Information System (INIS)

Smaoui, S.; Hilima, H.B.

2013-01-01

The present study aimed to formulate and subsequently evaluate a topical skin-care cream (o/w emulsion) from l-ascorbic acid and its derivatives (sodium ascorbyl phosphate and magnesium ascorbyl phosphate) at 2% versus its vehicle (Control). Formulations were developed by entrapping it in the oily phase of o/w emulsion and were stored at 8 degree C, 25 degree C and 40 degree C (in incubator) for a period of four weeks to investigate their stability. In the physical analysis, the evaluation parameters consisted of color, smell, phase separation, centrifugation, and liquefaction. Chemical stability of both derivatives was established by HPLC analysis. In the chemical analysis, the formulation with sodium ascorbyl phosphate was more stable than those with magnesium ascorbyl phosphate and l-ascorbic acid. The microbiological stability of the formulations was also evaluated. The findings indicated that the formulations with l-ascorbic acid and its derivatives were efficient against the proliferation of various spoilage microorganisms, including aerobic plate counts as well as Pseudomonas aeruginosa, Staphylococcus aureus, and yeast and mold counts. The results presented in this work showed good stability throughout the experimental period. Newly formulated emulsion proved to exhibit a number of promising properties and attributes that might open new opportunities for the construction of more efficient, safe, and cost-effective skin-care, cosmetic, and pharmaceutical products. (author)

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

DEFF Research Database (Denmark)

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

2016-01-01

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

MYBPH inhibits NM IIA assembly via direct interaction with NMHC IIA and reduces cell motility

International Nuclear Information System (INIS)

Hosono, Yasuyuki; Usukura, Jiro; Yamaguchi, Tomoya; Yanagisawa, Kiyoshi; Suzuki, Motoshi; Takahashi, Takashi

2012-01-01

Highlights: ► MYBPH inhibits NMHC IIA assembly and cell motility. ► MYBPH interacts to assembly-competent NM IIA. ► MYBPH inhibits RLC and NMHC IIA, independent components of NM IIA. -- Abstract: Actomyosin filament assembly is a critical step in tumor cell migration. We previously found that myosin binding protein H (MYBPH) is directly transactivated by the TTF-1 lineage-survival oncogene in lung adenocarcinomas and inhibits phosphorylation of the myosin regulatory light chain (RLC) of non-muscle myosin IIA (NM IIA) via direct interaction with Rho kinase 1 (ROCK1). Here, we report that MYBPH also directly interacts with an additional molecule, non-muscle myosin heavy chain IIA (NMHC IIA), which was found to occur between MYBPH and the rod portion of NMHC IIA. MYBPH inhibited NMHC IIA assembly and reduced cell motility. Conversely, siMYBPH-induced increased motility was partially, yet significantly, suppressed by blebbistatin, a non-muscle myosin II inhibitor, while more profound effects were attained by combined treatment with siROCK1 and blebbistatin. Electron microscopy observations showed well-ordered paracrystals of NMHC IIA reflecting an assembled state, which were significantly less frequently observed in the presence of MYBPH. Furthermore, an in vitro sedimentation assay showed that a greater amount of NMHC IIA was in an unassembled state in the presence of MYBPH. Interestingly, treatment with a ROCK inhibitor that impairs transition of NM IIA from an assembly-incompetent to assembly-competent state reduced the interaction between MYBPH and NMHC IIA, suggesting that MYBPH has higher affinity to assembly-competent NM IIA. These results suggest that MYBPH inhibits RLC and NMHC IIA, independent components of NM IIA, and negatively regulates actomyosin organization at 2 distinct steps, resulting in firm inhibition of NM IIA assembly.

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

Science.gov (United States)

Oliva, Raymond V; Bakris, George L

2014-05-01

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

Targeting Type 2 Diabetes with C-Glucosyl Dihydrochalcones as Selective Sodium Glucose Co-Transporter 2 (SGLT2) Inhibitors: Synthesis and Biological Evaluation.

Science.gov (United States)

Jesus, Ana R; Vila-Viçosa, Diogo; Machuqueiro, Miguel; Marques, Ana P; Dore, Timothy M; Rauter, Amélia P

2017-01-26

Inhibiting glucose reabsorption by sodium glucose co-transporter proteins (SGLTs) in the kidneys is a relatively new strategy for treating type 2 diabetes. Selective inhibition of SGLT2 over SGLT1 is critical for minimizing adverse side effects associated with SGLT1 inhibition. A library of C-glucosyl dihydrochalcones and their dihydrochalcone and chalcone precursors was synthesized and tested as SGLT1/SGLT2 inhibitors using a cell-based fluorescence assay of glucose uptake. The most potent inhibitors of SGLT2 (IC 50 = 9-23 nM) were considerably weaker inhibitors of SGLT1 (IC 50 = 10-19 μM). They showed no effect on the sodium independent GLUT family of glucose transporters, and the most potent ones were not acutely toxic to cultured cells. The interaction of a C-glucosyl dihydrochalcone with a POPC membrane was modeled computationally, providing evidence that it is not a pan-assay interference compound. These results point toward the discovery of structures that are potent and highly selective inhibitors of SGLT2.

Characterization of glial cell K-Cl cotransport.

Science.gov (United States)

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

2007-01-01

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

NELL-1 increases pre-osteoblast mineralization using both phosphate transporter Pit1 and Pit2

Energy Technology Data Exchange (ETDEWEB)

Cowan, Catherine M. [Department of Bioengineering, University of California, Los Angeles, 420 Westwood Plaza,7523 Boelter Hall, Los Angeles, CA 90095 (United States); Dental and Craniofacial Research Institute and Section of Orthodontics, School of Dentistry, University of California, Los Angeles, 40833 Le Conte Ave, Los Angeles, CA 90095 (United States); Zhang, Xinli; James, Aaron W.; Mari Kim, T.; Sun, Nichole [Dental and Craniofacial Research Institute and Section of Orthodontics, School of Dentistry, University of California, Los Angeles, 40833 Le Conte Ave, Los Angeles, CA 90095 (United States); Wu, Benjamin [Department of Bioengineering, University of California, Los Angeles, 420 Westwood Plaza,7523 Boelter Hall, Los Angeles, CA 90095 (United States); Dental and Craniofacial Research Institute and Section of Orthodontics, School of Dentistry, University of California, Los Angeles, 40833 Le Conte Ave, Los Angeles, CA 90095 (United States); Ting, Kang [Dental and Craniofacial Research Institute and Section of Orthodontics, School of Dentistry, University of California, Los Angeles, 40833 Le Conte Ave, Los Angeles, CA 90095 (United States); Soo, Chia, E-mail: bsoo@ucla.edu [UCLA and Orthopaedic Hospital Department of Orthopaedic Surgery and the Orthopaedic, Hospital Research Center, University of California, Los Angeles, 2641 Charles E. Young Dr. South, Los Angeles, CA 90095 (United States)

2012-06-08

Highlights: Black-Right-Pointing-Pointer NELL-1 accelerates extracellular matrix mineralization in MC3T3-E1 pre-osteoblasts. Black-Right-Pointing-Pointer NELL-1 significantly increases intracellular inorganic phosphate levels. Black-Right-Pointing-Pointer NELL-1 positively regulates osteogenesis but not proliferation in MC3T3-E1 cells. Black-Right-Pointing-Pointer NELL-1 regulates inorganic phosphate transporter activity. -- Abstract: NELL-1 is a potent osteoinductive molecule that enhances bone formation in multiple animal models through currently unidentified pathways. In the present manuscript, we hypothesized that NELL-1 may regulate osteogenic differentiation accompanied by alteration of inorganic phosphate (Pi) entry into the osteoblast via sodium dependent phosphate (NaPi) transporters. To determine this, MC3T3-E1 pre-osteoblasts were cultured in the presence of recombinant human (rh)NELL-1 or rhBMP-2. Analysis was performed for intracellular Pi levels through malachite green staining, Pit-1 and Pit-2 expression, and forced upregulation of Pit-1 and Pit-2. Results showed rhNELL-1 to increase MC3T3-E1 matrix mineralization and Pi influx associated with activation of both Pit-1 and Pit-2 channels, with significantly increased Pit-2 production. In contrast, Pi transport elicited by rhBMP-2 showed to be associated with increased Pit-1 production only. Next, neutralizing antibodies against Pit-1 and Pit-2 completely abrogated the Pi influx effect of rhNELL-1, suggesting rhNELL-1 is dependent on both transporters. These results identify one potential mechanism of action for rhNELL-1 induced osteogenesis and highlight a fundamental difference between NELL-1 and BMP-2 signaling.

NELL-1 increases pre-osteoblast mineralization using both phosphate transporter Pit1 and Pit2

International Nuclear Information System (INIS)

Cowan, Catherine M.; Zhang, Xinli; James, Aaron W.; Mari Kim, T.; Sun, Nichole; Wu, Benjamin; Ting, Kang; Soo, Chia

2012-01-01

Highlights: ► NELL-1 accelerates extracellular matrix mineralization in MC3T3-E1 pre-osteoblasts. ► NELL-1 significantly increases intracellular inorganic phosphate levels. ► NELL-1 positively regulates osteogenesis but not proliferation in MC3T3-E1 cells. ► NELL-1 regulates inorganic phosphate transporter activity. -- Abstract: NELL-1 is a potent osteoinductive molecule that enhances bone formation in multiple animal models through currently unidentified pathways. In the present manuscript, we hypothesized that NELL-1 may regulate osteogenic differentiation accompanied by alteration of inorganic phosphate (Pi) entry into the osteoblast via sodium dependent phosphate (NaPi) transporters. To determine this, MC3T3-E1 pre-osteoblasts were cultured in the presence of recombinant human (rh)NELL-1 or rhBMP-2. Analysis was performed for intracellular Pi levels through malachite green staining, Pit-1 and Pit-2 expression, and forced upregulation of Pit-1 and Pit-2. Results showed rhNELL-1 to increase MC3T3-E1 matrix mineralization and Pi influx associated with activation of both Pit-1 and Pit-2 channels, with significantly increased Pit-2 production. In contrast, Pi transport elicited by rhBMP-2 showed to be associated with increased Pit-1 production only. Next, neutralizing antibodies against Pit-1 and Pit-2 completely abrogated the Pi influx effect of rhNELL-1, suggesting rhNELL-1 is dependent on both transporters. These results identify one potential mechanism of action for rhNELL-1 induced osteogenesis and highlight a fundamental difference between NELL-1 and BMP-2 signaling.

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

Directory of Open Access Journals (Sweden)

Sanon VP

2017-05-01

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

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

International Nuclear Information System (INIS)

Marshall, W.L.

1982-01-01

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

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

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Chang-Ik Choi

2016-08-01

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

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

DEFF Research Database (Denmark)

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

2004-01-01

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

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

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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.

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

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

2013-01-01

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

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

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Verónica Celeste De Giusti

2014-01-01

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

Effects of insecticides intended for Ceutorhynchus napi Gyll. control in oilseed rape on ground beetles

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Sivčev Lazar

2017-01-01

Full Text Available The effects of insecticides that are commonly used for conventional and integrated oilseed rape (OSR management on ground beetles were studied. Monitoring of harmful species showed that only insecticides intended against Ceutorhynchus napi should be applied. There were no differences in beetle numbers and phenology of settling of C. napi in the OSR fields that received different management practices. The type of OSR management has a primary and significant impact on ground beetles abundance. Early in the spring, ground beetles settled more massively on the non-tilled OSR field with abundant weed cover and mulch on soil surface. However, there were no significant differences in species richness between the OSR fields managed differently. A total of 22 species were recorded. Early in the spring, the granivorous ground beetles Amara aenea (47.3% and Harpalus distinguendus (32.5% were dominant. When insecticides were applied, immigration of ground beetles began, so that their adverse effect was minimal. In both management systems the number of ground beetles and their diversity increased after spraying. In conclusion, no significant harmful effects of the insecticides on ground beetles were detected in OSR fields managed in two different ways.

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

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Braun, U; Grob, D; Hässig, M

2016-09-01

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

Tanshinone IIA Sodium Sulfonate Attenuates LPS-Induced Intestinal Injury in Mice

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Xin-Jing Yang

2018-01-01

Full Text Available Background. Tanshinone IIA sodium sulfonate (TSS is known to possess anti-inflammatory effects and has exhibited protective effects in various inflammatory conditions; however, its role in lipopolysaccharide- (LPS- induced intestinal injury is still unknown. Objective. The present study is designed to explore the role and possible mechanism of TSS in LPS-induced intestinal injury. Methods. Male C57BL/6J mice, challenged with intraperitoneal LPS injection, were treated with or without TSS 0.5 h prior to LPS exposure. At 1, 6, and 12 h after LPS injection, mice were sacrificed, and the small intestine was excised. The intestinal tissue injury was analyzed by HE staining. Inflammatory factors (TNF-α, IL-1β, and IL-6 in the intestinal tissue were examined by ELISA and RT-PCR. In addition, expressions of autophagy markers (microtubule-associated light chain 3 (LC3 and Beclin-1 were detected by western blot and RT-PCR. A number of autophagosomes were also observed under electron microscopy. Results. TSS treatment significantly attenuated small intestinal epithelium injury induced by LPS. LPS-induced release of inflammatory mediators, including TNF-α, IL-1β, and IL-6, were markedly inhibited by TSS. Furthermore, TSS treatment could effectively upregulate LPS-induced decrease of autophagy levels, as evidenced by the increased expression of LC3 and Beclin-1, and more autophagosomes. Conclusion. The protective effect of TSS on LPS-induced small intestinal injury may be attributed to the inhibition of inflammatory factors and promotion of autophagy levels. The present study may provide novel insight into the molecular mechanisms of TSS on the treatment of intestinal injury.

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

OpenAIRE

Katakam, Prakash; Sireesha, Karanam R.

2012-01-01

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

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...

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

Science.gov (United States)

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

2012-06-01

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

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

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Opie, L H

2014-08-01

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

Ameloblast modulation and transport of Cl-, Na+, and K+ during amelogenesis

NARCIS (Netherlands)

Bronckers, A.L.J.J.; Lyaruu, D.; Jalali, R.; Medina, J.F.; Zandieh-Doulabi, B.; DenBesten, P.K.

2015-01-01

Ameloblasts express transmembrane proteins for transport of mineral ions and regulation of pH in the enamel space. Two major transporters recently identified in ameloblasts are the Na+K+-dependent calcium transporter NCKX4 and the Na+-dependent HPO42- (Pi) cotransporter NaPi-2b. To regulate pH,

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

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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.

Downregulation of surface sodium pumps by endocytosis during meiotic maturation of Xenopus laevis oocytes

International Nuclear Information System (INIS)

Schmalzing, G.; Eckard, P.; Kroener, S.P.; Passow, H.

1990-01-01

During meiotic maturation, plasma membranes of Xenopus laevis oocytes completely lose the capacity to transport Na and K and to bind ouabain. To explore whether the downregulation might be due to an internalization of the sodium pump molecules, the intracellular binding of ouabain was determined. Selective permeabilization of the plasma membrane of mature oocytes (eggs) by digitonin almost failed to disclose ouabain binding sites. However, when the eggs were additionally treated with 0.02% sodium dodecyl sulfate (SDS) to permeabilize inner membranes, all sodium pumps present before maturation were recovered. Phosphorylation by [gamma-32P]ATP combined with SDS-polyacrylamide gel electrophoresis (PAGE) and autoradiography showed that sodium pumps were greatly reduced in isolated plasma membranes of eggs. According to sucrose gradient fractionation, maturation induced a shift of sodium pumps from the plasma membrane fraction to membranes of lower buoyant density with a protein composition different from that of the plasma membrane. Endocytosed sodium pumps identified on the sucrose gradient from [3H]ouabain bound to the cell surface before maturation could be phosphorylated with inorganic [32P]phosphate. The findings suggest that downregulation of sodium pumps during maturation is brought about by translocation of surface sodium pumps to an intracellular compartment, presumably endosomes. This contrasts the mechanism of downregulation of Na-dependent cotransport systems, the activities of which are reduced as a consequence of a maturation-induced depolarization of the membrane without a removal of the corresponding transporter from the plasma membrane

Final report of the safety assessment of L-Ascorbic Acid, Calcium Ascorbate, Magnesium Ascorbate, Magnesium Ascorbyl Phosphate, Sodium Ascorbate, and Sodium Ascorbyl Phosphate as used in cosmetics.

Science.gov (United States)

Elmore, Amy R

2005-01-01

L-Ascorbic Acid, Calcium Ascorbate, Magnesium Ascorbate, Magnesium Ascorbyl Phosphate, Sodium Ascorbate, and Sodium Ascorbyl Phosphate function in cosmetic formulations primarily as antioxidants. Ascorbic Acid is commonly called Vitamin C. Ascorbic Acid is used as an antioxidant and pH adjuster in a large variety of cosmetic formulations, over 3/4 of which were hair dyes and colors at concentrations between 0.3% and 0.6%. For other uses, the reported concentrations were either very low (cosmetics, but are not currently used. Sodium Ascorbyl Phosphate functions as an antioxidant in cosmetic products and is used at concentrations ranging from 0.01% to 3%. Magnesium Ascorbyl Phosphate functions as an antioxidant in cosmetics and was reported being used at concentrations from 0.001% to 3%. Sodium Ascorbate also functions as an antioxidant in cosmetics at concentrations from 0.0003% to 0.3%. Related ingredients (Ascorbyl Palmitate, Ascorbyl Dipalmitate, Ascorbyl Stearate, Erythorbic Acid, and Sodium Erythorbate) have been previously reviewed by the Cosmetic Ingredient Review (CIR) Expert Panel and found "to be safe for use as cosmetic ingredients in the present practices of good use." Ascorbic Acid is a generally recognized as safe (GRAS) substance for use as a chemical preservative in foods and as a nutrient and/or dietary supplement. Calcium Ascorbate and Sodium Ascorbate are listed as GRAS substances for use as chemical preservatives. L-Ascorbic Acid is readily and reversibly oxidized to L-dehydroascorbic acid and both forms exist in equilibrium in the body. Permeation rates of Ascorbic Acid through whole and stripped mouse skin were 3.43 +/- 0.74 microg/cm(2)/h and 33.2 +/- 5.2 microg/cm(2)/h. Acute oral and parenteral studies in mice, rats, rabbits, guinea pigs, dogs, and cats demonstrated little toxicity. Ascorbic Acid and Sodium Ascorbate acted as a nitrosation inhibitor in several food and cosmetic product studies. No compound-related clinical signs or gross or

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

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Packer, Milton

2018-06-01

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

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

Science.gov (United States)

AlAani, Hashem; Alnukkary, Yasmin

2016-03-01

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

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

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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.

Sodium Phosphate Supplementation and Time Trial Performance in Female Cyclists

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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.

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

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Hadeel Alfahmi

2017-01-01

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

Effects of antidiabetic drugs on the incidence of macrovascular complications and mortality in type 2 diabetes mellitus: a new perspective on sodium-glucose co-transporter 2 inhibitors.

Science.gov (United States)

Rahelić, Dario; Javor, Eugen; Lucijanić, Tomo; Skelin, Marko

2017-02-01

Elevated hemoglobin A 1c (HbA 1c ) values correlate with microvascular and macrovascular complications. Thus, patients with type 2 diabetes mellitus (T2DM) are at an increased risk of developing macrovascular events. Treatment of T2DM should be based on a multifactorial approach because of its evidence regarding reduction of macrovascular complications and mortality in T2DM. It is well known that intensive glucose control reduces the risk of microvascular complications in T2DM, but the effects of antidiabetic drugs on macrovascular complications and mortality in T2DM are less clear. The results of recent trials have demonstrated clear evidence that empagliflozin and liraglutide reduce cardiovascular (CV) and all-cause mortality in T2DM, an effect that is absent in other members of antidiabetic drugs. Empagliflozin is a member of a novel class of antidiabetic drugs, the sodium-glucose co-transporter 2 (SGLT2) inhibitors. Two ongoing randomized clinical trials involving other SGLT2 inhibitors, canagliflozin and dapagliflozin, will provide additional evidence of the beneficial effects of SGLT2 inhibitors in T2DM population. The aim of this paper is to systematically present the latest evidence regarding the usage of antidiabetic drugs, and the reduction of macrovascular complications and mortality. A special emphasis is put on the novel class of antidiabetic drugs, of SGLT2 inhibitors. Key messages Macrovascular complications and mortality are best clinical trial endpoints for evaluating the efficacy of antidiabetic drugs. The first antidiabetic drug that demonstrated a reduction in mortality in the treatment of type 2 diabetes mellitus (T2DM) was empagliflozin, a sodium-glucose co-transporter 2 (SGLT2) inhibitor. SGLT2 inhibitors are novel class of antidiabetic drugs that play a promising role in the treatment of T2DM.

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

Science.gov (United States)

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

2012-06-01

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

The dissociation of NZP (Ca{sub 0.5}Sr{sub 0.5}Zr{sub 4}P{sub 6}O{sub 24}) during plasma spraying[Sodium Zirconium Phosphate

Energy Technology Data Exchange (ETDEWEB)

Trice, R.W.; Brewer, L.N.; Faber, K.T.

2000-04-01

Sodium zirconium phosphate (NaZr{sub 2}P{sub 3}O{sub 12} or NZP) was first systematically evaluated in the early 1980s by Roy and co-workers, who demonstrated its extremely low coefficient of thermal expansion (CTE). It was later shown that other group IA and IIA atoms can be ionically substituted into the NZP crystal structure to adjust the CTE. As a result of their low and tailorable CTEs, NZP's have potential use as a protective coating for silicon-based ceramics and carbon-carbon composites. One technique for the application of ceramic coatings employs plasma-spraying. In this process, powders are injected into a plasma flame, melted, and propelled onto a substrate. The resulting coating microstructure is typically composed of thin lamellae (from each melted particle) stacked on top of one another during each pass of the torch. In the current research, NZP has been plasma-sprayed using the recently patented small particle plasma-spray process. The microstructure was then analyzed using transmission electron microscopy and x-ray diffraction to identify the phases in the complex coating that resulted.

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

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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

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

DEFF Research Database (Denmark)

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

2000-01-01

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

Effects of Jerusalem Artichoke Powder and Sodium Carbonate as Phosphate Replacers on the Quality Characteristics of Emulsified Chicken Meatballs.

Science.gov (United States)

Öztürk, Burcu; Serdaroğlu, Meltem

2018-02-01

Today incorporation of natural ingredients as inorganic phosphate replacers has come into prominence as a novel research topic due to health concerns about phosphates. In this study, we aimed to investigate the quality of emulsified chicken meatballs produced with Jerusalem artichoke powder (JAP), either alone or in combination with sodium carbonate (SC) as sodium tripolyphosphate (STPP) replacers. The results showed that naturally dried JAP showed favorable technological properties in terms of water-oil binding and gelling. Emulsion batters formulated with JAP-SC mixture showed lower jelly and fat separation, higher water-holding capacity and higher emulsion stability than control samples with STPP. In final product, incorporation of JAP-SC mixture increased moisture and reduced lipid and energy values, and kept the pH value similar to control. Added JAP lead to increments in b* values whereas decreases L* values. Cook yield was similar to control in phosphate-free samples formulated with JAP-SC mix. Either low or medium ratios of JAP in combination with SC managed to protect most of the sensory parameters, while sensory scores tend to decrease in samples containing high levels of JAP. Addition of JAP to formulations presented samples that have equivalent behavior to phosphates in terms of lipid oxidation. In conclusion, our study confirms that utilization of JAP in combination with SC had promising effects as phosphate replacers by presenting natural solutions and providing equivalent quality to standard phosphate containing products.

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

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

2016-04-29

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

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

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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.

Prostaglandin-E2 Mediated Increase in Calcium and Phosphate Excretion in a Mouse Model of Distal Nephron Salt Wasting.

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Manoocher Soleimani

Full Text Available Contribution of salt wasting and volume depletion to the pathogenesis of hypercalciuria and hyperphosphaturia is poorly understood. Pendrin/NCC double KO (pendrin/NCC-dKO mice display severe salt wasting under basal conditions and develop profound volume depletion, prerenal renal failure, and metabolic alkalosis and are growth retarded. Microscopic examination of the kidneys of pendrin/NCC-dKO mice revealed the presence of calcium phosphate deposits in the medullary collecting ducts, along with increased urinary calcium and phosphate excretion. Confirmatory studies revealed decreases in the expression levels of sodium phosphate transporter-2 isoforms a and c, increases in the expression of cytochrome p450 family 4a isotypes 12 a and b, as well as prostaglandin E synthase 1, and cyclooxygenases 1 and 2. Pendrin/NCC-dKO animals also had a significant increase in urinary prostaglandin E2 (PGE-2 and renal content of 20-hydroxyeicosatetraenoic acid (20-HETE levels. Pendrin/NCC-dKO animals exhibit reduced expression levels of the sodium/potassium/2chloride co-transporter 2 (NKCC2 in their medullary thick ascending limb. Further assessment of the renal expression of NKCC2 isoforms by quantitative real time PCR (qRT-PCR reveled that compared to WT mice, the expression of NKCC2 isotype F was significantly reduced in pendrin/NCC-dKO mice. Provision of a high salt diet to rectify volume depletion or inhibition of PGE-2 synthesis by indomethacin, but not inhibition of 20-HETE generation by HET0016, significantly improved hypercalciuria and salt wasting in pendrin/NCC dKO mice. Both high salt diet and indomethacin treatment also corrected the alterations in NKCC2 isotype expression in pendrin/NCC-dKO mice. We propose that severe salt wasting and volume depletion, irrespective of the primary originating nephron segment, can secondarily impair the reabsorption of salt and calcium in the thick ascending limb of Henle and/or proximal tubule, and reabsorption of

sPLA2-IIA

Indian Academy of Sciences (India)

67

Recent research showed that maslinic acid interacts with sPLA2-IIA ... Further analysis revealed that sPLA2-IIA only induced modest LDL ..... MDA/mg protein) compared to native LDL (2.043 nmol MDA/mg protein) while .... to modify extracellular non-cellular lipid components such as lipoproteins, ... The main pathway for.

Deregulated Renal Calcium and Phosphate Transport during Experimental Kidney Failure.

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Wilco P Pulskens

Full Text Available Impaired mineral homeostasis and inflammation are hallmarks of chronic kidney disease (CKD, yet the underlying mechanisms of electrolyte regulation during CKD are still unclear. Here, we applied two different murine models, partial nephrectomy and adenine-enriched dietary intervention, to induce kidney failure and to investigate the subsequent impact on systemic and local renal factors involved in Ca(2+ and Pi regulation. Our results demonstrated that both experimental models induce features of CKD, as reflected by uremia, and elevated renal neutrophil gelatinase-associated lipocalin (NGAL expression. In our model kidney failure was associated with polyuria, hypercalcemia and elevated urinary Ca(2+ excretion. In accordance, CKD augmented systemic PTH and affected the FGF23-αklotho-vitamin-D axis by elevating circulatory FGF23 levels and reducing renal αklotho expression. Interestingly, renal FGF23 expression was also induced by inflammatory stimuli directly. Renal expression of Cyp27b1, but not Cyp24a1, and blood levels of 1,25-dihydroxy vitamin D3 were significantly elevated in both models. Furthermore, kidney failure was characterized by enhanced renal expression of the transient receptor potential cation channel subfamily V member 5 (TRPV5, calbindin-D28k, and sodium-dependent Pi transporter type 2b (NaPi2b, whereas the renal expression of sodium-dependent Pi transporter type 2a (NaPi2a and type 3 (PIT2 were reduced. Together, our data indicates two different models of experimental kidney failure comparably associate with disturbed FGF23-αklotho-vitamin-D signalling and a deregulated electrolyte homeostasis. Moreover, this study identifies local tubular, possibly inflammation- or PTH- and/or FGF23-associated, adaptive mechanisms, impacting on Ca(2+/Pi homeostasis, hence enabling new opportunities to target electrolyte disturbances that emerge as a consequence of CKD development.

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.

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

DEFF Research Database (Denmark)

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

1997-01-01

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

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

International Nuclear Information System (INIS)

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

2011-01-01

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

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

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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.

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

Science.gov (United States)

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

2015-01-01

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

In vivo PTH provokes apical NHE3 and NaPi2 redistribution and Na-K-ATPase inhibition

DEFF Research Database (Denmark)

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

1999-01-01

and to determine whether the same cellular signals drive the changes in apical and basolateral transporters. PTH-(1-34) (20 U), which couples to adenylate cyclase (AC), phospholipase C (PLC), and phospholipase A2 (PLA2), or [Nle8,18,Tyr34]PTH-(3-34) (10 U), which couples to PLC and PLA2 but not AC, were given....../diuresis and NHE3 and NaPi2 internalization, and that Na-K-ATPase inhibition is not secondary to depressed apical Na+ transport....

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

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Salem A. Beshyah

2016-06-01

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

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

International Nuclear Information System (INIS)

Marshall, W.L.

1981-12-01

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

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

Science.gov (United States)

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

2018-02-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

1991-02-01

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

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

Science.gov (United States)

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

2009-04-01

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

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.

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

Science.gov (United States)

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

2017-09-01

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

Peculiarities of the diffusion of silver and sodium ions in phosphate glasses with a high content of sodium oxide

International Nuclear Information System (INIS)

Syutkin, V.M.; Tolkatchev, V.A.

1996-01-01

The phosphate glasses with a high content of alkali metal ions are good ionic conductors. Despite active studies, the mechanism of ion diffusion is not so far clear. The present work discusses the characteristics of ion diffusion in phosphate glasses with a high content of sodium oxide. An effective method to study ion transport is the investigation of relaxation processes the kinetics of which depends on ion diffusion. We use the data for two types of relaxation processes the kinetics of which is determined by ion diffusion. This is the conductivity relaxation due to sodium (host) ions and the decay of radiation-induced centers controlled by silver (guest) ion diffusion. Both of the processes being actually the first-order processes display a nonexponential kinetic behavior. The relaxation law can be interpreted either as the inherently nonexponential function or as the weighted sum of exponential decay functions with a distribution of relaxation times. It has been demonstrated that on the molecular level the relaxation function should be interpreted in the frame of the scheme of parallel first-order processes. This fact allows one to formulate a number of features of ion diffusion: (i) the mean square displacement of ions does not exceed several angstrom when transport becomes non-dispersive; (ii) the diffusion coefficient of ions is the function of coordinates. In this case, a characteristic distance at which D(r) noticeably varies is no less than a hundred of angstrom; (iii) the instantaneous concentration of mobile ions is well below the overall concentration ions

Rescue therapy with Tanshinone IIA hinders transition of acute kidney injury to chronic kidney disease via targeting GSK3β

Science.gov (United States)

Jiang, Chunming; Zhu, Wei; Yan, Xiang; Shao, Qiuyuan; Xu, Biao; Zhang, Miao; Gong, Rujun

2016-01-01

Acute kidney injury (AKI) remains challenging for clinical practice and poses a risk of developing progressive chronic kidney disease (CKD) with no definitive treatment available yet. Tanshinone IIA, an active ingredient of Chinese herbal Salvia miltiorrhiza, has been widely used in Asia for the remarkable organoprotective activities. Its effect on established AKI, however, remains unknown. In mice with folic acid-induced AKI, delayed treatment with Tanshinone IIA, commenced early or late after injury, diminished renal expression of kidney injury markers, reduced apoptosis and improved kidney dysfunction, concomitant with mitigated histologic signs of AKI to CKD transition, including interstitial fibrosis and tubular atrophy, and with an ameliorated inflammatory infiltration in tubulointerstitium and a favored M2-skewed macrophage polarization. Mechanistically, Tanshinone IIA blunted glycogen synthase kinase (GSK)3β overactivity and hyperactivation of its downstream mitogen-activated protein kinases that are centrally implicated in renal fibrogenesis and inflammation. Inhibition of GSK3β is likely a key mechanism mediating the therapeutic activity of Tanshinone IIA, because sodium nitroprusside, a GSK3β activator, largely offset its renoprotective effect. In confirmatory studies, rescue treatment with Tanshinone IIA likewise ameliorated ischemia/reperfusion-induced kidney destruction in mice. Our data suggest that Tanshinone IIA represents a valuable treatment that improves post-AKI kidney salvage via targeting GSK3β. PMID:27857162

Modifications on the properties of a calcium phosphate cement by additions of sodium alginate

International Nuclear Information System (INIS)

Coelho, W.T.; Fernandes, J.M.; Vieira, R.S.; Thurmer, M.B.; Santos, L.A.

2012-01-01

The Calcium Phosphate Cement (CPC) are bone substitutes with great potential for use in orthopedics, traumatology and dentistry due to its biocompatibility, bioactivity and osteoconductivity, and form a paste that can be easily shaped and placed into the surgical site. However, CPCs have low mechanical strength, which equals the maximum mechanical strength of trabecular bone. In order to assess the strength and time to handle a CPC composed primarily of alpha phase, were added sodium alginate (1%, 2% and 3% wt) and an accelerator in an aqueous solution. The cement powder was mixed with liquid of setting, shaped into specimens and evaluated for apparent density and porosity by Archimedes method, X-ray diffraction and compressive strength. A significant increase in compressive strength by adding sodium alginate was verified. (author)

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

International Nuclear Information System (INIS)

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

1990-02-01

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

Crystal structure of MboIIA methyltransferase.

Science.gov (United States)

Osipiuk, Jerzy; Walsh, Martin A; Joachimiak, Andrzej

2003-09-15

DNA methyltransferases (MTases) are sequence-specific enzymes which transfer a methyl group from S-adenosyl-L-methionine (AdoMet) to the amino group of either cytosine or adenine within a recognized DNA sequence. Methylation of a base in a specific DNA sequence protects DNA from nucleolytic cleavage by restriction enzymes recognizing the same DNA sequence. We have determined at 1.74 A resolution the crystal structure of a beta-class DNA MTase MboIIA (M.MboIIA) from the bacterium Moraxella bovis, the smallest DNA MTase determined to date. M.MboIIA methylates the 3' adenine of the pentanucleotide sequence 5'-GAAGA-3'. The protein crystallizes with two molecules in the asymmetric unit which we propose to resemble the dimer when M.MboIIA is not bound to DNA. The overall structure of the enzyme closely resembles that of M.RsrI. However, the cofactor-binding pocket in M.MboIIA forms a closed structure which is in contrast to the open-form structures of other known MTases.

Application and Mechanism of Anionic Collector Sodium Dodecyl Sulfate (SDS in Phosphate Beneficiation

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Kun Sun

2017-02-01

Full Text Available Phosphate ore is a valuable strategic resource. Most phosphate ore in China is collophane. Utilization of mid-low grade collophane is necessary to maintain social sustainable development. The gravity-flotation combination separation process can be utilized to separate mid-low grade collophane, but the process consumes a large quantity of acid in the reverse stage. Sodium dodecyl sulfate (SDS was used as a dolomite collector in this study to reduce the acid consumption of collophane flotation. SDS effectively removed dolomite from the gravity concentrate when no other reagents were present. Flotation test results showed that, compared to the conventional gravity-flotation process, the proposed SDS-based process reduced phosphoric acid dosage from 6.1 kg/t to 3.9 kg/t with similar separation results. The SDS action mechanisms on dolomite were further investigated by zeta potential analysis, single mineral flotation tests, infrared spectrum detection, and theoretical analysis. The results indicate that the SDS adsorption on dolomite is mainly physical adsorption, and that favorable separation effects between collophane and dolomite may be attributed to physical adsorption and entrainment. In addition, it also indicates that the physical adsorption can be utilized to remove dolomite from phosphate on account of zeta potential differences when the separate feed is coarse.

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

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Shoko Horita

2015-01-01

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

Tanshinone IIA stimulates erythrocyte phosphatidylserine exposure

NARCIS (Netherlands)

Zelenak, C.; Pasham, V.; Jilani, K.; Tripodi, P.M.; Rosaclerio, L.; Pathare, G.T.; Lupescu, A.; Faggio, C.; Qadri, S.M.; Lang, F.

2012-01-01

Tanshinone IIA, an antimicrobial, antioxidant, antianaphylactic, antifibrotic, vasodilating, antiatherosclerotic, organo-protective and antineoplastic component from the rhizome of Salvia miltiorrhiza, is known to trigger apoptosis of tumor cells. Tanshinone IIA is effective in part through

Sodium phosphate as a solid catalyst for biodiesel preparation

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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%.

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

Science.gov (United States)

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

2013-10-01

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

Addition of 1, 2 and 3% in mass of sodium alginate in calcium phosphate cement

International Nuclear Information System (INIS)

Coelho, W.T.; Fernandes, J.M.; Vieira, R.S.; Thurmer, M.B.; Santos, L.A.

2011-01-01

The calcium phosphate cement (CFC) are bone substitutes with great potential for use in orthopedics, traumatology and dentistry because of their biocompatibility, bioactivity, osteoconductivity and osteotransdutivity, and a paste that can be easily molded and placed into the surgical site. However, CFCs have low mechanical strength, which equals the maximum mechanical strength of trabecular bone. Aiming to evaluate the strength and time to handle a CFC phase composed mainly of alpha were added to sodium alginate (1%, 2% and 3% wt) and an accelerator handle in an aqueous medium. The cement powder was mixed with liquid takes 2 minutes and resigned in specimens and assessed for apparent density and porosity by the Archimedes method, X-ray diffraction and mechanical strength. We noticed a significant increase in mechanical properties of cement added sodium alginate. (author)

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.

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.

Elaboration and test of the method of separation of alkaline metals ions with tin phosphate

International Nuclear Information System (INIS)

Smirnov, G.I.; Chernyak, A.S.; Kostromina, O.N.; Kachur, N.Ya.; Shpeyzer, B.G.

1986-01-01

Present work is devoted to elaboration and test of the method of separation of alkaline metals ions with tin phosphate. Thus, the isotherms of sorption of lithium, sodium, potassium, rubidium and cesium ions with amorphous tin phosphate depending on their concentration, ph of solution, sorbent quantity are obtained. The parameters of extraction of potassium microquantities from sodium salts are defined. Ultra pure sodium chloride, sodium iodide, sodium sulphate, sodium nitrate, sodium nitrite, sodium phosphate are synthesized.

Sodium-Glucose Linked Cotransporter-2 Inhibition Does Not Attenuate Disease Progression in the Rat Remnant Kidney Model of Chronic Kidney Disease.

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Yanling Zhang

Full Text Available Pharmacological inhibition of the proximal tubular sodium-glucose linked cotransporter-2 (SGLT2 leads to glycosuria in both diabetic and non-diabetic settings. As a consequence of their ability to modulate tubuloglomerular feedback, SGLT2 inhibitors, like agents that block the renin-angiotensin system, reduce intraglomerular pressure and single nephron GFR, potentially affording renoprotection. To examine this further we administered the SGLT2 inhibitor, dapagliflozin, to 5/6 (subtotally nephrectomised rats, a model of progressive chronic kidney disease (CKD that like CKD in humans is characterised by single nephron hyperfiltration and intraglomerular hypertension and where angiotensin converting enzyme inhibitors and angiotensin receptor blockers are demonstrably beneficial. When compared with untreated rats, both sham surgery and 5/6 nephrectomised rats that had received dapagliflozin experienced substantial glycosuria. Nephrectomised rats developed hypertension, heavy proteinuria and declining GFR that was unaffected by the administration of dapagliflozin. Similarly, SGLT2 inhibition did not attenuate the extent of glomerulosclerosis, tubulointerstitial fibrosis or overexpression of the profibrotic cytokine, transforming growth factor-ß1 mRNA in the kidneys of 5/6 nephrectomised rats. While not precluding beneficial effects in the diabetic setting, these findings indicate that SGLT2 inhibition does not have renoprotective effects in this classical model of progressive non-diabetic CKD.

In silico analysis and experimental validation of azelastine hydrochloride (N4) targeting sodium taurocholate co-transporting polypeptide (NTCP) in HBV therapy.

Science.gov (United States)

Fu, L-L; Liu, J; Chen, Y; Wang, F-T; Wen, X; Liu, H-Q; Wang, M-Y; Ouyang, L; Huang, J; Bao, J-K; Wei, Y-Q

2014-08-01

The aim of this study was to explore sodium taurocholate co-transporting polypeptide (NTCP) exerting its function with hepatitis B virus (HBV) and its targeted candidate compounds, in HBV therapy. Identification of NTCP as a novel HBV target for screening candidate small molecules, was used by phylogenetic analysis, network construction, molecular modelling, molecular docking and molecular dynamics (MD) simulation. In vitro virological examination, q-PCR, western blotting and cytotoxicity studies were used for validating efficacy of the candidate compound. We used the phylogenetic analysis of NTCP and constructed its protein-protein network. Also, we screened compounds from Drugbank and ZINC, among which five were validated for their authentication in HepG 2.2.15 cells. Then, we selected compound N4 (azelastine hydrochloride) as the most potent of them. This showed good inhibitory activity against HBsAg (IC50 = 7.5 μm) and HBeAg (IC50 = 3.7 μm), as well as high SI value (SI = 4.68). Further MD simulation results supported good interaction between compound N4 and NTCP. In silico analysis and experimental validation together demonstrated that compound N4 can target NTCP in HepG2.2.15 cells, which may shed light on exploring it as a potential anti-HBV drug. © 2014 John Wiley & Sons Ltd.

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

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Ziad G Nasr

2017-01-01

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

Characteristic of Lamb Sausages Fermented by Indonesian Meat-Derived Probiotic, Lactobacillus plantarum IIA-2C12 and Lactobacillus acidophilus IIA-2B4

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Noraimah Binti Sulaiman

2016-08-01

Full Text Available Probiotic is a group of microorganism, mainly from lactic acid bacteria (LAB, widely used to increase functionality of various foodstuffs, including lamb which was limited by its goaty odor and short life issue. This study aimed to evaluate the characteristic of lamb sausages fermented by either Lactobacillus plantarum IIA-2C12 or L. acidophilus IIA-2B4 isolated from local cattle in Indonesia, and stored for 21 days at low temperature (4oC. Fermented lamb sausages were made with the addition of L. plantarum IIA-2C12 and L. acidophilus IIA-2B4 with three replications. The result showed that pH value, protein, and cholesterol contents of the sausages with addition of L. acidophilus IIA-2B4 were higher (P<0.05 than that of L. plantarum IIA-2C12. Meanwhile, the sausage fermented with L. plantarum IIA-2C12 had higher titratable acid (TA value, texture, and the content of fat, carbohydrate, tyrosine, lysine, myristoleic (C14:1, pentadecanoic (C15:0, heneicosanoic (C21:0 and cis-11-eicosatrienoic (C20:1 as compared to that of  L. acidophilus 2C12-2B4. Final population of LAB in the sausage fermented by L. plantarum IIA-2C12 was also higher than that of L. acidophilus IIA-2B4, yet both can be categorized as a probiotic. The differences between characteristics of the physicochemical traits and microbiological quality of the sausage fermentation associated with the addition of L. plantarum IIA-2C12 or L. acidophilus IIA-2B4. The 21 days of storage at cold temperatures with probiotics addition could extend shelf life and maintain quality of fermented sausage.

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

Science.gov (United States)

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

2002-05-15

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

Increased Urinary Extracellular Vesicle Sodium Transporters in Cushing's Syndrome with Hypertension.

Science.gov (United States)

Salih, Mahdi; Bovée, Dominique M; van der Lubbe, Nils; Danser, Alexander H J; Zietse, Robert; Feelders, Richard A; Hoorn, Ewout J

2018-05-02

Increased renal sodium reabsorption contributes to hypertension in Cushing's syndrome (CS). Renal sodium transporters can be analyzed non-invasively in urinary extracellular vesicles (uEVs). To analyze renal sodium transporters in uEVs of patients with CS and hypertension. Observational study. University hospital. uEVs were isolated by ultracentrifugation and analyzed by immunoblotting in 10 CS patients and 7 age-matched healthy subjects. In 7 CS patients uEVs were analyzed before and after treatment. uEV protein abundance. The 10 CS patients were divided in those with suppressed and non-suppressed renin-angiotensin-aldosterone system (RAAS, n = 5/group). CS patients with suppressed RAAS had similar blood pressure but significantly lower serum potassium than CS patients with non-suppressed RAAS. Compared to healthy subjects, only those with suppressed RAAS had higher phosphorylated Na+-K+-Cl- cotransporter type 2 (pNKCC2) and higher total and phosphorylated Na+-Cl- cotransporter (NCC) in uEVs. Serum potassium but not urinary free cortisol correlated with pNKCC2, pNCC, and NCC in uEVs. Treatment of CS reversed the increases in pNKCC2, NCC, and pNCC. CS increases renal sodium transporter abundance in uEVs especially in patients with hypertension and suppressed RAAS. As potassium has recently been identified as an important driver of NCC activity, low serum potassium may also contribute to increased renal sodium reabsorption and hypertension in CS. These results may also be relevant for hypertension induced by exogenous glucocorticoids.

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

Science.gov (United States)

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

2016-10-01

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

Potential Therapeutic Roles of Tanshinone IIA in Human Bladder Cancer Cells

Directory of Open Access Journals (Sweden)

Sheng-Chun Chiu

2014-09-01

Full Text Available Tanshinone IIA (Tan-IIA, one of the major lipophilic components isolated from the root of Salviae Miltiorrhizae, has been found to exhibit anticancer activity in various cancer cells. We have demonstrated that Tan-IIA induces apoptosis in several human cancer cells through caspase- and mitochondria-dependent pathways. Here we explored the anticancer effect of Tan-IIA in human bladder cancer cell lines. Our results showed that Tan-IIA caused bladder cancer cell death in a time- and dose-dependent manner. Tan-IIA induced apoptosis through the mitochondria-dependent pathway in these bladder cancer cells. Tan-IIA also suppressed the migration of bladder cancer cells as revealed by the wound healing and transwell assays. Finally, combination therapy of Tan-IIA with a lower dose of cisplatin successfully killed bladder cancer cells, suggesting that Tan-IIA can serve as a potential anti-cancer agent in bladder cancer.

Structural and functional significance of water permeation through cotransporters

DEFF Research Database (Denmark)

Zeuthen, Thomas; Gorraitz, Edurne; Her, Ka

2016-01-01

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

Preparation of calcium phosphate paste

International Nuclear Information System (INIS)

Mohd Reusmaazran Yusof; Norzita Yaacob; Idris Besar; Che Seman Mahmood; Rusnah Mustafa

2010-01-01

Calcium phosphate paste were prepared by mixing between calcium sodium potassium phosphate, Ca 2 NaK (PO 4 ) 2 (CSPP) and monocalcium phosphate monohydrate, Ca(H 2 PO 4 ) 2 .H 2 O (MCPM). CSPP were obtained by reaction between calcium hydrogen phosphate (CaHPO 4 ), potassium carbonate (K 2 CO 3 ) and sodium carbonate (Na 2 CO 3 ) in solid state sintering process followed by quenching in air at 1000 degree Celsius. The paste was aging in simulated body fluid (SBF) for 0.5, 1, 3, 6, 12, 24, 48 hrs, 3, 7 and 14 days. The morphological investigation indicated the formation of apatite crystal were first growth after 24 hours. The obvious growth of apatite crystal was shown at 3 days. The obvious growth of apatite crystal was shown in 7 and 14 days indicated the prediction of paste would have rapid reaction with bone after implantation. (author)

The phosphaturic effect of sodium bicarbonate and acetazolamide in dogs

Science.gov (United States)

Fulop, Milford; Brazeau, Paul

1968-01-01

Urinary inorganic phosphate excretion was studied before and during the administration of sodium bicarbonate and acetazolamide in dogs that were not given infusions of phosphate. The excretion fraction of filtered phosphate increased after sodium bicarbonate or acetazolamide was given. This phosphaturia was attributed to decreased tubular reabsorption of phosphate consequent to alkalinization of either tubular urine or cells. PMID:5645865

Effects of neutral sodium hydrogen phosphate on setting reaction and mechanical strength of hydroxyapatite putty.

Science.gov (United States)

Ishikawa, K; Miyamoto, Y; Takechi, M; Ueyama, Y; Suzuki, K; Nagayama, M; Matsumura, T

1999-03-05

The setting reaction and mechanical strength in terms of diametral tensile strength (DTS) of hydroxyapatite (HAP) putty made of tetracalcium phosphate, dicalcium phosphate anhydrous, and neutral sodium hydrogen phosphate (Na1.8H1.2PO4) solution containing 8 wt % sodium alginate were evaluated as a function of the Na1.8H1.2PO4 concentration. In one condition, HAP putty was placed in an incubator kept at 37 degrees C and 100% relative humidity. In the other condition, immediately after mixing HAP putty was immersed in serum kept at 37 degrees C. Longer setting times and lower DTS values were observed when HAP putty was immersed in serum regardless of the Na1.8H1.2PO4 concentration. The setting times of the HAP putty in both conditions became shorter with an increase in the Na1. 8H1.2PO4 concentration, reaching approximately 7-13 min when the Na1. 8H1.2PO4 concentration was 0.6 mol/L or higher. The DTS value of HAP putty was relatively constant (10 MPa) regardless of the Na1.8H1. 2PO4 concentration (0.2-1.0 mol/L) when HAP putty was kept in an incubator. In contrast, when HAP putty was immersed in serum, the DTS value was dependent on the Na1.8H1.2PO4 concentration. It increased with the Na1.8H1.2PO4 concentration and reached approximately 5 MPa when the Na1.8H1.2PO4 concentration was 0.6 mol/L, after which it showed a relatively constant DTS value. We therefore would recommend a HAP putty that uses 0.6 mol/L Na1.8H1. 2PO4 since at that concentration the putty's setting time (approximately 10 min) is proper for clinical use and it shows good DTS value (approximately 5 MPa) even when it is immersed in serum immediately after mixing. Copyright 1999 John Wiley & Sons, Inc.

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

International Nuclear Information System (INIS)

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

1987-01-01

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

Effect of sodium-glucose cotransporter 2 (SGLT2) inhibition on weight loss is partly mediated by liver-brain-adipose neurocircuitry.

Science.gov (United States)

Sawada, Yoshikazu; Izumida, Yoshihiko; Takeuchi, Yoshinori; Aita, Yuichi; Wada, Nobuhiro; Li, EnXu; Murayama, Yuki; Piao, Xianying; Shikama, Akito; Masuda, Yukari; Nishi-Tatsumi, Makiko; Kubota, Midori; Sekiya, Motohiro; Matsuzaka, Takashi; Nakagawa, Yoshimi; Sugano, Yoko; Iwasaki, Hitoshi; Kobayashi, Kazuto; Yatoh, Shigeru; Suzuki, Hiroaki; Yagyu, Hiroaki; Kawakami, Yasushi; Kadowaki, Takashi; Shimano, Hitoshi; Yahagi, Naoya

2017-11-04

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have both anti-diabetic and anti-obesity effects. However, the precise mechanism of the anti-obesity effect remains unclear. We previously demonstrated that the glycogen depletion signal triggers lipolysis in adipose tissue via liver-brain-adipose neurocircuitry. In this study, therefore, we investigated whether the anti-obesity mechanism of SGLT2 inhibitor is mediated by this mechanism. Diet-induced obese mice were subjected to hepatic vagotomy (HVx) or sham operation and loaded with high fat diet containing 0.015% tofogliflozin (TOFO), a highly selective SGLT2 inhibitor, for 3 weeks. TOFO-treated mice showed a decrease in fat mass and the effect of TOFO was attenuated in HVx group. Although both HVx and sham mice showed a similar level of reduction in hepatic glycogen by TOFO treatment, HVx mice exhibited an attenuated response in protein phosphorylation by protein kinase A (PKA) in white adipose tissue compared with the sham group. As PKA pathway is known to act as an effector of the liver-brain-adipose axis and activate triglyceride lipases in adipocytes, these results indicated that SGLT2 inhibition triggered glycogen depletion signal and actuated liver-brain-adipose axis, resulting in PKA activation in adipocytes. Taken together, it was concluded that the effect of SGLT2 inhibition on weight loss is in part mediated via the liver-brain-adipose neurocircuitry. Copyright © 2017 Elsevier Inc. All rights reserved.

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

Science.gov (United States)

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

2017-02-01

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

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

Science.gov (United States)

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

2014-08-01

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

Assessing climate change impacts on the rape stem weevil, Ceutorhynchus napi Gyll., based on bias- and non-bias-corrected regional climate change projections

Science.gov (United States)

Junk, J.; Ulber, B.; Vidal, S.; Eickermann, M.

2015-11-01

Agricultural production is directly affected by projected increases in air temperature and changes in precipitation. A multi-model ensemble of regional climate change projections indicated shifts towards higher air temperatures and changing precipitation patterns during the summer and winter seasons up to the year 2100 for the region of Goettingen (Lower Saxony, Germany). A second major controlling factor of the agricultural production is the infestation level by pests. Based on long-term field surveys and meteorological observations, a calibration of an existing model describing the migration of the pest insect Ceutorhynchus napi was possible. To assess the impacts of climate on pests under projected changing environmental conditions, we combined the results of regional climate models with the phenological model to describe the crop invasion of this species. In order to reduce systematic differences between the output of the regional climate models and observational data sets, two different bias correction methods were applied: a linear correction for air temperature and a quantile mapping approach for precipitation. Only the results derived from the bias-corrected output of the regional climate models showed satisfying results. An earlier onset, as well as a prolongation of the possible time window for the immigration of Ceutorhynchus napi, was projected by the majority of the ensemble members.

Assessing climate change impacts on the rape stem weevil, Ceutorhynchus napi Gyll., based on bias- and non-bias-corrected regional climate change projections.

Science.gov (United States)

Junk, J; Ulber, B; Vidal, S; Eickermann, M

2015-11-01

Agricultural production is directly affected by projected increases in air temperature and changes in precipitation. A multi-model ensemble of regional climate change projections indicated shifts towards higher air temperatures and changing precipitation patterns during the summer and winter seasons up to the year 2100 for the region of Goettingen (Lower Saxony, Germany). A second major controlling factor of the agricultural production is the infestation level by pests. Based on long-term field surveys and meteorological observations, a calibration of an existing model describing the migration of the pest insect Ceutorhynchus napi was possible. To assess the impacts of climate on pests under projected changing environmental conditions, we combined the results of regional climate models with the phenological model to describe the crop invasion of this species. In order to reduce systematic differences between the output of the regional climate models and observational data sets, two different bias correction methods were applied: a linear correction for air temperature and a quantile mapping approach for precipitation. Only the results derived from the bias-corrected output of the regional climate models showed satisfying results. An earlier onset, as well as a prolongation of the possible time window for the immigration of Ceutorhynchus napi, was projected by the majority of the ensemble members.

Intracellular sodium concentration and transport in red cells in essential hypertension, hyperthyroidism, pregnancy and hypokalemia.

Science.gov (United States)

Gless, K H; Sütterlin, U; Schaz, K; Schütz, V; Hunstein, W

1986-01-01

Intracellular sodium content ([Nai]), ouabain-sensitive ('Na-K ATPase') and ouabain-insensitive ('passive permeability') sodium efflux, Na-K cotransport and Na-Li ('Na-Na') countertransport were estimated in erythrocytes in 39 control subjects, 20 patients with essential hypertension, 14 patients with hypokalemia of renal or unknown etiology, 13 hyperthyroid patients and 19 pregnant women. In normokalemic essential hypertension there was only a moderate, but significant elevation of the activity of the Na-Li countertransport system. In the group of patients with hypokalemia, there was a significant increase of [Nai], ouabain-insensitive sodium efflux and Na-Li countertransport. In hyperthyroidism, a marked decrease of Na-Li countertransport was associated with a marked elevation of [Nai], in pregnancy an elevation of the Na-Li countertransport with a [Nai] 43% lower than the control values. The ouabain-sensitive sodium efflux was elevated in hyperthyroidism and hypokalemia, in which [Nai] was increased. In the control subjects there was a positive linear correlation between ouabain-sensitive sodium efflux and [Nai]. The sodium component of the Na-K cotransport was decreased to about one third of the unchanged furosemide-sensitive potassium component during pregnancy. The changes of cellular sodium metabolism in essential hypertension are of minor degree as compared to those in the other conditions studied. Cellular sodium metabolism in blood cells is influenced by thyroid hormones and metabolic disorders. Na-Li countertransport, i.e. Na-Na countertransport, seems to be involved in the regulation of [Nai]: an increase of its activity diminishes [Nai] (pregnancy); a decrease elevates [Nai] (hyperthyroidism). Ouabain-sensitive sodium efflux, i.e. 'Na-K ATPase', is mainly regulated by its substrate, [Nai].

IIA/B, Wound and Wrapped

International Nuclear Information System (INIS)

Danielsson, Ulf H.; Guijosa, Alberto; Kruczenski, Martin

2000-01-01

We examine the T-duality relation between 1+1 NCOS and the DLCQ limit of type IIA string theory. We show that, as long as there is a compact dimension, one can meaningfully define an 'NCOS' limit of IIB/A string theory even in the absence of D-branes (and even if there is no B-field). This yields a theory of closed strings with strictly positive winding, which is T-dual to DLCQ IIA/B without any D-branes. We call this the Type IIB/A Wound String Theory. The existence of decoupled sectors can be seen directly from the energy spectrum, and mirrors that of the DLCQ theory. It becomes clear then that all of the different p+1 NCOS theories are simply different states of this single Wound IIA/B theory which contain D-branes. We study some of the properties of this theory. In particular, we show that upon toroidal compactification, Wound string theory is U-dual to various Wrapped Brane theories which contain OM theory and the ODp theories as special states. (author)

{tau} - hydrogen phosphate of zirconia in sodium salt form and some of its properties; {tau} - hidrogenofosfato de zirconio en forma sodica y algunas de sus propiedades

Energy Technology Data Exchange (ETDEWEB)

Fernandez V, S.M.; Ordonez R, E. [ININ, 52045 Ocoyoacac, Estado de Mexico (Mexico)

2004-07-01

It is reported the obtaining and characterization in the sodium salt form of the {tau}-hydrogen phosphate of zirconium in sodium form, this compound it was synthesized, for a new technique developed in the laboratory of Dept. of Chemistry of the ININ. The characterization was carried out for XRD, IR, Sem and EDS the thermal gravimetric analysis is also reported. (Author)

Secretory Phospholipase A2-IIA and Cardiovascular Disease

DEFF Research Database (Denmark)

Holmes, Michael V; Simon, Tabassome; Exeter, Holly J

2013-01-01

This study sought to investigate the role of secretory phospholipase A2 (sPLA2)-IIA in cardiovascular disease.......This study sought to investigate the role of secretory phospholipase A2 (sPLA2)-IIA in cardiovascular disease....

PHYSICAL AND CHEMICAL STABILITY ANALYSIS OF COSMETIC MULTI- PLE EMULSIONS LOADED WITH ASCORBYL PALMITATE AND SODIUM ASCORBYL PHOSPHATE SALTS.

Science.gov (United States)

Khan, Hira; Akhtar, Naveed; Ali, Atif; Khan, Haji M Shoaib; Sohail, Muhammad; Naeem, Muhammad; Nawaz, Zarqa

2016-09-01

Stability of hydrophilic and lipophilic vitamin C derivatives for quenching synergistic antioxidant activities and to treat oxidative related diseases is a major issue. This study was aimed to encapsulate hydrophilic and lipophilic vitamin C derivatives (ascorbyl palmitate and sodium ascorbyl phosphate) as functional ingredients in a newly formulated multiple emulsion of the W//W type to attain the synergistic antioxidant effects and the resultant system's long term physical and chemical stability. Several multiple emulsions using the same concentration of emulsifiers but different concentrations of ascorbyl palmitate and sodium ascorbyl phosphate were developed. Three finally selected multiple emulsions (ME₁, ME₂ and ME₃) were evaluated for physical stability in terms of rheology, microscopy, conductivity, pH, and organoleptic characteristics under different storage conditions for 3 months. Chemical stability was determined by HPLC on Sykam GmbH HPLC system (Germany), equipped with a variable UV detector. Results showed that at accelerated storage conditions all the three multiple emulsions had shear thinning behavior of varying shear stress with no influence of location of functional ingredients in a carrier system. Conductivity values increased and pH values remained within the skin pH range for 3 months. Microscopic analysis showed an increase in globule size with the passage of time, especially at higher temperatures while decreased at low temperatures. Centrifugation test did not cause phase separation till the 45th day, but little effects after 2 months. Chemical stability analysis by HPLC at the end of 3 months showed that ascorbyl palmitate and sodium ascorbyl phosphate were almost stable in all multiple emulsions with no influence of their location in a carrier system. Multiple emulsions were found a stable carrier for hydrophilic and lipophilic vitamin C derivatives to enhance their desired effects. Considering that many topical formulations

Massive type IIA supergravity and E10

International Nuclear Information System (INIS)

Henneaux, M.; Kleinschmidt, A.; Persson, D.; Jamsin, E.

2009-01-01

In this talk we investigate the symmetry under E 10 of Romans' massive type IIA supergravity. We show that the dynamics of a spinning particle in a non-linear sigma model on the coset space E 10 /K(E 10 ) reproduces the bosonic and fermionic dynamics of massive IIA supergravity, in the standard truncation. In particular, we identify Romans' mass with a generator of E 10 that is beyond the realm of the generators of E 10 considered in the eleven-dimensional analysis, but using the same, underformed sigma model. As a consequence, this work provides a dynamical unification of the massless and massive versions of type IIA supergravity inside E 10 . (Abstract Copyright [2009], Wiley Periodicals, Inc.)

Sodium zirconium phosphate (NZP) as a host structure for nuclear waste immobilization: A review

International Nuclear Information System (INIS)

Scheetz, B.E.; Agrawal, D.K.; Breval, E.; Roy, R.

1994-01-01

Sodium zirconium phosphate [NZP] structural family, of which NaZr 2 P 3 O 12 is the parent composition, has been reviewed as a host ceramic waste form for nuclear waste immobilization. NZP compounds are characterized for their ionic conductivity, low thermal expansion and structural flexibility to accommodate a large number of multivalent ions. This latter property of the [NZP] structure allows the incorporation of almost all 42 nuclides present in a typical commercial nuclear waste. The leach studies of simulated waste forms based on NZP have shown reasonable resistance for the release of its constituents. The calculation of dissolution rates of NZP structure has demonstrated that it would take 20,000 times longer to dissolved NZP than quartz

Effect of Phosphate, Fluoride, and Nitrate on Gibbsite Dissolution Rate and Solubility

International Nuclear Information System (INIS)

Herting, Daniel L.

2014-01-01

Laboratory tests have been completed with simulated tank waste samples to investigate the effects of phosphate, fluoride, and nitrate on the dissolution rate and equilibrium solubility of gibbsite in sodium hydroxide solution at 22 and 40 deg C. Results are compared to relevant literature data and to computer model predictions. The presence of sodium nitrate (3 M) caused a reduction in the rate of gibbsite dissolution in NaOH, but a modest increase in the equilibrium solubility of aluminum. The increase in solubility was not as large, though, as the increase predicted by the computer model. The presence of phosphate, either as sodium phosphate or sodium fluoride phosphate, had a negligible effect on the rate of gibbsite dissolution, but caused a slight increase in aluminum solubility. The magnitude of the increased solubility, relative to the increase caused by sodium nitrate, suggests that the increase is due to ionic strength (or water activity) effects, rather than being associated with the specific ion involved. The computer model predicted that phosphate would cause a slight decrease in aluminum solubility, suggesting some Al-PO4 interaction. No evidence was found of such an interaction

Evaluation of Erythrocyte Sodium-22 Influx as a Laboratory Test for the Diagnosis of Essential Hypertension.

Science.gov (United States)

1982-12-01

hyperten- sion. Clin. Sci. (suppl) 61:13s-15s, 1981. 8. Canessa, M., Adragna , N., Solomon, H.S., Connolly, T.M., and Tosteson, D.C. Increased sodium...H., Adragna , N., Tosteson, D.C., Dagher, G., Garay, R., and Meyer, P. Na counter- transport and cotransport in human red cells: function...reference range for apparently healthy adults. Clin. Chem. 23:275-278, 1977. 16. Garay, R., Adragna , N., Canessa, M., and Tosteson, D. Outward sodium

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

Science.gov (United States)

Kurosaki, Eiji; Ogasawara, Hideaki

2013-07-01

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

SODIUM DI-N-DODECYL PHOSPHATE VESICLES IN AQUEOUS-SOLUTION - EFFECTS OF ETHANOL, PROPANOL, AND TETRAHYDROFURAN ON THE GEL TO LIQUID-PHASE TRANSITION

NARCIS (Netherlands)

BLANDAMER, MJ; BRIGGS, B; BUTT, MD; WATERS, M; CULLIS, PM; ENGBERTS, JBFN; HOEKSTRA, D; MOHANTY, RK

1994-01-01

For aqueous solutions containing vesicles formed by sodium di-n-dodecyl phosphate, the gel to liquid-crystal transition occurs near 35 degrees C, the temperature T-m. When ethanol is added, T-m decreases, but the scan shows evidence of several transitions as more alcohol is added. The effect of

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

Science.gov (United States)

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

2015-01-01

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

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™.

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

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Eun Namkoong

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

Investigation of the benzotriazole as addictive for carbon steel phosphating

International Nuclear Information System (INIS)

Annies, V.; Cunha, M.T.; Rodrigues, P.R.P.; Banczek, E.P.; Terada, M.

2010-01-01

This work studied the viability of substitution of sodium nitrite (NaNO 2 ) for benzotriazole (BTAH) in the zinc phosphate bath (PZn+NaNO 2 ) for phosphating of carbon steel (SAE 1010). The characterization of the samples was carried out by Scanning Electron Microscopy, Optical Microscopy and X-ray diffraction. The chemical composition was evaluated by Energy Dispersive Spectroscopy. The corrosion behavior of the samples was investigated by Open Circuit Potential, Electrochemical Impedance Spectroscopy and Anodic Potentiodynamic Polarization Curves in a 0.5 mol L -1 NaCl electrolyte. The experimental results showed that the phosphate layer obtained in the solution with benzotriazole (PZn+BTAH) presented better corrosion resistance properties than that obtained in sodium nitrite. The results demonstrated that the sodium nitrite NaNO 2 can be replaced by benzotriazole (BTAH) in zinc phosphate baths. (author)

Dynamical symmetry enhancement near IIA horizons

International Nuclear Information System (INIS)

Gran, University; Gutowski, J.; Kayani, University; Papadopoulos, G.

2015-01-01

We show that smooth type IIA Killing horizons with compact spatial sections preserve an even number of supersymmetries, and that the symmetry algebra of horizons with non-trivial fluxes includes an sl(2,ℝ) subalgebra. This confirms the conjecture of http://dx.doi.org/10.1007/JHEP11(2013)104 for type IIA horizons. As an intermediate step in the proof, we also demonstrate new Lichnerowicz type theorems for spin bundle connections whose holonomy is contained in a general linear group.

Crystal structure of MboIIA methyltransferase

OpenAIRE

Osipiuk, Jerzy; Walsh, Martin A.; Joachimiak, Andrzej

2003-01-01

DNA methyltransferases (MTases) are sequence-specific enzymes which transfer a methyl group from S-adenosyl-l-methionine (AdoMet) to the amino group of either cytosine or adenine within a recognized DNA sequence. Methylation of a base in a specific DNA sequence protects DNA from nucleolytic cleavage by restriction enzymes recognizing the same DNA sequence. We have determined at 1.74 Å resolution the crystal structure of a β-class DNA MTase MboIIA (M·MboIIA) from the bacterium Moraxella bovis,...

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

Science.gov (United States)

Wu, George; Yeung, Stanley; Chen, Frank

2017-01-01

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

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

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Masanori Wakisaka

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

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

Science.gov (United States)

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

2017-12-01

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

Second trimester amniotic fluid glucose, uric acid, phosphate, potassium, and sodium concentrations in relation to maternal pre-pregnancy BMI and birth weight centiles.

Science.gov (United States)

Fotiou, Maria; Michaelidou, Alexandra Maria; Athanasiadis, Apostolos P; Menexes, Georgios; Symeonidou, Maria; Koulourida, Vasiliki; Ganidou, Maria; Theodoridis, Theodoros D; Tarlatzis, Basil C

2015-05-01

To study the evolution profile of amniotic fluid (AF) glucose, uric acid, phosphate, potassium, and sodium, in the second trimester of pregnancy, and explore the possible relations between the concentration of these components and maternal, as well as neonatal characteristics. AF of 52 pregnant women was analyzed using an automatic multichannel analyzer. Maternal age, pre-pregnancy Body Mass Index (BMI), inter-pregnancy intervals, and smoking status were derived from questionnaires. Information on pregnancy and delivery was collected from medical records. Uric acid increased (r = 0.423, p pregnancy (r = -0.590, p pregnancy BMI was significantly correlated with AF uric acid concentration (r = 0.460, p sodium (r = 0.254, p = 0.070) levels. Multiple linear regression indicated that mid-trimester AF uric acid and phosphate levels were significantly related to birth weight centiles (R(2)( )= 0.345, p pregnancy BMI is significantly correlated with AF uric acid concentration, and (c) in appropriate for gestational age infants, AF phosphate and uric acid levels may serve as potential biomarkers of birth weight centiles. Further studies on AF composition may help to unravel the biochemical pathways underlying fetal development and could offer insight on the potential impact of maternal nutritional management on fetal growth regulation.

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

Science.gov (United States)

Jaraswekin, Saowanee; Prakongpan, Sompol; Bodmeier, Roland

2007-03-01

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

Secretory Phospholipase A(2)-IIA and Cardiovascular Disease

NARCIS (Netherlands)

Holmes, Michael V.; Simon, Tabassome; Exeter, Holly J.; Folkersen, Lasse; Asselbergs, Folkert W.; Guardiola, Montse; Cooper, Jackie A.; Palmen, Jutta; Hubacek, Jaroslav A.; Carruthers, Kathryn F.; Horne, Benjamin D.; Brunisholz, Kimberly D.; Mega, Jessica L.; Van Iperen, Erik P. A.; Li, Mingyao; Leusink, Maarten; Trompet, Stella; Verschuren, Jeffrey J. W.; Hovingh, G. Kees; Dehghan, Abbas; Nelson, Christopher P.; Kotti, Salma; Danchin, Nicolas; Scholz, Markus; Haase, Christiane L.; Rothenbacher, Dietrich; Swerdlow, Daniel I.; Kuchenbaecker, Karoline B.; Staines-Urias, Eleonora; Goel, Anuj; van 't Hooft, Ferdinand; Gertow, Karl; de Faire, Ulf; Panayiotou, Andrie G.; Tremoli, Elena; Baldassarre, Damiano; Veglia, Fabrizio; Holdt, Lesca M.; Beutner, Frank; Gansevoort, Ron T.; Navis, Gerjan J.; Mateo Leach, Irene; Breitling, Lutz P.; Brenner, Hermann; Thiery, Joachim; Dallmeier, Dhayana; Franco-Cereceda, Anders; Boer, Jolanda M. A.; Stephens, Jeffrey W.; Hofker, Marten H.; Tedgui, Alain; Hofman, Albert; Uitterlinden, Andre G.; Adamkova, Vera; Pitha, Jan; Onland-Moret, N. Charlotte; Cramer, Maarten J.; Nathoe, Hendrik M.; Spiering, Wilko; Klungel, Olaf H.; Kumari, Meena; Whincup, Peter H.; Morrow, David A.; Braund, Peter S.; Hall, Alistair S.; Olsson, Anders G.; Doevendans, Pieter A.; Trip, Mieke D.; Tobin, Martin D.; Hamsten, Anders; Watkins, Hugh; Koenig, Wolfgang; Nicolaides, Andrew N.; Teupser, Daniel; Day, Ian N. M.; Carlquist, John F.; Gaunt, Tom R.; Ford, Ian; Sattar, Naveed; Tsimikas, Sotirios; Schwartz, Gregory G.; Lawlor, Debbie A.; Morris, Richard W.; Sandhu, Manjinder S.; Poledne, Rudolf; Maitland-van der Zee, Anke H.; Khaw, Kay-Tee; Keating, Brendan J.; van der Harst, Pim; Price, Jackie F.; Mehta, Shamir R.; Yusuf, Salim; Witteman, Jaqueline C. M.; Franco, Oscar H.; Jukema, J. Wouter; de Knijff, Peter; Tybjaerg-Hansen, Anne; Rader, Daniel J.; Farrall, Martin; Samani, Nilesh J.; Kivimaki, Mika; Fox, Keith A. A.; Humphries, Steve E.; Anderson, Jeffrey L.; Boekholdt, S. Matthijs; Palmer, Tom M.; Eriksson, Per; Pare, Guillaume; Hingorani, Aroon D.; Sabatine, Marc S.; Mallat, Ziad; Casas, Juan P.; Talmud, Philippa J.

2013-01-01

Objectives This study sought to investigate the role of secretory phospholipase A(2) (sPLA(2))-IIA in cardiovascular disease. Background Higher circulating levels of sPLA(2)-IIA mass or sPLA(2) enzyme activity have been associated with increased risk of cardiovascular events. However, it is not

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...

Inhibitory effect of tanshinone IIA on rat hepatic stellate cells.

Directory of Open Access Journals (Sweden)

Ya-Wei Liu

Full Text Available Anti-inflammation via inhibition of NF-κB pathways in hepatic stellate cells (HSCs is one therapeutic approach to hepatic fibrosis. Tanshinone IIA (C19H18O3, Tan IIA is a lipophilic diterpene isolated from Salvia miltiorrhiza Bunge, with reported anti-inflammatory activity. We tested whether Tan IIA could inhibit HSC activation.The cell line of rat hepatic stellate cells (HSC-T6 was stimulated with lipopolysaccharide (LPS (100 ng/ml. Cytotoxicity was assessed by MTT assay. HSC-T6 cells were pretreated with Tan IIA (1, 3 and 10 µM, then induced by LPS (100 ng/ml. NF-κB activity was evaluated by the luciferase reporter gene assay. Western blotting analysis was performed to measure NF-κB-p65, and phosphorylations of MAPKs (ERK, JNK, p38. Cell chemotaxis was assessed by both wound-healing assay and trans-well invasion assay. Quantitative real-time PCR was used to detect gene expression in HSC-T6 cells.All concentrations of drugs showed no cytotoxicity against HSC-T6 cells. LPS stimulated NF-κB luciferase activities, nuclear translocation of NF-κB-p65, and phosphorylations of ERK, JNK and p38, all of which were suppressed by Tan IIA. In addition, Tan IIA significantly inhibited LPS-induced HSCs chemotaxis, in both wound-healing and trans-well invasion assays. Moreover, Tan IIA attenuated LPS-induced mRNA expressions of CCL2, CCL3, CCL5, IL-1β, TNF-α, IL-6, ICAM-1, iNOS, and α-SMA in HSC-T6 cells.Our results demonstrated that Tan IIA decreased LPS-induced HSC activation.

Massive IIA string theory and Matrix theory compactification

International Nuclear Information System (INIS)

Lowe, David A.; Nastase, Horatiu; Ramgoolam, Sanjaye

2003-01-01

We propose a Matrix theory approach to Romans' massive Type IIA supergravity. It is obtained by applying the procedure of Matrix theory compactifications to Hull's proposal of the massive Type IIA string theory as M-theory on a twisted torus. The resulting Matrix theory is a super-Yang-Mills theory on large N three-branes with a space-dependent noncommutativity parameter, which is also independently derived by a T-duality approach. We give evidence showing that the energies of a class of physical excitations of the super-Yang-Mills theory show the correct symmetry expected from massive Type IIA string theory in a lightcone quantization

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

Molecular cloning, characterization and expression analysis of two members of the Pht1 family of phosphate transporters in Glycine max.

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Zhaoyun Wu

Full Text Available BACKGROUND: Phosphorus is one of the macronutrients essential for plant growth and development. The acquisition and translocation of phosphate are pivotal processes of plant growth. In a large number of plants, phosphate uptake by roots and translocation within the plant are presumed to occur via a phosphate/proton cotransport mechanism. PRINCIPAL FINDINGS: We cloned two cDNAs from soybean (Glycine max, GmPT1 and GmPT2, which show homology to the phosphate/proton cotransporter PHO84 from the budding yeast Saccharomyces cerevisiae. The amino acid sequence of the products predicted from GmPT1 and GmPT2 share 61% and 63% identity, respectively, with the PHO84 in amino acid sequence. The deduced structure of the encoded proteins revealed 12 membrane-spanning domains with a central hydrophilic region. The molecular mass values are ∼58.7 kDa for GmPT1 and ∼58.6 kDa for GmPT2. Transiently expressed GFP-protein fusions provide direct evidence that the two Pi transporters are located in the plasma membrane. Uptake of radioactive orthophosphate by the yeast mutant MB192 showed that GmPT1 and GmPT2 are dependent on pH and uptake is reduced by the addition of uncouplers of oxidative phosphorylation. The K(m for phosphate uptake by GmPT1 and GmPT2 is 6.65 mM and 6.63 mM, respectively. A quantitative real time RT-PCR assay indicated that these two genes are expressed in the roots and shoots of seedlings whether they are phosphate-deficient or not. Deficiency of phosphorus caused a slight change of the expression levels of GmPT1 and GmPT2. CONCLUSIONS: The results of our experiments show that the two phosphate transporters have low affinity and the corresponding genes are constitutively expressed. Thereby, the two phosphate transporters can perform translocation of phosphate within the plant.

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

Science.gov (United States)

Adragna, Norma C; Lauf, Peter K

2007-12-01

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

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

Science.gov (United States)

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

2016-01-01

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

Position of nonmuscle myosin heavy chain IIA (NMMHC-IIA) mutations predicts the natural history of MYH9-related disease

DEFF Research Database (Denmark)

Pecci, A.; Panza, E.; Pujol-Moix, N.

2008-01-01

MYH9-related disease (MYH9-RD) is a rare autosomal-dominant disorder caused by mutations in MYH9, the gene for the heavy chain of nonmuscle myosin IIA (NMMHC-IIA). All patients present from birth with macrothrombocytopenia, but in infancy or adult life, some of them develop sensorineural deafness...... to 50 unrelated pedigrees. The risk of noncongenital manifestations associated with different genotypes was estimated over time by event-free survival analysis. We demonstrated that all subjects with mutations in the motor domain of NMMHC-IIA present with severe thrombocytopenia and develop nephritis...... and deafness before the age of 40 years, while those with mutations in the tail domain have a much lower risk of noncongenital complications and significantly higher platelet counts. We also evaluated the clinical course of patients with mutations in the four most frequently affected residues of NMMHC...

Maslinic acid modulates secreted phospholipase A2-IIA (sPLA2-IIA ...

Indian Academy of Sciences (India)

Wei Hsum Yap

2018-03-29

Mar 29, 2018 ... Further analysis revealed that sPLA2-IIA only induced modest LDL oxidation and that inhibitory .... COX-2, was also reduced in primary human chondrocyte, primary rat .... oxidation (4.34 nmol MDA/mg protein) compared to native ..... rheumatoid fibroblast-like synoviocyte arachidonic acid meta- bolism.

Tricalcium Phosphate Containing Sodium Hexametaphosphate as Polymer Suspension Stabilizer

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K. Rahbar Shamskar

2008-12-01

Full Text Available Tricalcium phosphate as hydroxyapatite is used as a suspension stabilizer in styrene polymerization process. Particle size of TCP plays an essential role in the particles’ size distribution and geometrical form of polystyrene products. As the particle size of TCP is reduced, there will be much better chance to engulf the styrene particles. The higher the number of TCP particles surrounding each styrene particle, the lesser will be their tendency to form a large particle after collision. Therefore, there will be higher percentages of spherical polystyrene with small particle size and narrower size distribution in the product. Experimental results have indicated that the addition of sodium hexametaphosphate (SHMP to the reaction mixture of lime and phosphoric acid, after drying the product by spray dryer, lead to decrease the size of TCP particles from ca. 5 μm (without SHMP to ca. 1.5 μm (with SHMP. In this study, the role of TCP containing SHMP as polymer suspension stabilizer and consequently the beads size of polystyrene is investigated in laboratory scale. The results show that despite addition of SHMP to the reaction mixture of lime and phosphoric acid decreases the TCP particles size and the mean bead size of the product of polystyrene become larger than the product prepared by TCP without SHMP.

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

DEFF Research Database (Denmark)

Zeuthen, Thomas; Macaulay, Nanna

2012-01-01

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

Sodium-glucose co-transporter 2 inhibitors in addition to insulin therapy for management of type 2 diabetes mellitus: A meta-analysis of randomized controlled trials.

Science.gov (United States)

Tang, Huilin; Cui, Wei; Li, Dandan; Wang, Tiansheng; Zhang, Jingjing; Zhai, Suodi; Song, Yiqing

2017-01-01

Given inconsistent trial results of sodium-glucose cotransporter 2 (SGLT2) inhibitors in addition to insulin therapy for treating type 2 diabetes mellitus (T2DM), a meta-analysis was performed to evaluate the efficacy and safety of this combination for T2DM by searching available randomized trials from PubMed, Embase, CENTRAL and ClinicalTrials.gov. Our meta-analysis included seven eligible placebo-controlled trials involving 4235 patients. Compared with placebo, SGLT2 inhibitor treatment was significantly associated with a mean reduction in HbA1c of -0.56%, fasting plasma glucose of -0.95 mmol/L, body weight of -2.63 kg and insulin dose of -8.79 IU, but an increased risk of drug-related adverse events by 36%, urinary tract infections by 29% and genital infections by 357%. No significant increase was observed in risk of overall adverse events [risk ratio (RR), 1.00], serious adverse events (RR, 0.90), adverse events leading to discontinuation (RR, 1.16), hypoglycaemia events (RR, 1.07) and severe hypoglycaemia events (RR, 1.24). No diabetic ketoacidosis events were reported. Further studies are needed to establish optimal combination type and dose. © 2016 John Wiley & Sons Ltd.

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.

Cellular ATP synthesis mediated by type III sodium-dependent phosphate transporter Pit-1 is critical to chondrogenesis.

Science.gov (United States)

Sugita, Atsushi; Kawai, Shinji; Hayashibara, Tetsuyuki; Amano, Atsuo; Ooshima, Takashi; Michigami, Toshimi; Yoshikawa, Hideki; Yoneda, Toshiyuki

2011-01-28

Disturbed endochondral ossification in X-linked hypophosphatemia indicates an involvement of P(i) in chondrogenesis. We studied the role of the sodium-dependent P(i) cotransporters (NPT), which are a widely recognized regulator of cellular P(i) homeostasis, and the downstream events in chondrogenesis using Hyp mice, the murine homolog of human X-linked hypophosphatemia. Hyp mice showed reduced apoptosis and mineralization in hypertrophic cartilage. Hyp chondrocytes in culture displayed decreased apoptosis and mineralization compared with WT chondrocytes, whereas glycosaminoglycan synthesis, an early event in chondrogenesis, was not altered. Expression of the type III NPT Pit-1 and P(i) uptake were diminished, and intracellular ATP levels were also reduced in parallel with decreased caspase-9 and caspase-3 activity in Hyp chondrocytes. The competitive NPT inhibitor phosphonoformic acid and ATP synthesis inhibitor 3-bromopyruvate disturbed endochondral ossification with reduced apoptosis in vivo and suppressed apoptosis and mineralization in conjunction with reduced P(i) uptake and ATP synthesis in WT chondrocytes. Overexpression of Pit-1 in Hyp chondrocytes reversed P(i) uptake and ATP synthesis and restored apoptosis and mineralization. Our results suggest that cellular ATP synthesis consequent to P(i) uptake via Pit-1 plays an important role in chondrocyte apoptosis and mineralization, and that chondrogenesis is ATP-dependent.

Gibbs free energy of transfer of a methylene group on {UCON + (sodium or potassium) phosphate salts} aqueous two-phase systems: Hydrophobicity effects

International Nuclear Information System (INIS)

Silverio, Sara C.; Rodriguez, Oscar; Teixeira, Jose A.; Macedo, Eugenia A.

2010-01-01

The Gibbs free energy of transfer of a suitable hydrophobic probe can be regarded as a measure of the relative hydrophobicity of the different phases. The methylene group (CH 2 ) can be considered hydrophobic, and thus be a suitable probe for hydrophobicity. In this work, the partition coefficients of a series of five dinitrophenylated-amino acids were experimentally determined, at 23 o C, in three different tie-lines of the biphasic systems: (UCON + K 2 HPO 4 ), (UCON + potassium phosphate buffer, pH 7), (UCON + KH 2 PO 4 ), (UCON + Na 2 HPO 4 ), (UCON + sodium phosphate buffer, pH 7), and (UCON + NaH 2 PO 4 ). The Gibbs free energy of transfer of CH 2 units were calculated from the partition coefficients and used to compare the relative hydrophobicity of the equilibrium phases. The largest relative hydrophobicity was found for the ATPS formed by dihydrogen phosphate salts.

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

OpenAIRE

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

2012-01-01

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

Superdualities, brane tensions and massive IIA/IIB duality

International Nuclear Information System (INIS)

Lavrinenko, I.V.; Lue, H.; Pope, C.N.; Stelle, K.S.

1999-01-01

The gauge transformations of p-form fields in supergravity theories acquire a non-commuting character when one introduces potentials both for the theory's original field strengths and for their duals. This has previously been shown in the 'doubled' formalism for maximal supergravities, where a generalised duality relation between original and dual field strengths replaces the equations of motion. In the doubled formalism, the gauge transformations generate a superalgebra, and the corresponding symmetries have accordingly been called 'superdualities'. The corresponding Noether charges form a representation of the cohomology ring on the space-time manifold. In this paper, we show that the gauge symmetry superalgebra implies certain non-trivial relations among the various p-brane tensions, which can straightforwardly be read off from the superalgebra commutation relations. This provides an elegant derivation of the brane-tension relations purely within a given theory, without the need to make use of duality relations between different theories, such as the type IIA/IIB T-duality, although the results are consistent with such dualities. We present the complete set of brane-tension relations in M-theory, in the type IIA and type IIB theories, and in all the lower-dimensional maximal supergravities. We also construct a doubled formalism for massive type IIA supergravity, and this enables us to obtain the brane-tension relations involving the D8-brane, purely within the framework of the massive IIA theory. We also obtain explicit transformations for the nine-dimensional T-duality between the massive type IIA theory and the Scherk-Schwarz reduced type IIB theory

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

DEFF Research Database (Denmark)

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

2010-01-01

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

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

Science.gov (United States)

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

2009-12-01

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

Analysis of tanshinone IIA induced cellular apoptosis in leukemia cells by genome-wide expression profiling

Directory of Open Access Journals (Sweden)

Liu Chang

2012-01-01

Full Text Available Abstract Background Tanshinone IIA (Tan IIA is a diterpene quinone extracted from the root of Salvia miltiorrhiza, a Chinese traditional herb. Although previous studies have reported the anti-tumor effects of Tan IIA on various human cancer cells, the underlying mechanisms are not clear. The current study was undertaken to investigate the molecular mechanisms of Tan IIA's apoptotic effects on leukemia cells in vitro. Methods The cytotoxicity of Tan IIA on different types of leukemia cell lines was evaluated by the 3-[4,5-dimethylthiazol-2,5]-diphenyl tetrazolium bromide (MTT assay on cells treated without or with Tan IIA at different concentrations for different time periods. Cellular apoptosis progression with and without Tan IIA treatment was analyzed by Annexin V and Caspase 3 assays. Gene expression profiling was used to identify the genes regulated after Tan IIA treatment and those differentially expressed among the five cell lines. Confirmation of these expression regulations was carried out using real-time quantitative PCR and ELISA. The antagonizing effect of a PXR inhibitor L-SFN on Tan IIA treatment was tested using Colony Forming Unit Assay. Results Our results revealed that Tan IIA had different cytotoxic activities on five types of leukemia cells, with the highest toxicity on U-937 cells. Tan IIA inhibited the growth of U-937 cells in a time- and dose-dependent manner. Annexin V and Caspase-3 assays showed that Tan IIA induced apoptosis in U-937 cells. Using gene expression profiling, 366 genes were found to be significantly regulated after Tan IIA treatment and differentially expressed among the five cell lines. Among these genes, CCL2 was highly expressed in untreated U-937 cells and down-regulated significantly after Tan IIA treatment in a dose-dependent manner. RT-qPCR analyses validated the expression regulation of 80% of genes. Addition of L- sulforaphane (L-SFN, an inhibitor of Pregnane × receptor (PXR significantly

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

Science.gov (United States)

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

2017-12-01

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

Japanese contributions to IAEA INTOR workshop, phase IIA

International Nuclear Information System (INIS)

Naruse, Yuji; Hiraoka, Toru; Tanaka, Kichizo

1982-11-01

Tritium breeding blanket is incorporated in the INTOR design based on economic and tritium availability considerations. In Phase IIA, critical issues on 'Tritium', which were identified during the Phase I Workshop, were investigated. Main objectives of Phase IIA are to develop a tritium breeding blanket and to evaluate tritium containment. Data base assessments of tritium containment were made. The design of the tritium breeding blanket was also revised. (author)

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

DEFF Research Database (Denmark)

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

2001-01-01

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

Chemically durable iron phosphate glasses for vitrifying sodium bearing waste (SBW) using conventional and cold crucible induction melting (CCIM) techniques

Energy Technology Data Exchange (ETDEWEB)

Kim, C.W. E-mail: cheol@umr.edu; Ray, C.S.; Zhu, D.; Day, D.E.; Gombert, D.; Aloy, A.; Mogus-Milankovic, A.; Karabulut, M

2003-11-01

A simulated sodium bearing waste (SBW) was successfully vitrified in iron phosphate glasses (IPG) at a maximum waste loading of 40 wt% using conventional and cold crucible induction melting (CCIM) techniques. No sulfate segregation or crystalline phases were detectable in the IPG when examined by SEM and XRD. The IPG wasteforms containing 40 wt% SBW satisfy current DOE requirements for aqueous chemical durability as evaluated from their bulk dissolution rate (D{sub R}), product consistency test, and vapor hydration test. The fluid IPG wasteforms can be melted at a relatively low temperature (1000 deg. C) and for short times (<6 h). These properties combined with a significantly higher waste loading, and the feasibility of CCIM melting offer considerable savings in time, energy, and cost for vitrifying the SBW stored at the Idaho National Engineering and Environmental Laboratory in iron phosphate glasses.

The chemistry of high temperature phosphate solutions in relation to steam generation

International Nuclear Information System (INIS)

Broadbent, D.; Lewis, G.G.; Wetton, E.A.M.

1978-01-01

The problems associated with the use of phosphate for chemical treatment of the P.W.R. secondary circuit have prompted renewed interest in the physical chemistry of these solutions. Solubility and phase studies have been carried out at 250, 300 and 350 0 C with solutions having sodium to phosphate ratios from 1.0 to above 3.0. A solid phase of ratio about 2.8 exists in equilibrium with a wide range of saturated solution compositions at each temperature. Invariant points at which three phases are in equilibrium have been identified and at the two higher temperatures a region of liquid-liquid immiscibility occurs. Phase diagrams have been constructed for each temperature from which it is possible to predict the compositional changes occurring during the isothermal evaporation process. The corrosivity of these phosphate solutions to a range of steel alloys is being studied, the results reported in the present work, however, are confined to mild steel in the temperature and phosphate composition ranges of the phase studies. The corrosion of mild steel is generally considerably less than in sodium hydroxide solutions of equivalent concentration. The dependence of corrosion rate on sodium and phosphate concentrations in not readily explicable in terms of the solubility and phase studies and it is thought that the solubility of iron in the phosphate solutions is an important rate-determining factor since several complex compounds containing sodium, phosphorus and ferrous iron are present in the corrosion films. (author)

An integrated field-effect microdevice for monitoring membrane transport in Xenopus laevis oocytes via lateral proton diffusion.

Directory of Open Access Journals (Sweden)

Daniel Felix Schaffhauser

Full Text Available An integrated microdevice for measuring proton-dependent membrane activity at the surface of Xenopus laevis oocytes is presented. By establishing a stable contact between the oocyte vitelline membrane and an ion-sensitive field-effect (ISFET sensor inside a microperfusion channel, changes in surface pH that are hypothesized to result from facilitated proton lateral diffusion along the membrane were detected. The solute diffusion barrier created between the sensor and the active membrane area allowed detection of surface proton concentration free from interference of solutes in bulk solution. The proposed sensor mechanism was verified by heterologously expressing membrane transport proteins and recording changes in surface pH during application of the specific substrates. Experiments conducted on two families of phosphate-sodium cotransporters (SLC20 & SLC34 demonstrated that it is possible to detect phosphate transport for both electrogenic and electroneutral isoforms and distinguish between transport of different phosphate species. Furthermore, the transport activity of the proton/amino acid cotransporter PAT1 assayed using conventional whole cell electrophysiology correlated well with changes in surface pH, confirming the ability of the system to detect activity proportional to expression level.

Sodium/bicarbonate cotransporter NBCn1/slc4a7 increases cytotoxicity in magnesium depletion in primary cultures of hippocampal neurons

Science.gov (United States)

Cooper, Deborah S.; Yang, Han Soo; He, Peijian; Kim, Eunjin; Rajbhandari, Ira; Yun, Chris C.; Choi, Inyeong

2009-01-01

Growing evidence suggests that pharmacological inhibition of Na/H exchange and Na/HCO3 transport provides protection against damage or injury in cardiac ischemia. In this study, we examined the contribution of the sodium/bicarbonate cotransporter NBCn1 (slc4a7) to cytotoxicity in cultured hippocampal neurons of rats. In neurons exposed to extracellular pH (pHo) ranging from 6.2 to 8.3, NBCn1 protein expression increased by fivefold at pH < 6.5 compared to the expression at pHo 7.4. At pHo 6.5, the intracellular pH of neurons was ~1 unit lower than that at pH 7.4. Immunochemistry showed a marked increase in NBCn1 immunofluorescence in plasma membranes and cytosol of the soma as well as in dendrites, at pHo 6.5. NBCn1 expression also increased by 40% in a prolonged Mg2+-free incubation at normal pHo. Knockdown of NBCn1 in neurons had negligible effect on cell viability. The effect of NBCn1 knockdown on cytotoxicity was then determined by exposing neurons to 0.5 mM glutamate for 10 min and measuring lactate dehydrogenase (LDH) release from neurons. Compared to normal incubation (pHo 7.2 for 6 h) after glutamate exposure, acidic incubation (pHo 6.3 for 6 h) reduced cytotoxicity by 75% for control neurons and 78% for NBCn1-knockdown neurons. Thus, both controls and knockdown neurons showed acidic protection from cytotoxicity. However, in Mg2+-free incubation after glutamate exposure, NBCn1 knockdown progressively attenuated cytotoxicity. This attenuation was unaffected by acidic preincubation before glutamate exposure. We conclude that NBCn1 has a dynamic upregulation in low pHo and Mg2+ depletion. NBCn1 is not required for acidic protection, but increases cytotoxicity in Mg2+-free conditions. PMID:19170751

Effect of Sodium-Glucose Cotransport-2 Inhibitors on Blood Pressure in People With Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis of 43 Randomized Control Trials With 22 528 Patients.

Science.gov (United States)

Mazidi, Mohsen; Rezaie, Peyman; Gao, Hong-Kai; Kengne, Andre Pascal

2017-05-25

The sodium-glucose cotransporter 2 (SGLT2) inhibitors are a class of oral hypoglycemic agents. We undertake a systematic review and meta-analysis of prospective studies to determine the effect of SGLT2 on blood pressure (BP) among individuals with type 2 diabetes mellitus. PubMed-Medline, Web of Science, Cochrane Database, and Google Scholar databases were searched to identify trial registries evaluating the impact of SGLT2 on BP. Random-effects models meta-analysis was used for quantitative data synthesis. The meta-analysis indicated a significant reduction in systolic BP following treatment with SGLT2 (weighted mean difference -2.46 mm Hg [95% CI -2.86 to -2.06]). The weighted mean differences for the effect on diastolic BP was -1.46 mm Hg (95% CI -1.82 to -1.09). In these subjects the weighted mean difference effects on serum triglycerides and total cholesterol were -2.08 mg/dL (95% CI -2.51 to -1.64) and 0.77 mg/dL (95% CI 0.33-1.21), respectively. The weighted mean differences for the effect of SGLT2 on body weight was -1.88 kg (95% CI -2.11 to -1.66) across all studies. These findings were robust in sensitivity analyses. Treatment with SGLT2 glucose cotransporter inhibitors therefore has beneficial off-target effects on BP in patients with type 2 diabetes mellitus and may also be of value in improving other cardiometabolic parameters including lipid profile and body weight in addition to their expected effects on glycemic control. However, our findings should be interpreted with consideration for the moderate statistical heterogeneity across the included studies. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Phosphate analysis of natural sausage casings preserved in brines with phosphate additives as inactivating agent - Method validation.

Science.gov (United States)

Wijnker, J J; Tjeerdsma-van Bokhoven, J L M; Veldhuizen, E J A

2009-01-01

Certain phosphates have been identified as suitable additives for the improvement of the microbial and mechanical properties of processed natural sausage casings. When mixed with NaCl (sodium chloride) and used under specific treatment and storage conditions, these phosphates are found to prevent the spread of foot-and-mouth disease and classical swine fever via treated casings. The commercially available Quantichrom™ phosphate assay kit has been evaluated as to whether it can serve as a reliable and low-tech method for routine analysis of casings treated with phosphate. The outcome of this study indicates that this particular assay kit has sufficient sensitivity to qualitatively determine the presence of phosphate in treated casings without interference of naturally occurring phosphate in salt used for brines in which casings are preserved.

Effects of phosphate environments on turbine materials: preliminary results

International Nuclear Information System (INIS)

Chen, M.C.; Shalvoy, R.S.; Gould, G.C.

1985-01-01

Stress corrosion cracking (SCC) is a serious hazard to large steam turbines. In many cases, this cracking is thought caused by concentrated deposits of caustics or chlorides, formed from the steam by concentrating mechanisms. To minimize the likelihood of forming these corrosive deposits, turbine manufacturers recommend that the levels of contaminants in the steam be maintained at low levels. The steam purity needed to prevent the formation of corrosive deposits is at present uncertain. As an aid in judging the steam purity needed to avoid corrosive deposits, the General Electric Company surveyed the utility industry to determine current feedwater practices, the levels of steam purity attained, and the nature of the corrosion problems encountered. One hypothesis to explain the lower corrosivity of steam from drum boilers concerns the sodium phosphate to compounds commonly added to drum boiler water for pH control. To test this hypothesis, the present program was undertaken to study the effect of sodium phosphate on the corrosivity of the two most common corrosive turbine deposits, sodium chloride and sodium hydroxide. Four turbine materials - a rotor steel, a disc steel, and two turbine blade steels - were chosen for this study. The results from the first half of a two-year project are described. So far the corrosivity of the deposits without phosphate has been determined. Work to determine the corrosivity of deposits with phosphate is presently under way and only the electrochemical test results are discussed

Passive water and ion transport by cotransporters

DEFF Research Database (Denmark)

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

1999-01-01

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

Compactifications of IIA supergravity on SU(2)-structure manifolds

Energy Technology Data Exchange (ETDEWEB)

Spanjaard, B.

2008-07-15

In this thesis, we study compactifications of type IIA supergravity on six-dimensional manifolds with an SU(2)-structure. A general study of six-dimensional manifolds with SU(2)-structure shows that IIA supergravity compactified on such a manifold should yield a four-dimensional gauged N=4 supergravity. We explicitly derive the bosonic spectrum, gauge transformations and action for IIA supergravity compactified on two different manifolds with SU(2)-structure, one of which also has an H{sup (3)}{sub 10}-flux, and confirm that the resulting four-dimensional theories are indeed N=4 gauged supergravities. In the second chapter, we study an explicit construction of a set of SU(2)-structure manifolds. This construction involves a Scherk-Schwarz duality twist reduction of the half-maximal six-dimensional supergravity obtained by compactifying IIA supergravity on a K3. This reduction results in a gauged N=4 four-dimensional supergravity, where the gaugings can be divided into three classes of parameters. We relate two of the classes to parameters we found before, and argue that the third class of parameters could be interpreted as a mirror flux. (orig.)

Removal of phosphate and nitrate from aqueous solution using ...

African Journals Online (AJOL)

The aim of the present study was the removal of phosphate and nitrate by sodium alginate seagrass (Cymodocea rotundata) beads from aqueous solutions. The adsorption characteristics of phosphate and nitrate on the seagrass beads were optimized under different operational parameters like adsorbent dosage, initial ...

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.

Intronic deletions in the SLC34A3 gene: A cautionary tale for mutation analysis of hereditary hypophosphatemic rickets with hypercalciuria

OpenAIRE

Ichikawa, Shoji; Tuchman, Shamir; Padgett, Leah R.; Gray, Amie K.; Baluarte, H. Jorge; Econs, Michael J.

2013-01-01

Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is a rare metabolic disorder, characterized by hypophosphatemia, variable degrees of rickets/osteomalacia, and hypercalciuria secondary to increased serum 1,25-dihydroxyvitamin D [1,25(OH)2D] levels. HHRH is caused by mutations in the SLC34A3 gene, which encodes sodium-phosphate co-transporter type IIc. A 6 ½-year-old female presented with a history of nephrolithiasis. Her metabolic evaluation revealed increased 24- hour urine cal...

Long-term progress prediction for the carbon steel corrosion in diluted artificial seawater with and without zinc / sodium carbonate mixed phosphate

International Nuclear Information System (INIS)

Fujii, Kazumi; Ishioka, Shinichi; Iwanami, Masaru; Kaneko, Tetsuji; Tanaka, Norihiko; Kawaharada, Yoshiyuki; Yokoyama, Yutaka; Umehara, Ryuji; Kato, Chiaki; Ueno, Fumiyoshi; Fukaya, Yuichi; Kumaga, Katsuhiko

2017-01-01

The Fukushima Daiichi Nuclear Power Plants (1F) were damaged by an unprecedented severe accident in the great east Japan earthquake on 11th, March, 2011, and seawater and fresh water were injected as an emergency countermeasure for the core cooling. The primary containment vessels (PCVs), made of carbon steel, were exposed to seawater and fresh water, and have had the possibility of corrosion. The PCVs of 1F are the most important equipment for the core cooling and removal of the fuel debris, the structural integrity of the PCV must be maintained until decommissioning. Therefore, evaluation of PCV carbon steel corrosion behavior is important, as well as evaluation of corrosion inhibitors as one of the corrosion protection methods. In this study, long-term immersion corrosion tests for up to 10000 hours were performed in diluted artificial seawater simulating 1F with and without zinc / sodium carbonate mixed phosphate. Based on the long-term immersion corrosion test results, diagnosis method of the reduction in plate thickness of the nuclear vessel was examined. The validity of the existing corrosion progress models following parabolic rate law was confirmed. The corrosion progress models were also applicable to the corrosion inhibited condition adding zinc / sodium carbonate mixed phosphate. It was found that the corrosion rate of carbon steel drastically fell down by adding this corrosion inhibitor. (author)

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

Science.gov (United States)

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

2013-10-01

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

Effects of diuretics on sodium-dependent glucose cotransporter 2 inhibitor-induced changes in blood pressure in obese rats suffering from the metabolic syndrome.

Science.gov (United States)

Rahman, Asadur; Kittikulsuth, Wararat; Fujisawa, Yoshihide; Sufiun, Abu; Rafiq, Kazi; Hitomi, Hirofumi; Nakano, Daisuke; Sohara, Eisei; Uchida, Shinichi; Nishiyama, Akira

2016-05-01

Experiments were carried out to investigate whether diuretics (hydrochlorothiazide + furosemide) impact on the effects of a sodium-dependent glucose cotransporter 2 (SGLT2) inhibitor on glucose metabolism and blood pressure (BP) in metabolic syndrome SHR/NDmcr-cp(+/+) rats (SHRcp). Male 13-week-old SHRcp were treated with: vehicle; the SGLT2-inhibitor luseogliflozin (10 mg/kg per day); diuretics (hydrochlorothiazide; 10 mg/kg/day + furosemide; 5 mg/kg per day); or luseogliflozin + diuretics (n = 5-8 for each group) daily by oral gavage for 5 weeks. BP and glucose metabolism were evaluated by a telemetry system and oral glucose tolerance test, respectively. Vehicle-treated SHRcp developed nondipper type hypertension (dark vs. light-period mean arterial pressure: 148.6 ± 0.7 and 148.0 ± 0.7 mmHg, respectively, P = 0.2) and insulin resistance. Compared with vehicle-treated animals, luseogliflozin-treated rats showed an approximately 4000-fold increase in urinary excretion of glucose and improved glucose metabolism. Luseogliflozin also significantly decreased BP and turned the circadian rhythm of BP from a nondipper to dipper pattern (dark vs. light-period mean arterial pressure: 138.0 ± 1.6 and 132.0 ± 1.3 mmHg, respectively, P diuretics did not influence luseogliflozin-induced improvement of glucose metabolism and circadian rhythm of BP in SHRcp. These data suggest that a SGLT2 inhibitor elicits its beneficial effects on glucose metabolism and hypertension in study participants with metabolic syndrome undergoing treatment with diuretics.

Comparison of Clinical Efficacies of Preoperatively Initiated Naproxen Sodium-Codeine Phosphate in Combination, Diclofenac Potassium, and Benzydamine Hydrochloride for Pain, Edema, and Trismus After Extraction of Impacted Lower Third Molar: A Randomized Double-Blind Study.

Science.gov (United States)

Cigerim, Levent; Eroglu, Cennet Neslihan

2018-03-01

The aim of this study was to compare the clinical efficacies of naproxen sodium-codeine phosphate in combination, benzydamine hydrochloride, and diclofenac potassium for pain, edema, and trismus after lower third molar extraction. Ninety healthy volunteers in whom impacted third molar extraction was indicated were randomly distributed into 3 groups. One hour before the tooth-extraction process, patients were administered one of the following drugs: naproxen sodium, 550 mg, and codeine phosphate, 30 mg, in a tablet; diclofenac potassium, 50 mg, in a coated pill; or benzydamine hydrochloride, 50 mg, in a coated pill. Pain assessment was conducted via a visual analog scale; edema assessment, by measuring the distances between predetermined facial landmarks; and trismus assessment, by measuring interincisal distance. Regarding rescue analgesics (paracetamol, 500 mg), the number and time of use by patients were recorded. Naproxen sodium-codeine phosphate was more effective for pain, edema, and trismus than diclofenac potassium and benzydamine hydrochloride (P hydrochloride yielded similar clinical responses to diclofenac potassium (P > .05). No drug-related side effects were observed. Naproxen sodium-codeine phosphate constitutes the drug of choice after the extraction of a patient's impacted lower third molar. Benzydamine hydrochloride has similar efficacy to diclofenac potassium, and it can be used as a nonsteroidal anti-inflammatory analgesic drug. Copyright © 2017 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Value of urinary topoisomerase-IIA cell-free DNA for diagnosis of bladder cancer.

Science.gov (United States)

Kim, Ye-Hwan; Yan, Chunri; Lee, Il-Seok; Piao, Xuan-Mei; Byun, Young Joon; Jeong, Pildu; Kim, Won Tae; Yun, Seok-Joong; Kim, Wun-Jae

2016-03-01

Topoisomerase-II alpha (TopoIIA ), a DNA gyrase isoform that plays an important role in the cell cycle, is present in normal tissues and various human cancers, and can show altered expression in both. The aim of the current study was to examine the value of urinary TopoIIA cell-free DNA as a noninvasive diagnosis of bladder cancer (BC). Two patient cohorts were examined. Cohort 1 (73 BC patients and seven controls) provided bladder tissue samples, whereas cohort 2 (83 BC patients, 54 nonmalignant hematuric patients, and 61 normal controls) provided urine samples. Real-time quantitative polymerase chain reaction was used to measure expression of TopoIIA mRNA in tissues and TopoIIA cell-free DNA in urine samples. The results showed that expression of TopoIIA mRNA in BC tissues was significantly higher than that in noncancer control tissues (pbladder cancer (MIBC) when compared with nonmuscle invasive bladder cancer (NMIBC) (p=0.002). Receiver operating characteristics (ROC) curve analysis was performed to examine the sensitivity/specificity of urinary TopoIIA cell-free DNA for diagnosing BC, NMIBC, and MIBC. The areas under the ROC curve for BC, NMIBC, and MIBC were 0.741, 0.701, and 0.838, respectively. In summary, the results of this study provide evidence that cell-free TopoIIA DNA may be a potential biomarker for BC.

Long-term treatment with the sodium glucose cotransporter 2 inhibitor, dapagliflozin, ameliorates glucose homeostasis and diabetic nephropathy in db/db mice.

Directory of Open Access Journals (Sweden)

Naoto Terami

Full Text Available Inhibition of sodium glucose cotransporter 2 (SGLT2 has been reported as a new therapeutic strategy for treating diabetes. However, the effect of SGLT2 inhibitors on the kidney is unknown. In addition, whether SGLT2 inhibitors have an anti-inflammatory or antioxidative stress effect is still unclear. In this study, to resolve these issues, we evaluated the effects of the SGLT2 inhibitor, dapagliflozin, using a mouse model of type 2 diabetes and cultured proximal tubular epithelial (mProx24 cells. Male db/db mice were administered 0.1 or 1.0 mg/kg of dapagliflozin for 12 weeks. Body weight, blood pressure, blood glucose, hemoglobin A1c, albuminuria and creatinine clearance were measured. Mesangial matrix accumulation and interstitial fibrosis in the kidney and pancreatic β-cell mass were evaluated by histological analysis. Furthermore, gene expression of inflammatory mediators, such as osteopontin, monocyte chemoattractant protein-1 and transforming growth factor-β, was evaluated by quantitative reverse transcriptase-PCR. In addition, oxidative stress was evaluated by dihydroethidium and NADPH oxidase 4 staining. Administration of 0.1 or 1.0 mg/kg of dapagliflozin ameliorated hyperglycemia, β-cell damage and albuminuria in db/db mice. Serum creatinine, creatinine clearance and blood pressure were not affected by administration of dapagliflozin, but glomerular mesangial expansion and interstitial fibrosis were suppressed in a dose-dependent manner. Dapagliflozin treatment markedly decreased macrophage infiltration and the gene expression of inflammation and oxidative stress in the kidney of db/db mice. Moreover, dapagliflozin suppressed the high-glucose-induced gene expression of inflammatory cytokines and oxidative stress in cultured mProx24 cells. These data suggest that dapagliflozin ameliorates diabetic nephropathy by improving hyperglycemia along with inhibiting inflammation and oxidative stress.

Supersymmetric geometries of IIA supergravity III

International Nuclear Information System (INIS)

Gran, Ulf; Papadopoulos, George; Schultz, Christian von

2016-01-01

We find that (massive) IIA backgrounds that admit a G 2 ⋉ℝ 8 invariant Killing spinor must exhibit a null Killing vector field which leaves the Killing spinor invariant and that the rotation of the Killing vector field satisfies a certain g 2 instanton condition. This result together with those in http://dx.doi.org/10.1007/JHEP05(2014)024 and http://dx.doi.org/10.1007/JHEP12(2015)113 complete the classification of geometries of all (massive) IIA backgrounds that preserve one supersymmetry. We also explore the geometry of a class of backgrounds which admit a G 2 ⋉ℝ 8 invariant Killing spinor and where in addition an appropriate 1-form bilinear vanishes. In all cases, we express the fluxes of the theory in terms of the geometry.

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

DEFF Research Database (Denmark)

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

2000-01-01

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

Effects of Incretin-Based Therapies and SGLT2 Inhibitors on Skeletal Health.

Science.gov (United States)

Egger, Andrea; Kraenzlin, Marius E; Meier, Christian

2016-12-01

Anti-diabetic drugs are widely used and are essential for adequate glycemic control in patients with type 2 diabetes. Recently, marketed anti-diabetic drugs include incretin-based therapies (GLP-1 receptor agonists and DPP-4 inhibitors) and sodium-glucose co-transporter 2 (SGLT2) inhibitors. In contrast to well-known detrimental effects of thiazolidinediones on bone metabolism and fracture risk, clinical data on the safety of incretin-based therapies is limited. Based on meta-analyses of trials investigating the glycemic-lowering effect of GLP-1 receptor agonists and DPP4 inhibitors, it seems that incretin-based therapies are not associated with an increase in fracture risk. Sodium-glucose co-transporter 2 inhibitors may alter calcium and phosphate homeostasis as a result of secondary hyperparathyroidism induced by increased phosphate reabsorption. Although these changes may suggest detrimental effects of SGLT-2 inhibitors on skeletal integrity, treatment-related direct effects on bone metabolism seem unlikely. Observed changes in BMD, however, seem to result from increased bone turnover in the early phase of drug-induced weight loss. Fracture risk, which is observed in older patients with impaired renal function and elevated cardiovascular disease risk treated with SGLT2 inhibitors, seems to be independent of direct effects on bone but more likely to be associated with falls and changes in hydration status secondary to osmotic diuresis.

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

Science.gov (United States)

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

2018-02-15

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

The antitumor natural product tanshinone IIA inhibits protein kinase C and acts synergistically with 17-AAG.

Science.gov (United States)

Lv, Chao; Zeng, Hua-Wu; Wang, Jin-Xin; Yuan, Xing; Zhang, Chuang; Fang, Ting; Yang, Pei-Ming; Wu, Tong; Zhou, Yu-Dong; Nagle, Dale G; Zhang, Wei-Dong

2018-02-07

Tanshinone IIA (Tan IIA), the primary bioactive compound derived from the traditional Chinese medicine (TCM) Salvia miltiorrhiza Bunge, has been reported to possess antitumor activity. However, its antitumor mechanisms are not fully understood. To resolve the potential antitumor mechanism(s) of Tan IIA, its gene expression profiles from our database was analyzed by connectivity map (CMAP) and the CMAP-based mechanistic predictions were confirmed/validated in further studies. Specifically, Tan IIA inhibited total protein kinase C (PKC) activity and selectively suppressed the expression of cytosolic and plasma membrane PKC isoforms ζ and ε. The Ras/MAPK pathway that is closely regulated by the PKC signaling is also inhibited by Tan IIA. While Tan IIA did not inhibit heat shock protein 90 (Hsp90), it synergistically enhanced the antitumor efficacy of the Hsp90 inhibitors 17-AAG and ganetespib in human breast cancer MCF-7 cells. In addition, Tan IIA significantly inhibited PI3K/Akt/mTOR signaling, and induced both cell cycle arrest and autophagy. Collectively, these studies provide new insights into the molecular mechanisms responsible for antitumor activity of Tan IIA.

Anti-Inflammatory and Immunomodulatory Mechanism of Tanshinone IIA for Atherosclerosis

Directory of Open Access Journals (Sweden)

Zhuo Chen

2014-01-01

Full Text Available Tanshinone IIA (Tan II A is widely used in the treatment of cardiovascular diseases as an active component of Salvia miltiorrhiza Bunge. It has been demonstrated to have pleiotropic effects for atherosclerosis. From the anti-inflammatory and immunomodulatory mechanism perspective, this paper reviewed major progresses of Tan IIA in antiatherosclerosis research, including immune cells, antigens, cytokines, and cell signaling pathways.

Evaluation of the stability of enterovirus 71 virus-like particle.

Science.gov (United States)

Lin, Shih-Yeh; Chung, Yao-Chi; Chiu, Hsin-Yi; Chi, Wei-Kuang; Chiang, Bor-Luen; Hu, Yu-Chen

2014-03-01

Enterovirus 71 (EV71) is responsible for the outbreaks of hand-foot-and-mouth disease that caused significant mortality in children, but no vaccine is available yet. EV71 virus-like particle (VLP) is the empty capsid consisting of viral structural proteins but can elicit potent immune responses, rendering VLP a promising EV71 vaccine candidate. To evaluate whether VLP remains stable after long-term storage, which is crucial for advancing the VLP vaccine to the clinical setting, we evaluated the effects of NaCl concentration, buffers and temperatures on the VLP stability. We first validated the use of dynamic light scattering (DLS) for measuring the hydrodynamic diameter (≈30-35 nm) of VLP, which was close to the VLP diameter (≈25-27 nm) as measured by transmission electron microscopy (TEM). Using these techniques, we found that EV71 VLP remained stable for 5 months in sodium phosphate (NaPi) buffers with various NaCl concentrations. EV71 VLP also remained morphologically stable in NaPi, citrate and TE(+) buffers for 5 months, yet the enzyme-linked immunosorbent assay (ELISA) revealed that the VLP stored in citrate and TE(+) buffers partially lost the immunogenicity after 5 months. In contrast, the VLP stored in the NaPi buffer at 4°C remained stable macroscopically and microscopically for 5 months, as judged from the DLS, TEM and ELISA. The VLP stored at 25°C and 37°C also retained stability for 1 month, which would obviate the need of a cold chain during the shipping. These data altogether proved the stability of EV71 VLP and suggested that the VLP is amenable to bioprocessing and storage. Copyright © 2013 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Study of mechanical properties of calcium phosphate cement with addition of sodium alginate and dispersant; Estudo das propriedades mecanicas de cimento de fosfato de calcio com adicao de alginato de sodio e defloculante

Energy Technology Data Exchange (ETDEWEB)

Fernandes, J.M.; Coelho, W.T.; Thurmer, M.B.; Vieira, P.S.; Santos, L.A., E-mail: julianafernandes2@yahoo.com.br [Universidade Federal do Rio Grande do Sul (UFRS), RS (Brazil)

2011-07-01

Several studies in literature have shown that the addition of polymer additives and deflocculant has a strong influence on the mechanical properties of cements in general.The low mechanical strength is the main impediment to wider use of bone cement of calcium phosphate (CFCs) as the implant material, since they have mechanical strength which equals the maximum of trabecular bone.In order to evaluate the strength of a CFC compound alpha-tricalcium phosphate, sodium alginate were added (1%, 2% and 3% by weight) and dispersant ammonium polyacrylate (3%) in aqueous solution.Specimens were made and evaluated for density, porosity, crystalline phases and mechanical strength.The results show the increase of the mechanical properties of cement when added sodium alginate and dispersant. (author)

Class IIa histone deacetylases are conserved regulators of circadian function.

Science.gov (United States)

Fogg, Paul C M; O'Neill, John S; Dobrzycki, Tomasz; Calvert, Shaun; Lord, Emma C; McIntosh, Rebecca L L; Elliott, Christopher J H; Sweeney, Sean T; Hastings, Michael H; Chawla, Sangeeta

2014-12-05

Class IIa histone deacetylases (HDACs) regulate the activity of many transcription factors to influence liver gluconeogenesis and the development of specialized cells, including muscle, neurons, and lymphocytes. Here, we describe a conserved role for class IIa HDACs in sustaining robust circadian behavioral rhythms in Drosophila and cellular rhythms in mammalian cells. In mouse fibroblasts, overexpression of HDAC5 severely disrupts transcriptional rhythms of core clock genes. HDAC5 overexpression decreases BMAL1 acetylation on Lys-537 and pharmacological inhibition of class IIa HDACs increases BMAL1 acetylation. Furthermore, we observe cyclical nucleocytoplasmic shuttling of HDAC5 in mouse fibroblasts that is characteristically circadian. Mutation of the Drosophila homolog HDAC4 impairs locomotor activity rhythms of flies and decreases period mRNA levels. RNAi-mediated knockdown of HDAC4 in Drosophila clock cells also dampens circadian function. Given that the localization of class IIa HDACs is signal-regulated and influenced by Ca(2+) and cAMP signals, our findings offer a mechanism by which extracellular stimuli that generate these signals can feed into the molecular clock machinery. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

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

Science.gov (United States)

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

2017-03-01

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

3D printing of mineral-polymer bone substitutes based on sodium alginate and calcium phosphate.

Science.gov (United States)

Egorov, Aleksey A; Fedotov, Alexander Yu; Mironov, Anton V; Komlev, Vladimir S; Popov, Vladimir K; Zobkov, Yury V

2016-01-01

We demonstrate a relatively simple route for three-dimensional (3D) printing of complex-shaped biocompatible structures based on sodium alginate and calcium phosphate (CP) for bone tissue engineering. The fabrication of 3D composite structures was performed through the synthesis of inorganic particles within a biopolymer macromolecular network during 3D printing process. The formation of a new CP phase was studied through X-ray diffraction, Fourier transform infrared spectroscopy and scanning electron microscopy. Both the phase composition and the diameter of the CP particles depend on the concentration of a liquid component (i.e., the "ink"). The 3D printed structures were fabricated and found to have large interconnected porous systems (mean diameter ≈800 μm) and were found to possess compressive strengths from 0.45 to 1.0 MPa. This new approach can be effectively applied for fabrication of biocompatible scaffolds for bone tissue engineering constructions.

Recovery of uranium from the Syrian phosphate by solid-liquid method using alkaline solutions

International Nuclear Information System (INIS)

Shlewit, H.; Alibrahim, M.

2007-01-01

Uranium concentrations were analyzed in the Syrian phosphate deposits. Mean concentrations were found between 50 and 110 ppm. As a consequence, an average phosphate dressing of 22 kg/ha phosphate would charge the soil with 5-20 g/ha uranium when added as a mineral fertilizer. Fine grinding phosphate produced at the Syrian mines was used for uranium recovery by carbonate leaching. The formation of the soluble uranyl tricarbonate anion UO 2 (CO 3 ) 3 4- permits use of alkali solutions of sodium carbonate and sodium bicarbonate salts for the nearly selective dissolution of uranium from phosphate. Separation of iron, aluminum, titanium, etc., from the uranium during leaching was carried out. Formation of some small amounts of molybdates, vanadates, phosphates, aluminates, and some complexes metal was investigated. This process could be used before the manufacture of TSP fertilizer, and the final products would contain smaller uranium quantities. (author)

On the mechanism of ion exchange in zirconium phosphates

International Nuclear Information System (INIS)

Clearfield, A.; Frianeza, T.N.

1978-01-01

α-titanium phosphate, Ti(HPO 4 ) 2 .H 2 O, was found to form two sodium ion exchanged phases. A half exchanged phase of ideal composition TiNaH(PO 4 ) 2 .4H 2 O formed first. However, before all of the titanium phosphate was converted to this phase a second phase of higher Na + content formed. Thus, a three phase solid existed until sufficient sodium ion uptake (approximately 5.5 meq/g) produced only the two exchanged phases. Finally, the half exchanged phase was converted to the more highly loaded one and this latter phase existed from 6 to 8 meq/g of Na + uptake. Severe disordering of the crystal lattice during exchange is proposed to explain this unusual exchange behavior. A broad range of titanium phosphate-zirconium phosphate solid solutions was found to form. Their behavior towards Na + -H + exchange was determined and interpreted on the basis of the known behavior of the pure phases. Mixed Ti-Zr solid solutions of their pyrophosphates were obtained at elevated temperatures. (author)

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

Science.gov (United States)

Rojas-Vega, Lorena; Gamba, Gerardo

2016-01-01

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

Hanford phosphate precipitation filtration process evaluation

International Nuclear Information System (INIS)

Walker, B.W.; McCabe, D.J.

1997-01-01

The purpose of this filter study was to evaluate cross-flow filtration as effective solid-liquid separation technology for treating Hanford wastes, outline operating conditions for equipment, examine the expected filter flow rates, and determine proper cleaning. A proposed Hanford waste pre-treatment process uses sodium hydroxide at high temperature to remove aluminum from sludge. This process also dissolves phosphates. Upon cooling to 40 degrees centigrade the phosphates form a Na7(PO4)2F9H2O precipitate which must be removed prior to further treatment. Filter studies were conducted with a phosphate slurry simulant to evaluate whether 0.5 micron cross-flow sintered metal Mott filters can separate the phosphate precipitate from the wash solutions. The simulant was recirculated through the filters at room temperature and filtration performance data was collected

3D printing of mineral–polymer bone substitutes based on sodium alginate and calcium phosphate

Directory of Open Access Journals (Sweden)

Aleksey A. Egorov

2016-11-01

Full Text Available We demonstrate a relatively simple route for three-dimensional (3D printing of complex-shaped biocompatible structures based on sodium alginate and calcium phosphate (CP for bone tissue engineering. The fabrication of 3D composite structures was performed through the synthesis of inorganic particles within a biopolymer macromolecular network during 3D printing process. The formation of a new CP phase was studied through X-ray diffraction, Fourier transform infrared spectroscopy and scanning electron microscopy. Both the phase composition and the diameter of the CP particles depend on the concentration of a liquid component (i.e., the “ink”. The 3D printed structures were fabricated and found to have large interconnected porous systems (mean diameter ≈800 μm and were found to possess compressive strengths from 0.45 to 1.0 MPa. This new approach can be effectively applied for fabrication of biocompatible scaffolds for bone tissue engineering constructions.

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

Research on preparation of phosphate-modified animal glue binder for foundry use

Science.gov (United States)

Wang, Tian-Shu; Liu, Wei-Hua; Li, Ying-Min

2018-03-01

In this paper, three phosphates were used as modifiers to modify animal glue binder. The structural characteristics and thermal properties of animal glue binder treated with phosphates were studied by Fourier transform-infrared spectroscopy, gel permeation chromatography and derivative thermogravimetric analysis. The results showed that the modified animal glue binder had better sand tensile strength and lower viscosity than untreated animal glue binder. The best modification process was as follows: the optimal amount of sodium carbonate was 4 wt% to animal glue; the optimal weight ratio of the modifiers was sodium pyrophosphate : sodium tripolyphosphate : sodium hexametaphosphate : animal glue = 3 : 3 : 4 : 100, and the optimal reaction should be performed at 80°C for a reaction time of 120 min. A final tensile strength of approximately 3.20 MPa was achieved and the viscosity value was approximately 880 mPa s.

Disruption of the Class IIa HDAC Corepressor Complex Increases Energy Expenditure and Lipid Oxidation

Directory of Open Access Journals (Sweden)

Vidhi Gaur

2016-09-01

Full Text Available Drugs that recapitulate aspects of the exercise adaptive response have the potential to provide better treatment for diseases associated with physical inactivity. We previously observed reduced skeletal muscle class IIa HDAC (histone deacetylase transcriptional repressive activity during exercise. Here, we find that exercise-like adaptations are induced by skeletal muscle expression of class IIa HDAC mutants that cannot form a corepressor complex. Adaptations include increased metabolic gene expression, mitochondrial capacity, and lipid oxidation. An existing HDAC inhibitor, Scriptaid, had similar phenotypic effects through disruption of the class IIa HDAC corepressor complex. Acute Scriptaid administration to mice increased the expression of metabolic genes, which required an intact class IIa HDAC corepressor complex. Chronic Scriptaid administration increased exercise capacity, whole-body energy expenditure and lipid oxidation, and reduced fasting blood lipids and glucose. Therefore, compounds that disrupt class IIa HDAC function could be used to enhance metabolic health in chronic diseases driven by physical inactivity.

Class IIa histone deacetylases are hormone-activated regulators of FOXO and mammalian glucose homeostasis.

Science.gov (United States)

Mihaylova, Maria M; Vasquez, Debbie S; Ravnskjaer, Kim; Denechaud, Pierre-Damien; Yu, Ruth T; Alvarez, Jacqueline G; Downes, Michael; Evans, Ronald M; Montminy, Marc; Shaw, Reuben J

2011-05-13

Class IIa histone deacetylases (HDACs) are signal-dependent modulators of transcription with established roles in muscle differentiation and neuronal survival. We show here that in liver, class IIa HDACs (HDAC4, 5, and 7) are phosphorylated and excluded from the nucleus by AMPK family kinases. In response to the fasting hormone glucagon, class IIa HDACs are rapidly dephosphorylated and translocated to the nucleus where they associate with the promoters of gluconeogenic enzymes such as G6Pase. In turn, HDAC4/5 recruit HDAC3, which results in the acute transcriptional induction of these genes via deacetylation and activation of FOXO family transcription factors. Loss of class IIa HDACs in murine liver results in inhibition of FOXO target genes and lowers blood glucose, resulting in increased glycogen storage. Finally, suppression of class IIa HDACs in mouse models of type 2 diabetes ameliorates hyperglycemia, suggesting that inhibitors of class I/II HDACs may be potential therapeutics for metabolic syndrome. Copyright © 2011 Elsevier Inc. All rights reserved.

Phosphate Reduction in Emulsified Meat Products: Impact of Phosphate Type and Dosage on Quality Characteristics.

Science.gov (United States)

Glorieux, Seline; Goemaere, Olivier; Steen, Liselot; Fraeye, Ilse

2017-09-01

Phosphate reduction is of important industrial relevance in the manufacturing of emulsified meat products because it may give rise to a healthier product. The effect of seven different phosphate types was tested on the physicochemical and quality characteristics to select the most promising phosphate type for further cooked sausage manufacturing. Next, phosphate mass fraction was gradually reduced. Tetrasodium di- or pyrophosphate (TSPP) and sodium tripolyphosphate (STPP) increased pH, reduced structural properties, resulted in the highest emulsion stability, lowest cooking loss and had little effect on hardness. Based on the viscoelastic properties, a minimum mass fraction of 0.06% TSPP was sufficient to obtain an acceptable quality product. Rheology proved to be a very useful tool to evaluate the quality of meat products, as it gives insight in the structure of the meat product and especially the functional properties of meat proteins. Based on the obtained results, it can be concluded that the current amount of phosphate added to emulsified meat products can be significantly reduced with minimal loss of product quality.

SwissProt search result: AK069337 [KOME

Lifescience Database Archive (English)

Full Text Available AK069337 J023014F07 (Q28727) Ileal sodium/bile acid cotransporter (Ileal Na(+)/bile... acid cotransporter) (Na(+) dependent ileal bile acid transporter) (Ileal sodium-dependent bile acid transpo

SwissProt search result: AK072870 [KOME

Lifescience Database Archive (English)

Full Text Available AK072870 J023142A17 (Q28727) Ileal sodium/bile acid cotransporter (Ileal Na(+)/bile... acid cotransporter) (Na(+) dependent ileal bile acid transporter) (Ileal sodium-dependent bile acid transpo

SwissProt search result: AK104932 [KOME

Lifescience Database Archive (English)

Full Text Available AK104932 001-047-B10 (Q28727) Ileal sodium/bile acid cotransporter (Ileal Na(+)/bile... acid cotransporter) (Na(+) dependent ileal bile acid transporter) (Ileal sodium-dependent bile acid transp

SwissProt search result: AK104932 [KOME

Lifescience Database Archive (English)

Full Text Available AK104932 001-047-B10 (Q60414) Ileal sodium/bile acid cotransporter (Ileal Na(+)/bile... acid cotransporter) (Na(+) dependent ileal bile acid transporter) (Ileal sodium-dependent bile acid transp

SwissProt search result: AK072870 [KOME

Lifescience Database Archive (English)

Full Text Available AK072870 J023142A17 (Q60414) Ileal sodium/bile acid cotransporter (Ileal Na(+)/bile... acid cotransporter) (Na(+) dependent ileal bile acid transporter) (Ileal sodium-dependent bile acid transpo

SwissProt search result: AK069337 [KOME

Lifescience Database Archive (English)

Full Text Available AK069337 J023014F07 (Q60414) Ileal sodium/bile acid cotransporter (Ileal Na(+)/bile... acid cotransporter) (Na(+) dependent ileal bile acid transporter) (Ileal sodium-dependent bile acid transpo

SwissProt search result: AK069337 [KOME

Lifescience Database Archive (English)

Full Text Available AK069337 J023014F07 (P70172) Ileal sodium/bile acid cotransporter (Ileal Na(+)/bile... acid cotransporter) (Na(+) dependent ileal bile acid transporter) (Ileal sodium-dependent bile acid transpo

SwissProt search result: AK072870 [KOME

Lifescience Database Archive (English)

Full Text Available AK072870 J023142A17 (P70172) Ileal sodium/bile acid cotransporter (Ileal Na(+)/bile... acid cotransporter) (Na(+) dependent ileal bile acid transporter) (Ileal sodium-dependent bile acid transpo

Tanshinon IIA injection accelerates tissue expansion by reducing the formation of the fibrous capsule.

Science.gov (United States)

Yu, Qingxiong; Sheng, Lingling; Yang, Mei; Zhu, Ming; Huang, Xiaolu; Li, Qingfeng

2014-01-01

The tissue expansion technique has been applied to obtain new skin tissue to repair large defects in clinical practice. The implantation of tissue expander could initiate a host response to foreign body (FBR), which leads to fibrotic encapsulation around the expander and prolongs the period of tissue expansion. Tanshinon IIA (Tan IIA) has been shown to have anti-inflammation and immunoregulation effect. The rat tissue expansion model was used in this study to observe whether Tan IIA injection systematically could inhibit the FBR to reduce fibrous capsule formation and accelerate the process of tissue expansion. Forty-eight rats were randomly divided into the Tan IIA group and control group with 24 rats in each group. The expansion was conducted twice a week to maintain a capsule pressure of 60 mmHg. The expansion volume and expanded area were measured. The expanded tissue in the two groups was harvested, and histological staining was performed; proinflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) and transforming growth factor-β (TGF-β) were examined. The expansion volume and the expanded area in the Tan IIA group were greater than that of the control group. The thickness of the fibrous capsule in the Tan IIA group was reduced with no influence on the normal skin regeneration. Decreased infiltration of macrophages, lower level of TNF-α, IL-6, IL-1β and TGF-β, less proliferating myofibroblasts and enhanced neovascularization were observed in the Tan IIA group. Our findings indicated that the Tan IIA injection reduced the formation of the fibrous capsule and accelerated the process of tissue expansion by inhibiting the FBR.

Tanshinon IIA injection accelerates tissue expansion by reducing the formation of the fibrous capsule.

Directory of Open Access Journals (Sweden)

Qingxiong Yu

Full Text Available The tissue expansion technique has been applied to obtain new skin tissue to repair large defects in clinical practice. The implantation of tissue expander could initiate a host response to foreign body (FBR, which leads to fibrotic encapsulation around the expander and prolongs the period of tissue expansion. Tanshinon IIA (Tan IIA has been shown to have anti-inflammation and immunoregulation effect. The rat tissue expansion model was used in this study to observe whether Tan IIA injection systematically could inhibit the FBR to reduce fibrous capsule formation and accelerate the process of tissue expansion. Forty-eight rats were randomly divided into the Tan IIA group and control group with 24 rats in each group. The expansion was conducted twice a week to maintain a capsule pressure of 60 mmHg. The expansion volume and expanded area were measured. The expanded tissue in the two groups was harvested, and histological staining was performed; proinflammatory cytokines such as tumor necrosis factor-α (TNF-α, interleukin-6 (IL-6 and interleukin-1β (IL-1β and transforming growth factor-β (TGF-β were examined. The expansion volume and the expanded area in the Tan IIA group were greater than that of the control group. The thickness of the fibrous capsule in the Tan IIA group was reduced with no influence on the normal skin regeneration. Decreased infiltration of macrophages, lower level of TNF-α, IL-6, IL-1β and TGF-β, less proliferating myofibroblasts and enhanced neovascularization were observed in the Tan IIA group. Our findings indicated that the Tan IIA injection reduced the formation of the fibrous capsule and accelerated the process of tissue expansion by inhibiting the FBR.

Regulation of myosin IIA and filamentous actin during insulin-stimulated glucose uptake in 3T3-L1 adipocytes

International Nuclear Information System (INIS)

Stall, Richard; Ramos, Joseph; Kent Fulcher, F.; Patel, Yashomati M.

2014-01-01

Insulin stimulated glucose uptake requires the colocalization of myosin IIA (MyoIIA) and the insulin-responsive glucose transporter 4 (GLUT4) at the plasma membrane for proper GLUT4 fusion. MyoIIA facilitates filamentous actin (F-actin) reorganization in various cell types. In adipocytes F-actin reorganization is required for insulin-stimulated glucose uptake. What is not known is whether MyoIIA interacts with F-actin to regulate insulin-induced GLUT4 fusion at the plasma membrane. To elucidate the relationship between MyoIIA and F-actin, we examined the colocalization of MyoIIA and F-actin at the plasma membrane upon insulin stimulation as well as the regulation of this interaction. Our findings demonstrated that MyoIIA and F-actin colocalized at the site of GLUT4 fusion with the plasma membrane upon insulin stimulation. Furthermore, inhibition of MyoII with blebbistatin impaired F-actin localization at the plasma membrane. Next we examined the regulatory role of calcium in MyoIIA-F-actin colocalization. Reduced calcium or calmodulin levels decreased colocalization of MyoIIA and F-actin at the plasma membrane. While calcium alone can translocate MyoIIA it did not stimulate F-actin accumulation at the plasma membrane. Taken together, we established that while MyoIIA activity is required for F-actin localization at the plasma membrane, it alone is insufficient to localize F-actin to the plasma membrane. - Highlights: • Insulin induces colocalization of MyoIIA and F-actin at the cortex in adipocytes. • MyoIIA is necessary but not sufficient to localize F-actin at the cell cortex. • MyoIIA-F-actin colocalization is regulated by calcium and calmodulin

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....

Extreme hyperphosphatemia and hypocalcemic coma associated with phosphate enema.

Science.gov (United States)

Hsu, Heng Jung; Wu, Mai-Szu

2008-01-01

Fleet enema (sodium phosphate, C.B. Fleet Co., Inc., Lynchburg, Virginia) is widely used for bowel preparation or constipation relief in the hospital and over the counter. The potential risks, including hyperphosphatemia and hypocalcemic coma should be kept in mind of primary care physician. The patients with older age, bowel obstruction, small intestinal disorders, poor gut motility, and renal disease are contraindicated or should be administered with caution. We present a patient with old age and chronic renal failure who developed severe hyperphosphatemia and hypocalcemic tetany with coma after sodium phosphate enema. We recommend the use of alternative enema preparations, such as simple tap water or saline solution enemas, which can prevent fatal complications in high risk patients.

Development of Class IIa Bacteriocins as Therapeutic Agents

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Christopher T. Lohans

2012-01-01

Full Text Available Class IIa bacteriocins have been primarily explored as natural food preservatives, but there is much interest in exploring the application of these peptides as therapeutic antimicrobial agents. Bacteriocins of this class possess antimicrobial activity against several important human pathogens. Therefore, the therapeutic development of these bacteriocins will be reviewed. Biological and chemical modifications to both stabilize and increase the potency of bacteriocins are discussed, as well as the optimization of their production and purification. The suitability of bacteriocins as pharmaceuticals is explored through determinations of cytotoxicity, effects on the natural microbiota, and in vivo efficacy in mouse models. Recent results suggest that class IIa bacteriocins show promise as a class of therapeutic agents.

Secretory Phospholipase A2-IIA and Cardiovascular Disease: A Mendelian Randomization Study

NARCIS (Netherlands)

Holmes, Michael V.; Simon, Tabassome; Exeter, Holly J.; Folkersen, Lasse; Asselbergs, Folkert W.; Guardiola, Montse; Cooper, Jackie A.; Palmen, Jutta; Hubacek, Jaroslav A.; Carruthers, Kathryn F.; Horne, Benjamin D.; Brunisholz, Kimberly D.; Mega, Jessica L.; van Iperen, Erik P. A.; Li, Mingyao; Leusink, Maarten; Trompet, Stella; Verschuren, Jeffrey J. W.; Hovingh, G. Kees; Dehghan, Abbas; Nelson, Christopher P.; Kotti, Salma; Danchin, Nicolas; Scholz, Markus; Haase, Christiane L.; Rothenbacher, Dietrich; Swerdlow, Daniel I.; Kuchenbaecker, Karoline B.; Staines-Urias, Eleonora; Goel, Anuj; van 't Hooft, Ferdinand; Gertow, Karl; de Faire, Ulf; Panayiotou, Andrie G.; Tremoli, Elena; Baldassarre, Damiano; Veglia, Fabrizio; Holdt, Lesca M.; Beutner, Frank; Gansevoort, Ron T.; Navis, Gerjan J.; Mateo Leach, Irene; Breitling, Lutz P.; Brenner, Hermann; Thiery, Joachim; Dallmeier, Dhayana; Franco-Cereceda, Anders; Boer, Jolanda M. A.; Stephens, Jeffrey W.; Hofker, Marten H.; Tedgui, Alain; Hofman, Albert; Uitterlinden, André G.; Adamkova, Vera; Pitha, Jan; Onland-Moret, N. Charlotte; Cramer, Maarten J.; Nathoe, Hendrik M.; Spiering, Wilko; Klungel, Olaf H.; Kumari, Meena; Whincup, Peter H.; Morrow, David A.; Braund, Peter S.; Hall, Alistair S.; Olsson, Anders G.; Doevendans, Pieter A.; Trip, Mieke D.; Tobin, Martin D.; Hamsten, Anders; Watkins, Hugh; Koenig, Wolfgang; Nicolaides, Andrew N.; Teupser, Daniel; Day, Ian N. M.; Carlquist, John F.; Gaunt, Tom R.; Ford, Ian; Sattar, Naveed; Tsimikas, Sotirios; Schwartz, Gregory G.; Lawlor, Debbie A.; Morris, Richard W.; Sandhu, Manjinder S.; Poledne, Rudolf; Maitland-van der Zee, Anke H.; Khaw, Kay-Tee; Keating, Brendan J.; van der Harst, Pim; Price, Jackie F.; Mehta, Shamir R.; Yusuf, Salim; Witteman, Jaqueline C. M.; Franco, Oscar H.; Jukema, J. Wouter; de Knijff, Peter; Tybjaerg-Hansen, Anne; Rader, Daniel J.; Farrall, Martin; Samani, Nilesh J.; Kivimaki, Mika; Fox, Keith A. A.; Humphries, Steve E.; Anderson, Jeffrey L.; Boekholdt, S. Matthijs; Palmer, Tom M.; Eriksson, Per; Paré, Guillaume; Hingorani, Aroon D.; Sabatine, Marc S.; Mallat, Ziad; Casas, Juan P.; Talmud, Philippa J.

2013-01-01

This study sought to investigate the role of secretory phospholipase A2 (sPLA2)-IIA in cardiovascular disease. Higher circulating levels of sPLA2-IIA mass or sPLA2 enzyme activity have been associated with increased risk of cardiovascular events. However, it is not clear if this association is

Hydrogen sulfide upregulated mRNA expressions of sodium bicarbonate cotransporter1, trefoil factor1 and trefoil factor2 in gastric mucosa in rats.

Science.gov (United States)

Cheraghi, Parisa; Mard, Seyyed Ali; Nagi, Tahereh

2016-01-01

Hydrogen sulfide (H 2 S) has been shown to protect the gastric mucosa through several protective mechanisms but till now its effect on mRNA expression of sodium bicarbonate cotransporter 1 (NBC1), trefoil factor1 (TFF1) and trefoil factor2 (TFF2) was not investigated. This study was aimed to evaluate the effect of H 2 S on mRNA expression of NBC1, TFF1 and TFF2 in rat gastric mucosa in response to gastric distention. Thirty two rats were randomly assigned into four equal groups. They were control (C), distention (D), propargylglycine (PAG)-, and NaHS-treated groups. To evaluate the effect of exogenous and endogenous H 2 S on gene expression of NBC1, TFF1 and TFF2, two groups of rats were received H 2 S donor, intra-peritoneal NaHS (80 µg Kg -1 ), and PAG (50 mg kg -1 ), accompanied to stimulate the gastric acid secretion, respectively. Under general anesthesia and laparotomy, a catheter was inserted into the stomach through duodenum for instillation of isotonic saline for gastric distention. Ninety min after beginning the experiment, animals were sacrificed and the gastric mucosa was collected to determine total acid content of gastric effluents and to quantify the mRNA expression of studied genes by quantitative real-time polymerase chain reaction (qRT-PCR). Results showed that A) gastric distention increased the level of mRNA expressions of NBC1, TFF1 and TFF2; B) these levels in NaHS-treated rats were significantly higher than those in Distention group; and C) PAG decreased the expression levels of NBC1 and TFF1. The Findings showed H 2 S upregulated gene expression of NBC1, TFF1 and TFF2 in gastric mucosa.

Radiochemical studies on amorphous zirconium phosphate

Energy Technology Data Exchange (ETDEWEB)

Dyer, A; Moores, G E [Salford Univ. (UK). Dept. of Chemistry and Applied Chemistry

1981-01-01

Amorphous zirconium phosphate (ZrP) is used in some hemodialysis machines for the regeneration of dialysate. Its function is to adsorb ammonium ions formed by the pretreatment of urea by urease. It also adsorbs Ca, Mg and K ions but leaches phosphate ions which are then removed (along with F/sup -/ ions) by a bed of hydrous zirconium oxide. The sodium form of ZrP is used although other forms have been suggested for use. The work reported here describes some preliminary radiochemical studies on the mechanism of release of phosphate ions and its possible relationship to sodium ion-exchange. /sup 32/P labelled material (HHZrP) was used for elution experiments with deionized water and buffer solutions having the pH's 4.2, 7.0 and 9.2. Buffer solutions used were as supplied by BDH. Elution was at four different temperatures in the range 293 to 363/sup 0/C. In the second series of experiments HHZrP was suspended in a NaCl solution labelled with /sup 22/Na. From this, /sup 22/Na labelled ZrP (NaHZrP) was prepared and eluted in the same way as the HHZrP. Results are given and discussed.

Phosphate Reduction in Emulsifi ed Meat Products: Impact of Phosphate Type and Dosage on Quality Characteristics

Directory of Open Access Journals (Sweden)

Seline Glorieux

2017-01-01

Full Text Available Phosphate reduction is of important industrial relevance in the manufacturing of emulsifi ed meat products because it may give rise to a healthier product. The eff ect of seven diff erent phosphate types was tested on the physicochemical and quality characteristics to select the most promising phosphate type for further cooked sausage manufacturing. Next, phosphate mass fraction was gradually reduced. Tetrasodium di- or pyrophosphate (TSPP and sodium tripolyphosphate (STPP increased pH, reduced structural properties, resulted in the highest emulsion stability, lowest cooking loss and had litt le eff ect on hardness. Based on the viscoelastic properties, a minimum mass fraction of 0.06 % TSPP was suffi cient to obtain an acceptable quality product. Rheology proved to be a very useful tool to evaluate the quality of meat products, as it gives insight in the structure of the meat product and especially the functional properties of meat proteins. Based on the obtained results, it can be concluded that the current amount of phosphate added to emulsifi ed meat products can be signifi cantly reduced with minimal loss of product quality.

Changes in urinary excretion of water and sodium transporters during amiloride and bendroflumethiazide treatment

DEFF Research Database (Denmark)

Jensen, Janni M; Mose, Frank H; Kulik, Anna-Ewa O

2015-01-01

AIM: To quantify changes in urinary excretion of aquaporin2 water channels (u-AQP2), the sodium-potassium-chloride co-transporter (u-NKCC2) and the epithelial sodium channels (u-ENaC) during treatment with bendroflumethiazide (BFTZ), amiloride and placebo. METHODS: In a randomized, double....... General linear model with repeated measures or related samples Friedman's two-way analysis was used to compare differences. Post hoc Bonferroni correction was used for multiple comparisons of post infusion periods to baseline within each treatment group. RESULTS: At baseline there were no differences in u...... by the constant infusion clearance technique with (51)Cr-EDTA as reference substance. To estimate the changes in water transport via AQP2 and sodium transport via NKCC2 and ENaC, u-NKCC2, the gamma fraction of ENaC (u-ENaCγ), and u-AQP2 were measured at baseline and after infusion with 3% hypertonic saline. U...

Septin 7 reduces nonmuscle myosin IIA activity in the SNAP23 complex and hinders GLUT4 storage vesicle docking and fusion

Energy Technology Data Exchange (ETDEWEB)

Wasik, Anita A.; Dumont, Vincent [Department of Pathology, University of Helsinki, 00014 Helsinki (Finland); Tienari, Jukka [Department of Pathology, University of Helsinki and Helsinki University Hospital, 00290 Helsinki, 05850 Hyvinkää (Finland); Nyman, Tuula A. [Institute of Biotechnology, University of Helsinki, 00014 Helsinki (Finland); Fogarty, Christopher L.; Forsblom, Carol; Lehto, Markku [Folkhälsan Institute of Genetics, Folkhälsan Research Center, 00290 Helsinki (Finland); Abdominal Center Nephrology, University of Helsinki and Helsinki University Hospital, 000290 Helsinki (Finland); Diabetes& Obesity Research Program, Research Program´s Unit, 00014 University of Helsinki (Finland); Lehtonen, Eero [Department of Pathology, University of Helsinki, 00014 Helsinki (Finland); Laboratory Animal Centre, University of Helsinki, 00014 Helsinki (Finland); Groop, Per-Henrik [Folkhälsan Institute of Genetics, Folkhälsan Research Center, 00290 Helsinki (Finland); Abdominal Center Nephrology, University of Helsinki and Helsinki University Hospital, 000290 Helsinki (Finland); Diabetes& Obesity Research Program, Research Program´s Unit, 00014 University of Helsinki (Finland); Baker IDI Heart & Diabetes Institute, 3004 Melbourne (Australia); Lehtonen, Sanna, E-mail: sanna.h.lehtonen@helsinki.fi [Department of Pathology, University of Helsinki, 00014 Helsinki (Finland)

2017-01-15

Glomerular epithelial cells, podocytes, are insulin responsive and can develop insulin resistance. Here, we demonstrate that the small GTPase septin 7 forms a complex with nonmuscle myosin heavy chain IIA (NMHC-IIA; encoded by MYH9), a component of the nonmuscle myosin IIA (NM-IIA) hexameric complex. We observed that knockdown of NMHC-IIA decreases insulin-stimulated glucose uptake into podocytes. Both septin 7 and NM-IIA associate with SNAP23, a SNARE protein involved in GLUT4 storage vesicle (GSV) docking and fusion with the plasma membrane. We observed that insulin decreases the level of septin 7 and increases the activity of NM-IIA in the SNAP23 complex, as visualized by increased phosphorylation of myosin regulatory light chain. Also knockdown of septin 7 increases the activity of NM-IIA in the complex. The activity of NM-IIA is increased in diabetic rat glomeruli and cultured human podocytes exposed to macroalbuminuric sera from patients with type 1 diabetes. Collectively, the data suggest that the activity of NM-IIA in the SNAP23 complex plays a key role in insulin-stimulated glucose uptake into podocytes. Furthermore, we observed that septin 7 reduces the activity of NM-IIA in the SNAP23 complex and thereby hinders GSV docking and fusion with the plasma membrane. - Highlights: • Septin 7, nonmuscle myosin heavy chain IIA (NMHC-IIA) and SNAP23 form a complex. • Knockdown of septin 7 increases NM-IIA activity in the SNAP23 complex. • Insulin decreases septin 7 level and increases NM-IIA activity in the SNAP23 complex. • Septin 7 hinders GSV docking/fusion by reducing NM-IIA activity in the SNAP23 complex.

Septin 7 reduces nonmuscle myosin IIA activity in the SNAP23 complex and hinders GLUT4 storage vesicle docking and fusion

International Nuclear Information System (INIS)

Wasik, Anita A.; Dumont, Vincent; Tienari, Jukka; Nyman, Tuula A.; Fogarty, Christopher L.; Forsblom, Carol; Lehto, Markku; Lehtonen, Eero; Groop, Per-Henrik; Lehtonen, Sanna

2017-01-01

Glomerular epithelial cells, podocytes, are insulin responsive and can develop insulin resistance. Here, we demonstrate that the small GTPase septin 7 forms a complex with nonmuscle myosin heavy chain IIA (NMHC-IIA; encoded by MYH9), a component of the nonmuscle myosin IIA (NM-IIA) hexameric complex. We observed that knockdown of NMHC-IIA decreases insulin-stimulated glucose uptake into podocytes. Both septin 7 and NM-IIA associate with SNAP23, a SNARE protein involved in GLUT4 storage vesicle (GSV) docking and fusion with the plasma membrane. We observed that insulin decreases the level of septin 7 and increases the activity of NM-IIA in the SNAP23 complex, as visualized by increased phosphorylation of myosin regulatory light chain. Also knockdown of septin 7 increases the activity of NM-IIA in the complex. The activity of NM-IIA is increased in diabetic rat glomeruli and cultured human podocytes exposed to macroalbuminuric sera from patients with type 1 diabetes. Collectively, the data suggest that the activity of NM-IIA in the SNAP23 complex plays a key role in insulin-stimulated glucose uptake into podocytes. Furthermore, we observed that septin 7 reduces the activity of NM-IIA in the SNAP23 complex and thereby hinders GSV docking and fusion with the plasma membrane. - Highlights: • Septin 7, nonmuscle myosin heavy chain IIA (NMHC-IIA) and SNAP23 form a complex. • Knockdown of septin 7 increases NM-IIA activity in the SNAP23 complex. • Insulin decreases septin 7 level and increases NM-IIA activity in the SNAP23 complex. • Septin 7 hinders GSV docking/fusion by reducing NM-IIA activity in the SNAP23 complex.

Transport of protons and lactate in cultured human fetal retinal pigment epithelial cells

DEFF Research Database (Denmark)

Hamann, Steffen; Cour, Morten la; Ming Lui, Ge

2000-01-01

Electron microscopy, intracellular pH, monocarboxylate transport, pigment epithelium of eye, proton-lactate cotransport, retinal metabolism, sodium/proton exchange......Electron microscopy, intracellular pH, monocarboxylate transport, pigment epithelium of eye, proton-lactate cotransport, retinal metabolism, sodium/proton exchange...

Zespół napięcia przedmiesiączkowego – mit czy rzeczywistość = Premenstrual syndrome – myth or reality

Directory of Open Access Journals (Sweden)

Klaudia Pałucka

2016-06-01

  Adres do korespondencji: Klaudia Pałucka Katedra i Klinika Ginekologii i Endokrynologii Ginekologicznej UM w Lublinie Al. Racławickie 23 20-049 Lublin, Poland tel./fax. 81-7183286 claudiapalucka@onet.pl Kierownik kliniki: prof. dr hab. n. med. L. Putowski   Streszczenie Wprowadzenie. W drugiej fazie cyklu miesiączkowego u większości kobiet pojawiają się dość specyficzne objawy natury somatycznej i psychicznej, które uznawane są za fizjologię. U 20-40% z nich mogą jednak świadczyć o patologii. Cel pracy. Celem pracy było wyjaśnienie, czym jest zespół napięcia przedmiesiączkowego, jak go rozpoznać oraz na czym polega pomoc chorej kobiecie. Materiał i metoda. Przy użyciu haseł przedmiotowych przeszukano uniwersytecką bazę danych, PubMed i MEDLINE. Przeszukanie elektroniczne ograniczono do prac w języku polskim i angielskim, opublikowanych w latach 2005-2015. Wyłoniono ogółem 55 pozycji (głównie lekarskich, z czego wykorzystano 34 oraz jedną ze strony internetowej Amerykańskiego Towarzystwa Położników i Ginekologów. Opis zebranego materiału. Z przeglądu piśmiennictwa wynika, że zespół napięcia przedmiesiączkowego to nie mit, lecz realny problem osobisty i medyczny. Zaburza funkcjonowanie kobiet w życiu społecznym i zawodowym. Rozpoznanie wymaga minimum dwumiesięcznej obserwacji objawów oraz wykluczenia innych chorób. Modyfikacja stylu życia i ewentualne leczenie farmakologiczne poprawiają samopoczucie i jakość życia kobiet. Przegląd piśmiennictwa ukazał dużą rozbieżność stanowisk autorów w omawianych kwestiach oraz zasugerował kierunki dalszych dociekań.   Słowa kluczowe: cykl miesiączkowy, zespół napięcia przedmiesiączkowego, dysforyczne zaburzenia przedmiesiączkowe.     Summary Introduction. Specific symptoms of somatic and psychological nature appear in the second phase of the menstrual cycle of many women. These symptoms are considered to be physiological, however, 20-40 % of them

Sodium-Glucose Cotransporter 2 Inhibitor and a Low Carbohydrate Diet Affect Gluconeogenesis and Glycogen Content Differently in the Kidney and the Liver of Non-Diabetic Mice.

Science.gov (United States)

Atageldiyeva, Kuralay; Fujita, Yukihiro; Yanagimachi, Tsuyoshi; Mizumoto, Katsutoshi; Takeda, Yasutaka; Honjo, Jun; Takiyama, Yumi; Abiko, Atsuko; Makino, Yuichi; Haneda, Masakazu

2016-01-01

A low carbohydrate diet (LCHD) as well as sodium glucose cotransporter 2 inhibitors (SGLT2i) may reduce glucose utilization and improve metabolic disorders. However, it is not clear how different or similar the effects of LCHD and SGLT2i are on metabolic parameters such as insulin sensitivity, fat accumulation, and especially gluconeogenesis in the kidney and the liver. We conducted an 8-week study using non-diabetic mice, which were fed ad-libitum with LCHD or a normal carbohydrate diet (NCHD) and treated with/without the SGLT-2 inhibitor, ipragliflozin. We compared metabolic parameters, gene expression for transcripts related to glucose and fat metabolism, and glycogen content in the kidney and the liver among the groups. SGLT2i but not LCHD improved glucose excursion after an oral glucose load compared to NCHD, although all groups presented comparable non-fasted glycemia. Both the LCHD and SGLT2i treatments increased calorie-intake, whereas only the LCHD increased body weight compared to the NCHD, epididimal fat mass and developed insulin resistance. Gene expression of certain gluconeogenic enzymes was simultaneously upregulated in the kidney of SGLT2i treated group, as well as in the liver of the LCHD treated group. The SGLT2i treated groups showed markedly lower glycogen content in the liver, but induced glycogen accumulation in the kidney. We conclude that LCHD induces deleterious metabolic changes in the non-diabetic mice. Our results suggest that SGLT2i induced gluconeogenesis mainly in the kidney, whereas for LCHD it was predominantly in the liver.

Tanshinone IIA Inhibits Epithelial-Mesenchymal Transition in Bladder Cancer Cells via Modulation of STAT3-CCL2 Signaling

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Sung-Ying Huang

2017-07-01

Full Text Available Tanshinone IIA (Tan-IIA is an extract from the widely used traditional Chinese medicine (TCM Danshen (Salvia miltiorrhiza, and has been found to attenuate the proliferation of bladder cancer (BCa cells (The IC50 were: 5637, 2.6 μg/mL; BFTC, 2 μg/mL; T24, 2.7 μg/mL, respectively.. However, the mechanism of the effect of Tan-IIA on migration inhibition of BCa cells remains unclear. This study investigates the anti-metastatic effect of Tan-IIA in human BCa cells and clarifies its molecular mechanism. Three human BCa cell lines, 5637, BFTC and T24, were used for subsequent experiments. Cell migration and invasion were evaluated by transwell assays. Real-time RT-PCR and western blotting were performed to detect epithelial-mesenchymal transition (EMT-related gene expression. The enzymatic activity of matrix metalloproteinases (MMP was evaluated by zymography assay. Tan-IIA inhibited the migration and invasion of human BCa cells. Tan-IIA suppressed both the protein expression and enzymatic activity of MMP-9/-2 in human BCa cells. Tan-IIA up-regulated the epithelial marker E-cadherin and down-regulated mesenchymal markers such as N-cadherin and Vimentin, along with transcription regulators such as Snail and Slug in BCa cells in a time- and dose-dependent manner. Mechanism dissection revealed that Tan-IIA-inhibited BCa cell invasion could function via suppressed chemokine (C-C motif ligand 2 (CCL2 expression, which could be reversed by the addition of CCL2 recombinant protein. Furthermore, Tan-IIA could inhibit the phosphorylation of the signal transducer and activator of transcription 3 (STAT3 (Tyr705, which cannot be restored by the CCL2 recombinant protein addition. These data implicated that Tan-IIA might suppress EMT on BCa cells through STAT3-CCL2 signaling inhibition. Tan-IIA inhibits EMT of BCa cells via modulation of STAT3-CCL2 signaling. Our findings suggest that Tan-IIA can serve as a potential anti-metastatic agent in BCa therapy.

Domain-induced activation of human phospholipase A₂ type IIA: Local versus global lipid composition

DEFF Research Database (Denmark)

Leidy, C.; Linderoth, L.; Andresen, T.L.

2006-01-01

, we show that local enrichment of anionic lipids into fluid domains triggers PLA(2)-IIA activity. In addition, the compositional range of enzyme activity is shown to be related to the underlying lipid phase diagram. A comparison is done between PLA(2)-IIA and snake venom PLA(2), which in contrast...... to PLA(2)-IIA hydrolyzes both anionic and zwitterionic membranes. In general, this work shows that PLA(2)-IIA activation can be accomplished through local enrichment of anionic lipids into domains, indicating a mechanism for PLA(2)-IIA to target perturbed native membranes with low global anionic lipid...

A new paramagnetic center of copper ion γ-irradiated phosphate glasses

International Nuclear Information System (INIS)

Bogomolova, L.D.; Fedorov, A.G.; Jachkin, V.A.; Lazukin, V.N.; Pavlushkina, T.K.

1981-01-01

In the present paper are shown the results of EPR and optical absorption investigations of copper ions in γ-irradiated sodium-phosphate glasses and in MO-P 2 O 5 glasses (M = MG,Ca, Sr, Zn, Ba) containing copper and comparisons are made with the data for sodium-silicate glasses. (orig./HOF)

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

DEFF Research Database (Denmark)

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

1998-01-01

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

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

Science.gov (United States)

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

2013-04-01

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

On the mechanism of ion exchange in zirconium phosphates

International Nuclear Information System (INIS)

Kullberg, L.; Clearfield, A.

1981-01-01

An equilibrium study of the Na + -Cs + -H + exchange on crystalline α-zirconium phosphate has been carried out. Isotherms for the ion exchange have been determined and phases formed during the exchange have been identified. The surface groups of the exchanger were found to greatly prefer cesium to sodium. For exchange in the interior, cesium was found to be preferred to sodium for 0 to 50% of exchange, while sodium is slightly preferred to cesium for the second half of exchange. The influence of surface equilibria on the total exchange mechanism is discussed. (author)

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

Energy Technology Data Exchange (ETDEWEB)

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

2015-06-24

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

Structural and thermochemical properties of sodium magnesium phosphate glasses

Energy Technology Data Exchange (ETDEWEB)

Oueslati Omrani, Refka [Université de Tunis El Manar, Faculté des Sciences de Tunis, Chemistry Department, LR01SE10 Applied Thermodynamics Laboratory, 2092 Tunis (Tunisia); Kaoutar, Abdeltif; El Jazouli, Abdelaziz [LCMS, URAC 17, Faculté des Sciences Ben M’Sik, UH2MC, Casablanca (Morocco); Krimi, Saida [LPCMI, Faculté des Sciences Aïn Chok, UH2C, Casablanca (Morocco); Khattech, Ismail, E-mail: ismail.khattech@fst.rnu.tn [Université de Tunis El Manar, Faculté des Sciences de Tunis, Chemistry Department, LR01SE10 Applied Thermodynamics Laboratory, 2092 Tunis (Tunisia); Jemal, Mohamed [Université de Tunis El Manar, Faculté des Sciences de Tunis, Chemistry Department, LR01SE10 Applied Thermodynamics Laboratory, 2092 Tunis (Tunisia); Videau, Jean-Jacques [ICMCB, Institut de Chimie de la matière condensée, Université de Bordeaux 1 (France); Couzi, Michel [Institut des Sciences Moléculaires, CNRS-Université de Bordeaux 1 (France)

2015-05-25

Highlights: • Phosphate glasses were prepared by met quenching technique. • Structural study is investigated using FTIR, Raman and {sup 31}PNMR spectroscopy. • A 4.5% weight of H{sub 3}PO{sub 4} solution has use for glass dissolution. • Dissolution is endothermic for lower MgO content and becomes exothermic when x rises. - Abstract: Ternary phosphate based glasses with the general formula (50−x/2)Na{sub 2}O–xMgO–(50−x/2)P{sub 2}O{sub 5} (0 ⩽ x ⩽ 42.8 mol%), where the O/P ratio was varied from 3 to 3.75, have been prepared using a conventional melt quenching technique. Samples were investigated by means of density measurements, Fourier-transformed infrared (FTIR), Raman and {sup 31}P solid state magic angle spinning nuclear magnetic resonance (MAS-NMR) spectroscopies, differential scanning calorimetry (DSC), inductively coupled plasma atomic emission spectroscopy (ICP/AES) analysis and calorimetric dissolution. The depolymerization of metaphosphate chains are described by the decrease of Q{sup 2} tetrahedral sites allowing the formation of pyrophosphate groups (Q{sup 1}) revealed by spectroscopic investigations. As a result, the increase of density and glass transition temperature when x rises. Calorimetric study shows that the dissolution phenomenon is endothermic for a lower MgO content and becomes exothermic when magnesium oxide is gradually incorporated, suggesting the disruption of phosphate chains with increasing O/P ratio.

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.

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

Science.gov (United States)

Kashiwagi, Atsunori; Maegawa, Hiroshi

2017-07-01

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

The role of aspartic acid residues 405 and 416 of the kidney isotype of sodium-bicarbonate cotransporter 1 in its targeting to the plasma membrane

Science.gov (United States)

Kucher, Volodymyr; Li, Emily Y.; Conforti, Laura; Zahedi, Kamyar A.

2012-01-01

The NH2 terminus of the sodium-bicarbonate cotransporter 1 (NBCe1) plays an important role in its targeting to the plasma membrane. To identify the amino acid residues that contribute to the targeting of NBCe1 to the plasma membrane, polarized MDCK cells were transfected with expression constructs coding for green fluorescent protein (GFP)-tagged NBCe1 NH2-terminal deletion mutants, and the localization of GFP-tagged proteins was analyzed by confocal microscopy. Our results indicate that the amino acids between residues 399 and 424 of NBCe1A contain important sequences that contribute to its localization to the plasma membrane. Site-directed mutagenesis studies showed that GFP-NBCe1A mutants D405A and D416A are retained in the cytoplasm of the polarized MDCK epithelial cells. Examination of functional activities of D405A and D416A reveals that their activities are reduced compared with the wild-type NBCe1A. Similarly, aspartic acid residues 449 and 460 of pancreatic NBCe1 (NBCe1B), which correspond to residues 405 and 416 of NBCe1A, are also required for its full functional activity and accurate targeting to the plasma membrane. In addition, while replacement of D416 with glutamic acid did not affect the targeting or functional activity of NBCe1A, substitution of D405 with glutamic acid led to the retention of the mutated protein in the intracellular compartment and impaired functional activity. These studies demonstrate that aspartic acid residues 405 and 416 in the NH2 terminus of NBCe1A are important in its accurate targeting to the plasma membrane. PMID:22442137

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

Science.gov (United States)

1992-01-01

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

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

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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

Point of care testing of phospholipase A2 group IIA for serological diagnosis of rheumatoid arthritis

Science.gov (United States)

Liu, Nathan J.; Chapman, Robert; Lin, Yiyang; Mmesi, Jonas; Bentham, Andrew; Tyreman, Matthew; Abraham, Sonya; Stevens, Molly M.

2016-02-01

Secretory phospholipase A2 group IIA (sPLA2-IIA) was examined as a point of care marker for determining disease activity in rheumatoid (RA) and psoriatic (PsA) arthritis. Serum concentration and activity of sPLA2-IIA were measured using in-house antibodies and a novel point of care lateral flow device assay in patients diagnosed with varying severities of RA (n = 30) and PsA (n = 25) and found to correlate strongly with C-reactive protein (CRP). Levels of all markers were elevated in patients with active RA over those with inactive RA as well as both active and inactive PsA, indicating that sPLA2-IIA can be used as an analogue to CRP for RA diagnosis at point of care.Secretory phospholipase A2 group IIA (sPLA2-IIA) was examined as a point of care marker for determining disease activity in rheumatoid (RA) and psoriatic (PsA) arthritis. Serum concentration and activity of sPLA2-IIA were measured using in-house antibodies and a novel point of care lateral flow device assay in patients diagnosed with varying severities of RA (n = 30) and PsA (n = 25) and found to correlate strongly with C-reactive protein (CRP). Levels of all markers were elevated in patients with active RA over those with inactive RA as well as both active and inactive PsA, indicating that sPLA2-IIA can be used as an analogue to CRP for RA diagnosis at point of care. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr08423g

Contribution of Drinking Water Softeners to Daily Phosphate Intake in Slovenia.

Science.gov (United States)

Jereb, Gregor; Poljšak, Borut; Eržen, Ivan

2017-10-06

The cumulative phosphate intake in a typical daily diet is high and, according to several studies, already exceeds recommended values. The exposure of the general population to phosphorus via drinking water is generally not known. One of the hidden sources of phosphorus in a daily diet is sodium polyphosphate, commonly used as a drinking water softener. In Slovenia, softening of drinking water is carried out exclusively within the internal (household) drinking water supply systems to prevent the accumulation of limescale. The aim of the study was to determine the prevalence of sodium phosphates in the drinking water in Slovenia in different types of buildings, to determine residents' awareness of the presence of chemical softeners in their drinking water, and to provide an exposure assessment on the phosphorus intake from drinking water. In the current study, the presence of phosphates in the samples of drinking water was determined using a spectrophotometric method with ammonium molybdate. In nearly half of the samples, the presence of phosphates as water softeners was confirmed. The measured concentrations varied substantially from 0.2 mg PO4/L to 24.6 mg PO4/L. Nearly 70% of the respondents were not familiar with the exact data on water softening in their buildings. It follows that concentrations of added phosphates should be controlled and the consumers should be informed of the added chemicals in their drinking water. The health risks of using sodium polyphosphate as a drinking water softener have not been sufficiently investigated and assessed. It is highly recommended that proper guidelines and regulations are developed and introduced to protect human health from adverse effects of chemicals in water intended for human consumption.

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

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Alaaeldin Bashier

2018-03-01

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

Overexpressed human metallothionein IIA gene protects Chinese hamster ovary cells from killing by alkylating agents.

OpenAIRE

Kaina, B; Lohrer, H; Karin, M; Herrlich, P

1990-01-01

Experiments were designed to detect survival advantages that cells gain by overexpressing metallothionein (MT). Chinese hamster ovary K1-2 cells and an x-ray-sensitive derivative were transfected with a bovine papillomavirus (BPV)-linked construct carrying the human metallothionein IIA (hMT-IIA) gene. Transfectants survived 40-fold higher levels of cadmium chloride, harbored at least 30 copies of hMT-IIA, and contained 25- to 166-fold more MT than the parent cells. Even under conditions of re...

Inhibition of class IIa histone deacetylase activity by gallic acid, sulforaphane, TMP269, and panobinostat.

Science.gov (United States)

Choi, Sin Young; Kee, Hae Jin; Jin, Li; Ryu, Yuhee; Sun, Simei; Kim, Gwi Ran; Jeong, Myung Ho

2018-05-01

Histone deacetylase (HDAC) inhibitors are gaining increasing attention as potential therapeutics for cardiovascular diseases as well as cancer. We recently reported that the class II HDAC inhibitor, MC1568, and the phytochemical, gallic acid, lowered high blood pressure in mouse models of hypertension. We hypothesized that class II HDACs may be involved in the regulation of hypertension. The aim of this study was to determine and compare the effects of well-known HDAC inhibitors (TMP269, panobinostat, and MC1568), phytochemicals (gallic acid, sulforaphane, and piceatannol), and anti-hypertensive drugs (losartan, carvedilol, and furosemide) on activities of class IIa HDACs (HDAC4, 5, 7, and 9). The selective class IIa HDAC inhibitor, TMP269, and the pan-HDAC inhibitor, panobinostat, but not MC1568, clearly inhibited class IIa HDAC activities. Among the three phytochemicals, gallic acid showed remarkable inhibition, whereas sulforaphane presented mild inhibition of class IIa HDACs. Piceatannol inhibited only HDAC7 activity. As expected, the anti-hypertensive drugs losartan, carvedilol, and furosemide did not affect the activity of any class IIa HDAC. In addition, we evaluated the inhibitory effect of several compounds on the activity of class l HDACs (HDAC1, 2, 3, and 8) and class IIb HDAC (HDAC6). MC1568 did not affect the activities of HDAC1, HDAC2, and HDAC3, but it reduced the activity of HDAC8 at concentrations of 1 and 10 μM. Gallic acid weakly inhibited HDAC1 and HDAC6 activities, but strongly inhibited HDAC8 activity with effectiveness comparable to that of trichostatin A. Inhibition of HDAC2 activity by sulforaphane was stronger than that by piceatnnaol. These results indicated that gallic acid is a powerful dietary inhibitor of HDAC8 and class IIa/b HDAC activities. Sulforaphane may also be used as a dietary inhibitor of HDAC2 and class IIa HDAC. Our findings suggest that the class II HDAC inhibitor, MC1568, does not inhibit class IIa HDAC, but inhibits

Systems of amonium polyborates - monoammonium phosphate -water at 25 deg C

International Nuclear Information System (INIS)

Skvortsov, V.G.; Sadetdinov, Sh.V.; Polenov, A.D.; Mikhajlov, V.I.

1992-01-01

It is established by solubility and refractometry methods at 25 deg C that systems of ammonium tetraborate (pentaborate) monoammonium phosphate-water refer to sumple eutonic type. The ammonium borates and monoammoniumphosphate exert salting effect over each other. It is found that phosphate borate compositions on the basis of ammonium salts are characterized by lower inhibitor properties as compared to sodium salts

Energetics of sodium efflux from Escherichia coli

International Nuclear Information System (INIS)

Borbolla, M.G.; Rosen, B.P.

1984-01-01

When energy-starved cells of Escherichia coli were passively loaded with 22 Na+, efflux of sodium could be initiated by addition of a source of metabolic energy. Conditions were established where the source of energy was phosphate bond energy, an electrochemical proton gradient, or both. Only an electrochemical proton gradient was required for efflux from intact cells. These results are consistent with secondary exchange of Na+ for H+ catalyzed by a sodium/proton antiporter

Characterization of inorganic phosphate transport in the triple-negative breast cancer cell line, MDA-MB-231.

Science.gov (United States)

Russo-Abrahão, Thais; Lacerda-Abreu, Marco Antônio; Gomes, Tainá; Cosentino-Gomes, Daniela; Carvalho-de-Araújo, Ayra Diandra; Rodrigues, Mariana Figueiredo; Oliveira, Ana Carolina Leal de; Rumjanek, Franklin David; Monteiro, Robson de Queiroz; Meyer-Fernandes, José Roberto

2018-01-01

Recent studies demonstrate that interstitial inorganic phosphate is significantly elevated in the breast cancer microenvironment as compared to normal tissue. In addition it has been shown that breast cancer cells express high levels of the NaPi-IIb carrier (SLC34A2), suggesting that this carrier may play a role in breast cancer progression. However, the biochemical behavior of inorganic phosphate (Pi) transporter in this cancer type remains elusive. In this work, we characterize the kinetic parameters of Pi transport in the aggressive human breast cancer cell line, MDA-MB-231, and correlated Pi transport with cell migration and adhesion. We determined the influence of sodium concentration, pH, metabolic inhibitors, as well as the affinity for inorganic phosphate in Pi transport. We observed that the inorganic phosphate is dependent on sodium transport (K0,5 value = 21.98 mM for NaCl). Furthermore, the transport is modulated by different pH values and increasing concentrations of Pi, following the Michaelis-Menten kinetics (K0,5 = 0.08 mM Pi). PFA, monensin, furosemide and ouabain inhibited Pi transport, cell migration and adhesion. Taken together, these results showed that the uptake of Pi in MDA-MB-231 cells is modulated by sodium and by regulatory mechanisms of intracellular sodium gradient. General Significance: Pi transport might be regarded as a potential target for therapy against tumor progression.

Alkali metals and group IIA metals

International Nuclear Information System (INIS)

Fenton, D.E.

1987-01-01

This chapter on the coordination complexes of the alkali metals of group IIA starts with a historical perspective of their chemistry, from simple monodentate ligands, metal-β-diketonates to the macrocyclic polyethers which act as ligands to the alkali and akaline earth metals. Other macrocyclic ligands include quarterenes, calixarenes, porphyrins, phthalocyanines and chlorophylls. A section on the naturally occurring ionophores and carboxylic ionophores is included. (UK)

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

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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.

Metabolic Transition of Milk Lactose Synthesis and Up-regulation by AKT1 in Sows from Late Pregnancy to Lactation.

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Chen, Fang; Chen, Baoliang; Guan, Wutai; Chen, Jun; Lv, Yantao; Qiao, Hanzhen; Wang, Chaoxian; Zhang, Yinzhi

2017-03-01

Lactose plays a crucial role in controlling milk volume by inducing water toward into the mammary secretory vesicles from the mammary epithelial cell cytoplasm, thereby maintaining osmolality. In current study, we determined the expression of several lactose synthesis related genes, including glucose transporters (glucose transporter 1, glucose transporter 8, sodium-glucose cotransporter 1, sodium-glucose cotransporter 3, and sodium-glucose cotransporter 5), lactose synthases (α-lactalbumin and β1,4-galactosyltransferase), and hexokinases (hexokinase-1 and hexokinase-2) in sow mammary gland tissue at day 17 before delivery, on the 1st day of lactation and at peak lactation. The data showed that glucose transporter 1 was the dominant glucose transporter within sow mammary gland and that expression of each glucose transporter 1, sodium-glucose cotransporter 1, hexokinase-1, hexokinase-2, α-lactalbumin, and β1,4-galactosyltransferase were increased (p lactose synthesis was significantly elevated with the increase of milk production and AKT1 could positively regulate lactose synthesis.

Contribution of Drinking Water Softeners to Daily Phosphate Intake in Slovenia

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Gregor Jereb

2017-10-01

Full Text Available The cumulative phosphate intake in a typical daily diet is high and, according to several studies, already exceeds recommended values. The exposure of the general population to phosphorus via drinking water is generally not known. One of the hidden sources of phosphorus in a daily diet is sodium polyphosphate, commonly used as a drinking water softener. In Slovenia, softening of drinking water is carried out exclusively within the internal (household drinking water supply systems to prevent the accumulation of limescale. The aim of the study was to determine the prevalence of sodium phosphates in the drinking water in Slovenia in different types of buildings, to determine residents’ awareness of the presence of chemical softeners in their drinking water, and to provide an exposure assessment on the phosphorus intake from drinking water. In the current study, the presence of phosphates in the samples of drinking water was determined using a spectrophotometric method with ammonium molybdate. In nearly half of the samples, the presence of phosphates as water softeners was confirmed. The measured concentrations varied substantially from 0.2 mg PO4/L to 24.6 mg PO4/L. Nearly 70% of the respondents were not familiar with the exact data on water softening in their buildings. It follows that concentrations of added phosphates should be controlled and the consumers should be informed of the added chemicals in their drinking water. The health risks of using sodium polyphosphate as a drinking water softener have not been sufficiently investigated and assessed. It is highly recommended that proper guidelines and regulations are developed and introduced to protect human health from adverse effects of chemicals in water intended for human consumption.

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

Science.gov (United States)

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

2001-11-30

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

NCBI nr-aa BLAST: CBRC-CJAC-01-1252 [SEVENS

Lifescience Database Archive (English)

Full Text Available CBRC-CJAC-01-1252 ref|NP_004849.2| solute carrier family 4, sodium bicarbonate cotr...ansporter, member 8 isoform b [Homo sapiens] gb|EAW58193.1| solute carrier family 4, sodium bicarbonate cotransporter, member 8, isoform CRA_c [Homo sapiens] NP_004849.2 0.0 96% ...

Tanshinone IIA protects PC12 cells from β-amyloid(25-35)-induced apoptosis via PI3K/Akt signaling pathway.

Science.gov (United States)

Dong, Huimin; Mao, Shanping; Mao, Shanpin; Wei, Jiajun; Liu, Baohui; Zhang, Zhaohui; Zhang, Qian; Yan, Mingmin

2012-06-01

For the aging populations of any nation, Dementia is becoming a primary problem and Alzheimer’s dementia (AD) is the most common type. However, until now, there is no effective treatment for AD. Tanshinone IIA (Tan IIA) has been reported for neuroprotective potential to against amyloid β peptides (Aβ)-induced cytotoxicity in the rat pheochromocytoma cell line PC-12, which is widely used as AD research model, but the mechanism still remains unclear. To investigate the effect of Tan IIA and the possible molecular mechanism in the apoptosis of PC12 cells, we induced apoptosis in PC12 cells with β-amyloid(25-35), and treated cells with Tan IIA. After 24 h treatment, we found that Tan IIA increased the cell viability and reduced the number of apoptotic cells induced by Aβ(25-35). However, neuroprotection of Tan IIA was abolished by PI3K inhibitor LY294002. Meanwhile, Treatment with lithium chloride, a phosphorylation inhibitor of GSK3β, which is a downstream target of PI3K/Akt, can block Aβ(25-35)-induced cell apoptosis in a Tan IIA-like manner. Our findings suggest that Tan IIA is an effective neuroprotective agent and a viable candidate in AD therapy and PI3K/Akt activation and GSK3β phosphorylation are involved in the neuroprotection of Tan IIA.

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

Science.gov (United States)

Massover, William H

2010-06-01

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

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

Science.gov (United States)

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

2018-04-01

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

TGF-β signaling directly regulates transcription and functional expression of the electrogenic sodium bicarbonate cotransporter 1, NBCe1 (SLC4A4), via Smad4 in mouse astrocytes.

Science.gov (United States)

Khakipoor, Shokoufeh; Ophoven, Christian; Schrödl-Häußel, Magdalena; Feuerstein, Melanie; Heimrich, Bernd; Deitmer, Joachim W; Roussa, Eleni

2017-08-01

The electrogenic sodium bicarbonate cotransporter NBCe1 (SLC4A4) expressed in astrocytes regulates intracellular and extracellular pH. Here, we introduce transforming growth factor beta (TGF-β) as a novel regulator of NBCe1 transcription and functional expression. Using hippocampal slices and primary hippocampal and cortical astrocyte cultures, we investigated regulation of NBCe1 and elucidated the underlying signaling pathways by RT-PCR, immunoblotting, immunofluorescence, intracellular H( + ) recording using the H( + ) -sensitive dye 2',7'-bis-(carboxyethyl)-5-(and-6)-carboxyfluorescein, mink lung epithelial cell (MLEC) assay, and chromatin immunoprecipitation. Activation of TGF-β signaling significantly upregulated transcript, protein, and surface expression of NBCe1. These effects were TGF-β receptor-mediated and suppressed following inhibition of JNK and Smad signaling. Moreover, 4-aminopyridine (4AP)-dependent NBCe1 regulation requires TGF-β. TGF-β increased the rate and amplitude of intracellular H + changes upon challenging NBCe1 in wild-type astrocytes but not in cortical astrocytes from Slc4a4-deficient mice. A Smad4 binding sequence was identified in the NBCe1 promoter and Smad4 binding increased after activation of TGF-β signaling. The data show for the first time that NBCe1 is a direct target of TGF-β/Smad4 signaling. Through activation of the canonical pathway TGF-β acts directly on NBCe1 by binding of Smad4 to the NBCe1 promoter and regulating its transcription, followed by increased protein expression and transport activity. © 2017 The Authors GLIA Published by Wiley Periodicals, Inc.

Hydroxyurea with Radiation Therapy of the Carcinoma of the Cervix IIA, IIB

Energy Technology Data Exchange (ETDEWEB)

Kim, Jin Hee; Youn, Seon Min; Kim, Ok Bae [Keimyung University College of Medicine, Taegu (Korea, Republic of)

1995-12-15

Purpose : To evaluate the efficacy of hydroxyurea with radiation in carcinoma of the cervix, huge exophytic or endophytic stage IIa and Iib. Materials and Methods : Sixty four patients with carcinoma of the cervix stage IIA(29 patients) with exophytic({>=}3cm in diameter) or huge endophytic mass and IIB(35 patients) treated with radiation and hydroxyurea at the Department of Radiation Oncology, Dongsan Hospital, Keimyung University, School of Medicine from Aug, 1989 to May, 1991. The maximum and mean follow up durations were 68 and 57 months respectively. The radiation therapy consisted of external irradiation to the whole pelvis(3600-5400cGy) shield (4X10 cm), and combined with intracavitary irradiation (3000-3500cGy to point A). Hydroxyurea was to be taken in a single oral dose of 1.0gm/day during radiation therapy. Results : The control rate was 89.1%. The actuarial overall five year survival rate was 78.8% for stage IIA and 72.8% for stage IIB. The overall recurrence rate was 25%(16/64). Twenty-three percent of the patients developed or greater thrombocytopenia. Grade 3 or greater GI, GU complication and anemia were not noted. There was no treatment related death noted. Conclusion : We considered that hydroxyurea and radiation therapy may improve survival rate in huge exophytic and endophytic stage IIa cervical carcinoma with acceptible morbidity.

Hydroxyurea with Radiation Therapy of the Carcinoma of the Cervix IIA, IIB

International Nuclear Information System (INIS)

Kim, Jin Hee; Youn, Seon Min; Kim, Ok Bae

1995-01-01

Purpose : To evaluate the efficacy of hydroxyurea with radiation in carcinoma of the cervix, huge exophytic or endophytic stage IIa and Iib. Materials and Methods : Sixty four patients with carcinoma of the cervix stage IIA(29 patients) with exophytic(≥3cm in diameter) or huge endophytic mass and IIB(35 patients) treated with radiation and hydroxyurea at the Department of Radiation Oncology, Dongsan Hospital, Keimyung University, School of Medicine from Aug, 1989 to May, 1991. The maximum and mean follow up durations were 68 and 57 months respectively. The radiation therapy consisted of external irradiation to the whole pelvis(3600-5400cGy) shield (4X10 cm), and combined with intracavitary irradiation (3000-3500cGy to point A). Hydroxyurea was to be taken in a single oral dose of 1.0gm/day during radiation therapy. Results : The control rate was 89.1%. The actuarial overall five year survival rate was 78.8% for stage IIA and 72.8% for stage IIB. The overall recurrence rate was 25%(16/64). Twenty-three percent of the patients developed or greater thrombocytopenia. Grade 3 or greater GI, GU complication and anemia were not noted. There was no treatment related death noted. Conclusion : We considered that hydroxyurea and radiation therapy may improve survival rate in huge exophytic and endophytic stage IIa cervical carcinoma with acceptible morbidity

Investigation of the benzotriazole as addictive for carbon steel phosphating; Estudo da utilizacao do benzotriazol como aditivo para a fosfatizacao de aco carbono

Energy Technology Data Exchange (ETDEWEB)

Annies, V.; Cunha, M.T.; Rodrigues, P.R.P.; Banczek, E.P. [Universidade Estadual do Centro-Oeste, Guarapuava, PR (Brazil). Dept. de Quimica; Costa, I. [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil); Terada, M. [Universidade de Sao Paulo (POLI/USP), SP (Brazil). Escola Politecnica. Dept. de Engenharia Metalurgica e de Materiais

2010-07-01

This work studied the viability of substitution of sodium nitrite (NaNO{sub 2}) for benzotriazole (BTAH) in the zinc phosphate bath (PZn+NaNO{sub 2}) for phosphating of carbon steel (SAE 1010). The characterization of the samples was carried out by Scanning Electron Microscopy, Optical Microscopy and X-ray diffraction. The chemical composition was evaluated by Energy Dispersive Spectroscopy. The corrosion behavior of the samples was investigated by Open Circuit Potential, Electrochemical Impedance Spectroscopy and Anodic Potentiodynamic Polarization Curves in a 0.5 mol L{sup -1} NaCl electrolyte. The experimental results showed that the phosphate layer obtained in the solution with benzotriazole (PZn+BTAH) presented better corrosion resistance properties than that obtained in sodium nitrite. The results demonstrated that the sodium nitrite NaNO{sub 2} can be replaced by benzotriazole (BTAH) in zinc phosphate baths. (author)

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

International Nuclear Information System (INIS)

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

1987-01-01

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

Inositol hexa-phosphate: a potential chelating agent for uranium

International Nuclear Information System (INIS)

Cebrian, D.; Tapia, A.; Real, A.; Morcillo, M.A.

2007-01-01

Chelation therapy is an optimal method to reduce the radionuclide-related risks. In the case of uranium incorporation, the treatment of choice is so far i.v infusion of a 1.4% sodium bicarbonate solution, but the efficacy has been proved to be not very high. In this study, we examine the efficacy of some substances: bicarbonate, citrate, diethylenetriamine pentaacetic acid (DTPA), ethidronate (EHBP) and inositol hexa-phosphate (phytic acid) to chelate uranium using a test developed by Braun et al. Different concentrations of phytic acid, an abundant component of plant seeds that is widely distributed in animal cells and tissues in substantial levels, were tested and compared to the same concentrations of sodium citrate, bicarbonate, EHBP and DTPA. The results showed a strong affinity of inositol hexa-phosphate for uranium, suggesting that it could be an effective chelating agent for uranium in vivo. (authors)

Dysregulated gene expression in the primary osteoblasts and osteocytes isolated from hypophosphatemic Hyp mice.

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Kazuaki Miyagawa

Full Text Available Osteocytes express multiple genes involved in mineral metabolism including PHEX, FGF23, DMP1 and FAM20C. In Hyp mice, a murine model for X-linked hypophosphatemia (XLH, Phex deficiency results in the overproduction of FGF23 in osteocytes, which leads to hypophosphatemia and impaired vitamin D metabolism. In this study, to further clarify the abnormality in osteocytes of Hyp mice, we obtained detailed gene expression profiles in osteoblasts and osteocytes isolated from the long bones of 20-week-old Hyp mice and wild-type (WT control mice. The expression of Fgf23, Dmp1, and Fam20c was higher in osteocytic cells than in osteoblastic cells in both genotypes, and was up-regulated in Hyp cells. Interestingly, the up-regulation of these genes in Hyp bones began before birth. On the other hand, the expression of Slc20a1 encoding the sodium/phosphate (Na+/Pi co-transporter Pit1 was increased in osteoblasts and osteocytes from adult Hyp mice, but not in Hyp fetal bones. The direct effects of extracellular Pi and 1,25-dihydroxyvitamin D3 [1,25(OH2D3] on isolated osteoblastic and osteocytic cells were also investigated. Twenty-four-hour treatment with 10-8 M 1,25(OH2D3 increased the expression of Fgf23 in WT osteoblastic cells but not in osteocytic cells. Dmp1 expression in osteocytic cells was increased due to the 24-hour treatment with 10 mM Pi and was suppressed by 10-8 M 1,25(OH2D3 in WT osteocytic cells. We also found the up-regulation of the genes for FGF1, FGF2, their receptors, and Egr-1 which is a target of FGF signaling, in Hyp osteocytic cells, suggesting the activation of FGF/FGFR signaling. These results implicate the complex gene dysregulation in osteoblasts and osteocytes of Hyp mice, which might contribute to the pathogenesis.

Effects of Different End-Point Cooking Temperatures on the Efficiency of Encapsulated Phosphates on Lipid Oxidation Inhibition in Ground Meat.

Science.gov (United States)

Kılıç, B; Şimşek, A; Claus, J R; Atılgan, E; Aktaş, N

2015-10-01

Effects of 0.5% encapsulated (e) phosphates (sodium tripolyphosphate, STP; sodium hexametaphosphate, HMP; sodium pyrophosphate, SPP) on lipid oxidation during storage (0, 1, and 7 d) of ground meat (chicken, beef) after being cooked to 3 end-point cooking temperatures (EPCT; 71, 74, and 77 °C) were evaluated. The use of STP or eSTP resulted in lower (P cooking loss (CL) compared to encapsulated or unencapsulated forms of HMP and SPP. Increasing EPCT led to a significant increase in CL (P chicken compared to 74 and 71 °C (P chicken samples (P < 0.05). Findings suggest that encapsulated phosphates can be a strategy to inhibit lipid oxidation for meat industry and the efficiency of encapsulated phosphates on lipid oxidation inhibition can be enhanced by lowering EPCT. © 2015 Institute of Food Technologists®

Benefits and Harms of Sodium-Glucose Co-Transporter 2 Inhibitors in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis

Science.gov (United States)

Gluud, Lise L.; Bennett, Cathy; Grøndahl, Magnus F.; Christensen, Mikkel B.; Knop, Filip K.; Vilsbøll, Tina

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 Selection We included double-blinded, randomised controlled trials (RCTs) evaluating SGLT2-i administered in the highest approved therapeutic doses (canagliflozin 300 mg/day, dapagliflozin 10 mg/day, and empagliflozin 25 mg/day) for ≥12 weeks. Comparison groups could receive placebo or oral antidiabetic drugs (OAD) including metformin, sulphonylureas (SU), or dipeptidyl peptidase 4 inhibitors (DPP-4-i). Trials were identified through electronic databases and extensive manual searches. Primary outcomes were glycated haemoglobin A1c (HbA1c) levels, serious adverse events, death, severe hypoglycaemia, ketoacidosis and CVD. Secondary outcomes were fasting plasma glucose, body weight, blood pressure, heart rate, lipids, liver function tests, creatinine and adverse events including infections. The quality of the evidence was assessed using GRADE. Results Meta-analysis of 34 RCTs with 9,154 patients showed that SGLT2-i reduced HbA1c compared with placebo (mean difference -0.69%, 95% confidence interval -0.75 to -0.62%). We downgraded the evidence to ‘low quality’ due to variability and evidence of publication bias (P = 0.015). Canagliflozin was associated with the largest reduction in HbA1c (-0.85%, -0.99% to -0.71%). There were no differences between SGLT2-i and placebo for serious adverse events. SGLT2-i increased the risk of urinary and genital tract infections and increased serum creatinine, and exerted beneficial effects on bodyweight, blood pressure, lipids and alanine aminotransferase (moderate to low quality evidence). Analysis of 12 RCTs found a beneficial effect of SGLT2-i on HbA1c compared with OAD (-0.20%, -0.28 to -0.13%; moderate quality evidence). Conclusion

Japanese contributions to IAEA INTOR workshop, phase IIA

International Nuclear Information System (INIS)

Fujisawa, Noboru; Sugihara, Masayoshi; Shimada, Michiya; Saito, Seiji.

1982-11-01

This report corresponds to Chapter VI of Japanese contribution report to IAEA INTOR workshop, Phase IIA. Special emphasis is placed on pumped limiter analysis for comparative studies between limiter and divertor concepts. Pumping characteristics of divertor/limiter and radiation cooling of diverted plasmas by impurities are also intensively studied. (author)

Tanshinone IIA inhibits metastasis after palliative resection of hepatocellular carcinoma and prolongs survival in part via vascular normalization

Directory of Open Access Journals (Sweden)

Wang Wen-Quan

2012-11-01

Full Text Available Abstract Background Promotion of endothelial normalization restores tumor oxygenation and obstructs tumor cells invasion, intravasation, and metastasis. We therefore investigated whether a vasoactive drug, tanshinone IIA, could inhibit metastasis by inducing vascular normalization after palliative resection (PR of hepatocellular carcinoma (HCC. Methods A liver orthotopic double-tumor xenograft model in nude mouse was established by implantation of HCCLM3 (high metastatic potential and HepG2 tumor cells. After removal of one tumor by PR, the effects of tanshinone IIA administration on metastasis, tumor vascularization, and survival were evaluated. Tube formation was examined in mouse tumor-derived endothelial cells (TECs treated with tanshinone IIA. Results PR significantly accelerated residual hepatoma metastases. Tanshinone IIA did not inhibit growth of single-xenotransplanted tumors, but it did reduce the occurrence of metastases. Moreover, it inhibited PR-enhanced metastases and, more importantly, prolonged host survival. Tanshinone IIA alleviated residual tumor hypoxia and suppressed epithelial-mesenchymal transition (EMT in vivo; however, it did not downregulate hypoxia-inducible factor 1α (HIF-1α or reverse EMT of tumor cells under hypoxic conditions in vitro. Tanshinone IIA directly strengthened tube formation of TECs, associated with vascular endothelial cell growth factor receptor 1/platelet derived growth factor receptor (VEGFR1/PDGFR upregulation. Although the microvessel density (MVD of residual tumor tissue increased after PR, the microvessel integrity (MVI was still low. While tanshinone IIA did not inhibit MVD, it did dramatically increase MVI, leading to vascular normalization. Conclusions Our results demonstrate that tanshinone IIA can inhibit the enhanced HCC metastasis associated with PR. Inhibition results from promoting VEGFR1/PDGFR-related vascular normalization. This application demonstrates the potential clinical

Hanford 100-N Area In Situ Apatite and Phosphate Emplacement by Groundwater and Jet Injection: Geochemical and Physical Core Analysis

Energy Technology Data Exchange (ETDEWEB)

Szecsody, James E.; Vermeul, Vincent R.; Fruchter, Jonathan S.; Williams, Mark D.; Rockhold, Mark L.; Qafoku, Nikolla; Phillips, Jerry L.

2010-07-01

The purpose of this study is to evaluate emplacement of phosphate into subsurface sediments in the Hanford Site 100-N Area by two different technologies: groundwater injection of a Ca-citrate-PO4 solution and water-jet injection of sodium phosphate and/or fish-bone apatite. In situ emplacement of phosphate and apatite adsorbs, then incorporates Sr-90 into the apatite structure by substitution for calcium. Overall, both technologies (groundwater injection of Ca-citrate-PO4) and water-jet injection of sodium phosphate/fish-bone apatite) delivered sufficient phosphate to subsur¬face sediments in the 100-N Area. Over years to decades, additional Sr-90 will incorporate into the apatite precipitate. Therefore, high pressure water jetting is a viable technology to emplace phosphate or apatite in shallow subsurface sediments difficult to emplace by Ca-citrate-PO4 groundwater injections, but further analysis is needed to quantify the relevant areal extent of phosphate deposition (in the 5- to 15-ft distance from injection points) and cause of the high deposition in finer grained sediments.

Effects of dietary glucose and sodium chloride on intestinal glucose absorption of common carp (Cyprinus carpio L.).

Science.gov (United States)

Qin, Chaobin; Yang, Liping; Zheng, Wenjia; Yan, Xiao; Lu, Ronghua; Xie, Dizhi; Nie, Guoxing

2018-01-08

The co-transport of sodium and glucose is the first step for intestinal glucose absorption. Dietary glucose and sodium chloride (NaCl) may facilitate this physiological process in common carp (Cyprinus carpio L.). To test this hypothesis, we first investigated the feeding rhythm of intestinal glucose absorption. Carps were fed to satiety once a day (09:00 a.m.) for 1 month. Intestinal samples were collected at 01:00, 05:00, 09:00, 13:00, 17:00 and 21:00. Result showed that food intake greatly enhanced sodium/glucose cotransporter 1 (SGLT1) and glucose transporter type 2 (GLUT2) expressions, and improved glucose absorption, with highest levels at 09:00 a.m.. Then we designed iso-nitrogenous and iso-energetic diets with graded levels of glucose (10%, 20%, 30%, 40% and 50%) and NaCl (0%, 1%, 3% and 5%), and submitted to feeding trial for 10 weeks. The expressions of SGLT1 and GLUT2, brush border membrane vesicles (BBMVs) glucose transport and intestinal villus height were determined after the feeding trial. Increasing levels of dietary glucose and NaCl up-regulated mRNA and protein levels of SGLT1 and GLUT2, enhanced BBMVs glucose transport in the proximal, mid and distal intestine. As for histological adaptive response, however, high-glucose diet prolonged while high-NaCl diet shrank intestinal villus height. Furthermore, we also found that higher mRNA levels of SGLT1 and GLUT2, higher glucose transport capacity of BBMVs, and higher intestinal villus were detected in the proximal and mid intestine, compared to the distal part. Taken together, our study indicated that intestinal glucose absorption in carp was primarily occurred in the proximal and mid intestine, and increasing levels of dietary glucose and NaCl enhanced intestinal glucose absorption in carp. Copyright © 2017 Elsevier Inc. All rights reserved.

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

Science.gov (United States)

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

2010-11-01

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

Encapsulated phosphates reduce lipid oxidation in both ground chicken and ground beef during raw and cooked meat storage with some influence on color, pH, and cooking loss.

Science.gov (United States)

Kılıç, B; Simşek, A; Claus, J R; Atılgan, E

2014-05-01

Effects of encapsulated sodium tripolyphosphate (STP), sodium hexametaphosphate (HMP) and sodium pyrophosphate (SPP) on lipid oxidation in uncooked (0, 2, 24h) and cooked (0, 1, 7 d) ground chicken and beef during storage were determined. Ten phosphate treatments included a control (no phosphate), three unencapsulated (u) at 0.5% and three encapsulated (e) phosphates (0.5%) each at a low (e-low) and high (e-high) coating level. Two heating rates (slow, fast) were investigated. Cooking loss (CL), pH, color, orthophosphate (OP), TBARS and lipid hydroperoxides (LPO) were determined. A fast heating and uSTP resulted in lower CL (pcooked samples. Not increased coating level but encapsulated phosphates decreased lipid oxidation in cooked samples (p<0.05). Copyright © 2014 Elsevier Ltd. All rights reserved.

Sodium aluminum-iron phosphate glass-ceramics for immobilization of lanthanide oxide wastes from pyrochemical reprocessing of spent nuclear fuel

Science.gov (United States)

Stefanovsky, S. V.; Stefanovsky, O. I.; Kadyko, M. I.; Nikonov, B. S.

2018-03-01

Sodium aluminum (iron) phosphate glass ceramics containing of up to 20 wt.% rare earth (RE) oxides simulating pyroprocessing waste were produced by melting at 1250 °C followed by either quenching or slow cooling to room temperature. The iron-free glass-ceramics were composed of major glass and minor phosphotridymite and monazite. The iron-bearing glass-ceramics were composed of major glass and minor monazite and Na-Al-Fe orthophosphate at low waste loadings (5-10 wt.%) and major orthophosphate and minor monazite as well as interstitial glass at high waste loadings (15-20 wt.%). Slowly cooled samples contained higher amount of crystalline phases than quenched ones. Monazite is major phase for REs. Leach rates from the materials of major elements (Na, Al, Fe, P) are 10-5-10-7 g cm-2 d-1, RE elements - lower than 10-5 g cm-2 d-1.

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

Science.gov (United States)

Delpire, Eric; Gagnon, Kenneth B

2018-03-25

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

Study of a hydraulic dicalcium phosphate dihydrate/calcium oxide-based cement for dental applications.

Science.gov (United States)

el-Briak, Hasna; Durand, Denis; Nurit, Josiane; Munier, Sylvie; Pauvert, Bernard; Boudeville, Phillipe

2002-01-01

By mixing CaHPO(4) x 2H(2)O (DCPD) and CaO with water or sodium phosphate buffers as liquid phase, a calcium phosphate cement was obtained. Its physical and mechanical properties, such as compressive strength, initial and final setting times, cohesion time, dough time, swelling time, dimensional and thermal behavior, and injectability were investigated by varying different parameters such as liquid to powder (L/P) ratio (0.35-0.7 ml g(-1)), molar calcium to phosphate (Ca/P) ratio (1.67-2.5) and the pH (4, 7, and 9) and the concentration (0-1 M) of the sodium phosphate buffer. The best results were obtained with the pH 7 sodium phosphate buffer at the concentration of 0.75 M. With this liquid phase, physical and mechanical properties depended on the Ca/P and L/P ratios, varying from 3 to 11 MPa (compressive strength), 6 to 10 min (initial setting time), 11 to 15 min (final setting time), 15 to 30 min (swelling time), 7 to 20 min (time of 100% injectability). The dough or working time was over 16 min. This cement expanded during its setting (1.2-5 % according to Ca/P and L/P ratios); this would allow a tight filling. Given the mechanical and rheological properties of this new DCPD/CaO-based cement, its use as root canal sealing material can be considered as classical calcium hydroxide or ZnO/eugenol-based pastes, without or with a gutta-percha point. Copyright 2002 Wiley Periodicals, Inc. J Biomed Mater Res (Appl Biomater) 63: 447-453, 2002

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

International Nuclear Information System (INIS)

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

1986-01-01

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

Uranium extraction from Uro area phosphate ore, Nuba mountains, Sudan

International Nuclear Information System (INIS)

Mohammed, A. A.; Eltayeb, M. A. H.

2003-01-01

This study was carried out mainly to extract uranium from Uro area phosphate ore in the eastern part of Nuba mountains near Abu Gibiha town in southern Kurdufan state. For this purpose first, the phosphate ore samples were decomposed with sulphuric acid. the resulting phosphoric acid was filtered off, and pretreated with pyrite and activated charcoal. the chemical analysis of the obtained grain phosphoric acid showed that about 98% of uranium content of the phosphate ore was rendered soluble in the phosphoric acid. The clear green phosphoric acid was introduced to uranium extraction by 25% tributylphosphate (Tbp) in kerosene. The effect of several factors on the extraction and stripping processes namely, interference's effect, the suitable strip solution, the required number of extraction and stripping stages, the optimum phase ratio have been studied in details. A three stage extraction at a phase ratio (aqueous/organic) of 1:2, followed by two stages stripping using 0.5 M sodium carbonate solution at a phase ratio (A/O) of 1:4 were found to be the optimum conditions to report more than 98% of uranium content in green phosphoric acid to the aqueous phase as uranyl tricarbonate complex (UO 2 (CO 3 ) 3 ) 4- . By applying sodica decomposition upon the stripping carbonate solution using 50% sodium hydroxide, about 98% of uranium content was precipitated as sodium diuranate concentrate (Na 2 U 2 O 7 ). The chemical analysis using atomic absorption spectrometry (Aas) showed a good agreement between the specification of the obtained uranium concentrate with the standard commercial specification of sodium diuranate concentrate. Further purification was achieved for the yellow cake by selective precipitation of uranium from the solution as uranium peroxide (UO 4 .2H 2 O) using 30% hydrogen peroxide. Finally the uranium peroxide precipitated was calcined at 450 degree C to obtain the orange powder uranium trioxide (UO 3 ). The chemical analysis of the final uranium trioxide

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

Science.gov (United States)

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

2013-12-20

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

Reference values for urinary oxalate, calcium, citrate, uric acid, phosphate, magnesium, sulphate and sodium in biochemistry students at Universidad Nacional del Litoral, Argentina

Directory of Open Access Journals (Sweden)

Verónica Fernández

2017-10-01

Full Text Available Introduction: Urolithiasis (UL is a common disease whose incidence increased in the last quarter of the twentieth century. Metabolic evaluation is necessary for diagnosis, which requires the establishment of reference values (RV for the population in question. Objective: To determine the RV for calcium, oxalate, citrate, uric acid, phosphate, magnesium, sulphate and sodium in 24-hour urine belonging to students from the School of Biochemistry and Biological Sciences at Universidad Nacional del Litoral, province of Santa Fe, Argentina. Once RV were established, a frequency of alterations was determined and then compared with literature data. Methods: The NCCLSC28-A3 guideline (2008 was used. The study group included 69 students. The enzymatic colorimetric method, a Metrolab 1600 plus spectrophotometer and a DIESTRO ionselective electrode were also employed. Results: The RV found (95 % CI were the following: oxalate, 1.96-45.08; calcium, 20.65-250.74; citrate, 112.78-666.01; uric acid, 58.73-782.17; phosphate, 238.37-1051.44; magnesium, 28.7-146.67, all these values expressed as mg/24h; sulphate, 3.15-25.18 mmol/24h, and sodium, 42.81-285.3 mEq/24h. These findings emerged as well: hyperoxaluria, 3 %; hypercalciuria 12 %; hypocitraturia, 3 %; hyperuricosuria, 6 %; hyperphosphaturia, 6 %; hypomagnesuria, 6 %; hypernatriuria, 7 %, and hypersulphaturia, 0 %. When RV were compared, some analyte levels were similar and others showed a considerable difference. Conclusions: The diagnosis of UL through the study of metabolic changes is different according to the reference value used. Applying reference values established for other populations, including those of commercial kits manufacturers, may lead to a diagnosis which does not match the clinical condition of the patient.

A dangerous liaison: Leptin and sPLA2-IIA join forces to induce proliferation and migration of astrocytoma cells.

Directory of Open Access Journals (Sweden)

Rubén Martín

Full Text Available Glioblastoma, the most aggressive type of primary brain tumour, shows worse prognosis linked to diabetes or obesity persistence. These pathologies are chronic inflammatory conditions characterized by altered profiles of inflammatory mediators, including leptin and secreted phospholipase A2-IIA (sPLA2-IIA. Both proteins, in turn, display diverse pro-cancer properties in different cell types, including astrocytes. Herein, to understand the underlying relationship between obesity and brain tumors, we investigated the effect of leptin, alone or in combination with sPLA2-IIA on astrocytoma cell functions. sPLA2-IIA induced up-regulation of leptin receptors in 1321N1 human astrocytoma cells. Leptin, as well as sPLA2-IIA, increased growth and migration in these cells, through activation/phosphorylation of key proteins of survival cascades. Leptin, at concentrations with minimal or no activating effects on astrocytoma cells, enhanced growth and migration promoted by low doses of sPLA2-IIA. sPLA2-IIA alone induced a transient phosphorylation pattern in the Src/ERK/Akt/mTOR/p70S6K/rS6 pathway through EGFR transactivation, and co-addition of leptin resulted in a sustained phosphorylation of these signaling regulators. Mechanistically, EGFR transactivation and tyrosine- and serine/threonine-protein phosphatases revealed a key role in this leptin-sPLA2-IIA cross-talk. This cooperative partnership between both proteins was also found in primary astrocytes. These findings thus indicate that the adipokine leptin, by increasing the susceptibility of cells to inflammatory mediators, could contribute to worsen the prognosis of tumoral and neurodegenerative processes, being a potential mediator of some obesity-related medical complications.

Synergism between sodium chloride, sucrose and tricalcium phosphate in the osmotic dehydration of oca (Oxalis tuberosa with and without chitosan coating

Directory of Open Access Journals (Sweden)

José Arroyo Portal

2010-12-01

Full Text Available We investigated the synergistic effect of three solutes (sodium chloride, sucrose, tricalcium phosphate in different combinations of concentration, on the moisture, solid gain and calcium gain in oca (Oxalis tuberosa with and without chitosan (CR and SR. In both cases applied the Simplex with Extended Centroid mixture design. Were used cylinders of oca of 0.9 cm of diameter and 3.4 cm of length. The kinetics of moisture, solid gain and calcium gain for 48 hours was evaluated. The effective diffusivity of water, solids and calcium was determined. We found that in samples CR is greater loss of water and less solid gain compared with SR samples mainly as sodium chloride or sucrose participate independently, while for the gain of calcium, in all cases, the CR samples gain more of calcium than SR samples. The effective diffusivities found are: water, 1.19E-09 m2 /s in samples CR and 1.34E-09 m2 /s in SR samples; for solid, 3.67E-09 m2 /s in samples CR and 5.43E-09 m2 /s in SR samples; and, for calcium 3.32E-11 m2 /s in samples CR and 1.57E-09 m2 /s in SR samples.

In-vitro Release Study of Carvedilol Phosphate Matrix Tablets ...

African Journals Online (AJOL)

Microcrystalline cellulose (Avicel PH 101), starch (Sta-Rx 1500) and lactose monohydrate were used as diluents in the formulations while the effect of sodium lauryl sulphate (wetting agent) was studied for some of the formulations. The tablets were characterized for carvedilol phosphate release in both simulated gastric and ...

Japanese contributions to IAEA INTOR workshop, phase IIA

International Nuclear Information System (INIS)

Tone, Tatsuzo; Shiraishi, Kensuke; Watanabe, Hitoshi

1982-11-01

This report describes the engineering testing to be carried out in INTOR, which has been presented for discussions of Group C in the Phase IIA of the INTOR Workshop. Structural material testing, blanket testing and long-term operation are covered. A design of test modules to be installed in the INTOR is proposed. (author)

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

DEFF Research Database (Denmark)

Zeuthen, Thomas; Belhage, Bo; Zeuthen, Emil

2005-01-01

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

Ameloblast Modulation and Transport of Cl⁻, Na⁺, and K⁺ during Amelogenesis.

Science.gov (United States)

Bronckers, A L J J; Lyaruu, D; Jalali, R; Medina, J F; Zandieh-Doulabi, B; DenBesten, P K

2015-12-01

Ameloblasts express transmembrane proteins for transport of mineral ions and regulation of pH in the enamel space. Two major transporters recently identified in ameloblasts are the Na(+)K(+)-dependent calcium transporter NCKX4 and the Na(+)-dependent HPO4 (2-) (Pi) cotransporter NaPi-2b. To regulate pH, ameloblasts express anion exchanger 2 (Ae2a,b), chloride channel Cftr, and amelogenins that can bind protons. Exposure to fluoride or null mutation of Cftr, Ae2a,b, or Amelx each results in formation of hypomineralized enamel. We hypothesized that enamel hypomineralization associated with disturbed pH regulation results from reduced ion transport by NCKX4 and NaPi-2b. This was tested by correlation analyses among the levels of Ca, Pi, Cl, Na, and K in forming enamel of mice with null mutation of Cftr, Ae2a,b, and Amelx, according to quantitative x-ray electron probe microanalysis. Immunohistochemistry, polymerase chain reaction analysis, and Western blotting confirmed the presence of apical NaPi-2b and Nckx4 in maturation-stage ameloblasts. In wild-type mice, K levels in enamel were negatively correlated with Ca and Cl but less negatively or even positively in fluorotic enamel. Na did not correlate with P or Ca in enamel of wild-type mice but showed strong positive correlation in fluorotic and nonfluorotic Ae2a,b- and Cftr-null enamel. In hypomineralizing enamel of all models tested, 1) Cl(-) was strongly reduced; 2) K(+) and Na(+) accumulated (Na(+) not in Amelx-null enamel); and 3) modulation was delayed or blocked. These results suggest that a Na(+)K(+)-dependent calcium transporter (likely NCKX4) and a Na(+)-dependent Pi transporter (potentially NaPi-2b) located in ruffle-ended ameloblasts operate in a coordinated way with the pH-regulating machinery to transport Ca(2+), Pi, and bicarbonate into maturation-stage enamel. Acidification and/or associated physicochemical/electrochemical changes in ion levels in enamel fluid near the apical ameloblast membrane may

30 CFR 57.22208 - Auxiliary fans (I-A, II-A, III, and V-A mines).

Science.gov (United States)

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Auxiliary fans (I-A, II-A, III, and V-A mines... fans (I-A, II-A, III, and V-A mines). (a) Auxiliary fans, except fans used in shops and other areas... applicable requirements of 30 CFR part 18, and be operated so that recirculation is minimized. Auxiliary fans...

Differential diagnosis of gastric adenoma and type IIa early gastric cancer

International Nuclear Information System (INIS)

Tsuchigame, T.; Ogata, Y.; Sumi, M.; Fukui, K.; Saito, R.; Nakashima, K.; Urata, J.; Arakawa, A.; Saito, Y.; Takahashi, M.

1991-01-01

The endoscopic and radiographic findings of 45 gastric adenomas in 39 patients were followed for 6 months to 13 years and compared with type IIa early gastric cancer observed in 9 patients. Difficulties in the diffential diagnosis of these disorders were evaluated. The following features were suggestive of gastric adenomas: clustered lesions; protuberance with gentle slope; smooth surface; and relatively young patients. Discrimination of adenoma from type IIa early gastric cancer is often difficult by visual observation alone; biopsy was essential in most patients. A group III adenoma verified on biopsy should be followed closely because the lesion may harbor a cancer (so-called carcinoma-in-adenoma) or a cancer may later develop. (orig.)

Japanese contributions to IAEA INTOR workshop, phase IIA

International Nuclear Information System (INIS)

Miyamoto, Kenro; Sugihara, Masayoshi; Kimura, Haruyuki

1982-11-01

This report corresponds to Chapter V of Japanese contribution report to IAEA INTOR workshop, Phase IIA. Physics studies for radio frequency heating are concentrated on heating to ignition by means of ion cyclotron and lower hybrid ranges of frequencies, and discharge start-up assist and current drive by lower hybrid range. Their system design studies are also performed. (author)

Vanadyl phosphates as high energy density cathode materials for rechargeable sodium battery

Science.gov (United States)

Zhang, Ruigang; Mizuno, Fuminori; Ling, Chen; Whittingham, Stanley M.; Zhang, Ruibo; Chen, Zehua

2017-08-01

A positive electrode comprising .epsilon.-VOPO.sub.4 and/or Na.sub.x(.epsilon.-VOPO.sub.4) wherein x is a value from 0.1 to 1.0 as an active ingredient, wherein the electrode is capable of insertion and release of sodium ions and a reversible sodium battery containing the positive electrode are provided.

Sodium hyaluronate enhances colorectal tumour cell metastatic potential in vitro and in vivo.

LENUS (Irish Health Repository)

Tan, B

2012-02-03

BACKGROUND: Sodium hyaluronate has been used intraperitoneally to prevent postoperative adhesions. However, the effect of sodium hyaluronate on tumour growth and metastasis in vitro and in vivo is still unknown. METHODS: Human colorectal tumour cell lines SW480, SW620 and SW707 were treated with sodium hyaluronate (10-500 microg\\/ml) and carboxymethylcellulose (0.125-1 per cent), and tumour cell proliferation and motility were determined in vitro. For the in vivo experiments male BD IX rats were randomized to a sodium hyaluronate group (n = 11; intraperitoneal administration of 0.5 x 10(6) DHD\\/K12 tumour cells and 5 ml 0.4 per cent sodium hyaluronate) or a phosphate-buffered saline group (n = 11; 0.5 x 10(6) DHD\\/K12 tumour cells and 5 ml phosphate-buffered saline intraperitoneally). Four weeks later the intraperitoneal tumour load was visualized directly. RESULTS: In vitro sodium hyaluronate increased tumour cell proliferation and motility significantly. Sodium hyaluronate-induced tumour cell motility appeared to be CD44 receptor dependent, whereas sodium hyaluronate-induced tumour cell proliferation was CD44 receptor independent. In vivo there was a significantly higher total tumour nodule count in the peritoneal cavity of the sodium hyaluronate-treated group compared with the control (P = 0.016). CONCLUSION: Sodium hyaluronate enhances tumour metastatic potential in vitro and in vivo, which suggests that use of sodium hyaluronate to prevent adhesions in colorectal cancer surgery may also potentiate intraperitoneal tumour growth. Presented to the Patey Prize Session of the Surgical Research Society and the annual scientific meeting of the Association of Surgeons of Great Britain and Ireland, Brighton, UK, 4-7 May 1999

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

Science.gov (United States)

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

2013-05-01

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

Increased expression and activity of group IIA and X secretory phospholipase A2 in peritumoral versus central colon carcinoma tissue

DEFF Research Database (Denmark)

Tribler, Line; Jensen, Lotte T.; Jørgensen, Kent

2007-01-01

Secretory phospholipase A2 (sPLA2) type IIA and X was analyzed in tumors from 22 patients with colon adenocarcinomas in order to determine the involvement and activity of sPLA2 in colon cancer. Evaluation of immunoreactive sPLA2 IIA by Western blotting showed a significantly higher level...... in the periphery of the tumors, compared to central tumor regions. Increased levels of sPLA2 IIA protein correlated with a two-fold increase in sPLA2 enzymatic activity in the peripheral regions compared to central regions. Nineteen out of 22 tumors showed high levels of sPLA2 IIA, whereas 7 out of the 22 tumors...... showed sPLA2 type X. These data demonstrate that both sPLA2 type IIA and X are present in human colon cancer and suggest a role for sPLA2 in colon cancer tumor immunology and tumorigenesis....

Massive deformations of Type IIA theory within double field theory

Science.gov (United States)

Çatal-Özer, Aybike

2018-02-01

We obtain massive deformations of Type IIA supergravity theory through duality twisted reductions of Double Field Theory (DFT) of massless Type II strings. The mass deformation is induced through the reduction of the DFT of the RR sector. Such reductions are determined by a twist element belonging to Spin+(10, 10), which is the duality group of the DFT of the RR sector. We determine the form of the twists and give particular examples of twists matrices, for which a massive deformation of Type IIA theory can be obtained. In one of the cases, requirement of gauge invariance of the RR sector implies that the dilaton field must pick up a linear dependence on one of the dual coordinates. In another case, the choice of the twist matrix violates the weak and the strong constraints explicitly in the internal doubled space.

Nuclear waste immobilization in iron phosphate glasses

International Nuclear Information System (INIS)

Garcia, D.A.; Rodriguez, Diego A.; Menghini, Jorge E.; Bevilacqua, Arturo

2007-01-01

Iron-phosphate glasses have become important in the nuclear waste immobilization area because they have some advantages over silicate-based glasses, such as a lower processing temperature and a higher nuclear waste load without losing chemical and mechanical properties. Structure and chemical properties of iron-phosphate glasses are determined in terms of the main components, in this case, phosphate oxide along with the other oxides that are added to improve some of the characteristics of the glasses. For example, Iron oxide improves chemical durability, lead oxide lowers fusion temperature and sodium oxide reduces viscosity at high temperature. In this work a study based on the composition-property relations was made. We used different techniques to characterize a series of iron-lead-phosphate glasses with uranium and aluminium oxide as simulated nuclear waste. We used the Arquimedes method to determine the bulk density, differential temperature analysis (DTA) to determine both glass transition temperature and crystallization temperature, dilatometric analysis to calculate the linear thermal expansion coefficient, chemical durability (MCC-1 test) and X-ray diffraction (XRD). We also applied some theoretic models to calculate activation energies associated with the glass transition temperature and crystallization processes. (author)

Structure and short time degradation studies of sodium zirconium phosphate ceramics loaded with simulated fast breeder (FBR) waste

Energy Technology Data Exchange (ETDEWEB)

Ananthanarayanan, A., E-mail: arvinda@barc.gov.in [Process Development Division, Bhabha Atomic Research Centre, Mumbai 400085 (India); Ambashta, R.D., E-mail: aritu@barc.gov.in [Process Development Division, Bhabha Atomic Research Centre, Mumbai 400085 (India); Sudarsan, V. [Chemistry Division, Bhabha Atomic Research Centre, Mumbai 400085 (India); Ajithkumar, T. [Applied Catalysis Unit, National Chemical Laboratory, Pune 411008 (India); Sen, D.; Mazumder, S. [Solid State Physics Division, Bhabha Atomic Research Centre, Mumbai 400085 (India); Wattal, P.K. [Process Development Division, Bhabha Atomic Research Centre, Mumbai 400085 (India)

2017-04-15

Sodium zirconium phosphate (NZP) ceramics have been prepared using conventional sintering and hot isostatic pressing (HIP) routes. The structure of NZP ceramics, prepared using the HIP route, has been compared with conventionally sintered NZP using a combination of X-ray diffraction (XRD) and ({sup 31}P and {sup 23}Na) nuclear magnetic resonance (NMR) spectroscopy techniques. It is observed that NZP with no waste loading is aggressive toward the steel HIP-can during hot isostatic compaction and significant fraction of cations from the steel enter the ceramic material. Waste loaded NZP samples (10 wt% simulated FBR waste) show significantly low can-interaction and primary NZP phase is evident in this material. Upon exposure of can-interacted and waste loaded NZP to boiling water and steam, {sup 31}P NMR does not detect any major modifications in the network structure. However, the {sup 23}Na NMR spectra indicate migration of Na{sup +} ions from the surface and possible re-crystallization. This is corroborated by Small-Angle Neutron Scattering (SANS) data and Scanning Electron Microscopy (SEM) measurements carried out on these samples.

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

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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.

Expression of Dihydropyridine and Ryanodine Receptors in Type IIA Fibers of Rat Skeletal Muscle

International Nuclear Information System (INIS)

Anttila, Katja; Mänttäri, Satu; Järvilehto, Matti

2007-01-01

In this study, the fiber type specificity of dihydropyridine receptors (DHPRs) and ryanodine receptors (RyRs) in different rat limb muscles was investigated. Western blot and histochemical analyses provided for the first time evidence that the expression of both receptors correlates to a specific myosin heavy chain (MHC) composition. We observed a significant (p=0.01) correlation between DHP as well as Ry receptor density and the expression of MHC IIa (correlation factor r=0.674 and r=0.645, respectively) in one slow-twitch, postural muscle (m. soleus), one mixed, fast-twitch muscle (m. gastrocnemius) and two fast-twitch muscles (m. rectus femoris, m. extensor digitorum longus). The highest DHP and Ry receptor density was found in the white part of m. rectus femoris (0.058±0.0060 and 0.057±0.0158 ODu, respectively). As expected, the highest relative percentage of MHC IIa was also found in the white part of m. rectus femoris (70.0±7.77%). Furthermore, histochemical experiments revealed that the IIA fibers stained most strongly for the fluorophore-conjugated receptor blockers. Our data clearly suggest that the expression of DHPRs and RyRs follows a fiber type-specific pattern, indicating an important role for these proteins in the maintenance of an effective Ca 2+ cycle in the fast contracting fiber type IIA

Effect of phosphate treatments on microbiological, physicochemical changes of spent hen muscle marinated with Tom Yum paste during chilled storage.

Science.gov (United States)

Wongwiwat, Pirinya; Wattanachant, Saowakon; Siripongvutikorn, Sunisa

2010-06-01

This research aimed to study the effect of phosphate on quality of ready-to-cook spent hen muscle marinated with Tom Yum paste, a famous Thai food made from chilli, lime leaves and garcinia (pH 2.5-2.9). The effects of phosphate treatments (phosphate types, soaking time, and phosphate concentration) on physical characteristics of spent hen muscle in high acid condition were investigated. Quality changes of muscles pretreated with or without phosphate and marinated with Tom Yum paste were determined during storage at 4 degrees C for 30 days. The acidified muscle pretreated with 40 g L(-1) sodium tripolyphosphate for 10 h had the highest marinade absorption, and the lowest cooking loss and shear force among all treatment samples. Microstructures of acidified muscle pretreated with and without sodium tripolyphosphate showed significant swelling with larger fibre diameter. Phosphate pretreatment had no influence on cooking loss, shear force and thiobarbituric acid reactive substance values of Tom Yum marinated muscle during storage. Tom Yum marination with phosphate pretreatment caused a higher increase in psychrophilic bacteria compared to that of marinating without phosphate. Phosphate pretreatment could not improve the physical quality of Tom-Yum marinated spent hen muscle and affected the antimicrobial property of Tom-Yum marinade, resulting in a reduction of shelf-life of the marinated muscle from 30 days to 20 days. Copyright (c) 2010 Society of Chemical Industry.

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

DEFF Research Database (Denmark)

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

2005-01-01

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

Optimization of the Use of Selected Non-Phosphate Water Retention Additives in Minced Beef Using Response Surface Methodology

Science.gov (United States)

Shang, Xiaolan; Qiao, Jie; Liu, Yujie

2017-12-01

This study looked to determine what the optimum cooking loss for minced beef was when three different non-phosphate water retention additives (L-Arginine, sodium carbonate, and sodium citrate) were combined; the optimum value was determined using a Box-Behnken response surface design method. The optimum value was found to be 8.26%, and it was obtained when 0.29% L-Arginine, 0.45% sodium carbonate, and 0.24% sodium citrate were added to the beef.

Tanshinone IIA increases the bystander effect of herpes simplex virus thymidine kinase/ganciclovir gene therapy via enhanced gap junctional intercellular communication.

Directory of Open Access Journals (Sweden)

Jianyong Xiao

Full Text Available The bystander effect is an intriguing phenomenon by which adjacent cells become sensitized to drug treatment during gene therapy with herpes simplex virus thymidine kinase/ganciclovir (HSV-tk/GCV. This effect is reported to be mediated by gap junctional intercellular communication (GJIC, and therefore, we postulated that upregulation of genes that facilitate GJIC may enhance the HSV-tk/GCV bystander effect. Previous findings have shown Tanshinone IIA (Tan IIA, a chemical substance derived from a Chinese medicine herb, promotes the upregulation of the connexins Cx26 and Cx43 in B16 cells. Because gap junctions are formed by connexins, we hypothesized that Tan IIA might increase GJIC. Our results show that Tan IIA increased GJIC in B16 melanoma cells, leading to more efficient GCV-induced bystander killing in cells stably expressing HSV-tk. Additionally, in vivo experiments demonstrated that tumors in mice with 10% HSV-tk positive B16 cells and 90% wild-type B16 cells became smaller following treatment with the combination of GCV and Tan IIA as compared to GCV or Tan IIA alone. These data demonstrate that Tan IIA can augment the bystander effect of HSV-tk/GCV system through increased gap junction coupling, which adds strength to the promising strategy that develops connexins inducer to potentiate the effects of suicide gene therapy.

Aluminum bioavailability from basic sodium aluminum phosphate, an approved food additive emulsifying agent, incorporated in cheese.

Science.gov (United States)

Yokel, Robert A; Hicks, Clair L; Florence, Rebecca L

2008-06-01

Oral aluminum (Al) bioavailability from drinking water has been previously estimated, but there is little information on Al bioavailability from foods. It was suggested that oral Al bioavailability from drinking water is much greater than from foods. The objective was to further test this hypothesis. Oral Al bioavailability was determined in the rat from basic [26Al]-sodium aluminum phosphate (basic SALP) in a process cheese. Consumption of approximately 1g cheese containing 1.5% or 3% basic SALP resulted in oral Al bioavailability (F) of approximately 0.1% and 0.3%, respectively, and time to maximum serum 26Al concentration (Tmax) of 8-9h. These Al bioavailability results were intermediate to previously reported results from drinking water (F approximately 0.3%) and acidic-SALP incorporated into a biscuit (F approximately 0.1%), using the same methods. Considering the similar oral bioavailability of Al from food vs. water, and their contribution to the typical human's daily Al intake ( approximately 95% and 1.5%, respectively), these results suggest food contributes much more Al to systemic circulation, and potential Al body burden, than does drinking water. These results do not support the hypothesis that drinking water provides a disproportionate contribution to total Al absorbed from the gastrointestinal tract.

Generation of transgenic corn-derived Actinobacillus pleuropneumoniae ApxIIA fused with the cholera toxin B subunit as a vaccine candidate

Science.gov (United States)

Shin, Min-Kyoung; Jung, Myung Hwan; Lee, Won-Jung; Choi, Pil Son; Jang, Yong-Suk

2011-01-01

Corn, one of the most important forage crops worldwide, has proven to be a useful expression vehicle due to the availability of established transformation procedures for this well-studied plant. The exotoxin Apx, a major virulence factor, is recognized as a common antigen of Actinobacillus (A.) pleuropneumoniae, the causative agent of porcine pleuropneumonia. In this study, a cholera toxin B (CTB)-ApxIIA#5 fusion protein and full-size ApxIIA expressed in corn seed, as a subunit vaccine candidate, were observed to induce Apx-specific immune responses in mice. These results suggest that transgenic corn-derived ApxIIA and CTB-ApxIIA#5 proteins are potential vaccine candidates against A. pleuropneumoniae infection. PMID:22122907

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

Science.gov (United States)

Robson, L; Hunter, M

1999-01-01

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

Development of Class IIa Bacteriocins as Therapeutic Agents

OpenAIRE

Christopher T. Lohans; John C. Vederas

2012-01-01

Class IIa bacteriocins have been primarily explored as natural food preservatives, but there is much interest in exploring the application of these peptides as therapeutic antimicrobial agents. Bacteriocins of this class possess antimicrobial activity against several important human pathogens. Therefore, the therapeutic development of these bacteriocins will be reviewed. Biological and chemical modifications to both stabilize and increase the potency of bacteriocins are discussed, as well as ...

Effect of various parameters on the efficiency of zinc phosphate ...

African Journals Online (AJOL)

... and CMG852 showed enhanced solubilization in presence of 1% sodium chloride. 1% glucose is required for the solubilization of zinc phosphate and no solubilization was appeared in presence of 0.1% glucose. CMG851 (A. lwoffi), CMG 860 (pseudomonas aeruginosa) CMG 857 (Bacillus thuringiensis) were found to be ...

Lar mountain phosphate ore processing using flotation approach

International Nuclear Information System (INIS)

Gharabaghi, M.; Noaparast, M.; Shafaei Tonkaboni, S. Z.

2007-01-01

The sample of Lar Mountain Phosphate deposit which is located in the southwest of Iran, was studied to upgrade its phosphate grade. The results obtained from mineralogical studies showed the presence of apatite, CaO, Al 2 O 3 , Fe 2 O 3 and SiO 2 , in which carbonate was detected as the main gangue. Two sets of direct and reverse flotation tests were performed using samples from this deposit with 10% P 2 O 5 . In phosphate flotation (direct approach), the samples were conditioned with sodium silica, oleic acid-fuel oil and Armac T-fuel oil. The direct flotation at pH=9.2 yielded a product with 23.2% of P 2 O 5 and 75.16% recovery. The reverse flotation tests were carried out at pH=5.2, with floating carbonate and pulp de-oiling, using H 2 SO 4 and wash water, and phosphate was then floated from siliceous gangue. In the second sets of the reverse approach, depressing the phosphate and floating silica with Amines in natural pH were done. However the best concentrate assay was 31.2% P 2 O 5 with a 71.12% recovery, which was obtained from reverse tests

Salt equivalence and temporal dominance of sensations of different sodium chloride substitutes in butter.

Science.gov (United States)

de Souza, Vanessa Rios; Freire, Tassyana Vieira Marques; Saraiva, Carla Gonçalves; de Deus Souza Carneiro, João; Pinheiro, Ana Carla Marques; Nunes, Cleiton Antônio

2013-08-01

Studies indicate a positive association between dietary salt intake and some diseases, which has promoted the tendency to reduce the sodium in foods. The objective of this study was to determine the equivalent amount of different sodium chloride replacements required to promote the same degree of ideal saltiness in butter and to study the sensory profile of sodium chloride and the substitutes using the analysis of Temporal Dominance of Sensations (TDS). Using the magnitude estimation method, it was determined that the potencies of potassium chloride, monosodium glutamate and potassium phosphate relative to the 1% sodium chloride in butter are 83·33, 31·59 and 33·32, respectively. Regarding the sensory profile of the tested salt substitutes, a bitter taste was perceived in the butter with potassium chloride, a sour taste was perceived in the butter with potassium phosphate and sweet and umami tastes were dominant in the butter with monosodium glutamate. Of all the salt substitutes tested calcium lactate, potassium lactate, calcium chloride and magnesium chloride were impractical to use in butter.

Myosin IIA participates in docking of Glut4 storage vesicles with the plasma membrane in 3T3-L1 adipocytes

International Nuclear Information System (INIS)

Chung, Le Thi Kim; Hosaka, Toshio; Harada, Nagakatsu; Jambaldorj, Bayasgalan; Fukunaga, Keiko; Nishiwaki, Yuka; Teshigawara, Kiyoshi; Sakai, Tohru; Nakaya, Yutaka; Funaki, Makoto

2010-01-01

In adipocytes and myocytes, insulin stimulation translocates glucose transporter 4 (Glut4) storage vesicles (GSVs) from their intracellular storage sites to the plasma membrane (PM) where they dock with the PM. Then, Glut4 is inserted into the PM and initiates glucose uptake into these cells. Previous studies using chemical inhibitors demonstrated that myosin II participates in fusion of GSVs and the PM and increase in the intrinsic activity of Glut4. In this study, the effect of myosin IIA on GSV trafficking was examined by knocking down myosin IIA expression. Myosin IIA knockdown decreased both glucose uptake and exposures of myc-tagged Glut4 to the cell surface in insulin-stimulated cells, but did not affect insulin signal transduction. Interestingly, myosin IIA knockdown failed to decrease insulin-dependent trafficking of Glut4 to the PM. Moreover, in myosin IIA knockdown cells, insulin-stimulated binding of GSV SNARE protein, vesicle-associated membrane protein 2 (VAMP2) to PM SNARE protein, syntaxin 4 was inhibited. These data suggest that myosin IIA plays a role in insulin-stimulated docking of GSVs to the PM in 3T3-L1 adipocytes through SNARE complex formation.

Comparative analysis of human conjunctival and corneal epithelial gene expression with oligonucleotide microarrays.

Science.gov (United States)

Turner, Helen C; Budak, Murat T; Akinci, M A Murat; Wolosin, J Mario

2007-05-01

To determine global mRNA expression levels in corneal and conjunctival epithelia and identify transcripts that exhibit preferential tissue expression. cDNA samples derived from human conjunctival and corneal epithelia were hybridized in three independent experiments to a commercial oligonucleotide array representing more than 22,000 transcripts. The resultant signal intensities and microarray software transcript present/absent calls were used in conjunction with the local pooled error (LPE) statistical method to identify transcripts that are preferentially or exclusively expressed in one of the two tissues at significant levels (expression >1% of the beta-actin level). EASE (Expression Analysis Systematic Explorer software) was used to identify biological systems comparatively overrepresented in either epithelium. Immuno-, and cytohistochemistry was performed to validate or expand on selected results of interest. The analysis identified 332 preferential and 93 exclusive significant corneal epithelial transcripts. The corresponding numbers of conjunctival epithelium transcripts were 592 and 211, respectively. The overrepresented biological processes in the cornea were related to cell adhesion and oxiredox equilibria and cytoprotection activities. In the conjunctiva, the biological processes that were most prominent were related to innate immunity and melanogenesis. Immunohistochemistry for antigen-presenting cells and melanocytes was consistent with these gene signatures. The transcript comparison identified a substantial number of genes that have either not been identified previously or are not known to be highly expressed in these two epithelia, including testican-1, ECM1, formin, CRTAC1, and NQO1 in the cornea and, in the conjunctiva, sPLA(2)-IIA, lipocalin 2, IGFBP3, multiple MCH class II proteins, and the Na-Pi cotransporter type IIb. Comparative gene expression profiling leads to the identification of many biological processes and previously unknown genes that

Tanshinone IIA suppresses FcεRI-mediated mast cell signaling and anaphylaxis by activation of the Sirt1/LKB1/AMPK pathway.

Science.gov (United States)

Li, Xian; Park, Soon Jin; Jin, Fansi; Deng, Yifeng; Yang, Ju Hye; Chang, Jae-Hoon; Kim, Dong-Young; Kim, Jung-Ae; Lee, Youn Ju; Murakami, Makoto; Son, Kun Ho; Chang, Hyeun Wook

2018-06-01

AMP-activated protein kinase (AMPK) and its upstream mediators liver kinase B1 (LKB1) and sirtuin 1 (Sirt1) are generally known as key regulators of metabolism. We have recently reported that the AMPK pathway negatively regulates mast cell activation and anaphylaxis. Tanshinone IIA (Tan IIA), an active component of Salvia miltiorrhiza extract that is currently used for the treatment of cardiovascular and cerebrovascular diseases, shows anti-diabetic activity and improves insulin resistance in db/db mice through activation of AMPK. The aim of this study was to evaluate the anti-allergic activity of Tan IIA in vivo and to investigate the underlying mechanism in vitro in the context of AMPK signaling. The anti-allergic effect of Tan IIA was evaluated using mouse bone marrow-derived mast cells (BMMCs) from AMPKα2 -/- or Sirt1 -/- mice, or BMMCs transfected with siRNAs specific for AMPKα2, LKB1, or Sirt1. AMPKα2 -/- and Sirt1 -/- mice were used to confirm the anti-allergic effect of Tan IIA in anaphylaxis in vivo. Tan IIA dose-dependently inhibited FcεRI-mediated degranulation and production of eicosanoids and cytokines in BMMCs. These inhibitory effects were diminished by siRNA-mediated knockdown or genetic deletion of AMPKα2 or Sirt1. Moreover, Tan IIA inhibited a mast cell-mediated local passive anaphylactic reaction in wild-type mice, but not in AMPKα2 -/- or Sirt1 -/- mice. In conclusion, Tan IIA suppresses FcεRI-mediated mast cell activation and anaphylaxis through activation of the inhibitory Sirt1-LKB1-AMPK pathway. Thus, Tan IIA may be useful as a new therapeutic agent for mast cell-mediated allergic diseases. Copyright © 2018 Elsevier Inc. All rights reserved.

Sodium Tanshinone IIA Sulfonate Ameliorates Bladder Fibrosis in a Rat Model of Partial Bladder Outlet Obstruction by Inhibiting the TGF-β/Smad Pathway Activation.

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Xiaoxiao Jiang

Full Text Available Transforming growth factor (TGF-β1 is known to play a pivotal role in a diverse range of biological systems including modulation of fibrosis in several organs. The precise role of TGF-β/Smad signaling in the progression of bladder fibrosis secondary to partial bladder outlet obstruction (PBOO is yet to be conclusively. Using a rat PBOO model, we investigated TGF-β1 expression and exaimined whether sodium tanshinone IIA sulfonate (STS could inhibit TGF-β/Smad signaling pathway activation and ameliorate bladder fibrosis. Forty-eight female Sprague-Dawley rats were randomly divided into three groups: sham operation group (n = 16, PBOO operation without STS treatment group (n = 16 and PBOO operation with STS treatment group (n = 16. Thirty-two rats underwent the operative procedure to create PBOO and subsequently received intraperitoneal injections of STS (10 mg/kg/d; n = 16 or vehicle (n = 16 two days after the surgery. Sham surgery was conducted on 16 rats, which received intraperitoneal vehicle injection two days later. In each of the three groups, an equal number of rats were sacrificed at weeks 4 and 8 after the PBOO or sham operation. The TGF-β/Smad signaling pathway was analyzed using western blotting, immunohistochemical staining and reverse transcriptase polymerase chain reaction (RT-PCR. One-way analysis of variance was conducted to draw statistical inferences. At 4 and 8 weeks, the expression of TGF-β1 and phosphorylated Smad2 and Smad3 in STS-treated PBOO rats was significantly lower than in the PBOO rats not treated with STS. Alpha smooth muscle actin (α-SMA, collagen I and collagen III expression at 4 and 8 weeks post PBOO was lower in STS-treated PBOO rats when compared to that in PBOO rats not treated with STS. Our findings indicate that STS ameliorates bladder fibrosis by inhibiting TGF-β/Smad signaling pathway activation, and may prove to be a potential therapeutic measure for preventing bladder fibrosis secondary to PBOO

Effectiveness of Sodium-Glucose Cotransporter-2 Inhibitor as an Add-on Drug to GLP-1 Receptor Agonists for Glycemic Control of a Patient with Prader-Willi Syndrome: A Case Report.

Science.gov (United States)

Horikawa, Yukio; Enya, Mayumi; Komagata, Makie; Hashimoto, Ken-Ichi; Kagami, Masayo; Fukami, Maki; Takeda, Jun

2018-02-01

Diabetes patients with Prader-Willi syndrome (PWS) are obese because of hyperphagia; weight control by dietary modification and medicine is required for glycemic control. There are several recent reports showing the effectiveness of GLP-1 receptor agonists (GLP-1RAs) for diabetes treatment in PWS. A 36-year-old Japanese male patient was diagnosed with PWS at 10 years of age. At age 16 years, he was diagnosed with diabetes and began to take several kinds of oral hypoglycemic agents. At age 29 years, his BMI was 39.1 kg/m 2 and he was referred to our department for diabetes and obesity treatment. In the present case, the HbA1c was not improved by GLP-1RAs despite a 28-kg BW reduction, which included a 9-kg loss of muscle. Apprehensive of further loss of muscle mass, basal insulin of insulin glargine was administered in addition to GLP-1RAs. Immediately after the addition of tofogliflozin, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, the patient's HbA1c decreased dramatically with only about an additional 3% BW reduction. We note an improvement in our case of lipid deposition in the pancreas confirmed by abdominal CT after the improvement of HbA1c. It is unknown whether this improvement of fatty pancreas was a cause or an effect of the improved glycemic control in the present case. This finding clearly supports the effectiveness of combining SGLT2 inhibitors with GLP-1RAs for treatment of patients with PWS and non-alcoholic fatty pancreas disease.

The effects of detergent, sodium tripoly-phosphate and ethoxyled oleyl-cetyl alcohol on metabolic parameters of the fungus Trichothecium roseum link

Directory of Open Access Journals (Sweden)

Stojanović Jelica

2011-01-01

Full Text Available The degradation of detergents that are dispersed in water and soil partially depends on the metabolic activities of fungi. Among the fungi that have this ability, Deuteromycetes are particularly noted for their biochemical characteristics. Taking this into account, it was of interest to analyze the influence of detergent and its main compounds, ethoxyled oleylcetyl alcohol (AOC and sodium tripoly-phosphate (TTP, on the metabolism of the fungus Trichothecium roseum. Our results revealed that both detergent and AOC had an inhibitory effect on the bioproduction of free organic acids, while TTP stimulated their production. Also, detergent inhibited the bioproduction of basic amino acids, with the exception of alanine. In addition, detergent applied at 1% concentration inhibited the bioproduction of proteins and the total biomass of the fungus, while AOC and TTP inhibited the production of proteins, but stimulatedl the production of Trichothecium.

Zirconium Phosphate Supported MOF Nanoplatelets.

Science.gov (United States)

Kan, Yuwei; Clearfield, Abraham

2016-06-06

We report a rare example of the preparation of HKUST-1 metal-organic framework nanoplatelets through a step-by-step seeding procedure. Sodium ion exchanged zirconium phosphate, NaZrP, nanoplatelets were judiciously selected as support for layer-by-layer (LBL) assembly of Cu(II) and benzene-1,3,5-tricarboxylic acid (H3BTC) linkers. The first layer of Cu(II) is attached to the surface of zirconium phosphate through covalent interaction. The successive LBL growth of HKUST-1 film is then realized by soaking the NaZrP nanoplatelets in ethanolic solutions of cupric acetate and H3BTC, respectively. The amount of assembled HKUST-1 can be readily controlled by varying the number of growth cycles, which was characterized by powder X-ray diffraction and gas adsorption analyses. The successful construction of HKUST-1 on NaZrP was also supported by its catalytic performance for the oxidation of cyclohexene.

Overexpressed human metallothionein IIA gene protects Chinese hamster ovary cells from killing by alkylating agents

International Nuclear Information System (INIS)

Kaina, B.; Lohrer, H.; Karin, M.; Herrlich, P.

1990-01-01

Experiments were designed to detect survival advantages that cells gain by overexpressing metallothionein (MT). Chinese hamster ovary K1-2 cells and an x-ray-sensitive derivative were transfected with a bovine papillomavirus (BPV)-linked construct carrying the human metallothionein IIA (hMT-IIA) gene. Transfectants survived 40-fold higher levels of cadmium chloride, harbored at least 30 copies of hMT-IIA, and contained 25- to 166-fold more MT than the parent cells. Even under conditions of reduced glutathione synthesis, the transfectants were not more resistant to the lethal effects of ionizing radiation and bleomycin than the parent cells. Thus free radicals generated by these agents cannot be scavenged efficiently by MT in vivo. The hMT-IIA transfectants, however, but not control transfectants harboring a BPV-MT promoter-neo construct, tolerated significantly higher doses of the alkylating agents N-methyl-N-nitrosourea and N-methyl-N'-nitro-N-nitrosoguanidine. Resistance and MT overexpression occurred irrespective of selection and cultivation in cadmium and zinc. There was no increase in resistance to methyl methanesulfonate and N-hydroxyethyl-N-chloroethylnitrosourea. MT did not affect the degree of overall DNA methylation after N-methyl-N-nitrosourea treatment nor the level of O6-methylguanine-DNA methyltransferase. The results suggest that MT participates as a cofactor or regulatory element in repair or tolerance of toxic alkylation lesions

Overexpressed human metallothionein IIA gene protects Chinese hamster ovary cells from killing by alkylating agents

Energy Technology Data Exchange (ETDEWEB)

Kaina, B.; Lohrer, H.; Karin, M.; Herrlich, P. (Kernforschungszentrum Karlsruhe, Karlsruhe (Germany, F.R.))

1990-04-01

Experiments were designed to detect survival advantages that cells gain by overexpressing metallothionein (MT). Chinese hamster ovary K1-2 cells and an x-ray-sensitive derivative were transfected with a bovine papillomavirus (BPV)-linked construct carrying the human metallothionein IIA (hMT-IIA) gene. Transfectants survived 40-fold higher levels of cadmium chloride, harbored at least 30 copies of hMT-IIA, and contained 25- to 166-fold more MT than the parent cells. Even under conditions of reduced glutathione synthesis, the transfectants were not more resistant to the lethal effects of ionizing radiation and bleomycin than the parent cells. Thus free radicals generated by these agents cannot be scavenged efficiently by MT in vivo. The hMT-IIA transfectants, however, but not control transfectants harboring a BPV-MT promoter-neo construct, tolerated significantly higher doses of the alkylating agents N-methyl-N-nitrosourea and N-methyl-N'-nitro-N-nitrosoguanidine. Resistance and MT overexpression occurred irrespective of selection and cultivation in cadmium and zinc. There was no increase in resistance to methyl methanesulfonate and N-hydroxyethyl-N-chloroethylnitrosourea. MT did not affect the degree of overall DNA methylation after N-methyl-N-nitrosourea treatment nor the level of O6-methylguanine-DNA methyltransferase. The results suggest that MT participates as a cofactor or regulatory element in repair or tolerance of toxic alkylation lesions.

Overexpressed human metallothionein IIA gene protects Chinese hamster ovary cells from killing by alkylating agents.

Science.gov (United States)

Kaina, B; Lohrer, H; Karin, M; Herrlich, P

1990-01-01

Experiments were designed to detect survival advantages that cells gain by overexpressing metallothionein (MT). Chinese hamster ovary K1-2 cells and an x-ray-sensitive derivative were transfected with a bovine papillomavirus (BPV)-linked construct carrying the human metallothionein IIA (hMT-IIA) gene. Transfectants survived 40-fold higher levels of cadmium chloride, harbored at least 30 copies of hMT-IIA, and contained 25- to 166-fold more MT than the parent cells. Even under conditions of reduced glutathione synthesis, the transfectants were not more resistant to the lethal effects of ionizing radiation and bleomycin than the parent cells. Thus free radicals generated by these agents cannot be scavenged efficiently by MT in vivo. The hMT-IIA transfectants, however, but not control transfectants harboring a BPV-MT promoter-neo construct, tolerated significantly higher doses of the alkylating agents N-methyl-N-nitrosourea and N-methyl-N'-nitro-N-nitrosoguanidine. Resistance and MT overexpression occurred irrespective of selection and cultivation in cadmium and zinc. There was no increase in resistance to methyl methanesulfonate and N-hydroxyethyl-N-chloroethylnitrosourea. MT did not affect the degree of overall DNA methylation after N-methyl-N-nitrosourea treatment nor the level of O6-methylguanine-DNA methyltransferase. The results suggest that MT participates as a cofactor or regulatory element in repair or tolerance of toxic alkylation lesions. Images PMID:2320583

SGLT2 Inhibition in the Diabetic Kidney—From Mechanisms to Clinical Outcome

Science.gov (United States)

Muskiet, Marcel H.A.; Tonneijck, Lennart; Kramer, Mark H.H.; Nieuwdorp, Max; van Raalte, Daniel H.

2017-01-01

Diabetic kidney disease not only has become the leading cause for ESRD worldwide but also, highly contributes to increased cardiovascular morbidity and mortality in type 2 diabetes. Despite increased efforts to optimize renal and cardiovascular risk factors, like hyperglycemia, hypertension, obesity, and dyslipidemia, they are often insufficiently controlled in clinical practice. Although current drug interventions mostly target a single risk factor, more substantial improvements of renal and cardiovascular outcomes can be expected when multiple factors are improved simultaneously. Sodium-glucose cotransporter type 2 in the renal proximal tubule reabsorbs approximately 90% of filtered glucose. In type 2 diabetes, the maladaptive upregulation of sodium-glucose cotransporter type 2 contributes to the maintenance of hyperglycemia. Inhibiting these transporters has been shown to effectively improve glycemic control through inducing glycosuria and is generally well tolerated, although patients experience more genital infections. In addition, sodium-glucose cotransporter type 2 inhibitors favorably affect body weight, BP, serum uric acid, and glomerular hyperfiltration. Interestingly, in the recently reported first cardiovascular safety trial with a sodium-glucose cotransporter type 2 inhibitor, empagliflozin improved both renal and cardiovascular outcomes in patients with type 2 diabetes and established cardiovascular disease. Because the benefits were seen rapidly after initiation of therapy and other glucose-lowering agents, with the exception of liraglutide and semaglutide, have not been able to improve cardiovascular outcome, these observations are most likely explained by effects beyond glucose lowering. In this mini review, we present the drug class of sodium-glucose cotransporter type 2 inhibitors, elaborate on currently available renal and cardiovascular outcome data, and discuss how the effects of these agents on renal physiology may explain the data. PMID

The calcium-paracaseinate-phosphate-complex under conditions similar to those in cheese

NARCIS (Netherlands)

Monib, A.M.M.F.

1962-01-01

The complex of calcium-paracaseinate-phosphate is the matrix substance of cheese. The changes it undergoes during maturing determines many characteristics of the finished product.

The preliminary studies of the effect of pH and sodium chloride on the swelling and solubility of the

30 CFR 57.22205 - Doors on main fans (I-A, II-A, III, and V-A mines).

Science.gov (United States)

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Doors on main fans (I-A, II-A, III, and V-A... main fans (I-A, II-A, III, and V-A mines). In mines ventilated by multiple main fans, each main fan... reversal through the fan. The doors shall be located so that they are not in direct line with explosive...

Effect of Fluoride, Casein Phosphopeptide–Amorphous Calcium Phosphate and Casein Phosphopeptide–Amorphous Calcium Phosphate Fluoride on Enamel Surface Microhardness After Microabrasion: An In Vitro Study

Directory of Open Access Journals (Sweden)

Ghazaleh Ahmadi Zenouz

2016-03-01

Full Text Available Objectives: This study aimed to assess the effect of applying casein phosphopeptide–amorphous calcium phosphate (CPP-ACP paste, casein phosphopeptide–amorphous calcium phosphate fluoride (CPP-ACPF paste and sodium fluoride gel on surface microhardness of enamel after microabrasion.Materials and Methods: Thirty freshly extracted human premolars were selected. All samples were subjected to hardness indentations made with the Vickers hardness machine and the average value was recorded as the initial surface microhardness. The specimens were then randomly divided into three groups (n=10 of CPP-ACPF, fluoride and CPP-ACP. The teeth were micro-abraded with Opalustre. Microhardness test was performed to assess the post-abrasion hardness. Three remineralization modalities were performed on samples of each group. The enamel surface microhardness measurements were performed. To compare the difference between groups, the rehardening and softening values were defined. One-way ANOVA and Tukey’s post hoc test at a significance level of 5% were used for statistical analysis.Results: The mean microhardness value (MMV had a significant decrease after microabrasion from baseline. The MMV had a significant increase after remineralization in all groups. The MMV of CPP-ACPF group was significantly more than that of fluoride group (P=0.027. The rehardening value of fluoride group was significantly more than that of other groups (P<0.001.Conclusion: All the remineralizing agents were effective for rehardening the enamel after microabrasion. The CPP-ACP and CPP-ACPF pastes are effective, but to a lesser extent than neutral sodium fluoride gel in remineralizing enamel surface. Incorporation of fluoride to CPP-ACP formulation does not provide any additional remineralizing potential.Keywords: Casein phosphopeptide-amorphous calcium phosphate nanocomplex; Enamel Microabrasion; Hardness; Sodium Fluoride

Effects of starch synthase IIa gene dosage on grain, protein and starch in endosperm of wheat.

Science.gov (United States)

Konik-Rose, Christine; Thistleton, Jenny; Chanvrier, Helene; Tan, Ihwa; Halley, Peter; Gidley, Michael; Kosar-Hashemi, Behjat; Wang, Hong; Larroque, Oscar; Ikea, Joseph; McMaugh, Steve; Regina, Ahmed; Rahman, Sadequr; Morell, Matthew; Li, Zhongyi

2007-11-01

Starch synthases (SS) are responsible for elongating the alpha-1,4 glucan chains of starch. A doubled haploid population was generated by crossing a line of wheat, which lacks functional ssIIa genes on each genome (abd), and an Australian wheat cultivar, Sunco, with wild type ssIIa alleles on each genome (ABD). Evidence has been presented previously indicating that the SGP-1 (starch granule protein-1) proteins present in the starch granule in wheat are products of the ssIIa genes. Analysis of 100 progeny lines demonstrated co-segregation of the ssIIa alleles from the three genomes with the SGP-1 proteins, providing further evidence that the SGP-1 proteins are the products of the ssIIa genes. From the progeny lines, 40 doubled haploid lines representing the eight possible genotypes for SSIIa (ABD, aBD, AbD, ABd, abD, aBd, Abd, abd) were characterized for their grain weight, protein content, total starch content and starch properties. For some properties (chain length distribution, pasting properties, swelling power, and gelatinization properties), a progressive change was observed across the four classes of genotypes (wild type, single nulls, double nulls and triple nulls). However, for other grain properties (seed weight and protein content) and starch properties (total starch content, granule morphology and crystallinity, granule size distribution, amylose content, amylose-lipid dissociation properties), a statistically significant change only occurred for the triple nulls, indicating that all three genes had to be missing or inactive for a change to occur. These results illustrate the importance of SSIIa in controlling grain and starch properties and the importance of amylopectin fine structure in controlling starch granule properties in wheat.

Optical Detection of Sodium Salts of Fluoride, Acetate and ...

Indian Academy of Sciences (India)

Administrator

Optical Detection of Sodium Salts of Fluoride, Acetate and Phosphate by a Diacylhydrazine. Ligand via the Formation of a Colour Alkali Metal Complex. Purnandhu Bose, Ranjan Dutta, I. Ravikumar and Pradyut Ghosh. ∗. Department of Inorganic Chemistry, Indian Association for the Cultivation of Science, 2A & 2B Raja ...

Nonmuscle myosin heavy chain IIA is a critical factor contributing to the efficiency of early infection of severe fever with thrombocytopenia syndrome virus.

Science.gov (United States)

Sun, Yinyan; Qi, Yonghe; Liu, Chenxuan; Gao, Wenqing; Chen, Pan; Fu, Liran; Peng, Bo; Wang, Haimin; Jing, Zhiyi; Zhong, Guocai; Li, Wenhui

2014-01-01

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a novel phlebovirus in the Bunyaviridae family. Most patients infected by SFTSV present with fever and thrombocytopenia, and up to 30% die due to multiple-organ dysfunction. The mechanisms by which SFTSV enters multiple cell types are unknown. SFTSV contains two species of envelope glycoproteins, Gn (44.2 kDa) and Gc (56 kDa), both of which are encoded by the M segment and are cleaved from a precursor polypeptide (about 116 kDa) in the endoplasmic reticulum (ER). Gn fused with an immunoglobulin Fc tag at its C terminus (Gn-Fc) bound to multiple cells susceptible to the infection of SFTSV and blocked viral infection of human umbilical vein endothelial cells (HUVECs). Immunoprecipitation assays following mass spectrometry analysis showed that Gn binds to nonmuscle myosin heavy chain IIA (NMMHC-IIA), a cellular protein with surface expression in multiple cell types. Small interfering RNA (siRNA) knockdown of NMMHC-IIA, but not the closely related NMMHC-IIB or NMMHC-IIC, reduced SFTSV infection, and NMMHC-IIA specific antibody blocked infection by SFTSV but not other control viruses. Overexpression of NMMHC-IIA in HeLa cells, which show limited susceptivity to SFTSV, markedly enhanced SFTSV infection of the cells. These results show that NMMHC-IIA is critical for the cellular entry of SFTSV. As NMMHC-IIA is essential for the normal functions of platelets and human vascular endothelial cells, it is conceivable that NMMHC-IIA directly contributes to the pathogenesis of SFTSV and may be a useful target for antiviral interventions against the viral infection.

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.

30 CFR 57.22204 - Main fan operation and inspection (I-A, II-A, III, and V-A mines).

Science.gov (United States)

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Main fan operation and inspection (I-A, II-A, III, and V-A mines). 57.22204 Section 57.22204 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION... Main fan operation and inspection (I-A, II-A, III, and V-A mines). Main fans shall be— (a) Provided...

Clinical profile of patients with type 2 diabetes mellitus treated with sodium- glucose cotransporter-2 inhibitors and experience in real-world clinical practice in Spain.

Science.gov (United States)

Cuatrecasas, Gabriel; Goñi-Goicoechea, Fernando

2016-11-01

The main aim of the treatment of type 2 diabetes is overall control of cardiovascular risk factors. Almost 50% of patients with type 2 diabetes do not achieve glycaemic targets, and a much higher percentage do not achieve weight and blood pressure targets, despite the therapeutic arsenal that has appeared in the last decade for the treatment of this disease. In addition, antidiabetic secretatogues and insulin are associated with weight gain and an increased risk of hyperglycaemic episodes. Clinical practice guidelines recommend sodium-glucose cotransporter-2 inhibitors (SGLT2i) as an alternative in the same therapeutic step as the other options after initiation of metformin therapy. The present study reviews the most appropriate patient profile for SGLT2i therapy, based on their safety and efficacy demonstrated in controlled clinical trials. The article discusses which patients are at risk of experiencing the possible secondary effects due to the mechanism of action of this new therapeutic class, in whom SGLT2i should be used with caution. These considerations on the profile of patients suitable for SGLT2i therapy are contrasted with the results obtained in daily clinical practice, both in retrospective studies from other countries and from real-world experiences in Spain. This article presents a selection of studies performed in distinct centres with a minimum follow-up of 6 months and compares their results with those from clinical trials. SGLT2i are used in clinical practice in any therapeutic step and the efficacy results are very similar to those reported by controlled clinical trials, with a slightly higher proportion of genitourinary infections and a low dropout rate. Half the reported patients are diabetics receiving insulin therapy plus a gliflozin, showing the wide uptake of this therapeutic strategy by clinicians. SGLT2i are especially attractive due to their additional effectiveness in weight and blood pressure control and the possibility of using them

Polyelectrolyte addition effect on the properties of setting hydraulic cements based on calcium phosphate

International Nuclear Information System (INIS)

Santos, Luis A. dos; Oliveira, Luci C. de; Rigo, Eliana C.S.; Boschi, Anselmo Ortega; Carrodeguas, Raul Gracia

1997-01-01

In the present work the effects of the addition of some poly electrolytes (sodium alginate and poly acrylic acid) on the solubility, crystalline phases, pH and mechanical strength under compression of three calcium phosphate cements were studied. (author)

Deformed N = 8 supergravity from IIA strings and its Chern-Simons duals

Energy Technology Data Exchange (ETDEWEB)

Guarino, Adolfo [Nikhef Theory Group, Amsterdam (Netherlands); Jafferis, Daniel L. [Center for the Fundamental Laws of Nature, Harvard University, Cambridge, MA (United States); Varela, Oscar [Center for the Fundamental Laws of Nature, Harvard University, Cambridge, MA (United States); Centre de Physique Theorique, Ecole Polytechnique, CNRS UMR 7644, Palaiseau (France)

2016-04-15

Do electric/magnetic deformations of N = 8 supergravity enjoy a string/M-theory origin, or are they just a fourdimensional artefact? We address this question for the gauging of a group closely related to SO(8): its contraction ISO(7). We argue that the deformed ISO(7) supergravity arises from consistent truncation of massive IIA supergravity on S{sup 6}, and its electric/magnetic deformation parameter descends directly from the Romans mass. The critical points of the supergravity uplift to AdS{sub 4} massive type IIA vacua and the corresponding CFT{sub 3} duals are identified as super-Chern-Simons-matter theories with gauge group SU(N) and level k given also by the Romans mass. (copyright 2015 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

Method for ion exchange purification of sodium iodide solution from heavy metals and potassium microimpurities

International Nuclear Information System (INIS)

Smirnov, G.I.; Kachur, N.Ya.; Kostromina, O.N.; Ogorodnikova, A.A.; Khajnakov, S.A.

1990-01-01

A method of deep ion exchange purification of sodium iodide solution from heavy metals (iron, nickel, copper, lead) and potassium microimpurities is developed. The method includes multiple sorption of microimpurities on titanium phosphate with their subsequent desorption by sorbent processing with a solution with a solution of 3-6 N nitric acid, first, and then with a neutral solution of 2 % sodium thiosulfate. The given method permits to increase the purification degree of sodium iodide solution by 25-30 %. 2 tabs

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.

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

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

DEFF Research Database (Denmark)

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

2005-01-01

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

Pulmonary alveolar microlithiasis

International Nuclear Information System (INIS)

Vallejo, Franco Javier; Vallejo, Alejandro; Parra, Maximiliano

2007-01-01

Pulmonary alveolar microlithiasis (PAM) is a rare disease characterized by the diffuse and bilateral presence of calcium phosphate microlite in the alveolar spaces. The progression of this potentially lethal disease is show and most of the patients remain asymptomatic during years or decades, resulting in a show deterioration of the pulmonary function. The typical finding of the sand storm in the chest X-ray is characteristic of this entity. Mutations in the SLC34A2 gene that does the coding for the type II co-transporter of sodium phosphate were identified as responsible for this disease. Of the almost 600 cases, only 6 have been reported in Colombia. We are presenting a case of pulmonary alveolar microlite in a 27 year old man, with progressive respiratory distress whose diagnosis was made by the X-ray findings and confirmed by trans bronchial biopsy. In the 2 years follow-up, shows evolution towards deterioration of his respiratory function making him a candidate for lung transplantation.

PDGF activates K-Cl cotransport through phosphoinositide 3-kinase and protein phosphatase-1 in primary cultures of vascular smooth muscle cells.

Science.gov (United States)

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

2005-07-15

K-Cl cotransport (K-Cl COT, KCC) is an electroneutrally coupled movement of K and Cl present in most cells. In this work, we studied the pathways of regulation of K-Cl COT by platelet-derived growth factor (PDGF) in primary cultures of vascular smooth muscle cells (VSMCs). Wortmannin and LY 294002 blocked the PDGF-induced K-Cl COT activation, indicating that the phosphoinositide 3-kinase (PI 3-K) pathway is involved. However, PD 98059 had no effect on K-Cl COT activation by PDGF, suggesting that the mitogen-activated protein kinase pathway is not involved under the experimental conditions tested. Involvement of phosphatases was also examined. Sodium orthovanadate, cyclosporin A and okadaic acid had no effect on PDGF-stimulated K-Cl COT. Calyculin A blocked the PDGF-stimulated K-Cl COT by 60%, suggesting that protein phosphatase-1 (PP-1) is a mediator in the PDGF signaling pathway/s. In conclusion, our results indicate that the PDGF-mediated pathways of K-Cl COT regulation involve the signaling molecules PI 3-K and PP-1.

Lack of evidence for a harmful effect of sodium-glucose co-transporter 2 (SGLT2) inhibitors on fracture risk among type 2 diabetes patients: a network and cumulative meta-analysis of randomized controlled trials.

Science.gov (United States)

Tang, H L; Li, D D; Zhang, J J; Hsu, Y H; Wang, T S; Zhai, S D; Song, Y Q

2016-12-01

To evaluate the comparative effects of sodium-glucose co-transporter 2 (SGLT2) inhibitors on risk of bone fracture in patients with type 2 diabetes mellitus (T2DM). PubMed, EMBASE, CENTRAL and ClinicalTrials.gov were systematically searched from inception to 27 January 2016 to identify randomized controlled trials (RCTs) reporting the outcome of fracture in patients with T2DM treated with SGLT2 inhibitors. Pairwise and network meta-analyses, as well as a cumulative meta-analysis, were performed to calculate odds ratios (ORs) and 95% confidence intervals (CIs). A total of 38 eligible RCTs (10 canagliflozin, 15 dapagliflozin and 13 empagliflozin) involving 30 384 patients, with follow-ups ranging from 24 to 160 weeks, were included. The fracture event rates were 1.59% in the SGLT2 inhibitor groups and 1.56% in the control groups. The incidence of fracture events was similar among these three SGLT2 inhibitor groups. Compared with placebo, canagliflozin (OR 1.15; 95% CI 0.71-1.88), dapagliflozin (OR 0.68; 95% CI 0.37-1.25) and empagliflozin (OR 0.93; 95% CI 0.74-1.18) were not significantly associated with an increased risk of fracture. Our cumulative meta-analysis indicated the robustness of the null findings with regard to SGLT2 inhibitors. Our meta-analysis based on available RCT data does not support the harmful effect of SGLT2 inhibitors on fractures, although future safety monitoring from RCTs and real-world data with detailed information on bone health is warranted. © 2016 John Wiley & Sons Ltd.

Synthesis and aggregation behavior of cyclic single- and double-tailed phosphate amphiphiles: A novel class of phosphate surfactants - Comparison with the aggregation behavior of sodium di-n-alkyl phosphates

NARCIS (Netherlands)

Buwalda, Rixt; Wagenaar, Anno; Engberts, Jan B.F.N.

Herein we describe the synthesis and aggregation of the sodium salts of a series of 5-alkyl-2-hydroxy-1,3,2-dioxaphosphorinan-2-ones and 5,5-dialkyl-2-hydroxy-1,3,2-dioxaphosphorinan-2-ones in aqueous solution. The results are compared with properties of previously studied sodium di-n-alkyl

An overview of the effect of sodium glucose cotransporter 2 inhibitor monotherapy on glycemic and other clinical laboratory parameters in type 2 diabetes patients

Directory of Open Access Journals (Sweden)

Wang Y

2016-07-01

Full Text Available Yaowen Wang,1 Xueting Hu,2 Xueying Liu,3 Zengqi Wang2 1Department of Clinical Laboratory, Weifang People’s Hospital, 2Department of Clinical Laboratory, Weifang Traditional Chinese Hospital, Weifang, 3Department of Clinical Laboratory, The Third Hospital of Jinan, Jinan, People’s Republic of China Objectives: We aimed to determine the effect of sodium glucose cotransporter 2 (SGLT2 inhibitor monotherapy on glycemic and other clinical laboratory parameters versus other antidiabetic medications or placebo therapy in patients with type 2 diabetes mellitus. In addition, we aimed to investigate the risk of diabetic ketoacidosis associated with SGLT2 inhibitor therapy and evaluate its weight-sparing ability. Design: Meta-analysis. Materials and methods: PubMed and MEDLINE were searched to identify eligible studies up to December 2015. Randomized controlled trials that assessed the efficacy and safety of SGLT2 inhibitor monotherapy versus placebo therapy or active control were considered. The Cochrane Collaboration Risk of Bias Tool was used to evaluate quality and bias. The mean ­difference was used to evaluate the glycemic and other clinical laboratory parameters for SGLT2 inhibitor intervention versus control by drugs or placebo. Similarly, the risk ratio was used to assess adverse events, and the I2 was used to evaluate heterogeneity. Results: SGLT2 inhibitors significantly decreased glycated hemoglobin (HbA1c (P<0.001, weight (P<0.001, and the low-density lipoprotein/high-density lipoprotein ratio (P=0.03 compared with placebo therapy. No statistically significant changes were found in fasting plasma glucose, 2-hour postprandial glucose, or lipid parameters. Significant changes in the uric acid level were found for SGLT2 inhibitors versus placebo therapy (P=0.005 or active control (P<0.001. Although no significant change in levels of ketones occurred (P=0.93, patients receiving SGLT2 inhibitors were at greater risk of increased ketone bodies

Surgery or radiation therapy for Stage I and IIA carcinoma of the cervix

International Nuclear Information System (INIS)

Brady, L.W.

1979-01-01

The choice of treatment in carcinoma of the cervix is best decided after careful individual appraisal has been carried out. For best results, a long-term view must be agreed upon initially and careful followup by the same team is obligatory. At present, surgery, radiation therapy, and a combination of these two modalities have been employed successfully to manage carcinoma of the cervix. To a great extent, the facilities, the experience, and the interest of the personnel involved influence the type of therapy that will be employed. Generally speaking, the choice of treatment is determined primarily by the stage of the disease process. Radical surgery in the management of patients with Stage I and Stage II-A carcinoma of the cervix must be planned to include within the en bloc dissection the uterus, tubes, ovaries, and regional lymph node drainage from those organs. Therefore, a radical lymphadnectomy is an integral and important part of the overall management program when radical surgery is performed. In most institutions, radiation therapy is used most frequently to treat carcinoma of the cervix in Stages I and II-A. The data from various institutions indicate significant survival potential from radiation therapy treatment programs that are appropriately devised. In Stages I and II-A the complications are minimal in character (primarily proctitis and cystitis); generally, they involve a potential incidence of about six percent

Anti-Inflammatory Effects of Tanshinone IIA on Atherosclerostic Vessels of Ovariectomized ApoE-/- Mice are Mediated by Estrogen Receptor Activation and Through the ERK Signaling Pathway

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Xin Liu

2015-03-01

Full Text Available Aims: Estrogen plays a protective role in atherosclerosis. Our preliminary work demonstrated that the active conformation of Tanshinone IIA(TanIIA is similar to the 17ß-estradiol and it can bind to the estrogen receptor. Here, we hypothesized that Tanshinone IIA might have anti-inflammatory and anti-oxidative effects in atherosclerosis, mediated through estrogen receptor activation. Methods: Subjects for this study were 120 apoE-/- female mice and 20 C57/BL female mice. The apoE-/- mice were ovariectomized (OVX and the C57/BL mice were sham ovariectomized. The sham OVX mice were maintained on a normal diet (NOR group. The OVX apoE-/- mice were fed a high fat diet and randomly divided into 6 groups: Model (MOD group which was fed a high fat diet only, E2 group were given estrogen (E2 0.13mg/kg/d; E2+ICI group were given E2:0.13mg/kg/d and ICI182780:65mg/kg/m; TLD group (TanIIA low dose were given TanIIA: 30mg/kg/d; THD group (TanIIA high dose were given TanIIA:60mg/kg/d; and TLD+ICI group were given TanIIA 30mg/kg/d and ICI182780 65mg/kg/m. After three months of treatment, the aorta and the blood of the mice from each group was collected. The aorta were used for testing the lipid deposition by using hematoxylin and eosin(HE and oil red O staining and for testing the expression of p-ERK1/2 by Western blot. The blood was used for testing the serum cholesterol, superoxide dismutase (SOD, methane dicarboxylic aldehyde (MDA, nuclear factor kappa (NF-κB, soluble intercellular cell adhesion molecule-1 (sICAM-1, activating protein-1 (AP-1, E-selectin and 17ß-estradiol in serum. Results: Tanshinone IIA significantly reduced the lipid deposition in aorta, decreased the levels of total cholesterol (TC, triglyceride (TG, low density lipoprotein (LDL, very low density lipoprotein (VLDL, MDA, NF-κB, sICAM-1, AP-1, and E-selectin in serum but increased the levels of high density lipoprotein (HDL and SOD in serum. Tanshinone IIA also suppressed the

Mechanism of mercurial inhibition of sodium-coupled alanine uptake in liver plasma membrane vesicles from Raja erinacea

International Nuclear Information System (INIS)

Sellinger, M.; Ballatori, N.; Boyer, J.L.

1991-01-01

In mammalian hepatocytes the L-alanine carrier contains a sulfhydryl group that is essential for its activity and is inhibited by mercurials. In hepatocytes of the evolutionarily primitive little skate (Raja erinacea), HgCl2 inhibits Na(+)-dependent alanine uptake and Na+/K(+)-ATPase and increase K+ permeability. To distinguish between direct effects of HgCl2 on the Na(+)-alanine cotransporter and indirect effects on membrane permeability, [3H]alanine transport was studied in plasma membrane vesicles. [3H]Alanine uptake was stimulated by an out-to-in Na+ but not K+ gradient and was saturable confirming the presence of Na(+)-alanine cotransport in liver plasma membranes from this species. Preincubation of the vesicles with HgCl2 for 5 min reduced initial rates of Na(+)-dependent but not Na(+)-independent alanine uptake in a dose-dependent manner (10-200 microM). In the presence of equal concentrations of NaCl or KCl inside and outside of the vesicles, 75 microM HgCl2 directly inhibited sodium-dependent alanine-[3H]alanine exchange, demonstrating that HgCl2 directly affected the alanine cotransporter. Inhibition of Na(+)-dependent alanine uptake by 30 microM HgCl2 was reversed by dithiothreitol (1 mM). HgCl2 (10-30 microM) also increased initial rates of 22Na uptake (at 5 sec), whereas 22Na uptake rates were decreased at HgCl2 concentrations greater than 50 microM. Higher concentrations of HgCl2 (100-200 microM) produced nonspecific effects on vesicle integrity. These studies indicate that HgCl2 inhibits Na(+)-dependent alanine uptake in skate hepatocytes by three different concentration-dependent mechanisms: direct interaction with the transporters, dissipation of the driving force (Na+ gradient), and loss of membrane integrity

Effects of a Dicalcium and Tetracalcium Phosphate-Based Desensitizer on In Vitro Dentin Permeability.

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Jianfeng Zhou

Full Text Available The present study evaluated the effectiveness of a dicalcium and tetracalcium phosphate-based desensitizer in reducing dentin permeability in vitro. Dentin fluid flow was measured before and after treatment of dentin with patent dentinal tubules using 1 or 3 applications of the dicalcium and tetracalcium phosphate containing agent TeethmateTM (TM and comparing the results with two sodium fluoride varnishes VellaTM (VLA and VanishTM (VAN, after storage in artificial saliva for 24 h, 48 h and 7 days. Significant differences were observed among the 4 methods employed for reducing dentin permeability (p < 0.001 and the 3 post-treatment times (p < 0.001. VLA and VAN never achieved 50% permeability reductions consistently in any of the 3 time periods. Only the calcium phosphate-based desensitizer applied for 3 times consistently reduced dentin permeability by 50% after 24 h. When applied once, the permeability reduction of TM increased progressively over the 3 time periods. After 7 days, only one and three applications of the calcium phosphate-based desensitizer consistently reduced dentin permeability by more than 50%. Permeability reductions corresponded well with scanning electron microscopy examination of dentinal tubule orifice occlusion in dentin specimens treated with the agents. Overall, the dicalcium and tetracalcium phosphate-based desensitizer is effective in reducing dentin permeability via a tubule occlusion mechanism. The ability of the agent to reduce dentin permeability renders it to be potentially useful as a clinical dentin desensitizing agent, which has to be confirmed in future clinical studies. By contrast, the two sodium fluoride varnishes are not effective in dentin permeability reduction and should be considered as topical fluoride delivering agents rather than tubular orifice-blocking agents.

Designing calcium phosphate-based bifunctional nanocapsules with bone-targeting properties

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Khung, Yit-Lung; Bastari, Kelsen; Cho, Xing Ling; Yee, Wu Aik; Loo, Say Chye Joachim, E-mail: joachimloo@ntu.edu.sg [Nanyang Technological University, School of Materials Science and Engineering (Singapore)

2012-06-15

Using sodium dodecyl sulphate micelles as template, hollow-cored calcium phosphate nanocapsules were produced. The surfaces of the nanocapsule were subsequently silanised by a polyethylene glycol (PEG)-based silane with an N-hydroxysuccinimide ester end groups which permits for further attachment with bisphosphonates (BP). Characterisations of these nanocapsules were investigated using Field Emission Scanning Electron Microscopy (FESEM), Transmission Electron Microscopy, Fourier Transform Infra-Red Spectroscopy, X-ray diffraction, X-ray photoelectron spectroscopy and Dynamic Light Scattering. To further validate the bone-targeting potential, dentine discs were incubated with these functionalised nanocapsules. FESEM analysis showed that these surface-modified nanocapsules would bind strongly to dentine surfaces compared to non-functionalised nanocapsules. We envisage that respective components would give this construct a bifunctional attribute, whereby (1) the shell of the calcium phosphate nanocapsule would serve as biocompatible coating aiding in gradual osteoconduction, while (2) surface BP moieties, acting as targeting ligands, would provide the bone-targeting potential of these calcium phosphate nanocapsules.

Designing calcium phosphate-based bifunctional nanocapsules with bone-targeting properties

International Nuclear Information System (INIS)

Khung, Yit-Lung; Bastari, Kelsen; Cho, Xing Ling; Yee, Wu Aik; Loo, Say Chye Joachim

2012-01-01

Using sodium dodecyl sulphate micelles as template, hollow-cored calcium phosphate nanocapsules were produced. The surfaces of the nanocapsule were subsequently silanised by a polyethylene glycol (PEG)-based silane with an N-hydroxysuccinimide ester end groups which permits for further attachment with bisphosphonates (BP). Characterisations of these nanocapsules were investigated using Field Emission Scanning Electron Microscopy (FESEM), Transmission Electron Microscopy, Fourier Transform Infra-Red Spectroscopy, X-ray diffraction, X-ray photoelectron spectroscopy and Dynamic Light Scattering. To further validate the bone-targeting potential, dentine discs were incubated with these functionalised nanocapsules. FESEM analysis showed that these surface-modified nanocapsules would bind strongly to dentine surfaces compared to non-functionalised nanocapsules. We envisage that respective components would give this construct a bifunctional attribute, whereby (1) the shell of the calcium phosphate nanocapsule would serve as biocompatible coating aiding in gradual osteoconduction, while (2) surface BP moieties, acting as targeting ligands, would provide the bone-targeting potential of these calcium phosphate nanocapsules.

Separation and recovery of sodium nitrate from low-level radioactive liquid waste by electrodialysis

International Nuclear Information System (INIS)

Meguro, Yoshihiro; Kato, Atsushi; Watanabe, Yoko; Takahashi, Kuniaki

2011-01-01

An advanced method, in which electrodialysis separation of sodium nitrate and decomposition of nitrate ion are combined, has been developed to remove nitrate ion from low-level radioactive liquid wastes including nitrate salts of high concentration. In the electrodialysis separation, the sodium nitrate was recovered as nitric acid and sodium hydroxide. When they are reused, it is necessary to reduce the quantity of impurities getting mixed with them from the waste fluid as much as possible. In this study, therefore, a cation exchange membrane with permselectivity for sodium ion and an anion exchange membrane with permselectivity for monovalent anion were employed. Using these membranes sodium and nitrate ions were effectively removed form a sodium nitrate solution of high concentration. And also it was confirmed that sodium ion was successfully separated from cesium and strontium ions and that nitrate ion was separated from sulfate and phosphate ions. (author)

Systems of amonium polyborates - monoammonium phosphate -water at 25 deg C. Sistemy poliboraty ammoniya - monoammonijfosfat - voda pri 25 grad S

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Skvortsov, V G; Sadetdinov, Sh V; Polenov, A D; Mikhajlov, V I [Chuvashskij Gosudarstvennyj Pedagogicheskij Inst., Cheboksary (Russian Federation)

1992-11-01

It is established by solubility and refractometry methods at 25 deg C that systems of ammonium tetraborate (pentaborate) monoammonium phosphate-water refer to sumple eutonic type. The ammonium borates and monoammoniumphosphate exert salting effect over each other. It is found that phosphate borate compositions on the basis of ammonium salts are characterized by lower inhibitor properties as compared to sodium salts.

The secretory phospholipase A2 group IIA: a missing link between inflammation, activated renin-angiotensin system, and atherogenesis?

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Dimitar Divchev

2008-06-01

Full Text Available Dimitar Divchev, Bernhard SchiefferDepartment of Cardiology and Angiology, Medizinische Hochschule Hannover, GermanyAbstract: Inflammation, lipid peroxidation and chronic activation of the renin–angiotensin system (RAS are hallmarks of the development of atherosclerosis. Recent studies have suggested the involvement of the pro-inflammatory secretory phospholipase A2 (sPLA2-IIA in atherogenesis. This enzyme is produced by different cell types through stimulation by proinflammatory cytokines. It is detectable in the intima and in media smooth muscle cells, not only in atherosclerotic lesions but also in the very early stages of atherogenesis. sPLA2-IIA can hydrolyse the phospholipid monolayers of low density lipoproteins (LDL. Such modified LDL show increased affinity to proteoglycans. The modified particles have a greater tendency to aggregate and an enhanced ability to insert cholesterol into cells. This modification may promote macrophage LDL uptake leading to the formation of foam cells. Furthermore, sPLA2-IIA is not only a mediator for localized inflammation but may be also used as an independent predictor of adverse outcomes in patients with stable coronary artery disease or acute coronary syndromes. An interaction between activated RAS and phospholipases has been indicated by observations showing that inhibitors of sPLA2 decrease angiotensin (Ang II-induced macrophage lipid peroxidation. Meanwhile, various interactions between Ang II and oxLDL have been demonstrated suggesting a central role of sPLA2-IIA in these processes and offering a possible target for treatment. The role of sPLA2-IIA in the perpetuation of atherosclerosis appears to be the missing link between inflammation, activated RAS and lipidperoxidation.Keywords: secretory phospholipase A2, lipoproteins, renin-angiotensin system, inflammation, atherosclerosis

Type IIA2 urethral duplication: report of an unusual case | Gupta ...

African Journals Online (AJOL)

This report describes a rare case of type IIA2 sagittal urethral duplication. The presentation, investigation, and management of this rare anomaly are briefly discussed. A 3½-year-old boy presented with urinary obstruction and recurrent urinary tract infection due to a stenosed dorsal urethra and segmental stenosis of the ...

Enhanced osteoconductivity of sodium-substituted hydroxyapatite by system instability.

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Sang Cho, Jung; Um, Seung-Hoon; Su Yoo, Dong; Chung, Yong-Chae; Hye Chung, Shin; Lee, Jeong-Cheol; Rhee, Sang-Hoon

2014-07-01

The effect of substituting sodium for calcium on enhanced osteoconductivity of hydroxyapatite was newly investigated. Sodium-substituted hydroxyapatite was synthesized by reacting calcium hydroxide and phosphoric acid with sodium nitrate followed by sintering. As a control, pure hydroxyapatite was prepared under identical conditions, but without the addition of sodium nitrate. Substitution of calcium with sodium in hydroxyapatite produced the structural vacancies for carbonate ion from phosphate site and hydrogen ion from hydroxide site of hydroxyapatite after sintering. The total system energy of sodium-substituted hydroxyapatite with structural defects calculated by ab initio methods based on quantum mechanics was much higher than that of hydroxyapatite, suggesting that the sodium-substituted hydroxyapatite was energetically less stable compared with hydroxyapatite. Indeed, sodium-substituted hydroxyapatite exhibited higher dissolution behavior of constituent elements of hydroxyapatite in simulated body fluid (SBF) and Tris-buffered deionized water compared with hydroxyapatite, which directly affected low-crystalline hydroxyl-carbonate apatite forming capacity by increasing the degree of apatite supersaturation in SBF. Actually, sodium-substituted hydroxyapatite exhibited markedly improved low-crystalline hydroxyl-carbonate apatite forming capacity in SBF and noticeably higher osteoconductivity 4 weeks after implantation in calvarial defects of New Zealand white rabbits compared with hydroxyapatite. In addition, there were no statistically significant differences between hydroxyapatite and sodium-substituted hydroxyapatite on cytotoxicity as determined by BCA assay. Taken together, these results indicate that sodium-substituted hydroxyapatite with structural defects has promising potential for use as a bone grafting material due to its enhanced osteoconductivity compared with hydroxyapatite. © 2013 Wiley Periodicals, Inc.

The selectivity of zirconium phosphate for caesium in electrochemical ion exchange

International Nuclear Information System (INIS)

Lain, M.J.

1988-11-01

The properties of amorphous zirconium phosphate are investigated as an inorganic ion exchanger for use in liquid waste treatment by electrochemical ion exchange. Experiments to determine and increase the selectivity for caesium exchange over sodium are discussed, including various pulsed waveforms and studies with rotating membranes. Automation of a sampling system with pH and atomic absorption measurements is described. (author)

Sodium-glucose co-transporter-2 inhibitors, the latest residents on the block: Impact on glycaemic control at a general practice level in England.

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Heald, Adrian H; Fryer, Anthony A; Anderson, Simon G; Livingston, Mark; Lunt, Mark; Davies, Mark; Moreno, Gabriela Y C; Gadsby, Roger; Young, Robert J; Stedman, Mike

2018-03-08

To determine, using published general practice-level data, how differences in Type 2 diabetes mellitus (T2DM) prescribing patterns relate to glycaemic target achievement levels. Multiple linear regression modelling was used to link practice characteristics and defined daily dose (DDD) of different classes of medication in 2015/2016 and changes between that year and the year 2014/2015 in medication to proportion of patients achieving target glycaemic control (glycated haemoglobin A1c [HbA1c] ≤58 mmol/mol [7.5%]) and proportion of patients at high glycaemic risk (HbA1c >86 mmol/mol [10.0%]) for practices in the National Diabetes Audit with >100 people with T2DM on their register. Overall, HbA1c outcomes were not different between the years studied. Although, in percentage terms, most practices increased their use of sodium-glucose co-transporter-2 (SGLT2) inhibitors (96%), dipeptidyl peptidase-4 (DPP-4) inhibitors (76%) and glucagon-like peptide 1 (GLP-1) analogues (53%), there was wide variation in the use of older and newer therapies. For example, 12% of practices used >200% of the national average for some newer agents. In cross-sectional analysis, greater prescribing of metformin and analogue insulin were associated with a higher proportion of patients achieving HbA1c ≤58 mmol/mol; the use of SGLT2 inhibitors and metformin was associated with a reduced proportion of patients with HbA1c >86 mol/mol; otherwise associations for sulphonylureas, GLP-1 analogues, SGLT2 inhibitors and DPP-4 inhibitors were neutral or negative. In year-on-year analysis there was ongoing deterioration in glycaemic control, which was offset to some extent by increased use of SGLT2 inhibitors and GLP-1 analogues, which were associated with a greater proportion of patients achieving HbA1c levels ≤58 mmol/mol and a smaller proportion of patients with HbA1c levels >86 mmol/mol. SGLT2 inhibitor prescribing was associated with significantly greater improvements than those found

Activity of Escherichia coli, Aspergillus niger, and Rye Phytase toward Partially Phosphorylated myo-Inositol Phosphates.

Science.gov (United States)

Greiner, Ralf

2017-11-08

Kinetic parameters for the dephosphorylation of sodium phytate and a series of partially phosphorylated myo-inositol phosphates were determined at pH 3.0 and pH 5.0 for three phytase preparations (Aspergillus niger, Escherichia coli, rye). The enzymes showed lower affinity and turnover numbers at pH 3 compared to pH 5 toward all myo-inositol phosphates included in the study. The number and distribution of phosphate groups on the myo-inositol ring affected the kinetic parameters. Representatives of the individual phytate dephosphorylation pathways were identified as the best substrates of the phytases. Within the individual phytate dephosphorylation pathways, the pentakisphosphates were better substrates compared to the tetrakisphosphates or phytate itself. E. coli and rye phytase showed comparable activities at both pH values toward the tetrakis- and trisphosphate, whereas A. niger phytase exhibited a higher activity toward the tetrakisphosphate. A myo-inositol phosphate with alternate phosphate groups was shown to be not significantly dephosphorylated by the phytases.

Biomimetic calcium phosphate coatings on recombinant spider silk fibres

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Yang Liang; Habibovic, Pamela; Van Blitterswijk, Clemens A [Department of Tissue Regeneration, University of Twente, PO Box 217, 7500 AE Enschede (Netherlands); Hedhammar, My; Johansson, Jan [Department of Anatomy, Physiology and Biochemistry, Swedish University of Agricultural Sciences, the Biomedical Centre, Box 575, 751 23 Uppsala (Sweden); Blom, Tobias; Leifer, Klaus [Department of Engineering Sciences, Uppsala University, Box 534, S-751 21 Uppsala (Sweden)

2010-08-01

Calcium phosphate ceramic coatings, applied on surfaces of metallic and polymeric biomaterials, can improve their performance in bone repair and regeneration. Spider silk is biocompatible, strong and elastic, and hence an attractive biomaterial for applications in connective tissue repair. Recently, artificial spider silk, with mechanical and structural characteristics similar to those of native spider silk, has been produced from recombinant minispidroins. In the present study, supersaturated simulated body fluid was used to deposit calcium phosphate coatings on recombinant spider silk fibres. The mineralization process was followed in time using scanning electron microscopy equipped with an energy dispersive x-ray (EDX) detector and Raman spectroscope. Focused ion beam technology was used to produce a cross section of a coated fibre, which was further analysed by EDX. Preliminary in vitro experiments using a culture of bone marrow-derived human mesenchymal stem cells (hMSCs) on coated fibres were also performed. This study showed that recombinant spider silk fibres were successfully coated with a homogeneous and thick crystalline calcium phosphate layer. In the course of the mineralization process from modified simulated body fluid, sodium chloride crystals were first deposited on the silk surface, followed by the deposition of a calcium phosphate layer. The coated silk fibres supported the attachment and growth of hMSCs.

Biomimetic calcium phosphate coatings on recombinant spider silk fibres

International Nuclear Information System (INIS)

Yang Liang; Habibovic, Pamela; Van Blitterswijk, Clemens A; Hedhammar, My; Johansson, Jan; Blom, Tobias; Leifer, Klaus

2010-01-01

Calcium phosphate ceramic coatings, applied on surfaces of metallic and polymeric biomaterials, can improve their performance in bone repair and regeneration. Spider silk is biocompatible, strong and elastic, and hence an attractive biomaterial for applications in connective tissue repair. Recently, artificial spider silk, with mechanical and structural characteristics similar to those of native spider silk, has been produced from recombinant minispidroins. In the present study, supersaturated simulated body fluid was used to deposit calcium phosphate coatings on recombinant spider silk fibres. The mineralization process was followed in time using scanning electron microscopy equipped with an energy dispersive x-ray (EDX) detector and Raman spectroscope. Focused ion beam technology was used to produce a cross section of a coated fibre, which was further analysed by EDX. Preliminary in vitro experiments using a culture of bone marrow-derived human mesenchymal stem cells (hMSCs) on coated fibres were also performed. This study showed that recombinant spider silk fibres were successfully coated with a homogeneous and thick crystalline calcium phosphate layer. In the course of the mineralization process from modified simulated body fluid, sodium chloride crystals were first deposited on the silk surface, followed by the deposition of a calcium phosphate layer. The coated silk fibres supported the attachment and growth of hMSCs.

Microwave assisted low temperature synthesis of sodium zirconium phosphate (NZP) and the leachability of some selected fission products incorporated in its structure

International Nuclear Information System (INIS)

Dharwadkar, S.R.

2008-01-01

Full text: Microwave assisted procedure for low temperature solid state synthesis of sodium zirconium phosphate (NZP), a material with the potential for immobilization and disposal of high level nuclear waste, was developed. Four selected fission products, namely cesium, strontium, tellurium and ruthenium were introduced (substituted) in the NZP matrix during its synthesis at 450 deg C. More than 85% of these elements incorporated at this temperature could be retained in the NZP compacts, sintered in air at 1000 deg C to nearly 90% of the theoretical density of pure sodium zirconium phosphate. Leaching studies were carried out on the fission product substituted sintered NZP compacts in pure de-ionized water and 80% saturated brine solution at the ambient temperatures of 30 deg C and 90 deg C for four weeks. The major part of leaching in all the cases was observed in the first week. The maximum amount of the substituted element leached in the liquid media after four weeks, however did not exceed 12% of the total amount originally present in the sample before leaching. No significant leaching was observed for any of the dopant elements after four weeks. Among the substituted elements maximum leaching was observed for tellurium followed by cesium and strontium. Ruthenium showed virtually no leaching under the conditions employed. Leaching was found to decrease considerably in multiple element substituted NZP. The effect of temperature on the leaching rate was marginal but substantial difference was observed when the leachant was changed from pure de-ionized water to brine solution. Tellurium and strontium exhibited three and two fold decrease in the leaching rate respectively on changing the leachant from pure de-ionized water to 80% saturated brine solution. The leach rate of Cs however remained virtually unaffected by this change. The SEM and EDX analysis of the surfaces of the leached pellets showed virtual absence of the dopants introduced in the NZP matrix

A regenerable potassium and phosphate sorbent system to enhance dialysis efficacy and device portability: a study in awake goats.

Science.gov (United States)

Wester, Maarten; Gerritsen, Karin G; Simonis, Frank; Boer, Walther H; Hazenbrink, Diënty H; Vaessen, Koen R; Verhaar, Marianne C; Joles, Jaap A

2017-06-01

Patients on standard intermittent haemodialysis suffer from strong fluctuations in plasma potassium and phosphate. Prolonged dialysis with a wearable device, based on continuous regeneration of a small volume of dialysate using ion exchangers, could moderate these fluctuations and offer increased clearance of these electrolytes. We report in vivo results on the efficacy of potassium and phosphate adsorption from a wearable dialysis device. We explore whether equilibration of ion exchangers at physiological Ca 2+ , Mg 2+ and hypotonic NaCl can prevent calcium/magnesium adsorption and net sodium release, respectively. Effects on pH and HCO3- were studied. Healthy goats were instrumented with a central venous catheter and dialysed. Potassium and phosphate were infused to achieve plasma concentrations commonly observed in dialysis patients. An adsorption cartridge containing 80 g sodium poly(styrene-divinylbenzene) sulphonate and 40 g iron oxide hydroxide beads for potassium and phosphate removal, respectively, was incorporated in a dialysate circuit. Sorbents were equilibrated and regenerated with a solution containing NaCl, CaCl 2 and MgCl 2 . Blood was pumped over a dialyser and dialysate was recirculated over the adsorption cartridge in a countercurrent direction. Potassium and phosphate adsorption was 7.7 ± 2.7 and 4.9 ± 1.3 mmol in 3 h, respectively. Adsorption capacity remained constant during consecutive dialysis sessions and increased with increasing K + and PO43-. Equilibration at physiological Ca 2+ and Mg 2+ prevented net adsorption, eliminating the need for post-cartridge calcium and magnesium infusion. Equilibration at hypotonic NaCl prevented net sodium release Fe 2+ and arterial pH did not change. Bicarbonate was adsorbed, which could be prevented by equilibrating at HCO3- 15 mM. We demonstrate clinically relevant, concentration-dependent, pH-neutral potassium and phosphate removal in vivo with small volumes of regenerable ion exchangers in our

An Amperometric Biosensor for the Determination of Bacterial Sepsis Biomarker, Secretory Phospholipase Group 2-IIA Using a Tri-Enzyme System

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Nik Nurhanan Nik Mansor

2018-02-01

Full Text Available A tri-enzyme system consisting of choline kinase/choline oxidase/horseradish peroxidase was used in the rapid and specific determination of the biomarker for bacterial sepsis infection, secretory phospholipase Group 2-IIA (sPLA2-IIA. These enzymes were individually immobilized onto the acrylic microspheres via succinimide groups for the preparation of an electrochemical biosensor. The reaction of sPLA2-IIA with its substrate initiated a cascading enzymatic reaction in the tri-enzyme system that led to the final production of hydrogen peroxide, which presence was indicated by the redox characteristics of potassium ferricyanide, K3Fe(CN6. An amperometric biosensor based on enzyme conjugated acrylic microspheres and gold nanoparticles composite coated onto a carbon-paste screen printed electrode (SPE was fabricated and the current measurement was performed at a low potential of 0.20 V. This enzymatic biosensor gave a linear range 0.01–100 ng/mL (R2 = 0.98304 with a detection limit recorded at 5 × 10−3 ng/mL towards sPLA2-IIA. Moreover, the biosensor showed good reproducibility (relative standard deviation (RSD of 3.04% (n = 5. The biosensor response was reliable up to 25 days of storage at 4 °C. Analysis of human serum samples for sPLA2-IIA indicated that the biosensor has potential for rapid bacterial sepsis diagnosis in hospital emergency department.

Tumorigenicity of sodium ascorbate in male rats.

Science.gov (United States)

Cohen, S M; Anderson, T A; de Oliveira, L M; Arnold, L L

1998-06-15

Sodium ascorbate, like other sodium salts such as saccharin, glutamate, and bicarbonate, produces urinary alterations when fed at high doses to rats, which results in mild superficial urothelial cytotoxicity and regeneration but not tumors in a standard 2-year bioassay. Sodium saccharin was shown to produce a low incidence of bladder tumors in rats if administered in a two-generation bioassay. In the present study, we evaluated sodium ascorbate in a two-generation bioassay that involved feeding to the male and female parental F344 rats for 4 weeks before mating, feeding the dams during gestation and lactation, and then feeding the weaned (at 28 days of age) male F1 generation rats for the remainder of their lifetime (up to 128 weeks of the experiment). Dietary levels of 1.0, 5.0, and 7.0% sodium ascorbate were tested. At 5.0 and 7.0% sodium ascorbate, there was an increase in urinary bladder urothelial papillary and nodular hyperplasia and the induction of a few papillomas and carcinomas. There was a dose-responsive increase in renal pelvic calcification and hyperplasia and inhibition of the aging nephropathy of rats even at the level of 1% sodium ascorbate. Because the short-term urothelial effects of sodium ascorbate in rats are inhibited by treatments producing urinary acidification to pH sodium ascorbate to evaluate the long-term effects. The combination of 7.0% sodium ascorbate plus 2.78% NH4Cl in the diet was toxic, and the group was terminated early during the course of the experiment. The group fed 5.0% sodium ascorbate plus 2.04% NH4Cl showed complete inhibition of the urothelial effects of sodium ascorbate and significant inhibition of its renal effects. We also demonstrated the presence of a calcium phosphate-containing urinary precipitate in rats fed sodium ascorbate at all doses, in a dose-responsive manner. The formation of the precipitate was inhibited by coadministration with NH4Cl. The proliferative effects of sodium ascorbate on the male rat

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

Science.gov (United States)

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

2010-10-01

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

Stopped-flow injection method for determination of phosphate in soils and fertilisers

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Jaroon Jakmunee

2008-02-01

Full Text Available A stopped-flow injection system for the determination of phosphate has been developed. It involves the phosphate-molybdate-ascorbic acid reactions in the molybdenum blue method. The system is controlled by a semi-automatic stopped-FI analyser with a light emitting diode (LED-colorimeter for monitoring the absorbance change relating to the concentration of a reaction product formed during the stopping period while the injected zone of a standard or sample is being in the flow cell. The slope of the FIAgram obtained is linearly proportional to the reaction rate, which depends on the phosphate concentration. Effects of concentration of reagents, viz. sodium molybdate, ascorbic acid and nitric acid, on the slope of the FIAgram were studied. The suitable concentration is 0.02 M, 0.25 %w/v and 0.15 M, respectively. A linear calibration graph in the range of 0.3-6.0 mg P L-1 was employed for the determination of phosphate in soil and fertiliser samples. The results obtained agree well with those from a standard spectrophotometric method.

Separating and stabilizing phosphate from high-level radioactive waste: process development and spectroscopic monitoring.

Science.gov (United States)

Lumetta, Gregg J; Braley, Jenifer C; Peterson, James M; Bryan, Samuel A; Levitskaia, Tatiana G

2012-06-05

Removing phosphate from alkaline high-level waste sludges at the Department of Energy's Hanford Site in Washington State is necessary to increase the waste loading in the borosilicate glass waste form that will be used to immobilize the highly radioactive fraction of these wastes. We are developing a process which first leaches phosphate from the high-level waste solids with aqueous sodium hydroxide, and then isolates the phosphate by precipitation with calcium oxide. Tests with actual tank waste confirmed that this process is an effective method of phosphate removal from the sludge and offers an additional option for managing the phosphorus in the Hanford tank waste solids. The presence of vibrationally active species, such as nitrate and phosphate ions, in the tank waste processing streams makes the phosphate removal process an ideal candidate for monitoring by Raman or infrared spectroscopic means. As a proof-of-principle demonstration, Raman and Fourier transform infrared (FTIR) spectra were acquired for all phases during a test of the process with actual tank waste. Quantitative determination of phosphate, nitrate, and sulfate in the liquid phases was achieved by Raman spectroscopy, demonstrating the applicability of Raman spectroscopy for the monitoring of these species in the tank waste process streams.

Crystal structure of a sodium, zinc and iron(III-based non-stoichiometric phosphate with an alluaudite-like structure: Na1.67Zn1.67Fe1.33(PO43

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Jamal Khmiyas

2015-06-01

Full Text Available The new title compound, disodium dizinc iron(III tris(phosphate, Na1.67Zn1.67Fe1.33(PO43, which belongs to the alluaudite family, has been synthesized by solid-state reactions. In this structure, all atoms are in general positions except for four, which are located on special positions of the C2/c space group. This structure is characterized by cation substitutional disorder at two sites, one situated on the special position 4e (2 and the other on the general position 8f. The 4e site is partially occupied by Na+ [0.332 (3], whereas the 8f site is entirely filled by a mixture of Fe and Zn. The full-occupancy sodium and zinc atoms are located at the Wyckoff positions on the inversion center 4a (-1 and on the twofold rotation axis 4e, respectively. Refinement of the occupancy ratios, bond-valence analysis and the electrical neutrality requirement of the structure lead to the given composition for the title compound. The three-dimensional framework of this structure consists of kinked chains of edge-sharing octahedra stacked parallel to [10-1]. The chains are formed by a succession of trimers based on [ZnO6] octahedra and the mixed-cation FeIII/ZnII [(Fe/ZnO6] octahedra [FeIII:ZnIII ratio 0.668 (3/0.332 (3]. Continuous chains are held together by PO4 phosphate groups, forming polyhedral sheets perpendicular to [010]. The stacked sheets delimit two types of tunnels parallel to the c axis in which the sodium cations are located. Each Na+ cation is coordinated by eight O atoms. The disorder of Na in the tunnel might presage ionic mobility for this material.

A counterselection method for Lactococcus lactis genome editing based on class IIa bacteriocin sensitivity.

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Wan, Xing; Usvalampi, Anne M; Saris, Per E J; Takala, Timo M

2016-11-01

In this paper, we present a new counterselection method for deleting fragments from Lactococcus lactis chromosome. The method uses a non-replicating plasmid vector, which integrates into the chromosome and makes the cell sensitive to bacteriocins. The integration vector carries pUC ori functional in Escherichia coli but not in L. lactis, an erythromycin resistance gene for selecting single crossover integrants, and two fragments from L. lactis chromosome for homologous recombinations. In addition, the integration vector is equipped with the Listeria monocytogenes gene mptC encoding the mannose-phosphotransferase system component IIC, the receptor for class IIa bacteriocins. Expression of mptC from the integration vector renders the naturally resistant L. lactis sensitive to class IIa bacteriocins. This sensitivity is then used to select the double crossover colonies on bacteriocin agar. Only the cells which have regained the endogenous bacteriocin resistance through the loss of the mptC plasmid will survive. The colonies carrying the desired deletion can then be distinguished from the wild-type revertants by PCR. By using the class IIa bacteriocins leucocin A, leucocin C or pediocin AcH as the counterselective agents, we deleted 22- and 33-kb chromosomal fragments from the wild-type nisin producing L. lactis strain N8. In conclusion, this counterselection method presented here is a convenient, efficient and inexpensive technique to generate successive deletions in L. lactis chromosome.

Is chloroplastic class IIA aldolase a marine enzyme?

Science.gov (United States)

Miyasaka, Hitoshi; Ogata, Takeru; Tanaka, Satoshi; Ohama, Takeshi; Kano, Sanae; Kazuhiro, Fujiwara; Hayashi, Shuhei; Yamamoto, Shinjiro; Takahashi, Hiro; Matsuura, Hideyuki; Hirata, Kazumasa

2016-01-01

Expressed sequence tag analyses revealed that two marine Chlorophyceae green algae, Chlamydomonas sp. W80 and Chlamydomonas sp. HS5, contain genes coding for chloroplastic class IIA aldolase (fructose-1, 6-bisphosphate aldolase: FBA). These genes show robust monophyly with those of the marine Prasinophyceae algae genera Micromonas, Ostreococcus and Bathycoccus, indicating that the acquisition of this gene through horizontal gene transfer by an ancestor of the green algal lineage occurred prior to the divergence of the core chlorophytes (Chlorophyceae and Trebouxiophyceae) and the prasinophytes. The absence of this gene in some freshwater chlorophytes, such as Chlamydomonas reinhardtii, Volvox carteri, Chlorella vulgaris, Chlorella variabilis and Coccomyxa subellipsoidea, can therefore be explained by the loss of this gene somewhere in the evolutionary process. Our survey on the distribution of this gene in genomic and transcriptome databases suggests that this gene occurs almost exclusively in marine algae, with a few exceptions, and as such, we propose that chloroplastic class IIA FBA is a marine environment-adapted enzyme. This hypothesis was also experimentally tested using Chlamydomonas W80, for which we found that the transcript levels of this gene to be significantly lower under low-salt (that is, simulated terrestrial) conditions. Expression analyses of transcriptome data for two algae, Prymnesium parvum and Emiliania huxleyi, taken from the Sequence Read Archive database also indicated that the expression of this gene under terrestrial conditions (low NaCl and low sulfate) is significantly downregulated. Thus, these experimental and transcriptome data provide support for our hypothesis. PMID:27058504

AMPK Signaling Involvement for the Repression of the IL-1β-Induced Group IIA Secretory Phospholipase A2 Expression in VSMCs.

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Khadija El Hadri

Full Text Available Secretory Phospholipase A2 of type IIA (sPLA2 IIA plays a crucial role in the production of lipid mediators by amplifying the neointimal inflammatory context of the vascular smooth muscle cells (VSMCs, especially during atherogenesis. Phenformin, a biguanide family member, by its anti-inflammatory properties presents potential for promoting beneficial effects upon vascular cells, however its impact upon the IL-1β-induced sPLA2 gene expression has not been deeply investigated so far. The present study was designed to determine the relationship between phenformin coupling AMP-activated protein kinase (AMPK function and the molecular mechanism by which the sPLA2 IIA expression was modulated in VSMCs. Here we find that 5-aminoimidazole-4-carboxamide-1-β-D-ribonucleotide (AICAR treatment strongly repressed IL-1β-induced sPLA2 expression at least at the transcriptional level. Our study reveals that phenformin elicited a dose-dependent inhibition of the sPLA2 IIA expression and transient overexpression experiments of constitutively active AMPK demonstrate clearly that AMPK signaling is involved in the transcriptional inhibition of sPLA2-IIA gene expression. Furthermore, although the expression of the transcriptional repressor B-cell lymphoma-6 protein (BCL-6 was markedly enhanced by phenformin and AICAR, the repression of sPLA2 gene occurs through a mechanism independent of BCL-6 DNA binding site. In addition we show that activation of AMPK limits IL-1β-induced NF-κB pathway activation. Our results indicate that BCL-6, once activated by AMPK, functions as a competitor of the IL-1β induced NF-κB transcription complex. Our findings provide insights on a new anti-inflammatory pathway linking phenformin, AMPK and molecular control of sPLA2 IIA gene expression in VSMCs.

Characterization, Leaching, and Filtration Testing for Bismuth Phosphate Sludge (Group 1) and Bismuth Phosphate Saltcake (Group 2) Actual Waste Sample Composites

International Nuclear Information System (INIS)

Lumetta, Gregg J.; Buck, Edgar C.; Daniel, Richard C.; Draper, Kathryn; Edwards, Matthew K.; Fiskum, Sandra K.; Hallen, Richard T.; Jagoda, Lynette K.; Jenson, Evan D.; Kozelisky, Anne E.; MacFarlan, Paul J.; Peterson, Reid A.; Shimskey, Rick W.; Sinkov, Sergey I.; Snow, Lanee A.

2009-01-01

A testing program evaluating actual tank waste was developed in response to Task 4 from the M-12 External Flowsheet Review Team (EFRT) issue response plan.() The test program was subdivided into logical increments. The bulk water-insoluble solid wastes that are anticipated to be delivered to the Waste Treatment and Immobilization Plant (WTP) were identified according to type such that the actual waste testing could be targeted to the relevant categories. Eight broad waste groupings were defined. Samples available from the 222S archive were identified and obtained for testing. The actual waste-testing program included homogenizing the samples by group, characterizing the solids and aqueous phases, and performing parametric leaching tests. Two of the eight defined groups - bismuth phosphate sludge (Group 1) and bismuth phosphate saltcake (Group 2) - are the subjects of this report. The Group 1 waste was anticipated to be high in phosphorus and was implicitly assumed to be present as BiPO4 (however, results presented here indicate that the phosphate in Group 1 is actually present as amorphous iron(III) phosphate). The Group 2 waste was also anticipated to be high in phosphorus, but because of the relatively low bismuth content and higher aluminum content, it was anticipated that the Group 2 waste would contain a mixture of gibbsite, sodium phosphate, and aluminum phosphate. Thus, the focus of the Group 1 testing was on determining the behavior of P removal during caustic leaching, and the focus of the Group 2 testing was on the removal of both P and Al. The waste-type definition, archived sample conditions, homogenization activities, characterization (physical, chemical, radioisotope, and crystal habit), and caustic leaching behavior as functions of time, temperature, and hydroxide concentration are discussed in this report. Testing was conducted according to TP-RPP-WTP-467

Interaction of c-Cbl with myosin IIA regulates Bleb associated macropinocytosis of Kaposi's sarcoma-associated herpesvirus.

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Mohanan Valiya Veettil

2010-12-01

Full Text Available KSHV is etiologically associated with Kaposi's sarcoma (KS, an angioproliferative endothelial cell malignancy. Macropinocytosis is the predominant mode of in vitro entry of KSHV into its natural target cells, human dermal microvascular endothelial (HMVEC-d cells. Although macropinocytosis is known to be a major route of entry for many viruses, the molecule(s involved in the recruitment and integration of signaling early during macropinosome formation is less well studied. Here we demonstrate that tyrosine phosphorylation of the adaptor protein c-Cbl is required for KSHV induced membrane blebbing and macropinocytosis. KSHV induced the tyrosine phosphorylation of c-Cbl as early as 1 min post-infection and was recruited to the sites of bleb formation. Infection also led to an increase in the interaction of c-Cbl with PI3-K p85 in a time dependent manner. c-Cbl shRNA decreased the formation of KSHV induced membrane blebs and macropinocytosis as well as virus entry. Immunoprecipitation of c-Cbl followed by mass spectrometry identified the interaction of c-Cbl with a novel molecular partner, non-muscle myosin heavy chain IIA (myosin IIA, in bleb associated macropinocytosis. Phosphorylated c-Cbl colocalized with phospho-myosin light chain II in the interior of blebs of infected cells and this interaction was abolished by c-Cbl shRNA. Studies with the myosin II inhibitor blebbistatin demonstrated that myosin IIA is a biologically significant component of the c-Cbl signaling pathway and c-Cbl plays a new role in the recruitment of myosin IIA to the blebs during KSHV infection. Myosin II associates with actin in KSHV induced blebs and the absence of actin and myosin ubiquitination in c-Cbl ShRNA cells suggested that c-Cbl is also responsible for the ubiquitination of these proteins in the infected cells. This is the first study demonstrating the role of c-Cbl in viral entry as well as macropinocytosis, and provides the evidence that a signaling complex

Synthesis of tritium labelled phosphonate analogues of sphinganine-1-phosphate

International Nuclear Information System (INIS)

Schick, Andreas; Schwarzmann, Guenter; Kolter, Thomas; Sandhoff, Konrad

1997-01-01

Tritiated phosphonate analogues 9 and 10 are prepared as analogues of sphinganine-1-phosphate 4. The key step in this synthesis is the catalytic tritiation of the triple bond in reduction of the protected diethyl-3-(S)-tert.-butoxycarbonylamino -4-hydroxy-5-tridecinyl-1-phosphonate by means of sodium boro[ 3 H]hydride as tritium source. These compounds are synthesized to study their metabolic stability and to evaluate their biological properties. (author)

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

NARCIS (Netherlands)

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

1998-01-01

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

The novel kasugamycin 2'-N-acetyltransferase gene aac(2')-IIa, carried by the IncP island, confers kasugamycin resistance to rice-pathogenic bacteria.

Science.gov (United States)

Yoshii, Atsushi; Moriyama, Hiromitsu; Fukuhara, Toshiyuki

2012-08-01

Kasugamycin (KSM), a unique aminoglycoside antibiotic, has been used in agriculture for many years to control not only rice blast caused by the fungus Magnaporthe grisea but also rice bacterial grain and seedling rot or rice bacterial brown stripe caused by Burkholderia glumae or Acidovorax avenae subsp. avenae, respectively. Since both bacterial pathogens are seed-borne and cause serious injury to rice seedlings, the emergence of KSM-resistant B. glumae and A. avenae isolates highlights the urgent need to understand the mechanism of resistance to KSM. Here, we identified a novel gene, aac(2')-IIa, encoding a KSM 2'-N-acetyltransferase from both KSM-resistant pathogens but not from KSM-sensitive bacteria. AAC(2')-IIa inactivates KSM, although it reveals no cross-resistance to other aminoglycosides. The aac(2')-IIa gene from B. glumae strain 5091 was identified within the IncP genomic island inserted into the bacterial chromosome, indicating the acquisition of this gene by horizontal gene transfer. Although excision activity of the IncP island and conjugational gene transfer was not detected under the conditions tested, circular intermediates containing the aac(2')-IIa gene were detected. These results indicate that the aac(2')-IIa gene had been integrated into the IncP island of a donor bacterial species. Molecular detection of the aac(2')-IIa gene could distinguish whether isolates are resistant or susceptible to KSM. This may contribute to the production of uninfected rice seeds and lead to the effective control of these pathogens by KSM.

One-step hydrothermal synthesis and electrochemical performance of sodium-manganese-iron phosphate as cathode material for Li-ion batteries

Science.gov (United States)

Karegeya, Claude; Mahmoud, Abdelfattah; Vertruyen, Bénédicte; Hatert, Frédéric; Hermann, Raphaël P.; Cloots, Rudi; Boschini, Frédéric

2017-09-01

The sodium-manganese-iron phosphate Na2Mn1.5Fe1.5(PO4)3 (NMFP) with alluaudite structure was obtained by a one-step hydrothermal synthesis route. The physical properties and structure of this material were obtained through XRD and Mössbauer analyses. X-ray diffraction Rietveld refinements confirm a cationic distribution of Na+ and presence of vacancies in A(2)', Na+ and small amounts of Mn2+ in A(1), Mn2+ in M(1), 0.5 Mn2+ and Fe cations (Mn2+,Fe2+ and Fe3+) in M(2), leading to the structural formula Na2Mn(Mn0.5Fe1.5)(PO4)3. The particles morphology was investigated by SEM. Several reactions with different hydrothermal reaction times were attempted to design a suitable synthesis protocol of NMFP compound. The time of reaction was varied from 6 to 48 h at 220 °C. The pure phase of NMFP particles was firstly obtained when the hydrothermal reaction of NMFP precursors mixture was maintained at 220 °C for 6 h. When the reaction time was increased from 6 to 12, 24 and 48 h, the dandelion structure was destroyed in favor of NMFP micro-rods. The combination of NMFP (NMFP-6H, NMFP-12H, NMFP-24H and NMFP-48H) structure refinement and Mössbauer characterizations shows that the increase of the reaction time leads to the progressive increment of Fe(III) and the decrease of the crystal size. The electrochemical tests indicated that NMFP is a 3 V sodium intercalating cathode. The comparison of the discharge capacity evolution of studied NMFP electrode materials at C/5 current density shows different capacities of 48, 40, 34 and 34 mA h g-1 for NMFP-6H, NMFP-12H, NMFP-24H and NMFP-48H respectively. Interestingly, all samples show excellent capacity retention of about 99% during 50 cycles.

Genetic organization of ascB-dapE internalin cluster serves as a potential marker for Listeria monocytogenes sublineages IIA, IIB, and IIC.

Science.gov (United States)

Chen, Jianshun; Fang, Chun; Zhu, Ningyu; Lv, Yonghui; Cheng, Changyong; Bei, Yijiang; Zheng, Tianlun; Fang, Weihuan

2012-05-01

Listeria monocytogenes is an important foodborne pathogen that comprises four genetic lineages: I, II, III, and IV. Of these, lineage II is frequently recovered from foods and environments and responsible for the increasing incidence of human listeriosis. In this study, the phylogenetic structure of lineage II was determined through sequencing analysis of the ascB-dapE internalin cluster. Fifteen sequence types proposed by multilocus sequence typing based on nine housekeeping genes were grouped into three distinct sublineages, IIA, IIB, and IIC. Organization of the ascBdapE internalin cluster could serve as a molecular marker for these sublineages, with inlGHE, inlGC2DE, and inlC2DE for IIA, IIB, and IIC, respectively. These sublineages displayed specific genetic and phenotypic characteristics. IIA and IIC showed a higher frequency of recombination (rho/theta). However, recombination events had greater effect (r/m) on IIB, leading to its high nucleotide diversity. Moreover, IIA and IIB harbored a wider range of internalin and stress-response genes, and possessed higher nisin tolerance, whereas IIC contained the largest portion of low-virulent strains owing to premature stop codons in inlA. The results of this study indicate that IIA, IIB, and IIC might occupy different ecological niches, and IIB might have a better adaptation to a broad range of environmental niches.

The crystal structure of the regulatory domain of the human sodium-driven chloride/bicarbonate exchanger.

Science.gov (United States)

Alvadia, Carolina M; Sommer, Theis; Bjerregaard-Andersen, Kaare; Damkier, Helle Hasager; Montrasio, Michele; Aalkjaer, Christian; Morth, J Preben

2017-09-21

The sodium-driven chloride/bicarbonate exchanger (NDCBE) is essential for maintaining homeostatic pH in neurons. The crystal structure at 2.8 Å resolution of the regulatory N-terminal domain of human NDCBE represents the first crystal structure of an electroneutral sodium-bicarbonate cotransporter. The crystal structure forms an equivalent dimeric interface as observed for the cytoplasmic domain of Band 3, and thus establishes that the consensus motif VTVLP is the key minimal dimerization motif. The VTVLP motif is highly conserved and likely to be the physiologically relevant interface for all other members of the SLC4 family. A novel conserved Zn 2+ -binding motif present in the N-terminal domain of NDCBE is identified and characterized in vitro. Cellular studies confirm the Zn 2+ dependent transport of two electroneutral bicarbonate transporters, NCBE and NBCn1. The Zn 2+ site is mapped to a cluster of histidines close to the conserved ETARWLKFEE motif and likely plays a role in the regulation of this important motif. The combined structural and bioinformatics analysis provides a model that predicts with additional confidence the physiologically relevant interface between the cytoplasmic domain and the transmembrane domain.

Impact of sodium–glucose cotransporter 2 inhibitors on blood pressure

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Reed JW

2016-10-01

Full Text Available James W Reed Morehouse School of Medicine, Atlanta, GA, USA Abstract: SGLT2 inhibitors are glucose-lowering agents used to treat type 2 diabetes mellitus (T2DM. These agents target the kidney to promote urinary glucose excretion, resulting in improved blood glucose control. SGLT2-inhibitor therapy is also associated with weight loss and blood pressure (BP lowering. Hypertension is a common comorbidity in patients with T2DM, and is associated with excess morbidity and mortality. This review summarizes data on the effect of SGLT2 inhibitors marketed in the US (namely canagliflozin, dapagliflozin, or empagliflozin on BP in patients with T2DM. Boolean searches were conducted that included terms related to BP or hypertension with terms for SGLT2 inhibitors, canagliflozin, dapagliflozin, or empagliflozin using PubMed, Google, and Google Scholar. Data from numerous randomized controlled trials of SGLT2 inhibitors in patients with T2DM demonstrated clinically relevant reductions in both systolic and diastolic BP, assessed via seated office measurements and 24-hour ambulatory BP monitoring. Observed BP lowering was not associated with compensatory increases in heart rate. Circadian BP rhythm was also maintained. The mechanism of SGLT2 inhibitor-associated BP reduction is not fully understood, but is assumed to be related to osmotic diuresis and natriuresis. Other factors that may also contribute to BP reduction include SGLT2 inhibitor-associated decreases in body weight and reduced arterial stiffness. Local inhibition of the renin–angiotensin–aldosterone system secondary to increased delivery of sodium to the juxtaglomerular apparatus during SGLT2 inhibition has also been postulated. Although SGLT2 inhibitors are not indicated as BP-lowering agents, the modest decreases in systolic and diastolic BP observed with SGLT2 inhibitors may provide an extra clinical advantage for the majority of patients with T2DM, in addition to improving blood glucose

Validation of polyethylene glycol 3350 as a poorly absorbable marker for intestinal perfusion studies.

Science.gov (United States)

Schiller, L R; Santa Ana, C A; Porter, J; Fordtran, J S

1997-01-01

Polyethylene glycol (PEG) has been used as a poorly absorbable marker in intestinal perfusion studies, but there is controversy about the absorbability of PEG, particularly when glucose-sodium cotransport is occurring. Total intestinal perfusion studies were done in five normal humans using three solutions containing 1 g/liter PEG 3350 and designed to produce low rates of water absorption, high rates of water absorption, or high rates of glucose-sodium cotransport. Water absorption rates were calculated by traditional nonabsorbable marker equations and by a novel balance technique in which absorption was taken as the difference between the volumes of solution infused and recovered during steady-state conditions. Effluent PEG recovery was 99 +/- 4%, 109 +/- 2%, and 104 +/- 6% of the amount infused with each solution. Water absorption rates measured by use of PEG concentrations were similar to those calculated by the balance technique (r = 0.99). The complete recovery of PEG confirms the poor absorbability of PEG 3350, and the excellent agreement between techniques validates PEG as a poorly absorbed marker, even when glucose-sodium cotransport is occurring.

Determination of Montelukast Sodium and Bambuterol Hydrochloride in Tablets using RP HPLC.

Science.gov (United States)

Patil, Smita; Pore, Y V; Kuchekar, B S; Mane, Aruna; Khire, V G

2009-01-01

An accurate, specific and precise assay level gradient reverse-phase high-performance liquid chromatographic method was developed for simultaneous determination of montelukast sodium and bambuterol hydrochloride in tablet dosage form. An inertsil ODS C-18, 5 mum column having 250x4.6 mm I.D. in gradient mode, with mobile phase A, containing 0.025 M sodium phosphate buffer: methanol (85:15) and mobile phase B, containing acetonitrile:methanol (85:15) was used at different time intervals. The flow rate was 1.5 ml/min and effluent was monitored at 218 nm. The retention times of montelukast sodium and bambuterol hydrochloride were 21.2 min and 5.8 min respectively. The linearity for both the drugs was in the range of 0.25-0.75 mg/ml with correlation coefficients of 0.9999 and 0.9996 for montelukast sodium and bambuterol hydrochloride, respectively.

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

Science.gov (United States)

Dantzler, William H.; Pannabecker, Thomas L.

2012-01-01

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

Effect of reagent type on the froth floatation of Sokoto phosphate ore

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U.A. Hassan

2016-06-01

Full Text Available Effect of reagent type on the froth floatation of Sokoto phosphate ore for its beneficiation has been established. The samples of the Sokoto phosphate mineral ore used for the research work were sourced from mining locations in Dange-Shuni, Bodinga, Yabo, Wurno, and Rabbah Local Government Areas of Sokoto State. Size-Assay analysis conducted on scrubbed Sokoto Phosphates nodules revealed that nodules had a size distribution with 80% passing 29.3 mm. Flotation Tests using AERO704 (fatty Acid, Alkyl Hydroxamates, Melamine as collectors (alone or mixed with diesel, MIBC as frother, Calcium Hydroxide and Sulphuric Acid as pH regulators and Dextrin, Sodium Silicate and Aluminium Chloride as depressants produced poor P2O5 separation in the flotation products due to very poor liberation associated with very fine mineral grains. Based on the results obtained, AERO704 Collector gave the best result with aP2O5 recovery pH of 10.

Immobilization of sodium and phosphorus-bearing PW-7a waste in SYNROC. Progress report

International Nuclear Information System (INIS)

Ringwood, A.E.

1982-01-01

The phosphorus, sodium and gadolinium-rich PW-7a waste can be successfully incorporated in SYNROC-C. However, a new accessory phase, a Ca,Na,Ba phosphate isostructural with Ca 5 Na 2 (PO 4 ) 4 apppears in the SYNROC mineralogy. There is no evidence for the partition of key radionuclides (e.g. Sr, REE and hence actinides) into this phosphate. Its poor resistance to groundwater dissolution, whilst hardly desirable, may therefore not have a serious effect on the leaching performance of SYNROC containing PW-7a. 9 tables

Studies on sorption of plutonium on inorganic exchangers from sodium carbonate medium

Energy Technology Data Exchange (ETDEWEB)

Pius, I C; Charyulu, M M; Sivaramakrishnan, C K [Fuel Chemistry Division, Bhabha Atomic Research Centre, Mumbai (India); Venkataramani, B [Chemistry Division, Bhabha Atomic Research Centre, Mumbai (India)

1994-06-01

Sorption of Pu(IV) from sodium carbonate medium has been investigated by using different inorganic exchangers alumina, silica gel and hydrous titanium oxide. Distribution ratios of Pu(IV) for its sorption on these exchangers from sodium carbonate medium were found to be sufficiently high indicating the suitability of these exchangers for the removal of Pu(IV). The presence of uranium and dibutyl phosphate do not have any effect on distribution ratio. The 10% Pu(IV) breakthrough capacities for above exchangers have been determined with 5 ml bed at a flow rate of 30 ml/hour. (author). 4 refs., 2 tabs.

Immobilisation of radio cesium loaded ammonium molybdo phosphate in glass matrices

International Nuclear Information System (INIS)

Yalmali, Vrunda S.; Singh, I.J.; Sathi Sasidharan, N.; Deshingkar, D.S.

2004-11-01

Long half life and easy availability from high level wastes make 137 Cesium most economical radiation source. High level liquid waste processing for 137 Cesium removal has become easier due to development of Cesium specific granulated ammonium molybdophosphate (AMP) composite. In such applications, resulting spent composite AMP itself represents high active solid waste and immobilization of these materials in cement may not be acceptable. Studies on immobilization of 137 Cs loaded AMP were taken up in order to achieve twin goals of increasing safety and minimizing processing costs of the final matrix. Studies indicated that phosphate modified sodium borosilicate SPNM glasses prepared under usual oxidizing conditions are not suitable for immobilization of 137 Cs loaded on AMP .Phosphate glasses containing Na 2 O, P 2 O 5 , B 2 O 3 , Fe 2 O 3 , Al 2 O 3 and SiO 2 as major constituents are capable of incorporating 6 to 8 % AMP. The Normalized Leach rates of these glasses for sodium, cesium, boron and silica are 10 -4 to 10 -6 gm/cm 2 /day which are comparable to or better than those reported for NBS glasses incorporating HLW. Homogeneity of the final matrix was confirmed by x-ray diffraction analysis. Further studies on characterization of these glasses would establish their acceptability. (author)

Phosphate attenuates the anti-proteinuric effect of very low-protein diet in CKD patients.

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Di Iorio, Biagio R; Bellizzi, Vincenzo; Bellasi, Antonio; Torraca, Serena; D'Arrigo, Graziella; Tripepi, Giovanni; Zoccali, Carmine

2013-03-01

High phosphate levels attenuate nephroprotection through angiotensin-converting enzyme inhibition in patients with proteinuric chronic kidney disease (CKD). Whether this phenomenon holds true for other nephroprotective interventions like very-low-protein diet (VLPD) is unknown. We tested the hypothesis that phosphate interferes with the anti-proteinuric response to VLPD in a non-randomized, sequential study in 99 proteinuric CKD patients who sequentially underwent low-protein diet (LPD; 0.6 g/kg) and VLPD (0.3 g/kg) supplemented with keto-analogues, each for periods longer than 1 year. Serum phosphate significantly reduced during VLPD (3.2 ± 0.6 mg/dL) when compared with LPD (3.7 ± 0.6 mg/dL, P diet periods. In linear mixed models including the diagnosis of renal disease, eGFR, 24-h urine sodium and urea and other potential confounders, there was a strong interaction between serum phosphate (P = 0.04) and phosphaturia (P < 0.001) with the anti-proteinuric response to VLPD. Accordingly, 24-h proteinuria reduced modestly in patients who maintained relatively higher serum phosphate levels or relatively higher phosphaturia to be maximal in those who achieved the lowest level of serum and urine phosphate. Phosphate is an important modifier of the anti-proteinuric response to VLPD. Reducing phosphate burden may decrease proteinuria and slow the progression of renal disease in CKD patients, an issue that remains to be tested in specific clinical trials.

The antitumor effect of tanshinone IIA on anti-proliferation and decreasing VEGF/VEGFR2 expression on the human non-small cell lung cancer A549 cell line

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Jun Xie

2015-11-01

Full Text Available The effects of tanshinone IIA on the proliferation of the human non-small cell lung cancer cell line A549 and its possible mechanism on the VEGF/VEGFR signal pathway were investigated. The exploration of the interaction between tanshinone IIA and its target proteins provides a feasible platform for studying the anticancer mechanism of active components of herbs. The CCK-8 assay was used to evaluate the proliferative activity of A549 cells treated with tanshinone IIA (2.5−80 μmol/L for 24, 48 and 72 h, respectively. Flow cytometry was used for the detection of cell apoptosis and cell cycle perturbation. VEGF and VEGFR2 expression were studied by Western blotting. The binding mode of tanshinone IIA within the crystal structure of the VEGFR2 protein was evaluated with molecular docking analysis by use of the CDOCKER algorithm in Discovery Studio 2.1. The CCK-8 results showed that tanshinone IIA can significantly inhibit A549 cell proliferation in a dose- and time-dependent manner. Flow cytometry results showed that the apoptosis rate of tested group was higher than the vehicle control, and tanshinone IIA-treated cells accumulated at the S phase, which was higher than the vehicle control. Furthermore, the expression of VEGF and VEGFR2 was decreased in Western blot. Finally, molecular docking analysis revealed that tanshinone IIA could be stably docked into the kinase domain of VEGFR2 protein with its unique modes to form H-bonds with Cys917 and π–π stacking interactions with Val848. In conclusion, tanshinone IIA may suppress A549 proliferation, induce apoptosis and cell cycle arrest at the S phase. This drug may suppress angiogenesis by targeting the protein kinase domains of VEGF/VEGFR2.

Inhibition of Tanshinone IIA, Salvianolic Acid A and Salvianolic Acid B on Areca Nut Extract-Induced Oral Submucous Fibrosis in Vitro

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Jian-Ping Dai

2015-04-01

Full Text Available Salvia miltiorrhiza Bunge has been reported to possess excellent antifibrotic activity. In this study, we have investigated the effect and mechanism of tanshinone IIA (Tan-IIA, salvianolic acid A (Sal-A and salvianolic acid B (Sal-B, the important active compounds of Salvia miltiorrhiza Bunge, on areca nut extract (ANE-induced oral submucous fibrosis (OSF in vitro. Through human procollagen gene promoter luciferase reporter plasmid assay, hydroxyproline assay, gelatin zymography assay, qRT-PCR, ELISA and Western blot assay, the influence of these three compounds on ANE-stimulated cell viability, collagen accumulation, procollagen gene transcription, MMP-2/-9 activity, MMP-1/-13 and TIMP-1/-2 expression, cytokine secretion and the activation of PI3K/AKT, ERK/JNK/p38 MAPK and TGF-β/Smads pathways were detected. The results showed that Tan-IIA, Sal-A and Sal-B could significantly inhibit the ANE-stimulated abnormal viability and collagen accumulation of mice oral mucosal fibroblasts (MOMFs, inhibit the transcription of procollagen gene COL1A1 and COL3A1, increase MMP-2/-9 activity, decrease TIMP-1/-2 expression and inhibit the transcription and release of CTGF, TGF-β1, IL-6 and TNF-α; Tan-IIA, Sal-A and Sal-B also inhibited the ANE-induced activation of AKT and ERK MAPK pathways in MOMFs and the activation of TGF-β/Smads pathway in HaCaT cells. In conclusion, Tan-IIA, Sal-A and Sal-B possess excellent antifibrotic activity in vitro and can possibly be used to promote the rehabilitation of OSF patients.

Products and stability of phosphate reactions with lead under freeze-thaw cycling in simple systems

International Nuclear Information System (INIS)

Hafsteinsdottir, Erla G.; White, Duanne A.; Gore, Damian B.; Stark, Scott C.

2011-01-01

Orthophosphate fixation of metal contaminated soils in environments that undergo freeze-thaw cycles is understudied. Freeze-thaw cycling potentially influences the reaction rate, mineral chemical stability and physical breakdown of particles during fixation. This study determines what products form when phosphate (triple superphosphate [Ca(H 2 PO 4 ) 2 ] or sodium phosphate [Na 3 PO 4 ]) reacts with lead (PbSO 4 or PbCl 2 ) in simple chemical systems in vitro, and assesses potential changes in formation during freeze-thaw cycles. Systems were subjected to multiple freeze-thaw cycles from +10 deg. C to -20 deg. C and then analysed by X-ray diffractometry. Pyromorphite formed in all systems and was stable over multiple freeze-thaw cycles. Low temperature lead orthophosphate reaction efficiency varied according to both phosphate and lead source; the most time-efficient pyromorphite formation was observed when PbSO 4 and Na 3 PO 4 were present together. These findings have implications for the manner in which metal contaminated materials in freezing ground can be treated with phosphate. - Highlights: → Formation of lead phosphate products in cold environments is identified. → Potential change in formation during freeze-thaw cycling is assessed. → Lead phosphate reaction efficiency varies according to phosphate and lead source. → Pyromorphite formation is stable during 240 freeze-thaw cycles. - Pyromorphite, formed from Pb phosphate fixation, is stable during multiple freeze-thaw cycles but the efficiency of the fixation depends on the phosphate source and the type of Pb mineral.

Visual Prognosis in USH2A-Associated Retinitis Pigmentosa Is Worse for Patients with Usher Syndrome Type IIa Than for Those with Nonsyndromic Retinitis Pigmentosa.

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Pierrache, Laurence H M; Hartel, Bas P; van Wijk, Erwin; Meester-Smoor, Magda A; Cremers, Frans P M; de Baere, Elfride; de Zaeytijd, Julie; van Schooneveld, Mary J; Cremers, Cor W R J; Dagnelie, Gislin; Hoyng, Carel B; Bergen, Arthur A; Leroy, Bart P; Pennings, Ronald J E; van den Born, L Ingeborgh; Klaver, Caroline C W

2016-05-01

USH2A mutations are an important cause of retinitis pigmentosa (RP) with or without congenital sensorineural hearing impairment. We studied genotype-phenotype correlations and compared visual prognosis in Usher syndrome type IIa and nonsyndromic RP. Clinic-based, longitudinal, multicenter study. Consecutive patients with Usher syndrome type IIa (n = 152) and nonsyndromic RP (n = 73) resulting from USH2A mutations from ophthalmogenetic clinics in the Netherlands and Belgium. Data on clinical characteristics, visual acuity, visual field measurements, retinal imaging, and electrophysiologic features were extracted from medical charts over a mean follow-up of 9 years. Cumulative lifetime risks of low vision and blindness were estimated using Kaplan-Meier survival analysis. Low vision and blindness. Participant groups had similar distributions of gender (48% vs. 45% males in Usher syndrome type IIa vs. nonsydromic RP; P = 0.8), ethnicity (97% vs. 99% European; P = 0.3), and median follow-up time (6.5 years vs. 3 years; P = 0.3). Usher syndrome type IIa patients demonstrated symptoms at a younger age (median age, 15 years vs. 25 years; P syndromic phenotype, whereas other combinations were present in both groups. We found novel variants in Usher syndrome type IIa (25%) and nonsyndromic RP (19%): 29 missense mutations, 10 indels, 14 nonsense mutations, 9 frameshift mutations, and 5 splice-site mutations. Most patients with USH2A-associated RP have severe visual impairment by age 50. However, those with Usher syndrome type IIa have an earlier decline of visual function and a higher cumulative risk of visual impairment than those without nonsyndromic RP. Complete loss of function of the USH2A protein predisposes to Usher syndrome type IIa, but remnant protein function can lead to RP with or without hearing loss. Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Value of diffusion-weighted imaging in predicting parametrial invasion in stage IA2-IIA cervical cancer

International Nuclear Information System (INIS)

Park, Jung Jae; Kim, Chan Kyo; Park, Sung Yoon; Park, Byung Kwan; Kim, Bohyun

2014-01-01

To investigate the value of diffusion-weighted imaging (DWI) in evaluating parametrial invasion (PMI) in stage IA2-IIA cervical cancer. A total of 117 patients with stage IA2-IIA cervical cancer who underwent preoperative MRI and radical hysterectomy were included in this study. Preoperative clinical variables and MRI variables were analysed and compared between the groups with and without pathologically proven PMI. All variables except age were significantly different between patients with and without pathologic PMI (P < 0.05). All variables except squamous cell carcinoma (SCC) antigen were also significantly correlated with pathologic PMI on univariate analysis (P < 0.05). Multivariate analysis indicated that PMI on MRI (P < 0.001) and tumour apparent diffusion coefficient (ADC) (P = 0.029) were independent predictors of pathologic PMI. Area under the curve of PMI on MRI increased significantly from 0.793 to 0.872 when combined with tumour ADC (P = 0.002). When PMI on MRI was further stratified by tumour ADC, the false negative rate was 2.0 % (1/49). In stage IA2-IIA cervical cancer, tumour ADC and PMI on MRI seem to be independent predictors of pathologic PMI. Combining the two predictors improved the diagnostic performance of identifying patients at low risk of pathologic PMI. (orig.)

Some properties of tetravalent actinide phosphates of M1M42(PO4)3 type and peculiarities of their structure

International Nuclear Information System (INIS)

Burnaeva, A.A.; Volkov, Yu.F.; Kryukova, A.I.; Skiba, O.V.; Spiryakov, V.I.; Korshunov, I.A.; Samojlova, T.K.

1987-01-01

Generalizing analysis of data on crystallographic and IR spectral properties of double phosphates of actinide and alkali elements of M (1) M 2 (4) (PO 4 ) 3 type is conducted. It is shown, that Li - , Na - , K - , Rb - , CsTh 2 (PO 4 ) 3 , Li - , Na - , KU 2 (PO 4 ) 3 , NaNp 2 (PO 4 ) 3 compounds crystallize in a monoclinic type structure and form an isostructural phosphate series. It is ascertained, that in rubidium-uranium, uranium-cesium systems double salt formation is not observed. Plutonium-sodium phosphate has a rhombic-type structure, which points out to the existence of a morphotropic transition in NaM 2 4 (PO 4 ) 3 phosphate series at the Np-Pu boundary. Some regularities of structure and effect of M 1 and M 4 nature on the double phosphate structure are revealed

Activity of NaOH buffered by silicate solids in molten sodium acetate-water at 3170C

International Nuclear Information System (INIS)

Weres, O.; Tsao, L.

1988-01-01

Silica and sodium acetate are present in the steam generator tube sheet crevices of many nuclear power plants. Trace solutes in the condensate are tremendously concentrated in the crevices by boiling. Sparingly soluble sodium silicates and other solids precipitate from the crevice liquid leaving an extremely concentrated molten mixture of water, sodium acetate and other salts. The precipitates buffer the activity of sodium hydroxide in the superheated liquid that remains. The activity of NaOH corresponding to the buffers quartz/sodium disilicate and sodium disilicate/sodium metasilicate at 317 0 C has been determined experimentally. The sodium hydroxide content of a sodium acetate-water melt buffered by these reactions was determined by chemical analysis, and the corresponding activity of NaOH at temperature was calculated using the recently published Pitzer-Simonson Model of molten salt-water mixtures. The molten mixture of sodium acetate and water plays the role solvent in these experiments and calculations. The free energies of formation of solid sodium silicates at 317 0 C were also determined. The activity of NaOH corresponding to other silicate and phosphate buffers was calculated using published thermodynamic data and estimated from phase diagrams

A regenerable potassium and phosphate sorbent system to enhance dialysis efficacy and device portability: an in vitro study.

Science.gov (United States)

Wester, Maarten; Simonis, Frank; Gerritsen, Karin G; Boer, Walther H; Wodzig, Will K; Kooman, Jeroen P; Joles, Jaap A

2013-09-01

Continuous dialysis could provide benefit by constant removal of potassium and phosphate. This study investigates the suitability of specific potassium and phosphate sorbents for incorporation in an extracorporeal device by capacity and regenerability testing. Capacity testing was performed in uraemic plasma. Regenerability was tested for potassium sorbents, with adsorption based on cationic exchange for sodium, with 0.1 M and 1.0 M NaCl. To regenerate phosphate sorbents, with adsorption based on anionic exchange, 0.1 M and 1.0 M NaHCO3 and NaOH were used. Subsequently, sodium polystyrene divinylbenzene sulphonate (RES-A) and iron oxide hydroxide (FeOOH) beads were incorporated in a cartridge for testing in bovine blood using a recirculating blood circuit and a dialysis circuit separated by a high-flux dialyzer (dynamic setup). Preloading was tested to assess whether this could limit calcium and magnesium adsorption. In the batch-binding assays, zirconium phosphate most potently adsorbed potassium (0.44 ± 0.05 mmol/g) and RES-A was the best regenerable potassium sorbent (92.9 ± 5.7% with 0.1 M NaCl). Zirconium oxide hydroxide (ZIR-hydr) most potently adsorbed phosphate (0.23 ± 0.05 mmol/g) and the polymeric amine sevelamer carbonate was the best regenerable sorbent (85.7 ± 5.2% with 0.1 M NaHCO3). In the dynamic setup, a potassium adsorption of 10.72 ± 2.06 mmol in 3 h was achieved using 111 g of RES-A and a phosphate adsorption of 4.73 ± 0.53 mmol in 3 h using 55 g of FeOOH. Calcium and magnesium preloading was shown to reduce the net adsorption in 3 h from 3.57 ± 0.91 to -0.29 ± 1.85 and 1.02 ± 0.05 to -0.31 ± 0.18 mmol, respectively. RES-A and FeOOH are suitable, regenerizable sorbents for potassium and phosphate removal in dialysate regeneration. Use of zirconium carbonate and ZIR-hydr may further increase phosphate adsorption, but may compromise sorbent regenerability. Use of polymeric amines for phosphate adsorption may enhance sorbent

Development of nano SiO2 incorporated nano zinc phosphate coatings on mild steel