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Sample records for bicarbonate production inhibitors

  1. In vitro dissolution of proton-pump inhibitor products intended for paediatric and geriatric use in physiological bicarbonate buffer.

    Science.gov (United States)

    Liu, Fang; Shokrollahi, Honaz

    2015-05-15

    Proton-pump inhibitor (PPI) products based on enteric coated multiparticulates are design to meet the needs of patients who cannot swallow tablets such as children and older adults. Enteric coated PPI preparations exhibit delays in in vivo absorption and onset of antisecretory effects, which is not reflected by the rapid in vitro dissolution in compendial pH 6.8 phosphate buffer commonly used for assessment of these products. A more representative and physiological medium, pH 6.8 mHanks bicarbonate buffer, was used in this study to evaluate the in vitro dissolution of enteric coated multiparticulate-based PPI products. Commercially available omeprazole, lansoprazole and esomeprazole products were subject to dissolution tests using USP-II apparatus in pH 4.5 phosphate buffer saline for 45 min (acid stage) followed by pH 6.8 phosphate buffer or pH 6.8 mHanks bicarbonate buffer. In pH 6.8 phosphate buffer, all nine tested products displayed rapid and comparable dissolution profiles meeting the pharmacopeia requirements for delayed release preparations. In pH 6.8 mHanks buffer, drug release was delayed and failed the pharmacopeia requirements from most enteric coated preparations. Despite that the same enteric polymer, methacrylic acid-ethyl acrylate copolymer (1:1), was applied to all commercial multiparticulate-based products, marked differences were observed between dissolution profiles of these preparations. The use of pH 6.8 physiological bicarbonate (mHanks) buffer can serve as a useful tool to provide realistic and discriminative in vitro release assessment of enteric coated PPI preparations and to assist rational formulation development of these products.

  2. 40 CFR 415.140 - Applicability; description of the sodium bicarbonate production subcategory.

    Science.gov (United States)

    2010-07-01

    ... sodium bicarbonate production subcategory. 415.140 Section 415.140 Protection of Environment... POINT SOURCE CATEGORY Sodium Bicarbonate Production Subcategory § 415.140 Applicability; description of the sodium bicarbonate production subcategory. The provisions of this subpart are applicable...

  3. Electrochemical Studies on Silicate and Bicarbonate Ions for Corrosion Inhibitors

    Science.gov (United States)

    Mohorich, Michael E.; Lamb, Joshua; Chandra, Dhanesh; Daemen, Jaak; Rebak, Raul B.

    2010-10-01

    Several types of carbon and high-strength low-alloy (HSLA) steels are being considered for use in the underground reinforcement of the Yucca Mountain Nuclear Waste Repository. In this study, potentiodynamic polarization under reducing conditions was used to determine the corrosion rates (CRs) and passivity behavior of AISI 4340 steel using different combinations of sodium silicate (Na2SiO3) and sodium bicarbonate (NaHCO3), in both pure water (PW) and simulated seawater (SW, 3.5 pct NaCl). These experiments were carried out to examine the potential inhibiting properties of the silicate or bicarbonate ions on the surface of the steel. The addition of sodium silicate to solution reduced the observed CR at room temperature to 19 μm/y at 0.005 M concentration and 7 μm/y at 0.025 M concentration in PW. The addition of sodium bicarbonate increased the CR from 84 μm/y (C = 0.1 M) to 455 μm/y (C = 1 M). These same behaviors were also observed at higher temperatures.

  4. Production of sodium bicarbonate from a basic process stream

    NARCIS (Netherlands)

    Witkamp, G.J.; Van Spronsen, J.; Hasselaar, M.

    2012-01-01

    The present invention is in the area of the treatment of a gas flow containing carbon dioxide obtained from burning at least one organic waste or feed stream, on the one hand to produce sodium bicarbonate and optionally remove and/or recover molybdenum compounds and/or other impurities from the said

  5. Increasing wheat production while decreasing nitrogen losses from ammonium bicarbonate

    International Nuclear Information System (INIS)

    The objectives of a 4-year field experiment were i) to investigate the effects of rate and timing of application of ammonium bicarbonate on N-uptake efficiency by irrigated winter wheat, ii) to determine the fate of fertilizer N in wheat followed by maize, and iii) to study nitrate dynamics in the soil after N-fertilizer application to evaluate groundwater pollution by leaching. Nitrogen-application rates significantly affected wheat grain yields and straw dry matter. Grain yields were higher with 150 than with 225 kg N ha-1, whereas the highest fractional recoveries of N from ammonium bicarbonate occurred with 75 kg N ha-1 (38.5% in 1994-95 and 33.5% in 1996-97). On the basis of grain yield, N recovery and soil-N balance, ammonium bicarbonate at 150 kg N ha-1, was the optimum rate, when applied basally and as a top dressing to wheat. Subsequent yields of maize stover and grain were affected by N applied to the wheat, suggesting that fertilizer recommendations, in terms of rate and timing, should be made on the basis of effects on the cropping rotation as a whole. Water-holding capacity of the soil was poor, therefore large applications of N are likely to cause nitrate pollution of ground water. (author)

  6. Bicarbonate-based Integrated Carbon Capture and Algae Production System with alkalihalophilic cyanobacterium.

    Science.gov (United States)

    Chi, Zhanyou; Xie, Yuxiao; Elloy, Farah; Zheng, Yubin; Hu, Yucai; Chen, Shulin

    2013-04-01

    An extremely alkalihalophilic cyanobacteria Euhalothece ZM001 was tested in the Bicarbonate-based Integrated Carbon Capture and Algae Production System (BICCAPS), which utilize bicarbonate as carbon source for algae culture and use the regenerated carbonate to absorb CO2. Culture conditions including temperature, inoculation rate, medium composition, pH, and light intensity were investigated. A final biomass concentration of 4.79 g/L was reached in tissue flask culture with 1.0 M NaHCO3/Na2CO3. The biomass productivity of 1.21 g/L/day was achieved under optimal conditions. When pH increased from 9.55 to 10.51, 0.256 M of inorganic carbon was consumed during the culture process. This indicated sufficient carbon can be supplied as bicarbonate to the culture. This study proved that a high biomass production rate can be achieved in a BICCAPS. This strategy can also lead to new design of photobioreactors that provides an alternative supply of CO2 to sparging.

  7. Production of the carbonate radical anion during xanthine oxidase turnover in the presence of bicarbonate.

    Science.gov (United States)

    Bonini, Marcelo G; Miyamoto, Sayuri; Di Mascio, Paolo; Augusto, Ohara

    2004-12-10

    Xanthine oxidase is generally recognized as a key enzyme in purine catabolism, but its structural complexity, low substrate specificity, and specialized tissue distribution suggest other functions that remain to be fully identified. The potential of xanthine oxidase to generate superoxide radical anion, hydrogen peroxide, and peroxynitrite has been extensively explored in pathophysiological contexts. Here we demonstrate that xanthine oxidase turnover at physiological pH produces a strong one-electron oxidant, the carbonate radical anion. The radical was shown to be produced from acetaldehyde oxidation by xanthine oxidase in the presence of catalase and bicarbonate on the basis of several lines of evidence such as oxidation of both dihydrorhodamine 123 and 5,5-dimethyl-1-pyrroline-N-oxide and chemiluminescence and isotope labeling/mass spectrometry studies. In the case of xanthine oxidase acting upon xanthine and hypoxanthine as substrates, carbonate radical anion production was also evidenced by the oxidation of 5,5-dimethyl-1-pyrroline-N-oxide and of dihydrorhodamine 123 in the presence of uricase. The results indicated that Fenton chemistry occurring in the bulk solution is not necessary for carbonate radical anion production. Under the conditions employed, the radical was likely to be produced at the enzyme active site by reduction of a peroxymonocarbonate intermediate whose formation and reduction is facilitated by the many xanthine oxidase redox centers. In addition to indicating that the carbonate radical anion may be an important mediator of the pathophysiological effects of xanthine oxidase, the results emphasize the potential of the bicarbonate-carbon dioxide pair as a source of biological oxidants. PMID:15448145

  8. Biosynthesis of the proteasome inhibitor syringolin A: the ureido group joining two amino acids originates from bicarbonate

    Directory of Open Access Journals (Sweden)

    Schellenberg Barbara

    2009-10-01

    Full Text Available Abstract Background Syringolin A, an important virulence factor in the interaction of the phytopathogenic bacterium Pseudomonas syringae pv. syringae B728a with its host plant Phaseolus vulgaris (bean, was recently shown to irreversibly inhibit eukaryotic proteasomes by a novel mechanism. Syringolin A is synthesized by a mixed non-ribosomal peptide synthetase/polyketide synthetase and consists of a tripeptide part including a twelve-membered ring with an N-terminal valine that is joined to a second valine via a very unusual ureido group. Analysis of sequence and architecture of the syringolin A synthetase gene cluster with the five open reading frames sylA-sylE allowed to formulate a biosynthesis model that explained all structural features of the tripeptide part of syringolin A but left the biosynthesis of the unusual ureido group unaccounted for. Results We have cloned a 22 kb genomic fragment containing the sylA-sylE gene cluster but no other complete gene into the broad host range cosmid pLAFR3. Transfer of the recombinant cosmid into Pseudomonas putida and P. syringae pv. syringae SM was sufficient to direct the biosynthesis of bona fide syringolin A in these heterologous organisms whose genomes do not contain homologous genes. NMR analysis of syringolin A isolated from cultures grown in the presence of NaH13CO3 revealed preferential 13C-labeling at the ureido carbonyl position. Conclusion The results show that no additional syringolin A-specific genes were needed for the biosynthesis of the enigmatic ureido group joining two amino acids. They reveal the source of the ureido carbonyl group to be bicarbonate/carbon dioxide, which we hypothesize is incorporated by carbamylation of valine mediated by the sylC gene product(s. A similar mechanism may also play a role in the biosynthesis of other ureido-group-containing NRPS products known largely from cyanobacteria.

  9. Natural Products as Aromatase Inhibitors

    OpenAIRE

    Balunas, Marcy J.; Su, Bin; Brueggemeier, Robert W.; Kinghorn, A. Douglas

    2008-01-01

    With the clinical success of several synthetic aromatase inhibitors (AIs) in the treatment of postmenopausal estrogen receptor-positive breast cancer, researchers have also been investigating also the potential of natural products as AIs. Natural products from terrestrial and marine organisms provide a chemically diverse array of compounds not always available through current synthetic chemistry techniques. Natural products that have been used traditionally for nutritional or medicinal purpos...

  10. Gram-scale solution-phase synthesis of selective sodium bicarbonate Co-transport Inhibitor S0859

    DEFF Research Database (Denmark)

    Larsen, Ann Møller; Krogsgaard-Larsen, Niels; Lauritzen, Gitte;

    2012-01-01

    Na+-coupled HCO3- transporters (NBCs) mediate the transport of bicarbonate ions across cell membranes and are thus ubiquitous regulators of intracellular pH. NBC dysregulation is associated with a range of diseases; for instance, NBCn1 is strongly up-regulated in a model of ErbB2-dependent breast...

  11. Selection of microalgae and cyanobacteria strains for bicarbonate-based integrated carbon capture and algae production system.

    Science.gov (United States)

    Chi, Zhanyou; Elloy, Farah; Xie, Yuxiao; Hu, Yucai; Chen, Shulin

    2014-01-01

    Using microalgae to capture CO2 from flue gas is an ideal way to reduce CO2 emission, but this is challenged by the high cost of carbon capture and transportation. To address this problem, a bicarbonate-based integrated carbon capture and algae production system (BICCAPS) has been proposed, in which bicarbonate is used for algae culture, and the regenerated carbonate from this process can be used to capture more CO2. High-concentration bicarbonate is obligate for the BICCAPS. Thus, different strains of microalgae and cyanobacteria were tested in this study for their capability to grow in high-concentration NaHCO3. The highest NaHCO3 concentrations they are tolerant to were determined as 0.30 M for Synechocystis sp. PCC6803, 0.60 M for Cyanothece sp., 0.10 M for Chlorella sorokiniana, 0.60 M for Dunaliella salina, and 0.30 M for Dunaliella viridis and Dunaliella primolecta. In further study, biomass production from culture of D. primolecta in an Erlenmeyer flask with either 0.30 M NaHCO3 or 2 % CO2 bubbling was compared, and no significant difference was detected. This indicates BICCAPS can reach the same biomass productivity as regular CO2 bubbling culture, and it is promising for future application.

  12. Selection of microalgae and cyanobacteria strains for bicarbonate-based integrated carbon capture and algae production system.

    Science.gov (United States)

    Chi, Zhanyou; Elloy, Farah; Xie, Yuxiao; Hu, Yucai; Chen, Shulin

    2014-01-01

    Using microalgae to capture CO2 from flue gas is an ideal way to reduce CO2 emission, but this is challenged by the high cost of carbon capture and transportation. To address this problem, a bicarbonate-based integrated carbon capture and algae production system (BICCAPS) has been proposed, in which bicarbonate is used for algae culture, and the regenerated carbonate from this process can be used to capture more CO2. High-concentration bicarbonate is obligate for the BICCAPS. Thus, different strains of microalgae and cyanobacteria were tested in this study for their capability to grow in high-concentration NaHCO3. The highest NaHCO3 concentrations they are tolerant to were determined as 0.30 M for Synechocystis sp. PCC6803, 0.60 M for Cyanothece sp., 0.10 M for Chlorella sorokiniana, 0.60 M for Dunaliella salina, and 0.30 M for Dunaliella viridis and Dunaliella primolecta. In further study, biomass production from culture of D. primolecta in an Erlenmeyer flask with either 0.30 M NaHCO3 or 2 % CO2 bubbling was compared, and no significant difference was detected. This indicates BICCAPS can reach the same biomass productivity as regular CO2 bubbling culture, and it is promising for future application. PMID:24092450

  13. Effects of bicarbonate/lactate solution on peritoneal advanced glycosylation end-product accumulation.

    Science.gov (United States)

    Park, M S; Kim, J K; Holmes, C; Weiss, M F

    2000-01-01

    Advanced glycosylation end-products (AGEs) are associated with diabetic complications and peritoneal damage after long-term peritoneal dialysis (PD) with high glucose dialysis solutions. Glucose degradation products (GDPs) derived during heat sterilization of high glucose dialysis solutions are thought to accelerate AGE formation. A new technique of separating glucose from electrolytes has yielded markedly lower GDP levels and permitted the use of dialysis solutions containing the physiologic buffer bicarbonate. Formation of AGEs in vitro with this new solution is significantly lower compared with formation of AGEs with conventional solutions. The purpose of the present study was to investigate the effect of long-term intraperitoneal use of new, neutral dialysis solution (B/L) containing bicarbonate (25 mmol/L) and lactate (15 mmol/L) on peritoneal AGE accumulation and permeability. Normal male Sprague-Dawley rats were used. Twice daily for 12 weeks, 30 mL of new solution (B/L) or conventional solution [Lac (lactate 40 mmol/L)] was injected into the peritoneal cavity of the test rats. As a control, rats that were not injected were kept for 12 weeks in the same manner as the test rats. After 12 weeks, a 2-hour peritoneal equilibration test (PET) was performed in the test rats. After the PET, the parietal peritoneum and liver were obtained for evaluation of peritoneal morphology and for immunohistochemistry for AGE. Intensity of AGE staining was semi-quantitatively graded from 0 to 3. The omentum was also obtained and immediately frozen for analysis of pentosidine content by high-performance liquid chromatography. Compared with findings in the control group, hematoxylin and eosin staining of the parietal peritoneum and liver samples revealed partial denudation of mesothelial cells in the Lac group; denudation was not remarkable in the B/L group. The B/L solution showed significantly less AGE staining in the peritoneal cavity compared to conventional solution. However

  14. Proportional influence of sea water and bicarbonate on the production of Spirulina sp. biomass with light-emitting diode lighting

    Directory of Open Access Journals (Sweden)

    Víctor Vasquez-Villalobos

    2014-12-01

    Full Text Available The study focused on the influence of the variables seawater proportion (% and bicarbonate concentration on Spirulina sp. biomass production, using a Central Composite Rotational Design (CCRD to evaluate the optimal regions of biomass production (ϕ, adaptation phase (λ, specific growth rate (µ and generation time (G, using for each treatment the Gompertz mathematical model. The highest values of biomass (ϕ log N/N0 : 0.93 were obtained at 168.8 hours; in a culture medium with pH 8.8±0.1; at a temperature of 25°C; with salinity of 1.2% and 1.6 gL of bicarbonate. The lowest value of ϕ was 0.45±0.01; coincidentally obtained in repetitions of the central point, using a salinity of 0.7% and 3.0g/L of bicarbonate; in a medium with pH 9.1±0.4 to 25°C; which shows the importance of salinity provided by the volume of seawater relative to bicarbonate, in the production of Spirulina biomass. The lighting was 2.7±1.2 klx, provided by a White LightEmitting Diode (WLED during 12 continuous hours and an air injection of 0.86±0.09 L/s by a photo bioreactor with a 200 mL capacity. Only the values of ϕ, adjusted properly to the Response Surface with an R2 of 0.99 for a quadratic mathematical model and p < 0.05 with a 2.4% average absolute error.

  15. Effects of gas composition in headspace and bicarbonate concentrations in media on gas and methane production, degradability, and rumen fermentation using in vitro gas production techniques.

    Science.gov (United States)

    Patra, Amlan Kumar; Yu, Zhongtang

    2013-07-01

    Headspace gas composition and bicarbonate concentrations in media can affect methane production and other characteristics of rumen fermentation in in vitro gas production systems, but these 2 important factors have not been evaluated systematically. In this study, these 2 factors were investigated with respect to gas and methane production, in vitro digestibility of feed substrate, and volatile fatty acid (VFA) profile using in vitro gas production techniques. Three headspace gas compositions (N2+ CO2+ H2 in the ratio of 90:5:5, CO2, and N2) with 2 substrate types (alfalfa hay only, and alfalfa hay and a concentrate mixture in a 50:50 ratio) in a 3×2 factorial design (experiment 1) and 3 headspace compositions (N2, N2 + CO2 in a 50:50 ratio, and CO2) with 3 bicarbonate concentrations (80, 100, and 120 mM) in a 3×3 factorial design (experiment 2) were evaluated. In experiment 1, total gas production (TGP) and net gas production (NGP) was the lowest for CO2, followed by N2, and then the gas mixture. Methane concentration in headspace gas after fermentation was greater for CO2 than for N2 and the gas mixture, whereas total methane production (TMP) and net methane production (NMP) were the greatest for CO2, followed by the gas mixture, and then N2. Headspace composition did not affect in vitro digestibility or the VFA profile, except molar percentages of propionate, which were greater for CO2 and N2 than for the gas mixture. Methane concentration in headspace gas, TGP, and NGP were affected by the interaction of headspace gas composition and substrate type. In experiment 2, increasing concentrations of CO2 in the headspace decreased TGP and NGP quadratically, but increased the concentrations of methane, NMP, and in vitro fiber digestibility linearly, and TMP quadratically. Fiber digestibility, TGP, and NGP increased linearly with increasing bicarbonate concentrations in the medium. Concentrations of methane and NMP were unaffected by bicarbonate concentration, but

  16. Toxicity of Sodium Bicarbonate to Fish from Coal-Bed Natural Gas Production in the Tongue and Powder River Drainages, Montana and Wyoming

    Science.gov (United States)

    U.S. Geological Survey

    2006-01-01

    This study evaluates the sensitivity of aquatic life to sodium bicarbonate (NaHCO3), a major constituent of coal-bed natural gas-produced water. Excessive amounts of sodium bicarbonate in the wastewater from coal-bed methane natural gas production released to freshwater streams and rivers may adversely affect the ability of fish to regulate their ion uptake. The collaborative study focuses on the acute and chronic toxicity of sodium bicarbonate on select fish species in the Tongue and Powder River drainages in southeastern Montana and northeastern Wyoming. Sodium bicarbonate is not naturally present in appreciable concentrations within the surface waters of the Tongue and Powder River drainages; however, the coal-bed natural gas wastewater can reach levels over 1,000 milligrams per liter. Large concentrations have been shown to be acutely toxic to native fish (Mount and others, 1997). In 2003, with funding and guidance provided by the U.S. Environmental Protection Agency, the Montana Fish, Wildlife, and Parks and the U.S. Geological Survey initiated a collaborative study on the potential effects of coal-bed natural gas wastewater on aquatic life. A major goal of the study is to provide information to the State of Montana Water Quality Program needed to develop an aquatic life standard for sodium bicarbonate. The standard would allow the State, if necessary, to establish targets for sodium bicarbonate load reductions.

  17. Comparison of hydrogen production and electrical power generation for energy capture in closed-loop ammonium bicarbonate reverse electrodialysis systems

    KAUST Repository

    Hatzell, Marta C.

    2014-01-01

    Currently, there is an enormous amount of energy available from salinity gradients, which could be used for clean hydrogen production. Through the use of a favorable oxygen reduction reaction (ORR) cathode, the projected electrical energy generated by a single pass ammonium bicarbonate reverse electrodialysis (RED) system approached 78 W h m-3. However, if RED is operated with the less favorable (higher overpotential) hydrogen evolution electrode and hydrogen gas is harvested, the energy recovered increases by as much ∼1.5× to 118 W h m-3. Indirect hydrogen production through coupling an RED stack with an external electrolysis system was only projected to achieve 35 W h m-3 or ∼1/3 of that produced through direct hydrogen generation.

  18. Formate-Dependent Microbial Conversion of CO2 and the Dominant Pathways of Methanogenesis in Production Water of High-temperature Oil Reservoirs Amended with Bicarbonate.

    Science.gov (United States)

    Yang, Guang-Chao; Zhou, Lei; Mbadinga, Serge M; Liu, Jin-Feng; Yang, Shi-Zhong; Gu, Ji-Dong; Mu, Bo-Zhong

    2016-01-01

    CO2 sequestration in deep-subsurface formations including oil reservoirs is a potential measure to reduce the CO2 concentration in the atmosphere. However, the fate of the CO2 and the ecological influences in carbon dioxide capture and storage (CDCS) facilities is not understood clearly. In the current study, the fate of CO2 (in bicarbonate form; 0∼90 mM) with 10 mM of formate as electron donor and carbon source was investigated with high-temperature production water from oilfield in China. The isotope data showed that bicarbonate could be reduced to methane by methanogens and major pathway of methanogenesis could be syntrophic formate oxidation coupled with CO2 reduction and formate methanogenesis under the anaerobic conditions. The bicarbonate addition induced the shift of microbial community. Addition of bicarbonate and formate was associated with a decrease of Methanosarcinales, but promotion of Methanobacteriales in all treatments. Thermodesulfovibrio was the major group in all the samples and Thermacetogenium dominated in the high bicarbonate treatments. The results indicated that CO2 from CDCS could be transformed to methane and the possibility of microbial CO2 conversion for enhanced microbial energy recovery in oil reservoirs. PMID:27047478

  19. Formate-Dependent Microbial Conversion of CO2 and the Dominant Pathways of methanogenesis in production water of high-temperature oil reservoirs amended with bicarbonate

    Directory of Open Access Journals (Sweden)

    Guang-Chao eYang

    2016-03-01

    Full Text Available CO2 sequestration in deep-subsurface formations including oil reservoirs is a potential measure to reduce the CO2 concentration in the atmosphere. However, the fate of the CO2 and the ecological influences in Carbon Dioxide Capture and Storage (CDCS facilities is not understood clearly. In the current study, the fate of CO2 (in bicarbonate form (0~90 mM with 10 mM of formate as electron donor and carbon source was investigated with high-temperature production water from oilfield in China. The isotope data showed that bicarbonate could be reduced to methane by methanogens and major pathway of methanogenesis could be syntrophic formate oxidation coupled with CO2 reduction and formate methanogenesis under the anaerobic conditions. The bicarbonate addition induced the shift of microbial community. Addition of bicarbonate and formate was associated with a decrease of Methanosarcinales, but promotion of Methanobacteriales in all treatments. Thermodesulfovibrio was the major group in all the samples and Thermacetogenium dominated in the high bicarbonate treatments. The results indicated that CO2 from CDCS could be transformed to methane and the possibility of microbial CO2 conversion for enhanced microbial energy recovery in oil reservoirs.

  20. Indomethacin decreases gastroduodenal mucosal bicarbonate secretion in humans

    DEFF Research Database (Denmark)

    Mertz-Nielsen, A; Hillingsø, Jens; Bukhave, K;

    1995-01-01

    BACKGROUND: Cyclooxygenase inhibitors reduce mucosal bicarbonate secretion in the duodenum, but the evidence for their effect on bicarbonate secretion in the stomach remains controversial. We have, therefore, studied how indomethacin influences gastroduodenal bicarbonate secretion and luminal...... healthy volunteers. Bicarbonate and PGE2 were measured in the gastroduodenal effluents by back-titration and radioimmunoassay, respectively. RESULTS: Vagal stimulation and duodenal luminal acidification (0.1 M HCl; 20 ml; 5 min) increased gastroduodenal bicarbonate secretion (p ... markedly inhibited both basal and stimulated gastric and duodenal mucosal bicarbonate secretion, and this reduction was similar to the degree of cyclooxygenase inhibition estimated by the luminal release of PGE2 (p

  1. The effect of feeding on CO2 production and energy expenditure in ponies measured by indirect calorimetry and the 13C-bicarbonate technique

    DEFF Research Database (Denmark)

    Jensen, Rasmus Bovbjerg; Kyrstein, T. D.; Junghans, P;

    2015-01-01

    Energy expenditure (EE) can be estimated based on respiratory gas exchange measurements, traditionally done in respiration chambers by indirect calorimetry (IC). However, the (13)C-bicarbonate technique ((13)C-BT) might be an alternative minimal invasive method for estimation of CO(2) production...

  2. Improvement in lipids extraction processes for biodiesel production from wet microalgal pellets grown on diammonium phosphate and sodium bicarbonate combinations.

    Science.gov (United States)

    Shah, Syed Hasnain; Raja, Iftikhar Ahmed; Mahmood, Qaisar; Pervez, Arshid

    2016-08-01

    Biomass productivity and growth kinetics for microalgae grown on sodium bicarbonate and diammonium phosphate were investigated. Different carbon and nitrogen ratios have shown different growth rates and biomass productivity and C:N ratio 50:10 as mgL(-1) has shown the best production than all. For effective lipids extraction from biomass thermolysis and sonolysis were carried out from wet biomass. Sonolysis at 2.3W intensity for 5min has released 8.58mg at neutral pH. More quantity of lipids was extracted when extraction was made at pH 4 and 10 which resulted 9mg and 9.28mg lipids respectively. Thermal treatment at 100°C for 10min has released 12.82mg lipid at neutral pH. In the same thermolysis at pH 4 and 10 more quantity of lipids was extracted which were 15.16mg and 14.81mg respectively. Finally transesterified lipids were analyzed through GC-MS for FAME composition analysis. PMID:27132228

  3. Evaluation of stainless steel cathodes and a bicarbonate buffer for hydrogen production in microbial electrolysis cells using a new method for measuring gas production

    KAUST Repository

    Ambler, Jack R.

    2011-01-01

    Microbial electrolysis cells (MECs) are often examined for hydrogen production using non-sustainable phosphate buffered solutions (PBS), although carbonate buffers have been shown to work in other bioelectrochemical systems with a platinum (Pt) catalyst. Stainless steel (SS) has been shown to be an effective catalyst for hydrogen evolution in MECs, but it has not been tested with carbonate buffers. We evaluated the combined using of SS cathodes and a bicarbonate buffer (BBS) at the applied voltages of 0.5, 0.7 and 0.9 V using a new inexpensive method for measuring gas production called the gas bag method (GBM). This method achieved an average error of only 5.0% based on adding known volumes of gas to the bag. Using the GBM, hydrogen production with SS and a BBS was 26.6 ± 1.8 mL which compared well to 26.4 ± 2.8 mL using Pt and BBS, and 26.8 ± 2.5 mL with a Pt cathode and PBS. Electrical energy efficiency was highest with a SS cathode and BBS at 159 ± 17%, compared to 126 ± 14% for the Pt cathode and BBS, and 134 ± 17% for a Pt cathode and PBS. The main disadvantage of the SS was a lower gas production rate of 1.1 ± 0.3 m3 H2-m-3 d-1 with BBS and 1.2 ± 0.3 m3 H2-m-3 d -1 with PBS, compared to 1.7 ± 0.4 m3 H 2-m-3 d-1 with Pt and PBS. These results show that the GBM is an effective new method for measuring gas production of anaerobic gas production processes, and that SS and bicarbonate buffers can be used to effectively produce hydrogen in MECs. © 2010 Professor T. Nejat Veziroglu. Published by Elsevier Ltd. All rights reserved.

  4. Acetate and bicarbonate assimilation and metabolite formation in Chlamydomonas reinhardtii: a 13C-NMR study.

    Directory of Open Access Journals (Sweden)

    Himanshu Singh

    Full Text Available Cellular metabolite analyses by (13C-NMR showed that C. reinhardtii cells assimilate acetate at a faster rate in heterotrophy than in mixotrophy. While heterotrophic cells produced bicarbonate and CO2aq, mixotrophy cells produced bicarbonate alone as predominant metabolite. Experiments with singly (13C-labelled acetate ((13CH(3-COOH or CH(3-(13COOH supported that both the (13C nuclei give rise to bicarbonate and CO2(aq. The observed metabolite(s upon further incubation led to the production of starch and triacylglycerol (TAG in mixotrophy, whereas in heterotrophy the TAG production was minimal with substantial accumulation of glycerol and starch. Prolonged incubation up to eight days, without the addition of fresh acetate, led to an increased TAG production at the expense of bicarbonate, akin to that of nitrogen-starvation. However, such TAG production was substantially high in mixotrophy as compared to that in heterotrophy. Addition of mitochondrial un-coupler blocked the formation of bicarbonate and CO2(aq in heterotrophic cells, even though acetate uptake ensued. Addition of PSII-inhibitor to mixotrophic cells resulted in partial conversion of bicarbonate into CO2(aq, which were found to be in equilibrium. In an independent experiment, we have monitored assimilation of bicarbonate via photoautotrophy and found that the cells indeed produce starch and TAG at a much faster rate as compared to that in mixotrophy and heterotrophy. Further, we noticed that the accumulation of starch is relatively more as compared to TAG. Based on these observations, we suggest that acetate assimilation in C. reinhardtii does not directly lead to TAG formation but via bicarbonate/CO2(aq pathways. Photoautotrophic mode is found to be the best growth condition for the production of starch and TAG and starch in C. reinhardtii.

  5. The potential effects of sodium bicarbonate, a major constituent from coalbed natural gas production, on aquatic life

    Science.gov (United States)

    Farag, Aida M.; Harper, David D.

    2012-01-01

    The production water from coalbed natural gas (CBNG) extraction contains many constituents. The U.S. Environmental Protection Agency has established aquatic life criteria for some of these constituents, and it is therefore possible to evaluate their risk to aquatic life. However, of the major ions associated with produced waters, chloride is the only one with an established aquatic life criterion (U.S. Environmental Protection Agency, 1988). The focus of this research was NaHCO3, a compound that is a major constituent of coalbed natural gas produced waters in the Tongue and Powder River Basins. This project included laboratory experiments, field in situ experiments, a field mixing zone study, and a fishery presence/absence assessment. Though this investigation focuses on the Tongue and Powder River Basins, the information is applicable to other watersheds where sodium bicarbonate is a principle component of product water either from CBNG or from traditional or unconventional oil and gas development. These data can also be used to separate effects of saline discharges from those potentially posed by other constituents. Finally, this research effort and the additional collaboration with USGS Water Resources and Mapping, Bureau of Land Management, US Environmental Protection Agency, State of Montana, State of Wyoming, Montana State University, University of Wyoming, and others as part of a Powder River Aquatic Task Group, can be used as a model for successful approaches to studying landscapes with energy development. The laboratory acute toxicity experiments were completed with a suite of organisms, including 7 species of fish, 5 species of invertebrates, and 1 amphibian species. Experiments performed on these multiple species resulted in LC50s that ranged from 1,120 to greater than (>) 8,000 milligrams sodium bicarbonate per liter (mg NaHCO3/L) (also defined as 769 to >8,000 milligrams bicarbonate per liter (mg HCO3-/L) or total alkalinity expressed as 608 to >4

  6. The potential effects of sodium bicarbonate, a major constituent from coalbed natural gas production, on aquatic life

    Science.gov (United States)

    Farag, Aida M.; Harper, David D.

    2012-01-01

    The production water from coalbed natural gas (CBNG) extraction contains many constituents. The U.S. Environmental Protection Agency has established aquatic life criteria for some of these constituents, and it is therefore possible to evaluate their risk to aquatic life. However, of the major ions associated with produced waters, chloride is the only one with an established aquatic life criterion (U.S. Environmental Protection Agency, 1988). The focus of this research was NaHCO3, a compound that is a major constituent of coalbed natural gas produced waters in the Tongue and Powder River Basins. This project included laboratory experiments, field in situ experiments, a field mixing zone study, and a fishery presence/absence assessment. Though this investigation focuses on the Tongue and Powder River Basins, the information is applicable to other watersheds where sodium bicarbonate is a principle component of product water either from CBNG or from traditional or unconventional oil and gas development. These data can also be used to separate effects of saline discharges from those potentially posed by other constituents. Finally, this research effort and the additional collaboration with USGS Water Resources and Mapping, Bureau of Land Management, US Environmental Protection Agency, State of Montana, State of Wyoming, Montana State University, University of Wyoming, and others as part of a Powder River Aquatic Task Group, can be used as a model for successful approaches to studying landscapes with energy development. The laboratory acute toxicity experiments were completed with a suite of organisms, including 7 species of fish, 5 species of invertebrates, and 1 amphibian species. Experiments performed on these multiple species resulted in LC50s that ranged from 1,120 to greater than (>) 8,000 milligrams sodium bicarbonate per liter (mg NaHCO3/L) (also defined as 769 to >8,000 milligrams bicarbonate per liter (mg HCO3-/L) or total alkalinity expressed as 608 to >4

  7. 21 CFR 582.1736 - Sodium bicarbonate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Sodium bicarbonate. 582.1736 Section 582.1736 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE General Purpose Food Additives § 582.1736 Sodium bicarbonate. (a)...

  8. The 13C bicarbonate method

    DEFF Research Database (Denmark)

    Junghans, Peter; Larsson, Caroline; Jensen, Rasmus Bovbjerg;

    2015-01-01

    We reconsider the principle of the (13)C bicarbonate (NaH(13)CO3) method ((13)C-BM) for the determination of the CO2 production to obtain an estimate of energy expenditure (EE). Its mathematical concept based on a three-compartmental model is related to the [(15)N]glycine end product method. The CO.......07; n = 8; p = .026). We suggest considering the (13)C-BM as a 'stand-alone' method to provide information on the total CO2 production as an index of EE....

  9. Bicarbonate is a recycling substrate for cyanase.

    Science.gov (United States)

    Johnson, W V; Anderson, P M

    1987-07-01

    Cyanase is an inducible enzyme in Escherichia coli that catalyzes bicarbonate-dependent decomposition of cyanate to ammonia and bicarbonate. Previous studies provided evidence that carbamate is an initial product and that the kinetic mechanism is rapid equilibrium random (bicarbonate serving as substrate as opposed to activator); the following mechanism was proposed (Anderson, P. M. (1980) Biochemistry 19, 2282-2888; Anderson, P. M., and Little, R. M. (1986) Biochemistry 25, 1621-1626). (formula; see text) Direct evidence for this mechanism was obtained in this study by 1) determining whether CO2 or HCO3- serves as substrate and is formed as product, 2) identifying the products formed from [14C]HCO3- and [14C] OCN-, 3) identifying the products formed from [13C] HCO3- and [12C]OCN- in the presence of [18O]H2O, and 4) determining whether 18O from [18O]HCO3- is incorporated into CO2 derived from OCN-. Bicarbonate (not CO2) is the substrate. Carbon dioxide (not HCO3-) is produced in stoichiometric amounts from both HCO3- and OCN-. 18O from [18O]H2O is not incorporated into CO2 formed from either HCO3- or OCN-. Oxygen-18 from [18O]HCO3- is incorporated into CO2 derived from OCN-. These results support the above mechanism, indicating that decomposition of cyanate catalyzed by cyanase is not a hydrolysis reaction and that bicarbonate functions as a recycling substrate.

  10. Pancreatic bicarbonate secretion involves two proton pumps

    DEFF Research Database (Denmark)

    Novak, Ivana; Wang, Jing; Henriksen, Katrine L.;

    2011-01-01

    Pancreas secretes fluid rich in digestive enzymes and bicarbonate. The alkaline secretion is important in buffering of acid chyme entering duodenum and for activation of enzymes. This secretion is formed in pancreatic ducts, and studies to date show that plasma membranes of duct epithelium express...... and non-gastric H(+)-K(+)-ATPases. We measured intracellular pH and secretion in small ducts isolated from rat pancreas and showed their sensitivity to H(+)-K(+) pump inhibitors and ion substitutions. Gastric and non-gastric H(+)-K(+) pumps were demonstrated on RNA and protein levels, and pumps were...... localized to the plasma membranes of pancreatic ducts. Quantitative analysis of H(+)/HCO(3)(-) and fluid transport shows that the H(+)-K(+) pumps can contribute to pancreatic secretion in several species. Our results call for revision of the bicarbonate transport physiology in pancreas, and most likely...

  11. BICARBONATE OF SODA BLASTING TECHNOLOGY FOR AIRCRAFT WHEEL DEPAINTING

    Science.gov (United States)

    This evaluation addressed product quality, waste reduction/pollution prevention and economics in replacing chemical solvent strippers with a bicarbonate of soda blasting technology for removal of point from aircraft wheels. he evaluation was conducted in the Paint Stripping Shop ...

  12. BICARBONATE OF SODA BLASTING TECHNOLOGY FOR AIRCRAFT WHEEL PAINTING

    Science.gov (United States)

    This evaluation addressed product quality, waste reduction/pollution prevention and economics in replacing chemical solvent strippers with a bicarbonate of soda blasting technology for removal of paint from aircraft wheels. The evaluation was conducted in the Paint Stripping Sho...

  13. Bicarbonate kinetics in Indian males

    Indian Academy of Sciences (India)

    T Raj; R Kuriyan; A V Kurpad

    2006-06-01

    Measurement of rates of in vivo substrate oxidation such as that of glucose, fatty acids and amino acids, are based on tracer (14C or 13C) data, and often depend on the isotopic content of expired CO2. The recovery of tracer-labelled CO2 generated from the oxidation of 13C labelled substrates may not be 100% over short term. This can lead to underestimation of oxidation rate of substrates, and consequently a correction for the incomplete recovery of tracer has to be applied by the determination of the recovery of 13CO2 in the breath during tracer bicarbonate infusions. We have studied the recovery of tracer-labelled bicarbonate using a bolus administration model, and further characterized kinetics of bicarbonate using a three-compartment model, to assess which compartmental fluxes changed during the change from a fasted state to fed state. Recovery of bicarbonate was lower at 69% and 67% (fasted and fed state) than the value of 71% and 74% found during earlier longer term of continuous infusions. During feeding, there was a 20-fold increase in the flux of bicarbonate between the central compartment and the compartment that was equivalent to the viscera. This study shows that the difference between the fasted and fed state recovery of tracer bicarbonate similar to that obtained with continuous infusions, and that bicarbonate fluxes show large changes between different compartments in the body depending on metabolic state.

  14. Omeprazole promotes proximal duodenal mucosal bicarbonate secretion in humans

    DEFF Research Database (Denmark)

    Mertz-Nielsen, Anette; Hillingsø, J; Bukhave, Klaus;

    1996-01-01

    The proton pump inhibitor, omeprazole, surprisingly resulted in higher rates of proximal duodenal mucosal bicarbonate secretion than previously reported using an H-2 receptor antagonist for gastric acid inhibition. Gastroduodenal perfusions were performed in healthy volunteers to evaluate whether...... this incidental finding is explained by more potent gastric acid inhibition by omeprazole or might be caused by the different mode of drug action. Basal and stimulated gastric and duodenal bicarbonate secretion rates were measured in the same subjects in control experiments (n=17) and after...... pretreatment with high dose omeprazole (n=17) and ranitidine (n=9), respectively, by use of a technique permitting simultaneous measurements. Concentrations of bicarbonate were measured in the respective effluents by the method of back titration. Both omeprazole and ranitidine completely inhibited gastric acid...

  15. Seawater bicarbonate removal during hydrothermal circulation

    Science.gov (United States)

    Proskurowski, G. K.; Seewald, J.; Sylva, S. P.; Reeves, E.; Lilley, M. D.

    2013-12-01

    High temperature fluids sampled at hydrothermal vents represent a complex alteration product of water-rock reactions on a multi-component mixture of source fluids. Sources to high-temperature hydrothermal samples include the 'original' seawater present in the recharge limb of circulation, magmatically influenced fluids added at depth as well as any seawater entrained during sampling. High-temperature hydrothermal fluids are typically enriched in magmatic volatiles, with CO2 the dominant species, characterized by concentrations of 10's-100's of mmol/kg (1, 2). Typically, the high concentration of CO2 relative to background seawater bicarbonate concentrations (~2.3 mmol/kg) obscures a full analysis of the fate of seawater bicarbonate during high-temperature hydrothermal circulation. Here we present data from a suite of samples collected over the past 15 years from high-temperature hydrothermal vents at 9N, Endeavour, Lau Basin, and the MAR that have endmember CO2 concentrations less than 10 mmol/kg. Using stable and radiocarbon isotope measurements these samples provide a unique opportunity to examine the balance between 'original' seawater bicarbonate and CO2 added from magmatic sources. Multiple lines of evidence from multiple hydrothermal settings consistently points to the removal of ~80% of the 'original' 2.3 mmol/kg seawater bicarbonate. Assuming that this removal occurs in the low-temperature, 'recharge' limb of hydrothermal circulation, this removal process is widely occurring and has important contributions to the global carbon cycle over geologic time. 1. Lilley MD, Butterfield DA, Lupton JE, & Olson EJ (2003) Magmatic events can produce rapid changes in hydrothermal vent chemistry. Nature 422(6934):878-881. 2. Seewald J, Cruse A, & Saccocia P (2003) Aqueous volatiles in hydrothermal fluids from the Main Endeavour Field, northern Juan de Fuca Ridge: temporal variability following earthquake activity. Earth and Planetary Science Letters 216(4):575-590.

  16. 21 CFR 184.1736 - Sodium bicarbonate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Sodium bicarbonate. 184.1736 Section 184.1736 Food... Specific Substances Affirmed as GRAS § 184.1736 Sodium bicarbonate. (a) Sodium bicarbonate (NaHCO3, CAS Reg. No. 144-55-8) is prepared by treating a sodium carbonate or a sodium carbonate and sodium...

  17. Sodium Bicarbonate mouth rinse: An Uncommon Complication

    OpenAIRE

    Fatih Mehmet Coskunses

    2012-01-01

    Sodium bicarbonate is a natural buffer that maintains a healthy pH in mouth to promote a clean and fresh oral environment. Sodium-bicarbonate rinse is empirically suggested to patients by dentist and people around, and may prove to be harmful. In this short communication, we present chemical burn of oral mucosa because of sodium-bicarbonate rinse after misfit dental impression.

  18. Inhibitors

    Science.gov (United States)

    ... wrong place in the body. Immune Tolerance Induction (ITI) Therapy: The goal of ITI therapy is to stop the inhibitor reaction from ... body to accept clotting factor concentrate treatments. With ITI therapy, people receive large amounts of clotting factor ...

  19. Effect of peroxodisulfate on uranium leaching with ammonium bicarbonate

    Directory of Open Access Journals (Sweden)

    Nurbek Nurpeisov

    2013-05-01

    Full Text Available In this study, uranium leaching from ore material using acid solution and bicarbonate in a presence peroxodisulfate ion was examined. For experiments two different tips of leaching methods were used: leaching in static and dynamic conditions. The determination of uranium concentrations in product solutions were analyzed by titrimetric (by ammonia vanadate solution method. The maximum yield of uranium leached with ammonium bicarbonate in a presence of ammonium peroxodisulfate (5 g/L was only 33%, which is half the corresponding value obtained by sulfuric acid (65%.

  20. Regulation of collagenase inhibitor production in chondrosarcoma chondrocytes

    International Nuclear Information System (INIS)

    Swarm rat chondrosarcoma chondrocytes produce an inhibitor of collagenase. This inhibitor is similar to those isolated from normal cartilage tissues. These cells will synthesize proteins in the absence of serum. Since serum contains inhibitors of collagenase, it is necessary to culture cells without serum in order to obtain accurate measurements of enzyme and inhibitor levels. They examined the effect of insulin on inhibitor secretion by cultures of Swarm rat chondrosarcoma chondrocytes. They observed a 2.5 to 3.5 fold stimulation of inhibitory activity in the presence of as little as 10 ng/ml insulin as compared to controls in serum free Dulbecco's modified Eagle's medium supplemented with 4.5 g/l glucose. The units of inhibitor were determined over a 7 day culture period. Medium was harvested daily and assayed for collagenase activity and for inhibition of a known collagenase from rabbit skin or human skin, using the 14C-glycine peptide release assay. The amount of inhibitor obtained from days 2 through 7 were: 1.4 unit (control), 3.8 units (10 ng/ml insulin), 5.2 units (1 μg/ml insulin). The addition of 1 mM dibutyryl cyclic AMP to these chondrocytes in the presence of 1 μg/ml insulin caused a decrease in the level of inhibitor, suggesting that a dephosphorylation event may be necessary for this stimulation by insulin to occur

  1. New natural product carbonic anhydrase inhibitors incorporating phenol moieties.

    Science.gov (United States)

    Karioti, Anastasia; Ceruso, Mariangela; Carta, Fabrizio; Bilia, Anna-Rita; Supuran, Claudiu T

    2015-11-15

    Carbonic anhydrases (CAs, EC 4.2.1.1) catalyze the fundamental reaction of CO2 hydration in all living organisms, being actively involved in the regulation of a plethora of patho/physiological conditions. They represent a typical example of enzyme convergent evolution, as six genetically unrelated families of such enzymes were described so far. The need to find selective CA inhibitors (CAIs) triggered the investigation of natural product libraries, which proved to be a valid source of agents with such an activity, as demonstrated for the phenols, polyamines and coumarins. Herein we report an in vitro inhibition study of human (h) CA isoforms hCAs I, II, IV, VII and XII with a panel of natural polyphenols including flavones, flavonols, flavanones, flavanols, isoflavones and depsides, some of which extracted from Quercus ilex and Salvia miltiorrhiza. Several of the investigated derivatives showed interesting inhibition activity and selectivities for inhibiting some important isoforms over the off-target ones hCA I and II.

  2. Critical role of bicarbonate and bicarbonate transporters in cardiac function

    Institute of Scientific and Technical Information of China (English)

    Hong-Sheng; Wang; Yamei; Chen; Kanimozhi; Vairamani; Gary; E; Shull

    2014-01-01

    Bicarbonate is one of the major anions in mammalian tissues and extracellular fluids. Along with accompanying H+, HCO3- is generated from CO2 and H2 O, either spontaneously or via the catalytic activity of carbonic anhydrase. It serves as a component of the major buffer system, thereby playing a critical role in pH homeostasis. Bicarbonate can also be utilized by a variety of ion transporters, often working in coupled systems, to transport other ions and organic substrates across cell membranes. The functions of HCO3- and HCO3--transporters in epithelial tissues have been studied extensively, but their functions in heart are less well understood. Here we review studies of the identities and physiological functions of Cl-/HCO3- exchangers and Na+/HCO3-cotransporters of the SLC4 A and SLC26 A families in heart. We also present RNA Seq analysis of their cardiac mRNA expression levels. These studies indicate that slc4a3(AE3) is the major Cl-/HCO3- exchanger and plays a protective role in heart failure, and that Slc4a4(NBCe1) is the major Na+/HCO3- cotransporter and affects action potential duration. In addition, previous studies show that HCO3- has a positive inotropic effect in the perfused heart that is largely independent of effects on intracellular Ca2+. The importance of HCO3- in the regulation of contractility is supported by experiments showing that isolated cardiomyocytes exhibit sharply enhanced contractility, with no change in Ca2+ transients, when switched from Hepes-buffered to HCO3-- buffered solutions. These studies demonstrate that HCO3- and HCO3--handling proteins play important roles in the regulation of cardiac function.

  3. Virtual screening and optimization of Type II inhibitors of JAK2 from a natural product library†

    OpenAIRE

    Ma, Dik-Lung; Chan, Daniel Shiu-Hin; Wei, Guo; Zhong, Hai-Jing; Yang, Hui; Leung, Lai To; Gullen, Elizabeth A.; Chiu, Pauline; Cheng, Yung-Chi; Leung, Chung-Hang

    2014-01-01

    Amentoflavone has been identified as a JAK2 inhibitor by structure-based virtual screening of a natural product library. In silico optimization using the DOLPHIN model yielded analogues with enhanced potency against JAK2 activity and HCV activity in cellulo. Molecular modeling and kinetic experiments suggested that the analogues may function as Type II inhibitors of JAK2.

  4. Bicarbonate is a recycling substrate for cyanase

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, W.V.; Anderson, P.M.

    1987-05-01

    Cyanase catalyzes HCO/sub 3//sup -/-dependent decomposition of cyanate to NH/sub 4//sup +/ and HCO/sub 3//sup -/. Previous studies provided evidence that carbamate is an initial product and that the kinetic mechanism is rapid equilibrium random (HCO/sub 3//sup -/ serving as substrate as opposed to activator). Direct evidence for this mechanism was obtained in this study by (1) identifying the products formed from (/sup 14/C)HCO/sub 3//sup -/ or (/sup 14/C)OCN/sup -/, (2) identifying the products formed from (/sup 13/C)HCO/sub 3//sup -/ in the presence of (/sup 18/O)H/sub 2/O, and (3) determining whether CO/sub 2/ or HCO/sub 3//sup -/ serve as substrate and are formed as product. Carbon dioxide (not HCO/sub 3//sup -/) is produced in stoichiometric amounts from both HCO/sub 3//sup -/ and OCN/sup -/. Bicarbonate (not CO/sub 2/) is the substrate. Oxygen-18 from (/sup 18/O)H/sub 2/O is not incorporated into CO/sub 2/ formed from either HCO/sub 3//sup -/ or OCN/sup -/. These results indicate that decomposition of cyanate is not a hydrolysis reaction and that HCO/sub 3//sup -/ functions as a substrate.

  5. Sodium-Coupled Bicarbonate Transporters

    Directory of Open Access Journals (Sweden)

    Boron WF

    2001-07-01

    Full Text Available Together, the Na(+-coupled HCO(3(- transporters and the AE family of anion exchangers (i.e., Cl-HCO3 exchangers comprise the bicarbonate transporter (BT superfamily. Virtually all BTs are important for the regulation of intracellular pH (pH(i in cells throughout the body. Specific BTs also play roles in cell-volume regulation, as well as for the transport of salt and/or acid-base equivalents across many epithelia. Electrogenic Na/HCO3 cotransporters (NBCe's play key roles in HCO(3(- reabsorption by the renal proximal tubule, and HCO(3(- secretion by the pancreatic duct. Electroneutral NBC's (NBCn's regulate pH(i in vascular smooth muscle and are present in/near axons in the brain. Finally, the Na(+-driven Cl-HCO3 exchanger (NDCBE's appear to be the major pH(i regulators in CNS neurons. A characteristic of most, but not all, BT's is that they are inhibited rather effectively by 4,4'-diisothiocyanostilbene-4,4'-disulfonate (DIDS.

  6. The origin of high sodium bicarbonate waters in the Atlantic and Gulf Coastal Plains

    Science.gov (United States)

    Foster, M.D.

    1950-01-01

    Some sodium bicarbonate waters at depth in the Atlantic and Gulf Coastal Plains have the same bicarbonate content as the shallower calcium bicarbonate waters in the same formation and appear to be the result of replacement of calcium by sodium through the action of base-exchange minerals. Others, however, contain several hundred parts per million more of bicarbonate than any of the calcium bicarbonate waters and much more bicarbonate than can be attributed to solution of calcium carbonate through the action of carbon dioxide derived from the air and soil. As the waters in the Potomac group (Cretaceous) are all low in sulphate and as the environmental conditions under which the sediments of the Potomac group were deposited do not indicate that large amounts of sulphate are available for solution, it does not seem probable that carbon dioxide generated by chemical or biochemical breakdown of sulphate is responsible for the high sodium bicarbonate waters in this area. Sulphate as a source of oxygen is not necessary for the generation of carbon dioxide by carbonaceous material. Oxygen is an important constituent of carbonaceous material and carbon dioxide is a characteristic decomposition product of such material-as, for example, peat and lignite. Experimental work showed that distilled water, calcium bicarbonate water, and sodium bicarbonate water, after contact with lignite, calcium carbonate, and permutite (a base-exchange material), had all increased greatly in sodium bicarbonate content and had become similar in chemical character and in mineral content to high sodium bicarbonate waters found in the Coastal Plain. The tests indicated that carbonaceous material can act as a source of carbon dioxide, which, when dissolved in water, enables it to take into solution more calcium carbonate. If base-exchange materials are also present to replace calcium with sodium, a still greater amount of bicarbonate can be held in solution. The presence of carbonaceous material

  7. Bicarbonate-Regulated Soluble Adenylyl Cyclase

    Directory of Open Access Journals (Sweden)

    Wuttke MS

    2001-07-01

    Full Text Available Soluble adenylyl cyclase (sAC represents a novel form of mammalian adenylyl cyclase structurally, molecularly, and biochemically distinct from the G protein-regulated, transmembrane adenylyl cyclases (tmACs. sAC possesses no transmembrane domains and is insensitive to classic modulators of tmACs, such as heterotrimeric G proteins and P site ligands. Thus, sAC defines an independently regulated cAMP signaling system within mammalian cells. sAC is directly stimulated by bicarbonate ion both in vivo in heterologously expressing cells and in vitro using purified protein. sAC appears to be the predominant form of adenylyl cyclase (AC in mammalian sperm, and its direct activation by bicarbonate provides a mechanism for generating the cAMP required to complete the bicarbonate-induced processes necessary for fertilization, including hyperactivated motility, capacitation, and the acrosome reaction. Immunolocalization studies reveal sAC is also abundantly expressed in other tissues which respond to bicarbonate or carbon dioxide levels suggesting it may function as a general bicarbonate/CO(2 sensor throughout the body.

  8. Removal of the Fermentation Inhibitor, Furfural, Using Activated Carbon in Cellulosic-Ethanol Production

    KAUST Repository

    Zhang, Kuang

    2011-12-21

    Ethanol can be produced from lignocellulosic biomass through fermentation; however, some byproducts from lignocellulosics, such as furfural compounds, are highly inhibitory to the fermentation and can substantially reduce the efficiency of ethanol production. In this study, commercial and polymer-derived activated carbons were utilized to selectively remove the model fermentation inhibitor, furfural, from water solution during bioethanol production. The oxygen functional groups on the carbon surface were found to influence the selectivity of sorbents between inhibitors and sugars during the separation. After inhibitors were selectively removed from the broth, the cell growth and ethanol production efficiency was recovered noticeably in the fermentation. A sorption/desorption cycle was designed, and the sorbents were regenerated in a fixed-bed column system using ethanol-containing standard solution. Dynamic mass balance was obtained after running four or five cycles, and regeneration results were stable even after twenty cycles. © 2011 American Chemical Society.

  9. Photosynthetic bicarbonate utilization in Porphyra haitanensis Bangiales,Rhodophyta

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    The activities of carbonic anhydrase (CA) and photosynthesis of Porphyra haitanensis were investigated in order to see its photosynthetic utilization of inorganic carbon source. Both intra- and extra-cellular CA activities existed in the thallus. CA inhibitors, acetazolamide (AZ) and ethoxyzolamide (EZ), remarkably depressed the photosynthetic oxygen evolution in seawater of pH 8.2 and 10.0, and EZ showed stronger inhibition than AZ. The observed net photosynthetic rate in seawater of pH 8.2 was much higher than that of CO2 supply theoretically derived from spontaneous dehydration of HCO3-. P. haitanensis also showed a rather high pH compensation point (9.9). The results demonstrated that P. haitanensis could utilize bicarbonate as the external inorganic carbon source for photosynthesis. The bicarbonate utilization was closely associated with dehydration catalyzed by extracellular CA activity. The inorganic carbon composition in seawater could well saturate the photosynthesis of P. haitanensis. The low Km value and compensation points for inorganic carbon reflected the existence of CO2- concentrating mechanism in this alga.

  10. Role of bicarbonate/CO2 in the inhibition of Escherichia coli growth by cyanate.

    Science.gov (United States)

    Kozliak, E I; Fuchs, J A; Guilloton, M B; Anderson, P M

    1995-06-01

    Cyanase is an inducible enzyme in Escherichia coli that catalyzes the reaction of cyanate with bicarbonate to give two CO2 molecules. The gene for cyanase is part of the cyn operon, which includes cynT and cynS, encoding carbonic anhydrase and cyanase, respectively. Carbonic anhydrase functions to prevent depletion of cellular bicarbonate during cyanate decomposition (the product CO2 can diffuse out of the cell faster than noncatalyzed hydration back to bicarbonate). Addition of cyanate to the culture medium of a delta cynT mutant strain of E. coli (having a nonfunctional carbonic anhydrase) results in depletion of cellular bicarbonate, which leads to inhibition of growth and an inability to catalyze cyanate degradation. These effects can be overcome by aeration with a higher partial CO2 pressure (M. B. Guilloton, A. F. Lamblin, E. I. Kozliak, M. Gerami-Nejad, C. Tu, D. Silverman, P. M. Anderson, and J. A. Fuchs, J. Bacteriol. 175:1443-1451, 1993). The question considered here is why depletion of bicarbonate/CO2 due to the action of cyanase on cyanate in a delta cynT strain has such an inhibitory effect. Growth of wild-type E. coli in minimal medium under conditions of limited CO2 was severely inhibited, and this inhibition could be overcome by adding certain Krebs cycle intermediates, indicating that one consequence of limiting CO2 is inhibition of carboxylation reactions. However, supplementation of the growth medium with metabolites whose syntheses are known to depend on a carboxylation reaction was not effective in overcoming inhibition related to the bicarbonate deficiency induced in the delta cynT strain by addition of cyanate. Similar results were obtained with a deltacyn strain (since cyanase is absent, this strain does not develop a bicarbonate deficiency when cyanate is added); however, as with the deltacynT strain, a higher partial CO(2) pressure in the aerating gas or expression of carbonic anhydrase activity (which contributes to a higher intercellular

  11. Marine Natural Products as Inhibitors of Hypoxic Signaling in Tumors

    OpenAIRE

    Nagle, Dale G.; Zhou, Yu-Dong

    2009-01-01

    Marine natural products have become a major source of new chemical entities in the discovery of potential anticancer agents that potently suppress various antitumor molecular targets. As a consequence of insufficient vascularization, hypoxic regions form within rapidly growing solid tumor masses. Specific alterations of gene expression in these hypoxic tumor cells help facilitate the survival and metastatic spread of solid tumors. The transcriptional response to cellular hypoxia is primarily ...

  12. Development of potent inhibitors of pyocyanin production in Pseudomonas aeruginosa

    OpenAIRE

    Miller, Laura C.; O’Loughlin, Colleen T.; Zhang, Zinan; Siryaporn, Albert; Silpe, Justin E.; Bassler, Bonnie L.; Semmelhack, Martin F.

    2015-01-01

    The development of new approaches for the treatment of antimicrobial-resistant infections is an urgent public health priority. The Pseudomonas aeruginosa pathogen, in particular, is a leading source of infection in hospital settings, with few available treatment options. In the context of an effort to develop antivirulence strategies to combat bacterial infection, we identified a series of highly effective small molecules that inhibit the production of pyocyanin, a redox-active virulence fact...

  13. Marine Natural Product Inhibitors of Neutrophil-Associated Inflammation

    Science.gov (United States)

    Chen, Chun-Yu; Tsai, Yung-Fong; Chang, Wen-Yi; Yang, Shun-Chin; Hwang, Tsong-Long

    2016-01-01

    Neutrophils are widely recognized to play an important role in acute inflammatory responses, and recent evidence has expanded their role to modulating chronic inflammatory and autoimmune diseases. Reactive oxygen species (ROS) and microbicidal compounds released from neutrophils that are recruited to the site of inflammation contribute to the pathogenesis of multiple inflammation-associated diseases such as chronic obstructive pulmonary disease, atherosclerosis, and hepatitis. Marine organisms are a valuable source of bioactive compounds with potential for industrial and pharmaceutical application. Marine natural products that inhibit neutrophil activation could be used as drugs for the treatment of inflammatory diseases. Numerous studies investigating marine natural products have reported novel anti-inflammatory agents. Nevertheless, the detailed mechanisms underlying their actions, which could facilitate our understanding of the molecular events occurring in neutrophils, have not been reported in most of the associated research studies. Therefore, in this review, we will present marine products that inhibit neutrophil-associated inflammation. Furthermore, we will be limiting the detailed discussion to agents with well-investigated molecular targets. PMID:27472345

  14. Advanced glycation end-products inhibitors isolated from Schisandra grandiflora.

    Science.gov (United States)

    Poornima, B; Kumar, D Anand; Siva, Bandi; Venkanna, A; Vadaparthi, P R Rao; Kumar, K; Tiwari, Ashok K; Babu, K Suresh

    2016-01-01

    Free radicals scavenging and advanced glycation end-products (AGEs) inhibitory potentials in crude chloroform extract of Schisandra grandiflora were evaluated. Bioassay-guided isolation of the chloroform extract led to the identification of 24 compounds. Among the isolates, ( ± ) gomisin M1, arisantetralone C and D, macelignan, saurulignan B and SZ-MO displayed potent-free radical scavenging as well as AGEs inhibitory potentials. This is the first report identifying the presence of AGEs inhibitory activity and assigning AGEs inhibitory activity to these compounds. Therefore, our research finds new application of traditional medicinal plant S. grandiflora having capacity to reduce formation and accumulation of AGEs in diabetes.

  15. Effect of lignocellulose-derived inhibitors on growth and hydrogen production by Thermoanaerobacterium thermosaccharolyticum W16

    Energy Technology Data Exchange (ETDEWEB)

    Cao, Guang-Li; Ren, Nan-Qi; Wang, Ai-Jie; Guo, Wan-Qian; Xu, Ji-Fei; Liu, Bing-Feng [State Key Lab of Urban Water Resource and Environment, Harbin Institute of Technology, Harbin 150090 (China)

    2010-12-15

    In the process of producing H{sub 2} from lignocellulosic materials, inhibitory compounds could be potentially formed during pre-treatment. This work experimentally investigated the effect of lignocellulose-derived inhibitors on growth and hydrogen production by Thermoanaerobacterium thermosaccharolyticum W16. Representative compounds presented in corn stover acid hydrolysate were added in various concentrations, individually or in various combinations and subsequently inhibitions on growth and H{sub 2} production were quantified. Acetate sodium was not inhibitory to T. thermosaccharolyticum W16, rather than it was stimulatory to the growth and H{sub 2} production. Alternatively, furfural, hydroxymethylfurfural (HMF), vanillin and syringaldehyde were potent inhibitors of growth and hydrogen production even though these compounds showed inhibitory effect depending on their concentrations. Synergistic inhibitory effects were exhibited in the introduction of combinations of inhibitors to the medium and in hydrolysate with concentrated inhibitors. Fermentation results from hydrolysates revealed that to increase the efficiency of this bioprocess from corn stover hydrolysate, the inhibitory compounds concentration must be reduced to the levels present in the raw hydrolysate. (author)

  16. Culture conditions supporting inhibitor tolerance and rapid production of ethanol by P. stipitis NRRL Y-7124

    Science.gov (United States)

    To expand the biomass to fuel ethanol industry, process strategies are needed to foster the production and utilization of microorganisms which can survive and ferment hexose and pentose sugars while exposed to inhibitors (such as ethanol, furfural, and hydroxymethylfurfural (HMF)). Furfural and HMF...

  17. Cholangiocyte anion exchange and biliary bicarbonate excretion

    Institute of Scientific and Technical Information of China (English)

    Jesús M Banales; Jesús Prieto; Juan F Medina

    2006-01-01

    Primary canalicular bile undergoes a process of fluidization and alkalinization along the biliary tract that is influenced by several factors including hormones, innervation/neuropeptides, and biliary constituents. Theexcretion of bicarbonate at both the canaliculi and the bile ducts is an important contributor to the generation of the so-called bile-salt independent flow. Bicarbonate is secreted from hepatocytes and cholangiocytes through parallel mechanisms which involve chloride efflux through activation of Cl- channels, and further bicarbonate secretion via AE2/SLC4A2-mediated Cl-/HCO3-exchange. Glucagon and secretin are two relevant hormones which seem to act very similarly in their target cells (hepatocytes for the former and cholangiocytes for the latter). These hormones interact with their specific G protein-coupled receptors, causing increases in intracellular levels of cAMP and activation of cAMP-dependent Cl- and HCO3- secretory mechanisms. Both hepatocytes and cholangiocytes appear to have cAMP-responsive intracellular vesicles in which AE2/SLC4A2 colocalizes with cell specific Cl- channels (CFTR in cholangiocytes and not yet determined in hepatocytes) and aquaporins (AQP8 in hepatocytes and AQP1 in cholangiocytes). cAMP-induced coordinated trafficking of these vesicles to either canalicular or cholangiocyte lumenal membranes and further exocytosis results in increased osmotic forces and passive movement of water with net bicarbonate-rich hydrocholeresis.

  18. Susceptibility of Saccharomyces cerevisiae to inhibitors and impact on bioethanol production yield

    OpenAIRE

    Fosso-Kankeu, Elvis; Marx, Sanette; Meyer, Anton

    2014-01-01

    There have been increasing concerns in developing countries over the competition between food and energy resulting from the production of bioethanol from edible biomass. Second generation lignocellulose feedstock is an attractive alternative, as bioethanol can be produced from non-edible materials. However, the pretreatment required for hydrolysis of lignocellulose into pentose and hexose sugars often results in the production of inhibitors likely to impede the activity of Saccharomyces cerev...

  19. Intestinal bicarbonate secretion by marine teleost fish - why and how?

    DEFF Research Database (Denmark)

    Wilson, Rod W.; Wilson, Jonathan M.; Grosell, Martin Hautopp

    2002-01-01

    Calcium, Precipitation, Osmoregulation, pH-stat titration, Water absorption, Chloride-bicarbonate exchange......Calcium, Precipitation, Osmoregulation, pH-stat titration, Water absorption, Chloride-bicarbonate exchange...

  20. Pro: Higher serum bicarbonate in dialysis patients is protective.

    Science.gov (United States)

    Misra, Madhukar

    2016-08-01

    Chronic metabolic acidosis is common in dialysis patients. Bicarbonate administration via the dialysate helps maintain the acid-base balance in these patients. Serum bicarbonate level in dialysis patients is determined by several factors that include dietary protein intake, nutritional status and dialysis prescription, etc. Additionally, a meaningful interpretation of serum bicarbonate in dialysis patients requires an understanding of complexities involving its measurement. Both very low as well very high levels of serum bicarbonate have been associated with adverse outcomes in observational studies. However, recent observational data, when adjusted for the confounding effects of nutritional status, do not associate higher predialysis serum bicarbonate with adverse consequences. At this time, there are no prospective studies available that have examined the association of serum bicarbonate with hard outcomes in dialysis patients. The ideal level of serum bicarbonate in dialysis patients is therefore unknown. This article examines the available data with regard to the benefits of higher predialysis serum bicarbonate. PMID:27411723

  1. Marine Natural Products as Breast Cancer Resistance Protein Inhibitors

    Directory of Open Access Journals (Sweden)

    Lilia Cherigo

    2015-04-01

    Full Text Available Breast cancer resistance protein (BCRP is a protein belonging to the ATP-binding cassette (ABC transporter superfamily that has clinical relevance due to its multi-drug resistance properties in cancer. BCRP can be associated with clinical cancer drug resistance, in particular acute myelogenous or acute lymphocytic leukemias. The overexpression of BCRP contributes to the resistance of several chemotherapeutic drugs, such as topotecan, methotrexate, mitoxantrone, doxorubicin and daunorubicin. The Food and Drugs Administration has already recognized that BCRP is clinically one of the most important drug transporters, mainly because it leads to a reduction of clinical efficacy of various anticancer drugs through its ATP-dependent drug efflux pump function as well as its apparent participation in drug resistance. This review article aims to summarize the different research findings on marine natural products with BCRP inhibiting activity. In this sense, the potential modulation of physiological targets of BCRP by natural or synthetic compounds offers a great possibility for the discovery of new drugs and valuable research tools to recognize the function of the complex ABC-transporters.

  2. Electron transport chain inhibitors induce microglia activation through enhancing mitochondrial reactive oxygen species production.

    Science.gov (United States)

    Ye, Junli; Jiang, Zhongxin; Chen, Xuehong; Liu, Mengyang; Li, Jing; Liu, Na

    2016-01-15

    Reactive oxygen species (ROS) are believed to be mediators of excessive microglial activation, yet the resources and mechanism are not fully understood. Here we stimulated murine microglial BV-2 cells and primary microglial cells with different inhibitors of electron transport chain (ETC), rotenone, thenoyltrifluoroacetone (TTFA), antimycin A, and NaN3 to induce mitochondrial ROS production and we observed the role of mitochondrial ROS in microglial activation. Our results showed that ETC inhibitors resulted in significant changes in cell viability, microglial morphology, cell cycle arrest and mitochondrial ROS production in a dose-dependent manner in both primary cultural microglia and BV-2 cell lines. Moreover, ETC inhibitors, especially rotenone and antimycin A stimulated secretion of interleukin 1β (IL-1β), interleukin 6 (IL-6), interleukin 12 (IL-12) and tumor necrosis factor α (TNF-α) by microglia with marked activation of mitogen-activated proteinkinases (MAPKs) and nuclear factor κB (NF-κB), which could be blocked by specific inhibitors of MAPK and NF-κB and mitochondrial antioxidants, Mito-TEMPO. Taken together, our results demonstrated that inhibition of mitochondrial respiratory chain in microglia led to production of mitochondrial ROS and therefore may activate MAPK/NF-кB dependent inflammatory cytokines release in microglia, which indicated that mitochondrial-derived ROS were contributed to microglial activation.

  3. Direct synthesis of dimethyl carbonate and propylene glycol using potassium bicarbonate as catalyst in supercritical CO2

    OpenAIRE

    Wen Yicun; Zhang Rui; Cang Yu; Zhang Jianchao; Liu Lixiao; Guo Xuhong; Fan Bin

    2015-01-01

    The improved one-pot synthesis of dimethyl carbonate and propylene glycol from propylene oxide, supercritical carbon dioxide, and methanol with potassium bicarbonate as the catalyst has been reported in this paper. As far as we know, it is the first time to use potassium bicarbonate only as the catalyst in the production process which is simple and cheap. Satisfactory conversion rate of propylene oxide and yield of the products could be achieved at the optimized conditions with quite a small ...

  4. Bicarbonate increases binding affinity of Vibrio cholerae ToxT to virulence gene promoters.

    Science.gov (United States)

    Thomson, Joshua J; Withey, Jeffrey H

    2014-11-01

    The major Vibrio cholerae virulence gene transcription activator, ToxT, is responsible for the production of the diarrhea-inducing cholera toxin (CT) and the major colonization factor, toxin coregulated pilus (TCP). In addition to the two primary virulence factors mentioned, ToxT is responsible for the activation of accessory virulence genes, such as aldA, tagA, acfA, acfD, tcpI, and tarAB. ToxT activity is negatively modulated by bile and unsaturated fatty acids found in the upper small intestine. Conversely, previous work identified another intestinal signal, bicarbonate, which enhances the ability of ToxT to activate production of CT and TCP. The work presented here further elucidates the mechanism for the enhancement of ToxT activity by bicarbonate. Bicarbonate was found to increase the activation of ToxT-dependent accessory virulence promoters in addition to those that produce CT and TCP. Bicarbonate is taken up into the V. cholerae cell, where it positively affects ToxT activity by increasing DNA binding affinity for the virulence gene promoters that ToxT activates regardless of toxbox configuration. The increase in ToxT binding affinity in the presence of bicarbonate explains the elevated level of virulence gene transcription.

  5. Regulators of Slc4 bicarbonate transporter activity

    Directory of Open Access Journals (Sweden)

    Ian M. Thornell

    2015-06-01

    Full Text Available The Slc4 family of transporters is comprised of anion exchangers (AE1-4, Na-coupled bicarbonate transporters (NCBTs including electrogenic Na/bicarbonate cotransporters (NBCe1 and NBCe2, electroneutral Na/bicarbonate cotransporters (NBCn1 and NBCn2, and the electroneutral Na-driven Cl-bicarbonate exchanger (NDCBE, as well as a borate transporter (BTR1. These transporters regulate intracellular pH (pHi and contribute to steady-state pHi, but are also involved in other physiological processes including CO2 carriage by red blood cells and solute secretion/reabsorption across epithelia. Acid-base transporters function as either acid extruders or acid loaders, with the Slc4 proteins moving HCO3– either into or out of cells. According to results from both molecular and functional studies, multiple Slc4 proteins and/or associated splice variants with similar expected effects on pHi are often found in the same tissue or cell. Such apparent redundancy is likely to be physiologically important. In addition to regulating pHi, a HCO3– transporter contributes to a cell’s ability to fine tune the intracellular regulation of the cotransported/exchanged ion(s (e.g., Na+ or Cl–. In addition, functionally similar transporters or splice variants with different regulatory profiles will optimize pH physiology and solute transport under various conditions or within subcellular domains. Such optimization will depend on activated signaling pathways and transporter expression profiles. In this review, we will summarize and discuss both classical and more recently identified regulators of the Slc4 proteins. Some of these regulators include traditional second messengers, lipids, binding proteins, autoregulatory domains, and less conventional regulators. The material presented will provide insight into the diversity and physiological significance of multiple members within the Slc4 gene family.

  6. Sodium bicarbonate and sodium citrate: ergogenic aids?

    Science.gov (United States)

    Requena, Bernardo; Zabala, Mikel; Padial, Paulino; Feriche, Belén

    2005-02-01

    Numerous studies have used exogenous administration of sodium bicarbonate (NaHCO(3)) and sodium citrate (Na-citrate) in an attempt to enhance human performance. After ingestion of NaHCO(3) and Na-citrate, two observations have been made: (a) There was great individual variability in the ergogenic benefit reached, which can be attributed to the level of physical conditioning of the subjects and to their tolerance of the buffer substance; and (b) the subjects who had ingested NaHCO(3) and Na-citrate show higher levels of pH, bicarbonate, and lactate ions concentrations in their exercising blood than do the subjects who had ingested the placebo. A majority of the studies have suggested that the ingestion of both substances provides an ergogenic effect due to the establishment and maintenance of an elevated pH level during exercise. However, the exact mechanism by which the ergogenic effects occur has not been demonstrated conclusively. Sodium bicarbonate and Na-citrate seem to be effective in activities with a sufficient duration to generate a difference in the hydrogen ion gradient, characterized by a very high intensity and involving large muscular groups. However, in activities of equally high intensity, but with longer duration, the results obtained have been conflicting and inconclusive. PMID:15705037

  7. Carotenoid inhibitors reduce strigolactone production and Striga hermonthica infection in rice.

    Science.gov (United States)

    Jamil, Muhammad; Charnikhova, Tatsiana; Verstappen, Francel; Bouwmeester, Harro

    2010-12-01

    The strigolactones are internal and rhizosphere signalling molecules in plants that are biosynthesised through carotenoid cleavage. They are secreted by host roots into the rhizosphere where they signal host-presence to the symbiotic arbuscular mycrorrhizal (AM) fungi and the parasitic plants of the Orobanche, Phelipanche and Striga genera. The seeds of these parasitic plants germinate after perceiving these signalling molecules. After attachment to the host root, the parasite negatively affects the host plant by withdrawing water, nutrients and assimilates through a direct connection with the host xylem. In many areas of the world these parasites are a threat to agriculture but so far very limited success has been achieved to minimize losses due to these parasitic weeds. Considering the carotenoid origin of the strigolactones, in the present study we investigated the possibilities to reduce strigolactone production in the roots of plants by blocking carotenoid biosynthesis using carotenoid inhibitors. Hereto the carotenoid inhibitors fluridone, norflurazon, clomazone and amitrole were applied to rice either through irrigation or through foliar spray. Irrigation application of all carotenoid inhibitors and spray application of amitrole significantly decreased strigolactone production, Striga hermonthica germination and Striga infection, also in concentrations too low to affect growth and development of the host plant. Hence, we demonstrate that the application of carotenoid inhibitors to plants can affect S. hermonthica germination and attachment indirectly by reducing the strigolactone concentration in the rhizosphere. This finding is useful for further studies on the relevance of the strigolactones in rhizosphere signalling. Since these inhibitors are available and accessible, they may represent an efficient technology for farmers, including poor subsistence farmers in the African continent, to control these harmful parasitic weeds.

  8. Influence of bicarbonate and carbonate ions on sonochemical degradation of Rhodamine B in aqueous phase.

    Science.gov (United States)

    Merouani, Slimane; Hamdaoui, Oualid; Saoudi, Fethi; Chiha, Mahdi; Pétrier, Christian

    2010-03-15

    The influence of bicarbonate and carbonate ions on sonolytic degradation of cationic dye, Rhodamine B (RhB), in water was investigated. As a consequence of ultrasonic cavitation that generates .OH radicals, carbonate radicals were secondary products of water sonochemistry when it contains dissolved bicarbonate or carbonate ions. The results clearly demonstrated the significant intensification of sonolytic destruction of RhB in the presence of bicarbonate and carbonate, especially at lower dye concentrations. Degradation intensification occurs because carbonate radicals sonochemically formed undergo radical-radical recombination at a lesser extent than hydroxyl radicals. The generated carbonate radicals are likely able to migrate far from the cavitation bubbles towards the solution bulk and are suitable for degradation of an organic dye such as RhB. Therefore, at low dye concentrations, carbonate radical presents a more selective reactivity towards RhB molecules than hydroxyl radical. In the presence of bicarbonate, degradation rate reached a maximum at 3 g L(-1) bicarbonate, but subsequent addition retards the destruction process. In RhB solutions containing carbonate, the oxidation rate gradually increased with increasing carbonate concentration up to 10 g L(-1) and slightly decreased afterward. Carbonate radicals sonochemically generated are suitable for total removal of COD of sonicated RhB solutions. PMID:19910116

  9. Biocompatibility and tolerability of a purely bicarbonate-buffered peritoneal dialysis solution.

    NARCIS (Netherlands)

    Weiss, L.; Stegmayr, B.; Malmsten, G.; Tejde, M.; Hadimeri, H.; Siegert, C.E.; Ahlmen, J.; Larsson, R.; Ingman, B.; Simonsen, O.; Hamersvelt, H.W. van; Johansson, A.C.; Hylander, B.; Mayr, M.; Nilsson, P.H.; Andersson, P.O.; Los Rios, T. De

    2009-01-01

    BACKGROUND: Novel peritoneal dialysis solutions are characterized by a minimal content of glucose degradation products and a neutral pH. Many studies have shown the biocompatibility of neutral lactate-buffered solutions; however, until now, the effect of purely bicarbonate-buffered solutions has not

  10. Radiolysis of aqueous solutions of ammonium bicarbonate over a large dose range

    DEFF Research Database (Denmark)

    Draganic, Z.D.; Negrón-Mendoza, A.; Sehested, K.;

    1991-01-01

    Oxygen-free aqueous solutions of 0.05 mol dm-3 ammonium and sodium bicarbonate were studied after receiving various doses of Co-60 gammas (0.01-400 kGy) or 0.5-20 Gy pulses of 10 Mev electrons. Formate and oxalate were found to be the main radiolytic products, in addition to trace amounts...

  11. Sodium Bicarbonate Therapy in Patients with Metabolic Acidosis

    OpenAIRE

    Adeva-Andany, María M.; Carlos Fernández-Fernández; David Mouriño-Bayolo; Elvira Castro-Quintela; Alberto Domínguez-Montero

    2014-01-01

    Metabolic acidosis occurs when a relative accumulation of plasma anions in excess of cations reduces plasma pH. Replacement of sodium bicarbonate to patients with sodium bicarbonate loss due to diarrhea or renal proximal tubular acidosis is useful, but there is no definite evidence that sodium bicarbonate administration to patients with acute metabolic acidosis, including diabetic ketoacidosis, lactic acidosis, septic shock, intraoperative metabolic acidosis, or cardiac arrest, is beneficial ...

  12. Pyrazole-5-carboxamides, novel inhibitors of receptor for advanced glycation end products (RAGE).

    Science.gov (United States)

    Han, Young Taek; Kim, Kyeojin; Choi, Gyeong-In; An, Hongchan; Son, Dohyun; Kim, Hee; Ha, Hee-Jin; Son, Jun-Hyeng; Chung, Suk-Jae; Park, Hyun-Ju; Lee, Jeewoo; Suh, Young-Ger

    2014-05-22

    In an effort to develop novel inhibitors of receptor for advanced glycation end products (RAGE) for the treatment of Alzheimer's disease, a series of pyrazole-5-carboxamides were designed, synthesized and biologically evaluated. Analyses of the extensive structure-activity relationship (SAR) led us to identify a 4-fluorophenoxy analog (40) that exhibited improved in vitro RAGE inhibitory activity and more favorable aqueous solubility than the parent 2-aminopyrimidine, 1. Surface plasmon resonance (SPR) and molecular docking study strongly supported the RAGE inhibitory activity of pyrazole-5-carboxamides. The brain Aβ-lowering effect of 40 is also described. PMID:24727489

  13. Direct synthesis of dimethyl carbonate and propylene glycol using potassium bicarbonate as catalyst in supercritical CO2

    Directory of Open Access Journals (Sweden)

    Wen Yicun

    2015-03-01

    Full Text Available The improved one-pot synthesis of dimethyl carbonate and propylene glycol from propylene oxide, supercritical carbon dioxide, and methanol with potassium bicarbonate as the catalyst has been reported in this paper. As far as we know, it is the first time to use potassium bicarbonate only as the catalyst in the production process which is simple and cheap. Satisfactory conversion rate of propylene oxide and yield of the products could be achieved at the optimized conditions with quite a small amount of by-products. Our new method offers an attractive choice for the production of dimethyl carbonate in large-scale industry efficiently and environmental friendly.

  14. Effect of sodium bicarbonate administration on mortality in patients with lactic acidosis: a retrospective analysis.

    Directory of Open Access Journals (Sweden)

    Hyun Jeong Kim

    Full Text Available BACKGROUND: Lactic acidosis is a common cause of high anion gap metabolic acidosis. Sodium bicarbonate may be considered for an arterial pH <7.15 but paradoxically depresses cardiac performance and exacerbates acidosis by enhancing lactate production. This study aimed to evaluate the cause and mortality rate of lactic acidosis and to investigate the effect of factors, including sodium bicarbonate use, on death. METHODS: We conducted a single center analysis from May 2011 through April 2012. We retrospectively analyzed 103 patients with lactic acidosis among 207 patients with metabolic acidosis. We used SOFA and APACHE II as severity scores to estimate illness severity. Multivariate logistic regression analysis and Cox regression analysis models were used to identify factors that affect mortality. RESULTS: Of the 103 patients with a mean age of 66.1±11.4 years, eighty-three patients (80.6% died from sepsis (61.4%, hepatic failure, cardiogenic shock and other causes. The percentage of sodium bicarbonate administration (p = 0.006, catecholamine use, ventilator care and male gender were higher in the non-survival group than the survival group. The non-survival group had significantly higher initial and follow-up lactic acid levels, lower initial albumin, higher SOFA scores and APACHE II scores than the survival group. The mortality rate was significantly higher in patients who received sodium bicarbonate. Sodium bicarbonate administration (p = 0.016 was associated with higher mortality. Independent factors that affected mortality were SOFA score (Exp (B = 1.72, 95% CI = 1.12-2.63, p = 0.013 and sodium bicarbonate administration (Exp (B = 6.27, 95% CI = 1.10-35.78, p = 0.039. CONCLUSIONS: Lactic acidosis, which has a high mortality rate, should be evaluated in patients with metabolic acidosis. In addition, sodium bicarbonate should be prescribed with caution in the case of lactic acidosis because sodium bicarbonate

  15. Biotechnological strategies to overcome inhibitors in lignocellulose hydrolysates for ethanol production: review.

    Science.gov (United States)

    Parawira, W; Tekere, M

    2011-03-01

    One of the major challenges faced in commercial production of lignocellulosic bioethanol is the inhibitory compounds generated during the thermo-chemical pre-treatment step of biomass. These inhibitory compounds are toxic to fermenting micro-organisms. The ethanol yield and productivity obtained during fermentation of lignocellulosic hydrolysates is decreased due to the presence of inhibiting compounds, such as weak acids, furans and phenolic compounds formed or released during thermo-chemical pre-treatment step such as acid and steam explosion. This review describes the application and/or effect of biological detoxification (removal of inhibitors before fermentation) or use of bioreduction capability of fermenting yeasts on the fermentability of the hydrolysates. Inhibition of yeast fermentation by the inhibitor compounds in the lignocellulosic hydrolysates can be reduced by treatment with enzymes such as the lignolytic enzymes, for example, laccase and micro-organisms such as Trichoderma reesei, Coniochaeta ligniaria NRRL30616, Trametes versicolor, Pseudomonas putida Fu1, Candida guilliermondii, and Ureibacillus thermosphaericus. Microbial and enzymatic detoxifications of lignocellulosic hydrolysate are mild and more specific in their action. The efficiency of enzymatic process is quite comparable to other physical and chemical methods. Adaptation of the fermentation yeasts to the lignocellulosic hydrolysate prior to fermentation is suggested as an alternative approach to detoxification. Increases in fermentation rate and ethanol yield by adapted micro-organisms to acid pre-treated lignocellulosic hydrolysates have been reported in some studies. Another approach to alleviate the inhibition problem is to use genetic engineering to introduce increased tolerance by Saccharomyces cerevisiae, for example, by overexpressing genes encoding enzymes for resistance against specific inhibitors and altering co-factor balance. Cloning of the laccase gene followed by

  16. Matrix Metalloproteinase Inhibitors (MMPIs from Marine Natural Products: the Current Situation and Future Prospects

    Directory of Open Access Journals (Sweden)

    Se-Kwon Kim

    2009-03-01

    Full Text Available Matrix metalloproteinases (MMPs are a family of more than twenty five secreted and membrane-bound zinc-endopeptidases which can degrade extracellular matrix (ECM components. They also play important roles in a variety of biological and pathological processes. Matrix metalloproteinase inhibitors (MMPIs have been identified as potential therapeutic candidates for metastasis, arthritis, chronic inflammation and wrinkle formation. Up to present, more than 20,000 new compounds have been isolated from marine organisms, where considerable numbers of these naturally occurring derivatives are developed as potential candidates for pharmaceutical application. Eventhough the quantity of marine derived MMPIs is less when compare with the MMPIs derived from terrestrial materials, huge potential for bioactivity of these marine derived MMPIs has lead to large number of researches. Saccharoids, flavonoids and polyphones, fatty acids are the most important groups of MMPIs derived from marine natural products. In this review we focus on the progress of MMPIs from marine natural products.

  17. Omeprazole promotes proximal duodenal mucosal bicarbonate secretion in humans

    DEFF Research Database (Denmark)

    Mertz-Nielsen, A; Hillingsø, Jens; Bukhave, K;

    1996-01-01

    with control experiments. Also the combination of omeprazole and ranitidine increased (p = 0.05) duodenal bicarbonate secretion, while ranitidine alone caused no change in either basal or stimulated secretion. In the stomach basal as well as vagally stimulated bicarbonate secretion was independent of the means...

  18. Reappraisal of bicarbonate secretion by the human oesophagus

    DEFF Research Database (Denmark)

    Mertz-Nielsen, A; Hillingsø, J; Bukhave, Klaus;

    1997-01-01

    BACKGROUND AND AIMS: Administration of omeprazole to healthy volunteers was recently reported to increase proximal duodenal mucosalbicarbonate secretion. As human oesophagus also secretes bicarbonate, the hypothesis was tested that omeprazole may stimulate oesophagealbicarbonate secretion and thus....../day omeprazole for three days and 80 mg intravenous omeprazole before perfusionor 600 mg/day ranitidine for three days and 50 mg/h intravenously during the perfusion. Saliva and samples of aspirate from the perfusedoesophagus and stomach were collected and bicarbonate concentrations were measured. RESULTS: The...... median rates (95% confidence intervals)of intrinsic oesophageal bicarbonate secretion, corrected for contaminating salivary and gastric bicarbonate, were 89 (33-150) and 121 (63-203)mumol/h/10 cm (p > 0.5) in omeprazole and ranitidine treated subjects respectively. Salivary and gastric bicarbonate...

  19. Reducing conditions are the key for efficient production of active ribonuclease inhibitor in Escherichia coli

    Directory of Open Access Journals (Sweden)

    Neubauer Peter

    2011-05-01

    Full Text Available Abstract Background The eukaryotic RNase ribonuclease/angiogenin inhibitors (RI are a protein group distinguished by a unique structure - they are composed of hydrophobic leucine-rich repeat motifs (LRR and contain a high amount of reduced cysteine residues. The members of this group are difficult to produce in E. coli and other recombinant hosts due to their high aggregation tendency. Results In this work dithiothreitol (DTT was successfully applied for improving the yield of correctly folded ribonuclease/angiogenin inhibitor in E. coli K12 periplasmic and cytoplasmic compartments. The feasibility of the in vivo folding concepts for cytoplasmic and periplasmic production were demonstrated at batch and fed-batch cultivation modes in shake flasks and at the bioreactor scale. Firstly, the best secretion conditions of RI in the periplasmic space were evaluated by using a high throughput multifactorial screening approach of a vector library, directly with the Enbase fed-batch production mode in 96-well plates. Secondly, the effect of the redox environment was evaluated in isogenic dsbA+ and dsbA- strains at the various cultivation conditions with reducing agents in the cultivation medium. Despite the fusion to the signal peptide, highest activities were found in the cytoplasmic fraction. Thus by removing the signal peptide the positive effect of the reducing agent DTT was clearly proven also for the cytoplasmic compartment. Finally, optimal periplasmic and cytoplasmic RI fed-batch production processes involving externally added DTT were developed in shake flasks and scaled up to the bioreactor scale. Conclusions DTT highly improved both, periplasmic and cytoplasmic accumulation and activity of RI at low synthesis rate, i.e. in constructs harbouring weak recombinant synthesis rate stipulating genetic elements together with cultivation at low temperature. In a stirred bioreactor environment RI folding was strongly improved by repeated pulse addition

  20. Structures of aminophenol dioxygenase in complex with intermediate, product and inhibitor.

    Science.gov (United States)

    Li, De Feng; Zhang, Jia Yue; Hou, Yan Jie; Liu, Lei; Hu, Yonglin; Liu, Shuang Jiang; Wang, Da Cheng; Liu, Wei

    2013-01-01

    Dioxygen activation by nonhaem Fe(II) enzymes containing the 2-His-1-carboxylate facial triad has been extensively studied in recent years. Here, crystal structures of 2-aminophenol 1,6-dioxygenase, an enzyme that represents a minor group of extradiol dioxygenases and that catalyses the ring opening of 2-aminophenol, in complex with the lactone intermediate (4Z,6Z)-3-iminooxepin-2(3H)-one and the product 2-aminomuconic 6-semialdehyde and in complex with the suicide inhibitor 4-nitrocatechol are reported. The Fe-ligand binding schemes observed in these structures revealed some common geometrical characteristics that are shared by the published structures of extradiol dioxygenases, suggesting that enzymes that catalyse the oxidation of noncatecholic compounds are very likely to utilize a similar strategy for dioxygen activation and the fission of aromatic rings as the canonical mechanism. The Fe-ligation arrangement, however, is strikingly enantiomeric to that of all other 2-His-1-carboxylate enzymes apart from protocatechuate 4,5-dioxygenase. This structural variance leads to the generation of an uncommon O(-)-Fe(2+)-O(-) species prior to O(2) binding, which probably forms the structural basis on which APD distinguishes its specific substrate and inhibitor, which share an analogous molecular structure.

  1. Effect of phosphodiesterase inhibitors on nitric oxide production by glial cells.

    Science.gov (United States)

    Yoshikawa, Minka; Suzumura, Akio; Ito, Atsushi; Tamaru, Tsukasa; Takayanagi, Tetsuya

    2002-03-01

    Nitric oxide (NO) is considered to play a crucial role in the development of various pathological processes in the CNS, such as neuronal degeneration, inflammation and demyelination. In order to search for the agents which suppress NO production in the CNS, we examined the effects of one of the agents which elevate cyclic AMP production, phosphodiesterase inhibitors (PDEIs), on NO production by glial cells in vitro. All the types of PDEIs, from type I- to V-specific and non-specific, suppressed the production of NO by mouse microglia and astrocytes stimulated with lipopolysaccharide, in a dose-dependent manner. Suppression of inducible NO synthase by PDEIs was confirmed by the expression of mRNA by RT-PCR. Although it required 10 microM or higher concentration to effectively suppress NO production in vitro, certain combinations of three different PDEIs synergistically suppressed NO production by astrocytes at 1 microM which could be obtained in vivo at usual therapeutic doses. Similary, combinations of three PDEIs at 1 microM synergistically increased intracellular cAMP in astrocytes. The suppressive effects of PDEIs on NO production were abolished by addition of tumor necrosis factor alpha (TNFalpha). Thus, the main suppression mechanism of NO might be indirect through suppression of TNFalpha. Since some PDEIs are reported to pass through the blood-brain-barrier, the combination of three PDEIs may be worth trying in neurological diseases, such as multiple sclerosis, human immunodeficiency virus-related neurological diseases and other neurodegenerative disorders in which NO may play a crucial role.

  2. Identification of hematein as a novel inhibitor of protein kinase CK2 from a natural product library

    International Nuclear Information System (INIS)

    Casein kinase 2 (CK2) is dysregulated in various human cancers and is a promising target for cancer therapy. To date, there is no small molecular CK2 inhibitor in clinical trial yet. With the aim to identify novel CK2 inhibitors, we screened a natural product library. We adopted cell-based proliferation and CK2 kinase assays to screen CK2 inhibitors from a natural compound library. Dose-dependent response of CK2 inhibitors in vitro was determined by a radioisotope kinase assay. Western blot analysis was used to evaluate down stream Akt phosphorylation and apoptosis. Apoptosis was also evaluated by annexin-V/propidium iodide (PI) labeling method using flow cytometry. Inhibition effects of CK2 inhibitors on the growth of cancer and normal cells were evaluated by cell proliferation and viability assays. Hematein was identified as a novel CK2 inhibitor that is highly selective among a panel of kinases. It appears to be an ATP non-competitive and partially reversible CK2 inhibitor with an IC50 value of 0.55 μM. In addition, hematein inhibited cancer cell growth partially through down-regulation of Akt phosphorylation and induced apoptosis in these cells. Furthermore, hematein exerted stronger inhibition effects on the growth of cancer cells than in normal cells. In this study, we showed that hematein is a novel selective and cell permeable small molecule CK2 inhibitor. Hematein showed stronger growth inhibition effects to cancer cells when compared to normal cells. This compound may represent a promising class of CK2 inhibitors

  3. Huntingtin cleavage product A forms in neurons and is reduced by gamma-secretase inhibitors

    Directory of Open Access Journals (Sweden)

    Betschart Claudia

    2010-12-01

    Full Text Available Abstract Background The mutation in Huntington's disease is a polyglutamine expansion near the N-terminus of huntingtin. Huntingtin expressed in immortalized neurons is cleaved near the N-terminus to form N-terminal polypeptides known as cleavage products A and B (cpA and cpB. CpA and cpB with polyglutamine expansion form inclusions in the nucleus and cytoplasm, respectively. The formation of cpA and cpB in primary neurons has not been established and the proteases involved in the formation of these fragments are unknown. Results Delivery of htt cDNA into the mouse striatum using adeno-associated virus or into primary cortical neurons using lentivirus generated cpA and cpB, indicating that neurons in brain and in vitro can form these fragments. A screen of small molecule protease inhibitors introduced to clonal striatal X57 cells and HeLa cells identified compounds that reduced levels of cpA and are inhibitors of the aspartyl proteases cathepsin D and cathepsin E. The most effective compound, P1-N031, is a transition state mimetic for aspartyl proteases. By western blot analysis, cathepsin D was easily detected in clonal striatal X57 cells, mouse brain and primary neurons, whereas cathepsin E was only detectible in clonal striatal X57 cells. In primary neurons, levels of cleavage product A were not changed by the same compounds that were effective in clonal striatal cells or by mRNA silencing to partially reduce levels of cathepsin D. Instead, treating primary neurons with compounds that are known to inhibit gamma secretase activity either indirectly (Imatinib mesylate, Gleevec or selectively (LY-411,575 or DAPT reduced levels of cpA. LY-411,575 or DAPT also increased survival of primary neurons expressing endogenous full-length mutant huntingtin. Conclusion We show that cpA and cpB are produced from a larger huntingtin fragment in vivo in mouse brain and in primary neuron cultures. The aspartyl protease involved in forming cpA has cathepsin

  4. Intestinal Bicarbonate Secretion in Cystic Fibrosis Mice

    Directory of Open Access Journals (Sweden)

    Clarke LL

    2001-07-01

    Full Text Available Gene-targeted disruption of the cystic fibrosis transmembrane conductance regulator (CFTR in mice results in an intestinal disease phenotype that is remarkably similar to bowel disease in cystic fibrosis patients. In the intestinal segment downstream from the stomach (i.e., the duodenum, CFTR plays an important role in bicarbonate secretion that protects the epithelium from acidic gastric effluent. In this report, we examine the role of CFTR in cAMP-stimulated bicarbonate secretion in the murine duodenum and the mechanisms of acid-base transport that are revealed in CFTR knockout (CF mice. Ion substitution, channel blocker and pH stat studies comparing duodena from wild-type and CF mice indicate that CFTR mediates a HCO(3(- conductance across the apical membrane of the epithelium. In the presence of a favorable cell-to-lumen HCO(3(- gradient, the CFTR-mediated HCO(3(- current accounts for about 80% of stimulated HCO(3(- secretion. Exposure of the duodenal mucosa to acidic pH reveals another role of CFTR in facilitating HCO(3(- secretion via an electroneutral, 4,4'-diisothiocyanato-stilbene-2,2' disulfonic acid (DIDS sensitive Cl(-/HCO(3(- exchange process. In CF duodenum, other apical membrane acid-base transporters retain function, thereby affording limited control of transepithelial pH. Activity of a Cl(--dependent anion exchanger provides near-constant HCO(3(- secretion in CF intestine, but under basal conditions the magnitude of secretion is lessened by simultaneous activity of a Na(+/H(+ exchanger (NHE. During cAMP stimulation of CF duodenum, a small increase in net base secretion is measured but the change results from cAMP inhibition of NHE activity rather than increased HCO(3(- secretion. Interestingly, a small inward current that is sensitive to the anion channel blocker, 5-nitro-2(3-phenylpropyl amino-benzoate (NPPB, is also activated during cAMP stimulation of the CFTR-null intestine but the identity of the current is yet to be

  5. DNA sequence, products, and transcriptional pattern of the genes involved in production of the DNA replication inhibitor microcin B17.

    Science.gov (United States)

    Genilloud, O; Moreno, F; Kolter, R

    1989-02-01

    The 3.8-kilobase segment of plasmid DNA that contains the genes required for production of the DNA replication inhibitor microcin B17 was sequenced. The sequence contains four open reading frames which were shown to be translated in vivo by the construction of fusions to lacZ. The location of these open reading frames fits well with the location of the four microcin B17 production genes, mcbABCD, identified previously through genetic complementation. The products of the four genes have been identified, and the observed molecular weights of the proteins agree with those predicted from the nucleotide sequence. The transcription of these genes was studied by using fusions to lacZ and physical mapping of mRNA start sites. Three promoters were identified in this region. The major promoter for all the genes is a growth phase-regulated OmpR-dependent promoter located upstream of mcbA. A second promoter is located within mcbC and is responsible for a low-level basal expression of mcbD. A third promoter, located within mcbD, promotes transcription in the reverse direction starting within mcbD and extending through mcbC. The resulting mRNA appears to be an untranslated antisense transcript that could play a regulatory role in the expression of these genes.

  6. Response in two commercial Holstein herds to addition of sodium bicarbonate to alfalfa hay-based diets.

    Science.gov (United States)

    Bath, D L; Bishop, S E; Peterson, N G; Hight, W B; De Peters, E J

    1985-07-01

    Feeding trials were conducted in two commercial dairy herds to evaluate the addition of .8% sodium bicarbonate to alfalfa hay-based diets. Approximately half of each herd served as controls and the other half was fed the same diet with sodium bicarbonate. A total of 1280 Dairy Herd Improvement Association lactation records were obtained in the two herds during the trials. Cows in herd 1 were milked three times daily and cows in herd 2 were milked twice daily. In herd 1, milk production from control and bicarbonate groups was: first lactation cows, 7491 and 7748 kg/cow; second lactation cows, 8363 and 8791 kg/cow; and third and higher lactation cows, 8713 and 9562 kg/cow. There were no differences in milkfat or solids-not-fat percentages between treatment groups. In herd 2, milk production from control and bicarbonate groups was: first lactation cows, 6800 and 7158 kg/cow; second lactation cows, 8487 and 8082 kg/cow; and third and higher lactation cows, 8807 and 8216 kg/cow. First lactation cows fed sodium bicarbonate had a lower milk fat percentage than controls. There were no other differences in milk fat or solids-not-fat percentages between treatment groups. PMID:2993391

  7. Metabolic attributes, yield and stability of milk in Jersey cows fed diets containing sodium citrate and sodium bicarbonate

    Directory of Open Access Journals (Sweden)

    Marcelo Tempel Stumpf

    2013-05-01

    Full Text Available The objective of this work was to evaluate the inclusion of sodium citrate and sodium bicarbonate in the diet of lactating Jersey cows, and its effects on the metabolic attributes, productivity and stability of milk. We evaluated urinary pH, levels of glucose and urea in blood, body weight, body condition score, milk yield, milk stability (ethanol test, and milk physicochemical properties of 17 cows fed diets containing sodium citrate (100 g per cow per day, sodium bicarbonate (40 g per cow per day or no additives. Assessments were made at the 28th and 44th days. Supply of sodium citrate or bicarbonate has no influence on the metabolic attributes, productivity, body weight, and body condition score of the cows, neither on the composition and stability of milk.

  8. Carbonic Anhydrase: In the Driver's Seat for Bicarbonate Transport

    Directory of Open Access Journals (Sweden)

    Sterling D

    2001-07-01

    Full Text Available Carbonic anhydrases are a widely expressed family of enzymes that catalyze the reversible reaction: CO(2 + H(2O = HCO(3(- + H(+. These enzymes therefore both produce HCO(3(- for transport across membranes and consume HCO(3(- that has been transported across membranes. Thus these enzymes could be expected to have a key role in driving the transport of HCO(3(- across cells and epithelial layers. Plasma membrane anion exchange proteins (AE transport chloride and bicarbonate across most mammalian membranes in a one-for-one exchange reaction and act as a model for our understanding of HCO(3(- transport processes. Recently it was shown that AE1, found in erythrocytes and kidney, binds carbonic anhydrase II (CAII via the cytosolic C-terminal tail of AE1. To examine the physiological consequences of the interaction between CAII and AE1, we characterized Cl(-/HCO(3(- exchange activity in transfected HEK293 cells. Treatment of AE1-transfected cells with acetazolamide, a CAII inhibitor, almost fully inhibited anion exchange activity, indicating that endogenous CAII activity is essential for transport. Further experiments to examine the role of the AE1/CAII interaction will include measurements of the transport activity of AE1 following mutation of the CAII binding site. In a second approach a functionally inactive CA mutant, V143Y, will be co-expressed with AE1 in HEK293 cells. Since over expression of V143Y CAII would displace endogenous wild-type CAII from AE1, a loss of transport activity would be observed if binding to the AE1 C-terminus is required for transport.

  9. Decreased hepatic glucose production in obese rats by dipeptidyl peptidase-Ⅳ inhibitor sitagliptin

    Institute of Scientific and Technical Information of China (English)

    LU Ying-li; ZHOU De-quan; ZHAI Hua-ling; WU Hui; GUO Zeng-kui

    2012-01-01

    Background Dipeptidyl peptidase-Ⅳ (DPP-4) inhibitors are now used to improve postprandial glycemic control in type 2 diabetes.However,their effects on hepatic glucose production (HGP) in obesity are not clear.This study was designed to test the hypothesis that gluconeogenesis and HGP can be modulated by DPP-4 inhibitors in obesity.Methods Sprague Dawley male rats were divided into four groups,each on a different diet:general rat chow,n=10 (G);G+sitagliptin,n=10; high fat chow (obesity),n=10 (55% fat calories,HFO); HFO+sitagliptin,n=10.After 10 weeks,the rats were fasted overnight and glucose metabolism was determined using 3-3H-glucose and 14C-glycerol as tracers.Results Glycerol rate of appearance (P<0.00001),plasma glycerol (P<0.05) and free fatty acid (FFA) (P<0.05)concentrations,and HGP (P<0.05) were decreased in HFO+sitagliptin group compared with HFO group,but there was no significant difference between G and G+sitagliptin groups (P>0.05).Gluconeogenesis in HFO group was five times of that in G rats (P<0.01),but was significantly declined in HFO+sitagliptin group (P<0.0001).Conclusions Gluconeogenesis and HGP were inhibited by sitagliptin in high fat-induced obese rats due to decreased glycerol availability,which was a result of reduced glycerol release from adipose tissues.The finding suggests that sitagliptin is potentially useful for controlling fasting glucose in obesity,thereby delaying or preventing the development of diabetes.

  10. Stilbene glycosides are natural product inhibitors of FGF-2-induced angiogenesis

    Directory of Open Access Journals (Sweden)

    Naz Humera

    2009-04-01

    Full Text Available Abstract Background Angiogenesis, the growth of new blood vessels from the pre-existing vasculature is associated with pathological processes, in particular tumour development, and is a target for the development of new therapies. We have investigated the anti-angiogenic potential of two naturally occurring stilbene glycosides (compounds 1 and 2 isolated from the medicinal plant Boswellia papyriferai using large and smallvessel-derived endothelial cells. Compound 1 (trans-4',5'-dihydroxy-3-methoxystilbene-5-O-{α-L-rhamnopyranosyl-(1→2-[α-L-rhamnopyranosyl-(1→6}-β-D-glucopyranoside was the more hydrophilic and inhibited FGF-2-induced proliferation, wound healing, invasion in Matrigel, tube formation and angiogenesis in large and small vessel-derived endothelial cells and also in the chick chorioallantoic membrane assay. Using a binding assay we were able to show compound 1 reduced binding of FGF-2 to fibroblast growth factor receptors-1 and -2. In all cases the concentration of compound 1 which caused 50% inhibition (IC50 was determined. The effect of compound 1 on EGF and VEGF-induced proliferation was also investigated. Results Compound 1 inhibited all stages of FGF-2 induced angiogenesis with IC50 values in the range 5.8 ± 0.18 – 48.90 ± 0.40 μM but did not inhibit EGF or VEGF-induced angiogenesis. It also inhibited FGF-2 binding to FGF receptor-1 and -2 with IC50 values of 5.37 ± 1.04 and 9.32 ± 0.082 μM respectively and with concommotant down-regulation of phosphorylated-ERK-1/-2 expression. Compound 2 was an ineffective inhibitor of angiogenesis despite its structural homology to compound 1. Conclusion Compound 1 inhibited FGF-2 induced angiogenesis by binding to its cognate receptors and is an addition to the small number of natural product inhibitors of angiogenesis

  11. Target prices for mass production of tyrosine kinase inhibitors for global cancer treatment

    Science.gov (United States)

    Hill, Andrew; Gotham, Dzintars; Fortunak, Joseph; Meldrum, Jonathan; Erbacher, Isabelle; Martin, Manuel; Shoman, Haitham; Levi, Jacob; Powderly, William G; Bower, Mark

    2016-01-01

    Objective To calculate sustainable generic prices for 4 tyrosine kinase inhibitors (TKIs). Background TKIs have proven survival benefits in the treatment of several cancers, including chronic myeloid leukaemia, breast, liver, renal and lung cancer. However, current high prices are a barrier to treatment. Mass production of low-cost generic antiretrovirals has led to over 13 million people being on HIV/AIDS treatment worldwide. This analysis estimates target prices for generic TKIs, assuming similar methods of mass production. Methods Four TKIs with patent expiry dates in the next 5 years were selected for analysis: imatinib, erlotinib, lapatinib and sorafenib. Chemistry, dosing, published data on per-kilogram pricing for commercial transactions of active pharmaceutical ingredient (API), and quotes from manufacturers were used to estimate costs of production. Analysis included costs of excipients, formulation, packaging, shipping and a 50% profit margin. Target prices were compared with current prices. Global numbers of patients eligible for treatment with each TKI were estimated. Results API costs per kg were $347–$746 for imatinib, $2470 for erlotinib, $4671 for lapatinib, and $3000 for sorafenib. Basing on annual dose requirements, costs of formulation/packaging and a 50% profit margin, target generic prices per person-year were $128–$216 for imatinib, $240 for erlotinib, $1450 for sorafenib, and $4020 for lapatinib. Over 1 million people would be newly eligible to start treatment with these TKIs annually. Conclusions Mass generic production of several TKIs could achieve treatment prices in the range of $128–$4020 per person-year, versus current US prices of $75161–$139 138. Generic TKIs could allow significant savings and scaling-up of treatment globally, for over 1 million eligible patients. PMID:26817636

  12. EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion on the substantiation of health claims related to sodium bicarbonate and maintenance of normal blood pressure (ID 1404) pursuant to Article 13(1) of Regulation (EC) No 1924/2006

    DEFF Research Database (Denmark)

    Tetens, Inge

    claims in relation to sodium bicarbonate and maintenance of normal blood pressure. The scientific substantiation is based on the information provided by the Member States in the consolidated list of Article 13 health claims and references that EFSA has received from Member States or directly from...... stakeholders. The food constituent that is the subject of the health claim is sodium bicarbonate. The Panel considers that sodium bicarbonate is sufficiently characterised. The claimed effect is “blood pressure reduction”. The target population is assumed to be the general population. In the context of the...... substantiation of the claim. On the basis of the data presented, the Panel concludes that a cause and effect relationship has not been established between the consumption of sodium bicarbonate and maintenance of normal blood pressure....

  13. Production of Proteasome Inhibitor Syringolin A by the Endophyte Rhizobium sp. Strain AP16

    Science.gov (United States)

    Bigler, Laurent; Dudler, Robert

    2014-01-01

    Syringolin A, the product of a mixed nonribosomal peptide synthetase/polyketide synthase encoded by the syl gene cluster, is a virulence factor secreted by certain Pseudomonas syringae strains. Together with the glidobactins produced by a number of beta- and gammaproteobacterial human and animal pathogens, it belongs to the syrbactins, a structurally novel class of proteasome inhibitors. In plants, proteasome inhibition by syringolin A-producing P. syringae strains leads to the suppression of host defense pathways requiring proteasome activity, such as the ones mediated by salicylic acid and jasmonic acid. Here we report the discovery of a syl-like gene cluster with some unusual features in the alphaproteobacterial endophyte Rhizobium sp. strain AP16 that encodes a putative syringolin A-like synthetase whose components share 55% to 65% sequence identity (72% to 79% similarity) at the amino acid level. As revealed by average nucleotide identity (ANI) calculations, this strain likely belongs to the same species as biocontrol strain R. rhizogenes K84 (formely known as Agrobacterium radiobacter K84), which, however, carries a nonfunctional deletion remnant of the syl-like gene cluster. Here we present a functional analysis of the syl-like gene cluster of Rhizobium sp. strain AP16 and demonstrate that this endophyte synthesizes syringolin A and some related minor variants, suggesting that proteasome inhibition by syrbactin production can be important not only for pathogens but also for endophytic bacteria in the interaction with their hosts. PMID:24727275

  14. Inhibitors of neutrophil recruitment identified using transgenic zebrafish to screen a natural product library

    Directory of Open Access Journals (Sweden)

    Xingang Wang

    2014-01-01

    Full Text Available Cell migration is fundamental to the inflammatory response, but uncontrolled cell migration and excess recruitment of neutrophils and other leukocytes can cause damage to the tissue. Here we describe the use of an in vivo model – the Tg(mpx:GFPi114 zebrafish line, in which neutrophils are labelled by green fluorescent protein (GFP – to screen a natural product library for compounds that can affect neutrophil migratory behaviour. Among 1040 fungal extracts screened, two were found to inhibit neutrophil migration completely. Subfractionation of these extracts identified sterigmatocystin and antibiotic PF1052 as the active components. Using the EZ-TAXIScan chemotaxis assay, both compounds were also found to have a dosage-dependent inhibitory effect on murine neutrophil migration. Furthermore, neutrophils treated with PF1052 failed to form pseudopods and appeared round in shape, suggesting a defect in PI3-kinase (PI3K signalling. We generated a transgenic neutrophil-specific PtdIns(3,4,5P3 (PIP3 reporter zebrafish line, which revealed that PF1052 does not affect the activation of PI3K at the plasma membrane. In human neutrophils, PF1052 neither induced apoptosis nor blocked AKT phosphorylation. In conclusion, we have identified an antibiotic from a natural product library with potent anti-inflammatory properties, and have established the utility of the mpx:GFP transgenic zebrafish for high-throughput in vivo screens for novel inhibitors of neutrophil migration.

  15. Inhibitors of neutrophil recruitment identified using transgenic zebrafish to screen a natural product library.

    Science.gov (United States)

    Wang, Xingang; Robertson, Anne L; Li, Jingyu; Chai, Ruth Jinfen; Haishan, Wang; Sadiku, Pranvera; Ogryzko, Nikolay V; Everett, Martin; Yoganathan, Kanagasundaram; Luo, Hongbo Robert; Renshaw, Stephen A; Ingham, Philip W

    2014-01-01

    Cell migration is fundamental to the inflammatory response, but uncontrolled cell migration and excess recruitment of neutrophils and other leukocytes can cause damage to the tissue. Here we describe the use of an in vivo model - the Tg(mpx:GFP)(i114) zebrafish line, in which neutrophils are labelled by green fluorescent protein (GFP) - to screen a natural product library for compounds that can affect neutrophil migratory behaviour. Among 1040 fungal extracts screened, two were found to inhibit neutrophil migration completely. Subfractionation of these extracts identified sterigmatocystin and antibiotic PF1052 as the active components. Using the EZ-TAXIScan chemotaxis assay, both compounds were also found to have a dosage-dependent inhibitory effect on murine neutrophil migration. Furthermore, neutrophils treated with PF1052 failed to form pseudopods and appeared round in shape, suggesting a defect in PI3-kinase (PI3K) signalling. We generated a transgenic neutrophil-specific PtdIns(3,4,5)P3 (PIP3) reporter zebrafish line, which revealed that PF1052 does not affect the activation of PI3K at the plasma membrane. In human neutrophils, PF1052 neither induced apoptosis nor blocked AKT phosphorylation. In conclusion, we have identified an antibiotic from a natural product library with potent anti-inflammatory properties, and have established the utility of the mpx:GFP transgenic zebrafish for high-throughput in vivo screens for novel inhibitors of neutrophil migration.

  16. MICROWAVE-ASSISTED SURFACE MODIFICATION OF CALCIUM BICARBONATE

    Institute of Scientific and Technical Information of China (English)

    Jing Ye; Xiaofei Zhang

    2004-01-01

    Surface modification of calcium bicarbonate powder with isopropyl triisostearoyl titanate (TTS) by microwave-assisted heating was studied in the present work. The features of microwave treated powder show obvious superiority to those of powder samples treated by traditional surface modification method and of untreated calcium bicarbonate - in suspension turbidity, suction potential, contact angle with water, and mechanical properties of their composites with PVC resin.

  17. Bicarbonate trigger for inducing lipid accumulation in algal systems

    Science.gov (United States)

    Gardner, Robert; Peyton, Brent; Cooksey, Keith E.

    2015-08-04

    The present invention provides bicarbonate containing and/or bicarbonate-producing compositions and methods to induce lipid accumulation in an algae growth system, wherein the algae growth system is under light-dark cycling condition. By adding said compositions at a specific growth stage, said methods lead to much higher lipid accumulation and/or significantly reduced total time required for accumulating lipid in the algae growth system.

  18. 1,8-Dihydroxynaphthalene (DHN)-Melanin Biosynthesis Inhibitors Increase Erythritol Production in Torula corallina, and DHN-Melanin Inhibits Erythrose Reductase

    OpenAIRE

    Lee, Jung-Kul; Jung, Hyung-Moo; Kim, Sang-Yong

    2003-01-01

    The yeast Torula corallina is a strong erythritol producer that is used in the industrial production of erythritol. However, melanin accumulation during culture represents a serious problem for the purification of erythritol from the fermentation broth. Melanin biosynthesis inhibitors such as 3,4-dihydroxyphenylalanine and 1,8-dihydroxynaphthalene (DHN)-melanin inhibitors were added to the T. corallina cultures. Only the DHN-melanin inhibitors showed an effect on melanin production, which sug...

  19. Practical considerations for bicarbonate loading and sports performance.

    Science.gov (United States)

    Burke, Louise M

    2013-01-01

    Consumption of sodium bicarbonate (300 mg/kg 1-2 h before exercise) can temporarily increase blood bicarbonate concentrations, enhancing extracellular buffering of hydrogen ions which accumulate and efflux from the working muscle. Such 'bicarbonate loading' provides an ergogenic strategy for sporting events involving high rates of anaerobic glycolysis which are otherwise limited by the body's capacity to manage the progressive increase in intracellular acidity. Studies show that bicarbonate loading strategies have a moderate positive effect on the performance of sports involving 1-7 min of sustained strenuous exercise, and may also be useful for prolonged sports involving intermittent or sustained periods of high-intensity work rates. This potential to enhance sports performance requires further investigation using appropriate research design, but may be limited by practical considerations such as gut discomfort or the logistics of the event. The effect of chronic use of bicarbonate supplementation prior to high-intensity workouts to promote better training performance and adaptations is worthy of further investigation. While this relatively simple dietary strategy has been studied and used by sports people for over 80 years, it is likely that there are still ways in which further benefits from bicarbonate supplementation can be developed and individualized for specific athletes or specific events.

  20. Isolation and identification of precocenes and piperitone from essential oils as specific inhibitors of trichothecene production by Fusarium graminearum.

    Science.gov (United States)

    Yaguchi, Atsushi; Yoshinari, Tomoya; Tsuyuki, Rie; Takahashi, Haruo; Nakajima, Takashi; Sugita-Konishi, Yoshiko; Nagasawa, Hiromichi; Sakuda, Shohei

    2009-02-11

    Inhibitors of deoxynivalenol production by Fusarium graminearum are useful for protecting crops from deoxynivalenol contamination. We isolated precocenes and piperitone from the essential oils of Matricaria recutita and Eucalyptus dives, respectively, as specific inhibitors of the production of 3-acetyldeoxynivalenol, a biosynthetic precursor of deoxynivalenol. Precocenes I and II and piperitone inhibited 3-acetyldeoxynivalenol production by F. graminearum in a liquid culture with IC(50) values of 16.6, 1.2, and 306 microM, respectively, without inhibiting fungal growth. Precocene II also inhibited deoxynivalenol production by the fungus in a solid culture on rice with an IC(50) value of 2.0 ppm. Precocene II and piperitone decreased the mRNA levels of Tri4, Tri5, Tri6, and Tri10 encoding proteins required for deoxynivalenol biosynthesis. PMID:19191669

  1. Characterization of the corrosion products formed on mild steel in acidic medium with N-octadecylpyridinium bromide as corrosion inhibitor

    Energy Technology Data Exchange (ETDEWEB)

    Nava, N., E-mail: tnava@imp.mx; Likhanova, N. V. [Direccion de Investigacion y Posgrado, Instituto Mexicano del Petroleo (Mexico); Olivares-Xometl, O. [Benemerita Universidad Autonoma de Puebla, Facultad de Ingenieria Quimica (Mexico); Flores, E. A. [Direccion de Investigacion y Posgrado, Instituto Mexicano del Petroleo (Mexico); Lijanova, I. V. [CIITEC, Instituto Politecnico Nacional (Mexico)

    2011-11-15

    The characterization of the corrosion products formed on mild steel SAE 1018 after 2 months exposure in aqueous sulfuric acid with and without corrosion inhibitor N-octadecylpyridinium bromide has been carried out by means of transmission {sup 57}Fe Moessbauer spectroscopy and X-ray powder diffraction (XRD). The major constituent of the rust formed in this environment without corrosion inhibitor is goethite ({alpha}-FeOOH). The samples with N-octadecylpyridinium bromide contain rozenite and large amounts of melanterite in the corrosion layers.

  2. Effects of PDE4 inhibitors on lipopolysaccharide-induced priming of superoxide anion production from human mononuclear cells

    Directory of Open Access Journals (Sweden)

    Noëlla Germain

    2001-01-01

    Full Text Available Aims: Phosphodiesterase 4 (PDE4 inhibitors have been described as potent anti-inflammatory compounds, involving an increase in intracellular levels of cyclic 3',5'-adenosine monophosphate (AMP. The aim of this study was to compare the effects of selective PDE4 inhibitors, rolipram and RP 73-401 with the cell permeable analogue of cyclic AMP, dibutyryl-cyclic AMP (db-cAMP and the anti-inflammatory cytokine interleukin-10 (IL-10 on superoxide anion production from peripheral blood mononuclear cells preincubated with lipopolysaccharide (LPS.

  3. Characterization of the corrosion products formed on mild steel in acidic medium with N-octadecylpyridinium bromide as corrosion inhibitor

    International Nuclear Information System (INIS)

    The characterization of the corrosion products formed on mild steel SAE 1018 after 2 months exposure in aqueous sulfuric acid with and without corrosion inhibitor N-octadecylpyridinium bromide has been carried out by means of transmission 57Fe Mössbauer spectroscopy and X-ray powder diffraction (XRD). The major constituent of the rust formed in this environment without corrosion inhibitor is goethite (α-FeOOH). The samples with N-octadecylpyridinium bromide contain rozenite and large amounts of melanterite in the corrosion layers.

  4. Vaginal estrogen products in hormone receptor-positive breast cancer patients on aromatase inhibitor therapy.

    Science.gov (United States)

    Sulaica, Elisabeth; Han, Tiffany; Wang, Weiqun; Bhat, Raksha; Trivedi, Meghana V; Niravath, Polly

    2016-06-01

    Atrophic vaginitis represents a major barrier to compliance with aromatase inhibitor (AI) therapy in breast cancer (BC) survivors. While local estrogen therapy is effective for postmenopausal vaginal dryness, the efficacy of such therapies has not been evaluated systematically in hormone receptor-positive (HR+) BC patients on AI therapy. Furthermore, the potential risk of breast cancer recurrence with vaginal estrogen therapy represents a long-term safety concern for the patients with HR + BC. Unfortunately, there is no standardized assay to measure very low concentrations of estradiol (E2) in these women being treated with AI therapy. This makes it difficult to evaluate even indirectly the potential risk of BC recurrence with vaginal estrogen therapy in HR + BC patients on AI therapy. In this review, we describe available assays to measure very low concentrations of E2, discuss the Food and Drug Administration-approved vaginal estrogen products on the market, and summarize published and ongoing clinical trials evaluating the safety and efficacy of vaginal estrogen in HR + BC patients on AI therapy. In the absence of any randomized controlled clinical trials, this review serves as a summary of available clinical data and ongoing studies to aid clinicians in selecting the best available option for their patients. PMID:27178335

  5. Extracellular production of riboflavin-binding protein, a potential bitter inhibitor, by Brevibacillus choshinensis.

    Science.gov (United States)

    Maehashi, Kenji; Matano, Mami; Saito, Makiko; Udaka, Shigezo

    2010-05-01

    Riboflavin-binding protein (RBP) is a glycophosphoprotein found in hen eggs. We previously identified the extraordinary characteristic of RBP in reducing bitterness. For a more detailed study on the mode of action and industrial application of this characteristic, we investigated the microbial production of recombinant RBP (rRBP). We constructed a chicken RBP gene expression vector by inserting the RBP cDNA in pNCMO2, the Escherichia coli-Brevibacillus choshinensis shuttle vector. B. choshinensis HPD31 transformants produced 0.8g/l of processed and unglycosylated RBP in a soluble form in the culture supernatant. However, the expressed RBP was partially dimerized and monomeric RBP was purified by two step anion-exchange and gel-filtration chromatographies. The purified rRBP elicited bitterness reduction against quinine and caffeine, although it largely lost its riboflavin-binding ability. These results indicated that glycosylation and riboflavin-binding ability are not essential for the bitterness reduction of RBP. In addition, we assessed the usefulness of the Brevibacillus system for the expression and secretion of RBP as a new type of bitterness inhibitor. PMID:20045733

  6. Vaginal estrogen products in hormone receptor-positive breast cancer patients on aromatase inhibitor therapy.

    Science.gov (United States)

    Sulaica, Elisabeth; Han, Tiffany; Wang, Weiqun; Bhat, Raksha; Trivedi, Meghana V; Niravath, Polly

    2016-06-01

    Atrophic vaginitis represents a major barrier to compliance with aromatase inhibitor (AI) therapy in breast cancer (BC) survivors. While local estrogen therapy is effective for postmenopausal vaginal dryness, the efficacy of such therapies has not been evaluated systematically in hormone receptor-positive (HR+) BC patients on AI therapy. Furthermore, the potential risk of breast cancer recurrence with vaginal estrogen therapy represents a long-term safety concern for the patients with HR + BC. Unfortunately, there is no standardized assay to measure very low concentrations of estradiol (E2) in these women being treated with AI therapy. This makes it difficult to evaluate even indirectly the potential risk of BC recurrence with vaginal estrogen therapy in HR + BC patients on AI therapy. In this review, we describe available assays to measure very low concentrations of E2, discuss the Food and Drug Administration-approved vaginal estrogen products on the market, and summarize published and ongoing clinical trials evaluating the safety and efficacy of vaginal estrogen in HR + BC patients on AI therapy. In the absence of any randomized controlled clinical trials, this review serves as a summary of available clinical data and ongoing studies to aid clinicians in selecting the best available option for their patients.

  7. Bicarbonate of soda paint stripping process validation and material characterization

    Science.gov (United States)

    Haas, Michael N.

    1995-01-01

    The Aircraft Production Division at San Antonio Air Logistics Center has conducted extensive investigation into the replacement of hazardous chemicals in aircraft component cleaning, degreasing, and depainting. One of the most viable solutions is process substitution utilizing abrasive techniques. SA-ALC has incorporated the use of Bicarbonate of Soda Blasting as one such substitution. Previous utilization of methylene chloride based chemical strippers and carbon removal agents has been replaced by a walk-in blast booth in which we remove carbon from engine nozzles and various gas turbine engine parts, depaint cowlings, and perform various other functions on a variety of parts. Prior to implementation of this new process, validation of the process was performed, and materials and waste stream characterization studies were conducted. These characterization studies examined the effects of the blasting process on the integrity of the thin-skinned aluminum substrates, the effects of the process on both air emissions and effluent disposal, and the effects on the personnel exposed to the process.

  8. The novel HDAC inhibitor AR-42-induced anti-colon cancer cell activity is associated with ceramide production

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Weihong; Xu, Bin; Yao, Yiting; Yu, Xiaoling [Department of Clinical Laboratory, Tongren Hospital, Shanghai (China); Shen, Jie, E-mail: tongrensj163@163.com [Department of Administrative, Tongren Hospital, No. 786 Yuyuan Road, Changning District, Shanghai (China)

    2015-08-07

    In the current study, we investigated the potential activity of AR-42, a novel histone deacetylase (HDAC) inhibitor, against colon cancer cells. Our in vitro results showed that AR-42 induced ceramide production, exerted potent anti-proliferative and pro-apoptotic activities in established (SW-620 and HCT-116 lines) and primary human colon cancer cells. Exogenously-added sphingosine 1-phosphate (S1P) suppressed AR-42-induced activity, yet a cell-permeable ceramide (C4) facilitated AR-42-induced cytotoxicity against colon cancer cells. In addition, AR-42-induced ceramide production and anti-colon cancer cell activity were inhibited by the ceramide synthase inhibitor fumonisin B1, but were exacerbated by PDMP, which is a ceramide glucosylation inhibitor. In vivo, oral administration of a single dose of AR-42 dramatically inhibited SW-620 xenograft growth in severe combined immunodeficient (SCID) mice, without inducing overt toxicities. Together, these results show that AR-42 dramatically inhibits colon cancer cell proliferation in vitro and in vivo, and ceramide production might be the key mechanism responsible for its actions. - Highlights: • AR-42 is anti-proliferative against primary/established colon cancer cells. • AR-42 induces significant apoptotic death in primary/established colon cancer cells. • Ceramide production mediates AR-42-induced cytotoxicity in colon cancer cells. • AR-42 oral administration potently inhibits SW-620 xenograft growth in SCID mice.

  9. Role of calcium signaling in epithelial bicarbonate secretion.

    Science.gov (United States)

    Jung, Jinsei; Lee, Min Goo

    2014-06-01

    Transepithelial bicarbonate secretion plays a key role in the maintenance of fluid and protein secretion from epithelial cells and the protection of the epithelial cell surface from various pathogens. Epithelial bicarbonate secretion is mainly under the control of cAMP and calcium signaling. While the physiological roles and molecular mechanisms of cAMP-induced bicarbonate secretion are relatively well defined, those induced by calcium signaling remain poorly understood in most epithelia. The present review summarizes the current status of knowledge on the role of calcium signaling in epithelial bicarbonate secretion. Specifically, this review introduces how cytosolic calcium signaling can increase bicarbonate secretion by regulating membrane transport proteins and how it synergizes with cAMP-induced mechanisms in epithelial cells. In addition, tissue-specific variations in the pancreas, salivary glands, intestines, bile ducts, and airways are discussed. We hope that the present report will stimulate further research into this important topic. These studies will provide the basis for future medicines for a wide spectrum of epithelial disorders including cystic fibrosis, Sjögren's syndrome, and chronic pancreatitis.

  10. Con: Higher serum bicarbonate in dialysis patients is protective.

    Science.gov (United States)

    Chauveau, Philippe; Rigothier, Claire; Combe, Christian

    2016-08-01

    Metabolic acidosis is often observed in advanced chronic kidney disease, with deleterious consequences on the nutritional status, bone and mineral status, inflammation and mortality. Through clearance of the daily acid load and a net gain in alkaline buffers, dialysis therapy is aimed at correcting metabolic acidosis. A normal bicarbonate serum concentration is the recommended target in dialysis patients. However, several studies have shown that a mild degree of metabolic acidosis in patients treated with dialysis is associated with better nutritional status, higher protein intake and improved survival. Conversely, a high bicarbonate serum concentration is associated with poor nutritional status and lower survival. It is likely that mild acidosis results from a dietary acid load linked to animal protein intake. In contrast, a high bicarbonate concentration in patients treated with dialysis could result mainly from an insufficient dietary acid load, i.e. low protein intake. Therefore, a high pre-dialysis serum bicarbonate concentration should prompt nephrologists to carry out nutritional investigations to detect insufficient dietary protein intake. In any case, a high bicarbonate concentration should be neither a goal of dialysis therapy nor an index of adequate dialysis, whereas mild acidosis could be considered as an indicator of appropriate protein intake. PMID:27411724

  11. Water absorption and bicarbonate secretion in the intestine of the sea bream are regulated by transmembrane and soluble adenylyl cyclase stimulation.

    Science.gov (United States)

    Carvalho, Edison S M; Gregório, Sílvia F; Power, Deborah M; Canário, Adelino V M; Fuentes, Juan

    2012-12-01

    In the marine fish intestine luminal, HCO₃⁻ can remove divalent ions (calcium and magnesium) by precipitation in the form of carbonate aggregates. The process of epithelial HCO₃⁻ secretion is under endocrine control, therefore, in this study we aimed to characterize the involvement of transmembrane (tmACs) and soluble (sACs) adenylyl cyclases on the regulation of bicarbonate secretion (BCS) and water absorption in the intestine of the sea bream (Sparus aurata). We observed that all sections of sea bream intestine are able to secrete bicarbonate as measured by pH-Stat in Ussing chambers. In addition, gut sac preparations reveal net water absorption in all segments of the intestine, with significantly higher absorption rates in the anterior intestine that in the rectum. BCS and water absorption are positively correlated in all regions of the sea bream intestinal tract. Furthermore, stimulation of tmACs (10 μM FK + 500 μM IBMX) causes a significant decrease in BCS, bulk water absorption and short circuit current (Isc) in a region dependent manner. In turn, stimulation of sACs with elevated HCO₃⁻ results in a significant increase in BCS, and bulk water absorption in the anterior intestine, an action completely reversed by the sAC inhibitor KH7 (200 μM). Overall, the results reveal a functional relationship between BCS and water absorption in marine fish intestine and modulation by tmACs and sAC. In light of the present observations, it is hypothesized that the endocrine effects on intestinal BCS and water absorption mediated by tmACs are locally and reciprocally modulated by the action of sACs in the fish enterocyte, thus fine-tuning the process of carbonate aggregate production in the intestinal lumen.

  12. [Effects of urease and nitrification inhibitors on alleviating the oxidation and leaching of soil urea's hydrolyzed product ammonium].

    Science.gov (United States)

    Chen, Zhenhua; Chen, Lijun; Wu, Zhijie

    2005-02-01

    With simulation test of in-situ soil column, this paper studied the effects of urease inhibitor hydroquinone (HQ), nitrification inhibitors coated calcium carbide (ECC) and dicyandiamide (DCD),and their different combinations on the persistence, oxidation, and leaching of soil urea's hydrolyzed product ammonium. The results showed that compared with other treatments, the combination of HQ and DCD could effectively inhibit the oxidation of the ammonium, and make it as exchangeable form reserve in soil in a larger amount and a longer period. The inhibition of this oxidation not only decreased the accumulation of oxidized product NO3- in soil, but also decreased the potential of NO3- leaching, making the NO3- only leach to 5-10 cm in depth, and the leached amount significantly decreased.

  13. Bicarbonate produced from carbon capture for algae culture.

    Science.gov (United States)

    Chi, Zhanyou; O'Fallon, James V; Chen, Shulin

    2011-11-01

    Using captured CO(2) to grow microalgae is limited by the high cost of CO(2) capture and transportation, as well as significant CO(2) loss during algae culture. Moreover, algae grow poorly at night, but CO(2) cannot be temporarily stored until sunrise. To address these challenges, we discuss a process where CO(2) is captured as bicarbonate and used as feedstock for algae culture, and the carbonate regenerated by the culture process is used as an absorbent to capture more CO(2). This process would significantly reduce carbon capture costs because it does not require additional energy for carbonate regeneration. Furthermore, not only would transport of the aqueous bicarbonate solution cost less than for that of compressed CO(2), but using bicarbonate would also provide a superior alternative for CO(2) delivery to an algae culture system.

  14. Focused library with a core structure extracted from natural products and modified: application to phosphatase inhibitors and several biochemical findings.

    Science.gov (United States)

    Hirai, Go; Sodeoka, Mikiko

    2015-05-19

    Synthesis of a focused library is an important strategy to create novel modulators of specific classes of proteins. Compounds in a focused library are composed of a common core structure and different diversity structures. In this Account, we describe our design and synthesis of libraries focused on selective inhibitors of protein phosphatases (PPases). We considered that core structures having structural and electronic features similar to those of PPase substrates, phosphate esters, would be a reasonable choice. Therefore, we extracted core structures from natural products already identified as PPase inhibitors. Since many PPases share similar active-site structures, such phosphate-mimicking core structures should interact with many enzymes in the same family, and therefore the choice of diversity structures is pivotal both to increase the binding affinity and to achieve specificity for individual enzymes. Here we present case studies of application of focused libraries to obtain PPase inhibitors, covering the overall process from selection of core structures to identification and evaluation of candidates in the focused libraries. To synthesize a library focused on protein serine-threonine phosphatases (PPs), we chose norcantharidin as a core structure, because norcantharidin dicarboxylate shows a broad inhibition profile toward several PPs. From the resulting focused library, we identified a highly selective PP2B inhibitor, NCA-01. On the other hand, to find inhibitors of dual-specificity protein phosphatases (DSPs), we chose 3-acyltetronic acid extracted from natural product RK-682 as a core structure, because its structure resembles the transition state in the dephosphorylation reaction of DSPs. However, a highly selective inhibitor was not found in the resulting focused library. Furthermore, an inherent drawback of compounds having the highly acidic 3-acyltetronic acid as a core structure is very weak potency in cellulo, probably due to poor cell membrane

  15. Some Investigations on Protease Enzyme Production Kinetics Using Bacillus licheniformis BBRC 100053 and Effects of Inhibitors on Protease Activity

    Directory of Open Access Journals (Sweden)

    Zahra Ghobadi Nejad

    2014-01-01

    Full Text Available Due to great commercial application of protease, it is necessary to study kinetic characterization of this enzyme in order to improve design of enzymatic reactors. In this study, mathematical modeling of protease enzyme production kinetics which is derived from Bacillus licheniformis BBRC 100053 was studied (at 37°C, pH 10 after 73 h in stationary phase, and 150 rpm. The aim of the present paper was to determine the best kinetic model and kinetic parameters for production of protease and calculating Ki (inhibition constant of different inhibitors to find the most effective one. The kinetic parameters Km (Michaelis-Menten constant and Vm (maximum rate were calculated 0.626 mM and 0.0523 mM/min. According to the experimental results, using DFP (diisopropyl fluorophosphate and PMSF (phenylmethanesulfonyl fluoride as inhibitors almost 50% of the enzyme activity could be inhibited when their concentrations were 0.525 and 0.541 mM, respectively. Ki for DFP and PMSF were 0.46 and 0.56 mM, respectively. Kinetic analysis showed that the Lineweaver-Burk model was the best fitting model for protease production kinetics DFP was more effective than PMSF and both of them should be covered in the group of noncompetitive inhibitors.

  16. Quorum sensing signals are produced by Aeromonas salmonicida and quorum sensing inhibitors can reduce production of a potential virulence factor

    DEFF Research Database (Denmark)

    Rasch, Maria; Kastbjerg, Vicky Gaedt; Bruhn, Jesper Bartholin;

    2007-01-01

    . Pigment production was only observed in broth under highly aerated conditions. Quorum sensing inhibitors (QSIs) are compounds that specifically block QS systems without affecting bacterial growth and 2 such compounds, sulphur-containing AHL-analogues, reduced production of protease in a typical strain...... of Aeromonas salmonicida strains. All 31 typical strains were AHL producers as were 21 of 26 atypical strains, but on a strain population basis, production of virulence factors such as protease, lipase, A-layer or pigment did not correlate with the production and accumulation of AHLs in the growth medium...... of Aeromonas salmonicida. The most efficient compound N-(heptylsulfanylacetyl)-L-homoserine lactone (HepS-AHL), reduced protease production by a factor of 10. Five extracellular proteases were detected on gelatin-containing sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) gels and 3...

  17. Utilização de Resíduos Gerados por Indústria do Setor Sucroalcoleiro, Pela RAUDI Indústria e Comércio LTDA, na Produção de Bicarbonato de Sódio. = Use of Residues Generated for the Sugar-Alcohol Industry Sector, by The RAUDI Industry and Commerce Limited, in the Sodium Bicarbonate Production.

    Directory of Open Access Journals (Sweden)

    Frederico F. da Silva

    2008-07-01

    Full Text Available A consciência ecológica está intimamente ligada à preservação do meio ambiente. A importância da preservação dos recursos naturais passou a ser preocupação mundial e nenhum país pode eximir-se de sua responsabilidade. Essa necessidade de proteção do ambiente é antiga e surgiu quando o homem passou a valorizar a natureza, mas não de maneira tão acentuada como nos dias de hoje. Esse trabalho tem como objetivo, passar ao leitor como é possível a utilização de resíduos na obtenção de novos produtos ecologicamente corretos, como o uso de resíduos poluentes de uma usina de álcool transformando-os em matéria prima no processo de fabricação do bicarbonato de sódio. = The ecological conscience is intimately linked to the preservation of the environment. The importance of the preservation of the natural resources became a world-wide concern and no country can be exempted of its responsibility. This necessity of protection of the environment is not a new thing and appeared when man started to value nature, but not in an accentuated way as nowadays. This work has as objective, to inform the reader as to the use of residues in the attainment of new ecologically correct products possible, as the use of pollutant residues of an alcohol plant transforming them into substance in the process of manufacturing sodium bicarbonate.

  18. New Naturally Occurring Product Extract as Corrosion Inhibitor for 316 Stainless Steel in 5% HCl

    Institute of Scientific and Technical Information of China (English)

    T.Y.Soror

    2004-01-01

    Medipolymorphol, a new sterol isolated from the whole plant of Medicago polymorpha Roxb was used as corrosion inhibitor for 316 stainless steel in 5% HCl at room temperature. Electrochemical techniques have been found to be reliable in evaluating corrosion characteristics of the system. Several techniques have been used including Tafel, linear polarization, potentiodynamic polarization, and open circuit potential (OCP) studies. The additives simultaneously deaccelerated the anodic process, intensified the cathodic process and provided a stable passive state, giving good inhibition efficiencies to stainless steel electrodes. In addition, adsorption isotherm have been fitted for the inhibitor under investigation.

  19. Na/K citrate versus sodium bicarbonate in prevention of contrast-induced nephropathy.

    Science.gov (United States)

    Abouzeid, Sameh Mohamed; ElHossary, Hossam E

    2016-05-01

    Contrast-induced nephropathy (CIN) is one of the important complications of radiographic procedures, especially in patients with chronic kidney disease. It is also one of the common causes of acute kidney injury. The pathogenesis is postulated to be the effect of oxygen- free radicals and hyperosmolar stress on the renal medulla. It is reported that the production of superoxide is most active at acid environment. K/Na citrate is well known as a urine alkalinization medium, and this has been evaluated earlier with standard hydration for reduction of CIN and was stated to be efficient. We aimed to determine the efficacy of Na/K citrate in reducing the frequency of CIN in comparison to sodium bicarbonate in patients after coronary angiography. Two hundred and ten patients with renal dysfunction [estimated glomerular filtration rate (eGFR), 60 mL/min/1.73 m(2) or less] who underwent elective or emergency coronary angiography (CAG) with/without percutaneous coronary intervention (PCI) at our institution were enrolled into the study. The patients were randomized into two groups, Group 1-Taking Na/K citrate and Group 2-Taking sodium bicarbonate. Radiographic contrast agent iohexol was used. Change in creatinine, percent change in creatinine, percent change in eGFR, change in serum potassium, and urine pH were all compared between the two groups. There was no significant difference for prevention of CIN when comparing the Na/K citrate with sodium bicarbonate solution in patients exposed to CAG with or without PCI. Mean absolute change in eGFR after 48 h after administration of contrast between sodium bicarbonate group and Na/K citrate group was -0.60 ± 1.58 versus -0.71 ± 1.38. Serum potassium decreased postprocedure in the sodium bicarbonate group than in the citrate group (3.90 ± 0.33 vs. 4.14 ± 0.39). Both agents are equally effective in reducing the incidence of CIN, but the citrate would possibly be a safer option for patients at risk of hypokalemia. PMID:27215244

  20. Na/K citrate versus sodium bicarbonate in prevention of contrast-induced nephropathy.

    Science.gov (United States)

    Abouzeid, Sameh Mohamed; ElHossary, Hossam E

    2016-05-01

    Contrast-induced nephropathy (CIN) is one of the important complications of radiographic procedures, especially in patients with chronic kidney disease. It is also one of the common causes of acute kidney injury. The pathogenesis is postulated to be the effect of oxygen- free radicals and hyperosmolar stress on the renal medulla. It is reported that the production of superoxide is most active at acid environment. K/Na citrate is well known as a urine alkalinization medium, and this has been evaluated earlier with standard hydration for reduction of CIN and was stated to be efficient. We aimed to determine the efficacy of Na/K citrate in reducing the frequency of CIN in comparison to sodium bicarbonate in patients after coronary angiography. Two hundred and ten patients with renal dysfunction [estimated glomerular filtration rate (eGFR), 60 mL/min/1.73 m(2) or less] who underwent elective or emergency coronary angiography (CAG) with/without percutaneous coronary intervention (PCI) at our institution were enrolled into the study. The patients were randomized into two groups, Group 1-Taking Na/K citrate and Group 2-Taking sodium bicarbonate. Radiographic contrast agent iohexol was used. Change in creatinine, percent change in creatinine, percent change in eGFR, change in serum potassium, and urine pH were all compared between the two groups. There was no significant difference for prevention of CIN when comparing the Na/K citrate with sodium bicarbonate solution in patients exposed to CAG with or without PCI. Mean absolute change in eGFR after 48 h after administration of contrast between sodium bicarbonate group and Na/K citrate group was -0.60 ± 1.58 versus -0.71 ± 1.38. Serum potassium decreased postprocedure in the sodium bicarbonate group than in the citrate group (3.90 ± 0.33 vs. 4.14 ± 0.39). Both agents are equally effective in reducing the incidence of CIN, but the citrate would possibly be a safer option for patients at risk of hypokalemia.

  1. Effects of bicarbonate and sulfate ions on the pitting corrosion behavior of copper

    International Nuclear Information System (INIS)

    The strategy for disposal of high-level radioactive waste in China is to enclose the spent nuclear fuel in sealed metal canisters which are embedded in bentonite clay hundreds meters down in the bed-rock. The choice of container material depends largely on the redox conditions and the aqueous environment of the repository. One of the choices for the fabrication of waste canisters is copper, because it is thermodynamically stable under the saline, anoxic conditions over the large majority of the container lifetime. However, in the early aerobic phase of the geological disposal the corrosion of copper could take place, and the corrosion behavior of copper would be influenced by the complex chemical conditions of groundwater markedly. Pitting corrosion of copper often take place in power plants or air-conditioning condensate water. The corrosion environment usually contains bicarbonate, sulfate and chloride ions. In the early stage of geological disposal, if the aerobic water with bicarbonate, sulfate and chloride ions immersion repository, the pitting corrosion of copper may occur. The content of bicarbonate and sulfate ion in the water chemistry environment, as well as the synergy between them, could affect the behavior of pitting seriously. The content of bicarbonate and chloride ion in the water chemistry environment, as well as the synergy between them, could affect the behavior of pitting seriously. The researchers generally agreed that chloride ions would promote the occurrence of pitting corrosion of copper, and bicarbonate ions will lead to surface passivation and inhibition of pitting. However, there is no systematic work in this area. In our work, the cycle polarization behavior and surface morphology of pitting has been investigated in HCO3- and Cl- mixed solution, respectively by electrochemical cyclic polarization test and scanning electron microscopy. The results show that the circular polarization curves of copper could be divided into four types. The

  2. Use of Sodium Bicarbonate in Diabetic Hyperglycemic Emergencies

    Directory of Open Access Journals (Sweden)

    Diana Machado Ramírez

    2013-09-01

    Full Text Available Background: diabetic ketoacidosis and hyperosmolar hyperglycemic nonketotic state are two of the major metabolic emergencies that may occur. These conditions are not always treated properly.Objective: to describe the metabolic hyperglycemic emergencies in diabetic patients treated in the Intensive Care Unit, and to assess the use of sodium bicarbonate. Methods: a descriptive, cross-sectional study was conducted including 52 patients admitted to the Intensive Care Unit of the Enrique Cabrera Hospital from 2000 through 2007. The following variables were analyzed: type of diabetes mellitus, type of acute complication, use or not of sodium bicarbonate, blood gases, ionogram and progress of patients. Kitabchi criteria were used for the diagnosis of diabetic ketoacidosis and its severity and for the diagnosis of the hyperglycemic state as well. Criteria proposed by an Expert Committee of the American Diabetes Association and a World Health Organization Expert Committee were adopted for the diagnosis of diabetes and its classification. Results: diabetic ketoacidosis was confirmed in 57,5 % of type 1 diabetic patients and in 42,5 % of those with type 2 diabetes. Hyperosmolar hyperglycemic nonketotic state was observed in 23,0 % of type 2 diabetics. There was not any death among patients with diabetic ketoacidosis who did not use sodium bicarbonate whereas 80,0 % of patients with hyperglycemic state who used it died. Conclusions: diabetic ketoacidosis was the most common complication. Mortality due to ketoacidosis and hyperosmolar hyperglycemic nonketotic state was high. Sodium bicarbonate was not properly used.

  3. Sodium bicarbonate-augmented stress thallium myocardial scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Sarin, Badal; Chugh, Pradeep Kumar; Kaushal, Dinesh; Soni, Nakse Lal; Sawroop, Kishan; Mondal, Anupam; Bhatnagar, Aseem [Department of Nuclear Medicine, Institute of Nuclear Medicine and Allied Sciences, Brig. S. K. Mazumdar Road, 110054, Delhi (India)

    2004-04-01

    It is well known that sodium bicarbonate in pharmacological doses induces transient alkalosis, causing intracellular transport of serum potassium. The aims of this study were (a) to investigate whether, in humans, myocardial thallium-201 uptake can be augmented by pretreatment with a single bolus of sodium bicarbonate at a pharmacological dose, (b) to verify general safety aspects of the intervention and (c) to evaluate the clinical implications of augmentation of {sup 201}Tl uptake, if any. Routine exercise myocardial scintigraphy was performed twice in eight adult volunteers (five normal and three abnormal), once without intervention and the second time (within a week) following intravenous administration of sodium bicarbonate (88 mEq in 50 ml) as a slow bolus 1 h prior to the injection of {sup 201}Tl. Conventional myocardial thallium study was compared with sodium bicarbonate interventional myocardial scintigraphy with respect to myocardial uptake (counts per minute per mCi injected dose), washout patterns in normal and abnormal myocardial segments, and overall clinical interpretation based on planar and single-photon emission tomographic (SPET) images. All patients remained asymptomatic after the intervention. A mean increase of 53% in myocardial uptake of thallium was noted in post-exercise acquisitions after the intervention, confirming uptake of the tracer via the potassium-hydrogen pump and its augmentation by transient alkalosis. The washout pattern remained unchanged. The visual quality of planar and SPET images improved significantly after the intervention. Out of the five abnormal myocardial segments identified in three cases, four showed significant filling-in after the intervention, causing the diagnosis to be upgraded from ''partial scar'' to ''ischaemia'', or from ''ischaemia'' to ''normal''. The overall scan impression changed in two out of three such cases. Sodium

  4. Comparison of Monoamine Oxidase Inhibitors in Decreasing Production of the Autotoxic Dopamine Metabolite 3,4-Dihydroxyphenylacetaldehyde in PC12 Cells.

    Science.gov (United States)

    Goldstein, David S; Jinsmaa, Yunden; Sullivan, Patti; Holmes, Courtney; Kopin, Irwin J; Sharabi, Yehonatan

    2016-02-01

    According to the catecholaldehyde hypothesis, the toxic dopamine metabolite 3,4-dihydroxyphenylacetaldehyde (DOPAL) contributes to the loss of nigrostriatal dopaminergic neurons in Parkinson's disease. Monoamine oxidase-A (MAO-A) catalyzes the conversion of intraneuronal dopamine to DOPAL and may serve as a therapeutic target. The "cheese effect"-paroxysmal hypertension evoked by tyramine-containing foodstuffs-limits clinical use of irreversible MAO-A inhibitors. Combined MAO-A/B inhibition decreases DOPAL production in rat pheochromocytoma PC12 cells, but whether reversible MAO-A inhibitors or MAO-B inhibitors decrease endogenous DOPAL production is unknown. We compared the potencies of MAO inhibitors in attenuating DOPAL production and examined possible secondary effects on dopamine storage, constitutive release, synthesis, and auto-oxidation. Catechol concentrations were measured in cells and medium after incubation with the irreversible MAO-A inhibitor clorgyline, three reversible MAO-A inhibitors, or the MAO-B inhibitors selegiline or rasagiline for 180 minutes. Reversible MAO-A inhibitors were generally ineffective, whereas clorgyline (1 nM), rasagiline (500 nM), and selegiline (500 nM) decreased DOPAL levels in the cells and medium. All three drugs also increased dopamine and norepinephrine, decreased 3,4-dihydroxyphenylalanine, and increased cysteinyl-dopamine concentrations in the medium, suggesting increased vesicular uptake and constitutive release, decreased dopamine synthesis, and increased dopamine spontaneous oxidation. In conclusion, clorgyline, rasagiline, and selegiline decrease production of endogenous DOPAL. At relatively high concentrations, the latter drugs probably lose their selectivity for MAO-B. Possibly offsetting increased formation of potentially toxic oxidation products and decreased formation of DOPAL might account for the failure of large clinical trials of MAO-B inhibitors to demonstrate slowing of neurodegeneration in Parkinson

  5. 40 CFR 180.1176 - Sodium bicarbonate; exemption from the requirement of a tolerance.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Sodium bicarbonate; exemption from the... Exemptions From Tolerances § 180.1176 Sodium bicarbonate; exemption from the requirement of a tolerance. The biochemical pesticide sodium bicarbonate is exempted from the requirement of a tolerance in or on all...

  6. Applications of Integrated Data Mining Methods to Exploring Natural Product Space for Acetylcholinesterase Inhibitors

    OpenAIRE

    Schuster, Daniela; Kern, Lisa; Hristozov, Dimitar P.; Terfloth, Lothar; Bienfait, Bruno; Laggner, Christian; Kirchmair, Johannes; Grienke, Ulrike; Wolber, Gerhard; Langer, Thierry; Stuppner, Hermann; Gasteiger, Johann; Rollinger, Judith M.

    2010-01-01

    Nature, especially the plant kingdom, is a rich source for novel bioactive compounds that can be used as lead compounds for drug development. In order to exploit this resource, the two neural network-based virtual screening techniques novelty detection with self-organizing maps (SOMs) and counterpropagation neural network were evaluated as tools for efficient lead structure discovery. As application scenario, significant descriptors for acetylcholinesterase (AChE) inhibitors were determined a...

  7. Discovery of an inhibitor of the production of the Pseudomonas aeruginosa virulence factor pyocyanin in wild-type cells

    Science.gov (United States)

    Morkunas, Bernardas; Gal, Balint; Galloway, Warren R J D; Hodgkinson, James T; Ibbeson, Brett M; Sing Tan, Yaw; Welch, Martin

    2016-01-01

    Summary Pyocyanin is a small molecule produced by Pseudomonas aeruginosa that plays a crucial role in the pathogenesis of infections by this notorious opportunistic pathogen. The inhibition of pyocyanin production has been identified as an attractive antivirulence strategy for the treatment of P. aeruginosa infections. Herein, we report the discovery of an inhibitor of pyocyanin production in cultures of wild-type P. aeruginosa which is based around a 4-alkylquinolin-2(1H)-one scaffold. To the best of our knowledge, this is the first reported example of pyocyanin inhibition by a compound based around this molecular framework. The compound may therefore be representative of a new structural sub-class of pyocyanin inhibitors, which could potentially be exploited in in a therapeutic context for the development of critically needed new antipseudomonal agents. In this context, the use of wild-type cells in this study is notable, since the data obtained are of direct relevance to native situations. The compound could also be of value in better elucidating the role of pyocyanin in P. aeruginosa infections. Evidence suggests that the active compound reduces the level of pyocyanin production by inhibiting the cell–cell signalling mechanism known as quorum sensing. This could have interesting implications; quorum sensing regulates a range of additional elements associated with the pathogenicity of P. aeruginosa and there is a wide range of other potential applications where the inhibition of quorum sensing is desirable. PMID:27559393

  8. Uranium(VI) interactions with mackinawite in the presence and absence of bicarbonate and oxygen

    Science.gov (United States)

    Gallegos, Tanya J.; Fuller, Christopher C.; Webb, Samuel M.; Betterton, William J.

    2013-01-01

    Mackinawite, Fe(II)S, samples loaded with uranium (10-5, 10-4, and 10-3 mol U/g FeS) at pH 5, 7, and 9, were characterized using X-ray absorption spectroscopy and X-ray diffraction to determine the effects of pH, bicarbonate, and oxidation on uptake. Under anoxic conditions, a 5 g/L suspension of mackinawite lowered 5 × 10-5 M uranium(VI) to below 30 ppb (1.26 × 10-7 M) U. Between 82 and 88% of the uranium removed from solution by mackinawite was U(IV) and was nearly completely reduced to U(IV) when 0.012 M bicarbonate was added. Near-neighbor coordination consisting of uranium–oxygen and uranium-uranium distances indicates the formation of uraninite in the presence and absence of bicarbonate, suggesting reductive precipitation as the dominant removal mechanism. Following equilibration in air, mackinawite was oxidized to mainly goethite and sulfur and about 76% of U(IV) was reoxidized to U(VI) with coordination of uranium to axial and equatorial oxygen, similar to uranyl. Additionally, uranium-iron distances, typical of coprecipitation of uranium with iron oxides, and uranium-sulfur distances indicating bidentate coordination of U(VI) to sulfate were evident. The affinity of mackinawite and its oxidation products for U(VI) provides impetus for further study of mackinawite as a potential reactive medium for remediation of uranium-contaminated water.

  9. Sodium bicarbonate in-duct injection with sodium sulfate recovery for SO2/NOx control

    International Nuclear Information System (INIS)

    Dry sodium injection with sodium bicarbonate has been used commercially at industrial sites since the mid 1980's. In the past three years, five full scale commercial demonstrations have been completed on electric utility coal fired units. Up to 75% SO2 removal with 0-40% NOx removal has been achieved on units equipped with ESPs. Recent slip stream studies have proven up to 90% SO2 removal and 25% NOx removal when injection is ahead of a baghouse. If dry sodium bicarbonate sorbent injection technology is used prior to a retrofitted baghouse, but after an existing ESP the sodium sulfate by-product/flyash mixture in the baghouse is over 90% Na2SO4. Simple filtration and crystallization will yield a high value 99% + pure Na2SO4 for sale. In this application, no liquid discharge occurs and potentially no solids discharge, since flyash recovered from the filter is either recycled to the boiler with the coal stream or reinjected into the boiler. EPA IAPCS model Version 4 is modified to project costs for this SO2/NOx removal technology when couples with Na2SO4 recovery. In this paper an example is used to show hardware requirements, consumables accountability, by-product recovery rates, capital costs and levelized costs

  10. Gadolinium block of calcium channels: influence of bicarbonate.

    Science.gov (United States)

    Boland, L M; Brown, T A; Dingledine, R

    1991-11-01

    The selectivity of block of voltage-activated barium (Ba2+) currents by lanthanide ions was studied in a rat dorsal root ganglion (DRG) cell line (F11-B9), rat and frog peripheral neurons, and rat cardiac myocytes using the whole-cell patch clamp technique. Gadolinium (Gd3+) produced a dose-dependent and complete inhibition of whole-cell Ba2+ current in all cells studied, including cells expressing identified dihydropyridine-sensitive L-type currents and omega-conotoxin-sensitive N-type currents. Like Gd3+, lutetium (Lu3+) and lanthanum (La3+) blocked all Ba2+ current with little selectivity for different components of the whole-cell current. Gd3+ block of Ba2+ currents was incomplete, however, when sodium bicarbonate (5-22.6 mM) was added to the standard HEPES-buffered external Ba2+ solution. In rat DRG neurons and F11-B9 cells, a fraction of the whole-cell Ba2+ current recorded in the presence of bicarbonate was resistant to block by saturating concentrations of Gd3+ (50-100 microM). The resistant current inactivated more rapidly than the original current giving the appearance that, under these conditions, Gd3+ block is more selective for the slowly inactivating component of the whole-cell current. Bicarbonate modification of Gd3+ block occurred both before and after omega-conotoxin block of N-type currents in rat DRG neurons, suggesting that even in the presence of bicarbonate, Gd3+ block was not selective for N-type currents. PMID:1786527

  11. Inhibitors of ROS production by the ubiquinone-binding site of mitochondrial complex I identified by chemical screening.

    Science.gov (United States)

    Orr, Adam L; Ashok, Deepthi; Sarantos, Melissa R; Shi, Tong; Hughes, Robert E; Brand, Martin D

    2013-12-01

    Mitochondrial production of reactive oxygen species is often considered an unavoidable consequence of aerobic metabolism and currently cannot be manipulated without perturbing oxidative phosphorylation. Antioxidants are widely used to suppress effects of reactive oxygen species after formation, but they can never fully prevent immediate effects at the sites of production. To identify site-selective inhibitors of mitochondrial superoxide/H2O2 production that do not interfere with mitochondrial energy metabolism, we developed a robust small-molecule screen and secondary profiling strategy. We describe the discovery and characterization of a compound (N-cyclohexyl-4-(4-nitrophenoxy)benzenesulfonamide; CN-POBS) that selectively inhibits superoxide/H2O2 production from the ubiquinone-binding site of complex I (site I(Q)) with no effects on superoxide/H2O2 production from other sites or on oxidative phosphorylation. Structure/activity studies identified a core structure that is important for potency and selectivity for site I(Q). By employing CN-POBS in mitochondria respiring on NADH-generating substrates, we show that site I(Q) does not produce significant amounts of superoxide/H2O2 during forward electron transport on glutamate plus malate. Our screening platform promises to facilitate further discovery of direct modulators of mitochondrially derived oxidative damage and advance our ability to understand and manipulate mitochondrial reactive oxygen species production under both normal and pathological conditions. PMID:23994103

  12. Virtual screening for novel Staphylococcus Aureus NorA efflux pump inhibitors from natural products.

    Science.gov (United States)

    Thai, Khac-Minh; Ngo, Trieu-Du; Phan, Thien-Vy; Tran, Thanh-Dao; Nguyen, Ngoc-Vinh; Nguyen, Thien-Hai; Le, Minh-Tri

    2015-01-01

    NorA is a member of the Major Facilitator Superfamily (MFS) drug efflux pumps that have been shown to mediate antibiotic resistance in Staphylococcus aureus (SA). In this study, QSAR analysis, virtual screening and molecular docking were implemented in an effort to discover novel SA NorA efflux pump inhibitors. Originally, a set of 47 structurally diverse compounds compiled from the literature was used to develop linear QSAR models and another set of 15 different compounds were chosen for extra validation. The final model which was estimated by statistical values for the full data set (n = 45, Q(2) = 0.80, RMSE = 0.20) and for the external test set (n = 15, R(2) = 0.60, |res|max = 0.75, |res|min = 0.02) was applied on the collection of 182 flavonoides and the traditional Chinese medicine (TCM) database to screen for novel NorA inhibitors. Finally, 33 lead compounds that met the Lipinski's rules of five/three and had good predicted pIC50 values from in silico screening process were employed to analyze the binding ability by docking studies on NorA homology model in place of its unavailable crystal structures at two active sites, the central channel and the Walker B. PMID:25181985

  13. Bicarbonate-dependent secretion and proteolytic processing of recombinant myocilin.

    Directory of Open Access Journals (Sweden)

    José-Daniel Aroca-Aguilar

    Full Text Available Myocilin is an extracellular glycoprotein of poorly understood function. Mutations of this protein are involved in glaucoma, an optic neuropathy characterized by a progressive and irreversible visual loss and frequently associated with elevated intraocular pressure. We previously showed that recombinant myocilin undergoes an intracellular proteolytic processing by calpain II which cleaves the central region of the protein, releasing one N- and one C-terminal fragment. Myocilin cleavage is reduced by glaucoma mutations and it has been proposed to participate in intraocular pressure modulation. To identify possible factors regulating the proteolytic processing of recombinant myocilin, we used a cellular model in which we analyzed how different culture medium parameters (i.e., culture time, cell density, pH, bicarbonate concentration, etc. affect the presence of the extracellular C-terminal fragment. Extracellular bicarbonate depletion associated with culture medium acidification produced a reversible intracellular accumulation of full-length recombinant myocilin and incremented its intracellular proteolytic processing, raising the extracellular C-terminal fragment percentage. It was also determined that myocilin intracellular accumulation depends on its N-terminal region. These data suggest that aqueous humor bicarbonate variations could also modulate the secretion and cleavage of myocilin present in ocular tissues.

  14. Is bicarbonate stable in and on the calcite surface?

    Science.gov (United States)

    Andersson, M. P.; Rodriguez-Blanco, J. D.; Stipp, S. L. S.

    2016-03-01

    We have used density functional theory with the COSMO-RS implicit solvent model to predict the pKa for the deprotonation of bicarbonate to carbonate, i.e. HCO3- CO32- + H+, when HCO3- is included in, and adsorbed on, a calcite surface. We have used cluster models (80-100 atoms) to represent the flat {10.4} surface, acute steps, obtuse steps, two types of kinks on the acute step and two types of kinks on the obtuse steps. Based on the predicted pKa values, which range from -6.0 to 2.4 depending on the surface site, we conclude that bicarbonate deprotonates to carbonate when it is in calcite even when pH in solution is very low. This is true for all surface sites, even for solutions where 2.4 pH pH units lower than in aqueous solution, 10.35. This means that adsorbed carbonate is stable even when the concentration of dissolved CO32- is several orders of magnitude lower. This has a significant effect on surface charge and thus the behaviour of the calcite surface. Our results help explain the potential determining behaviour of the carbonate species in calcite-water systems, particularly in the pH range where the bicarbonate species dominates in water and where the carbonate species dominates at the surface, i.e. when 7.5 pH high temperature and pressure.

  15. Reactive transport modeling of carbon dioxide sequestration via bicarbonate brine injection in the Rose Run sandstone formation: A comparison with traditional CCS

    Science.gov (United States)

    Lu, P.; Kendall, T.; Seeker, R.; Constantz, B. R.

    2010-12-01

    One by-product of the Calera process to make building materials from CO2 is a bicarbonate solution that contains a variable fraction of the CO2 captured from flue gas. Injection of this fluid into the subsurface has advantages over CO2 injection in terms of technical risks, environmental issues, cost, safety, and public acceptance. With bicarbonate injection, there is no need of a cap-rock, as the solution is non-volatile, and will not be buoyant because it is of comparable density to the host fluids. Although a bicarbonate fluid has less CO2 mass per unit volume than supercritical CO2 (in our example, 34 times less), a large injection zone footprint is not a strong disadvantage because detailed site characterization, in particular of cap-rock integrity, is less critical. Moreover, the amount of CO2 that needs trapping is reduced by an amount equal to the carbon in the mineralized cement by-product. Bicarbonate injection can be carried out in relatively shallow aquifers, which reduces the pumping energy needed for emplacement. In terms of desirable long-term CO2 trapping mechanisms, bicarbonate injection greatly accelerates solubility and mineral trapping into hours and days as compared to decades or more for liquid CO2 injection. Thus, bicarbonate injection is a practical demonstration of fluid mixing at field scale. To assess the potential for geological storage of CO2 in American Electric Power’s (AEP) Mountaineer site, 1D reactive transport models have been constructed to compare bicarbonate with CO2 injection and upscale the mixing problem from batch experiments to the field. For CO2 injection, CO2 forms a completely dried-out zone near the borehole, which may result in halite efflorescence and may be a concern for well-bore injectivity. Simulations predict that after 10,000 years, the CO2 partial pressure remains above 200 bars, and the solution pH remains below 5 within a one kilometer radius of the wellbore. Consequently, the dissolved CO2 is about 1

  16. Utilization of metabolic inhibitors for shifting product formation from xylitol to ethanol in pentose fermentations using Candida tropicalis

    Energy Technology Data Exchange (ETDEWEB)

    Lohmeier-Vogel, E.; Hahn-Haegerdal, B.

    1985-02-01

    Xylose, glucose and xylose/glucose mixtures were fermented with Candida tropicalis ATCC 32113 under aerobic, oxygen limited and anaerobic conditions. Ethanol yields were highest under oxygen limited conditions with xylose and xylose/glucose. Anaerobic conditions were best for glucose fermentations. The effect of four metabolic inhibitors (azide, carbonyl cyanide m-chlorophenyl hydrazone (CCCP), oligomycin A and valinomycin-K/sup +/) were then studied under oxygen limited conditions. Only azide had a significant influence on ethanol production. At 2x10/sup -4/ M concentrations, ethanol yield increased up to two times and xylitol levels were repressed by 90% for xylose and glucose/xylose fermentations. 4.2x10/sup -3/ M azide gave highest ethanol yields in glucose fermentations. At this concentration of azide, however, cell growth was inhibited, which seemed to prevent ethanol production in xylose fermentations. The effect of azide is discussed in terms of 'fine-tuning' the respiratory activity necessary for metabolism.

  17. JAK Inhibitors AG-490 and WHI-P154 Decrease IFN-γ-Induced iNOS Expression and NO Production in Macrophages

    OpenAIRE

    Eeva Moilanen; Hannu Kankaanranta; Riina Nieminen; Outi Kärpänniemi; Riku Korhonen; Outi Sareila

    2006-01-01

    In inflammation, inducible nitric oxide synthase (iNOS) produces nitric oxide (NO), which modulates inflammatory processes. We investigated the effects of Janus kinase (JAK) inhibitors, AG-490 and WHI-P154, on iNOS expression and NO production in J774 murine macrophages stimulated with interferon-γ (IFN-γ). JAK inhibitors AG-490 and WHI-P154 decreased IFN-γ-induced nuclear levels of signal transducer and activator of transcription 1α (STAT1α). JAK inhibitors AG-490 and WHI-P154 decreased also...

  18. Carbonate precipitates and bicarbonate secretion in the intestine of sea bass, Dicentrarchus labrax.

    Science.gov (United States)

    Faggio, Caterina; Torre, Agata; Lando, Gabriele; Sabatino, Giuseppe; Trischitta, Francesca

    2011-05-01

    The aim of this paper was to study the chemical composition of the precipitates found in the intestine of Dicentrarchus labrax and the source of HCO(3)(-) secreted into the intestinal lumen. The chemical analysis was performed by employing the potentiometric double titration method and by means of an electron microscope coupled with a spectrometer and X-ray powder diffraction. The results obtained suggest the presence of very insoluble intestinal precipitates, presumably formed by a mixture of CaCO(3) and MgCO(3), with a higher quantity of the former with respect to the latter. HCO(3)(-) secretion rate was investigated with the aid of the pH stat method in isolated tissues mounted in Ussing chamber, where the transepithelial electrical parameters were also measured. When the serosal surface of the intestinal mucosa was bathed in HCO(3)(-)-Ringer bubbled with 1% CO(2) in O(2) while the serosal surface was bathed in HCO(3)(-) free Ringer solution bubbled with pure O(2), bicarbonate secretion proceeded at an almost stable rate of 0.9 ± 0.05 μeq cm(-2) h(-1) for about 3 h while I(sc) maintained a constant value of 38 ± 1.5 μA cm(-2). The carbonic anhydrase inhibitor ethoxyzolamide elicited a progressive reduction of HCO(3)(-) secretion that was about 75% of the initial value after 80 min. When serosal HCO(3)(-)-CO(2) saline was substituted with Hepes-O(2) saline base secretion progressively declined reaching a value of about 20% of the initial value. It was also strongly inhibited when Na(+) was substituted with the impermeant cation choline and when either DIDS or ouabain were added to the basolateral side. These results suggest that most of the bicarbonate secreted is of extracellular source and is probably transported across the basolateral membrane by both Na(+) independent mechanism and Na(+) dependent transporter, presumably a NaHCO(3) cotransport. PMID:21152925

  19. Effective mitigation of nitrate leaching and nitrous oxide emissions in intensive vegetable production systems using a nitrification inhibitor, dicyandiamide

    Energy Technology Data Exchange (ETDEWEB)

    Cui, Min; Sun, Xuecheng; Hu, Chengxiao; Tan, Qiling; Zhao, Changsheng [Huazhong Agricultural Univ., Wuhan (China). Key Lab. of Subtropical Agricultural Resources and Environment; Di, Hong J. [Lincoln Univ., Christchurch (New Zealand). Center for Soil and Environment Research

    2011-07-15

    Vegetable production is one of the most intensive agricultural systems with high rates of nitrogen (N) fertilizer use and irrigation, conditions conducive for nitrate (NO{sub 3}{sup -}) leaching, and nitrous oxide (N{sub 2}O) emissions. The objective of this study was to determine the effectiveness of a nitrification inhibitor, dicyandiamide (DCD), in decreasing NO{sub 3}{sup -} leaching and N{sub 2}O emissions in vegetable production systems. Twenty-four undisturbed soil monolith lysimeters (610 mm in diameter; 700 mm in depth; surface area, 0.29 m{sup 2}) with two different soils, Huangzongrang (alfisol) and Chaotu (fluvisols), were collected and installed in a field lysimeter facility in Central China under irrigated vegetable production conditions. Urea fertilizer was applied at 650 kg N ha{sup -1}, and DCD was applied at 10 kg ha{sup -1} to the lysimeters planted with three kinds of vegetables (capsicum, Capsicum annuum L.; amaranth, Amaranthus mangostanus L.; radish, Raphanus sativus L.). The results showed that DCD reduced NO3- leaching by 58.5% and 36.2% and N{sub 2}O emissions factor by 83.8% and 72.7% in the two soils. The average NO{sub 3}{sup -}-N concentration in the drainage water was decreased from 4.9 mg NL{sup -1} to 2.3 mg NL{sup -1} and from 4.4 mg NL{sup -1} to 3.3 mg NL{sup -1}, in the Huangzongrang and Chaotu soils, respectively. In addition to the environmental benefits, the use of DCD also increased the yields of capsicum and radish in alfisol soil significantly (P < 0.01); only the amaranth yield in fluvisol soil was declined (P < 0.01), and the other vegetables yields were not affected. Total N concentrations of the three vegetables were increased significantly (P < 0.01) with the application of DCD with urea compared with urea alone. These results showed that the nitrification inhibitor DCD has the potential to significantly reduce NO{sub 3}{sup -} leaching and N{sub 2}O emissions and to make vegetable farming more environmentally

  20. Enzyme inhibition studies by integrated Michaelis-Menten equation considering simultaneous presence of two inhibitors when one of them is a reaction product.

    Science.gov (United States)

    Bezerra, Rui M F; Pinto, Paula A; Fraga, Irene; Dias, Albino A

    2016-03-01

    To determine initial velocities of enzyme catalyzed reactions without theoretical errors it is necessary to consider the use of the integrated Michaelis-Menten equation. When the reaction product is an inhibitor, this approach is particularly important. Nevertheless, kinetic studies usually involved the evaluation of other inhibitors beyond the reaction product. The occurrence of these situations emphasizes the importance of extending the integrated Michaelis-Menten equation, assuming the simultaneous presence of more than one inhibitor because reaction product is always present. This methodology is illustrated with the reaction catalyzed by alkaline phosphatase inhibited by phosphate (reaction product, inhibitor 1) and urea (inhibitor 2). The approach is explained in a step by step manner using an Excel spreadsheet (available as a template in Appendix). Curve fitting by nonlinear regression was performed with the Solver add-in (Microsoft Office Excel). Discrimination of the kinetic models was carried out based on Akaike information criterion. This work presents a methodology that can be used to develop an automated process, to discriminate in real time the inhibition type and kinetic constants as data (product vs. time) are achieved by the spectrophotometer.

  1. Saccharomyces cerevisiae strain improvement using selection, mutation, and adaptation for the resistance to lignocellulose-derived fermentation inhibitor for ethanol production.

    Science.gov (United States)

    Jang, Youri; Lim, Younghoon; Kim, Keun

    2014-05-01

    Twenty-five Saccharomyces cerevisiae strains were screened for the highest sugar tolerance, ethanol-tolerance, ethanol production, and inhibitor resistance, and S. cerevisiae KL5 was selected as the best strain. Inhibitor cocktail (100%) was composed of 75 mM formic acid, 75 mM acetic acid, 30 mM furfural, 30 mM hydroxymethyl furfural (HMF), and 2.7 mM vanillin. The cells of strain KL5 were treated with γ-irradiation, and among the survivals, KL5- G2 with improved inhibitor resistance and the highest ethanol yield in the presence of inhibitor cocktail was selected. The KL5-G2 strain was adapted to inhibitor cocktail by sequential transfer of cultures to a minimal YNB medium containing increasing concentrations of inhibitor cocktail. After 10 times of adaptation, most of the isolated colonies could grow in YNB with 80% inhibitor cocktail, whereas the parental KL5 strain could not grow at all. Among the various adapted strains, the best strain (KL5-G2-A9) producing the highest ethanol yield in the presence of inhibitor cocktail was selected. In a complex YP medium containing 60% inhibitor cocktail and 5% glucose, the theoretical yield and productivity (at 48 h) of KL5- G2-A9 were 81.3% and 0.304 g/l/h, respectively, whereas those of KL5 were 20.8% and 0.072 g/l/h, respectively. KL5-G2-A9 reduced the concentrations of HMF, furfural, and vanillin in the medium in much faster rates than KL5. PMID:24608567

  2. Inhibitors of MyD88-dependent proinflammatory cytokine production identified utilizing a novel RNA interference screening approach.

    Directory of Open Access Journals (Sweden)

    John S Cho

    Full Text Available BACKGROUND: The events required to initiate host defenses against invading pathogens involve complex signaling cascades comprised of numerous adaptor molecules, kinases, and transcriptional elements, ultimately leading to the production of proinflammatory cytokines, such as tumor necrosis factor alpha (TNF-alpha. How these signaling cascades are regulated, and the proteins and regulatory elements participating are still poorly understood. RESULTS: We report here the development a completely random short-hairpin RNA (shRNA library coupled with a novel forward genetic screening strategy to identify inhibitors of Toll-like receptor (TLR dependent proinflammatory responses. We developed a murine macrophage reporter cell line stably transfected with a construct expressing diphtheria toxin-A (DT-A under the control of the TNF-alpha-promoter. Stimulation of the reporter cell line with the TLR ligand lipopolysaccharide (LPS resulted in DT-A induced cell death, which could be prevented by the addition of an shRNA targeting the TLR adaptor molecule MyD88. Utilizing this cell line, we screened a completely random lentiviral short hairpin RNA (shRNA library for sequences that inhibited TLR-mediated TNF-alpha production. Recovery of shRNA sequences from surviving cells led to the identification of unique shRNA sequences that significantly inhibited TLR4-dependent TNF-alpha gene expression. Furthermore, these shRNA sequences specifically blocked TLR2 but not TLR3-dependent TNF-alpha production. CONCLUSIONS: Thus, we describe the generation of novel tools to facilitate large-scale forward genetic screens in mammalian cells and the identification of potent shRNA inhibitors of TLR2 and TLR4- dependent proinflammatory responses.

  3. Production of xylitol by a Coniochaeta ligniaria strain tolerant of inhibitors and defective in growth on xylose.

    Science.gov (United States)

    Nichols, Nancy N; Saha, Badal C

    2016-05-01

    In conversion of biomass to fuels or chemicals, inhibitory compounds arising from physical-chemical pretreatment of the feedstock can interfere with fermentation of the sugars to product. Fungal strain Coniochaeta ligniaria NRRL30616 metabolizes the furan aldehydes furfural and 5-hydroxymethylfurfural, as well as a number of aromatic and aliphatic acids and aldehydes. Use of NRRL30616 to condition biomass sugars by metabolizing the inhibitors improves their fermentability. Wild-type C. ligniaria has the ability to grow on xylose as sole source of carbon and energy, with no accumulation of xylitol. Mutants of C. ligniaria unable to grow on xylose were constructed. Xylose reductase and xylitol dehydrogenase activities were reduced by approximately two thirds in mutant C8100. The mutant retained ability to metabolize inhibitors in biomass hydrolysates. Although C. ligniaria C8100 did not grow on xylose, the strain converted a portion of xylose to xylitol, producing 0.59 g xylitol/g xylose in rich medium and 0.48 g xylitol/g xylose in corn stover dilute acid hydrolysate. 2016 American Institute of Chemical Engineers Biotechnol. Prog., 2016 © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:606-612, 2016. PMID:26950770

  4. Bicarbonate Plays a Critical Role in the Generation of Cytotoxicity during SIN-1 Decomposition in Culture Medium

    Directory of Open Access Journals (Sweden)

    Kyo Shirai

    2012-01-01

    Full Text Available 3-Morpholinosydnonimine (SIN-1 is used as a donor of peroxynitrite (ONOO− in various studies. We demonstrated, however, that, the cell-culture medium remains cytotoxic to PC12 cells even after almost complete SIN-1 decomposition, suggesting that reaction product(s in the medium, rather than ONOO−, exert cytotoxic effects. Here, we clarified that significant cytotoxicity persists after SIN-1 decomposes in bicarbonate, a component of the culture medium, but not in NaOH. Cytotoxic SIN-1-decomposed bicarbonate, which lacks both oxidizing and nitrosating activities, degrades to innocuous state over time. The extent of SIN-1 cytotoxicity, irrespective of its fresh or decomposed state, appears to depend on the total number of initial SIN-1 molecules per cell, rather than its concentration, and involves oxidative/nitrosative stress-related cell damage. These results suggest that, despite its low abundance, the bicarbonate-dependent cytotoxic substance that accumulates in the medium during SIN-1 breakdown is the cytotoxic entity of SIN-1.

  5. Effects of MEK-Specific Inhibitor U0126 on the Conidial Germination, Appressorium Production, and Pathogenicity of Setosphaeria turcica

    Institute of Scientific and Technical Information of China (English)

    FAN Yong-shan; GU Shou-qin; DONG Jin-gao; DONG Bing-fang

    2007-01-01

    Systemic studies on the effects of mitogen-activated protein kinase (MAPK) signal transduction pathway on the growth and development of Setosphaeria turcica is helpful not only in understanding the molecular mechanism of pathogenhost interaction but also in the effective control of the diseases caused by S. turcica. U0126, the specific MEK inhibitor, is used to treat S. turcica before the observation of the conidial germination, appressorium production, and pathogenicity of the pathogen. There is no significant effect of U0126 on the colony morphology and mycelium growth of the pathogen. After treatment with U0126, the growth of mycelium and conidia are normal, but the conidial germination, appressorium production, and pathogenicity of S. turcica on susceptible corn leaves are significantly inhibited. Under the definite concentration scope, an increase in U0126 concentration increases the inhibition degree of conidial germination and appressorium production, but the inhibition degree decreases with elongation of treatment time. The conidial germination, appressorium production, and pathogenicity of S. turcica on susceptible corn leaves are regulated by the MAPK pathway inhibited by U0126.

  6. Natural products inhibitors of the enzyme acetylcholinesterase Produtos naturais inibidores da enzima acetilcolinesterase

    Directory of Open Access Journals (Sweden)

    José M. Barbosa Filho

    2006-06-01

    Full Text Available Alzheimer's disease (AD is a progressive, neurodegenerative pathology that primarily affects the elderly population, and is estimated to account for 50-60% of dementia cases in persons over 65 years of age. The main symptoms associated with AD involve cognitive dysfunction, primarily memory loss. Other features associated with the later stages of AD include language deficits, depression, behavioural problems including agitation, mood disturbances and psychosis. One of the most promising approaches for treating this disease is to enhance the acetylcholine level in the brain using acetylcholinesterase (AChE inhibitors. The present work reviews the literature on plants and plant-derived compounds inhibitors of enzyme acetylcholinesterase. The review refers to 309 plant extracts and 260 compounds isolated from plants, which are classified in appropriate chemical groups and model tested, and cites their activity. For this purpose 175 references were consulted.A Doença de Alzheimer (DA é uma patologia neurodegenerativa, progressiva, que afeta principalmente a população idosa, responsável por 50-60% dos casos de demência em pessoas com mais de 65 anos de idade. Os principais sintomas associado a DA envolve deficiência orgânica cognitiva, principalmente perda de memória. Outras características associadas com os estágios avançados de DA inclui déficit na linguagem, depressão, problemas de comportamento, inclusive agitação, alterações de humor e psicose.Um dos mais promissores caminhos para tratar esta doença é aumentar o nível de acetilcolina no cérebro usando inibidores da acetilcolinesterase (AChE. Este trabalho teve como objetivo revisar a literatura das plantas e substâncias encontradas nas plantas, inibidores da enzima acetilcolinesterase. Foram levantadas 309 plantas e 260 substâncias isoladas de plantas que foram classificados em grupos químicos adequados, os modelo testados, e suas atividades. Foram consultados 175 referências.

  7. Essential motions in a fungal lipase with bound substrate, covalently attached inhibitor and product

    DEFF Research Database (Denmark)

    Peters, Günther H.J.; Bywater, R.P.

    2002-01-01

    protein flexibility suggesting that these processes occur along rough energy surfaces with only a few minima. Detailed energetic analyses along the trajectories indicated that in all cases binding is dominated by van der Waals interactions. The carboxylate form of the product is stabilized by a tight...... are significantly smaller than those observed for the substrate and product molecules, indicating that the energy surface is shallow and that a relatively large number of conformational substates are accessible. On the other hand, substrate binding and product release occur at distinct modes of the...

  8. A RIPK2 inhibitor delays NOD signalling events yet prevents inflammatory cytokine production

    DEFF Research Database (Denmark)

    Nachbur, Ueli; Stafford, Che A; Bankovacki, Aleksandra;

    2015-01-01

    Intracellular nucleotide binding and oligomerization domain (NOD) receptors recognize antigens including bacterial peptidoglycans and initiate immune responses by triggering the production of pro-inflammatory cytokines through activating NF-κB and MAP kinases. Receptor interacting protein kinase ...

  9. Titration-based screening for evaluation of natural product extracts: identification of an aspulvinone family of luciferase inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Cruz, P.G.; Auld, D.S.; Schultz, P.J.; Lovell, S.; Battaile, K.P.; MacArthur, R.; Shen, M.; Tamayo-Castillo, G.; Inglese, J.; Sherman, D.H. (Michigan); (NIH); (Kansas); (Costa Rica); (HWMRI)

    2011-11-28

    The chemical diversity of nature has tremendous potential for the discovery of molecular probes and medicinal agents. However, sensitivity of HTS assays to interfering components of crude extracts derived from plants, and macro- and microorganisms has curtailed their use in lead discovery. Here, we describe a process for leveraging the concentration-response curves obtained from quantitative HTS to improve the initial selection of actives from a library of partially fractionated natural product extracts derived from marine actinomycetes and fungi. By using pharmacological activity, the first-pass CRC paradigm improves the probability that labor-intensive subsequent steps of reculturing, extraction, and bioassay-guided isolation of active component(s) target the most promising strains and growth conditions. We illustrate how this process identified a family of fungal metabolites as potent inhibitors of firefly luciferase, subsequently resolved in molecular detail by X-ray crystallography.

  10. RGS2 is a feedback inhibitor of melatonin production in the pineal gland

    OpenAIRE

    Matsuo, Masahiro; Steven L Coon; Klein, David C.

    2013-01-01

    The 24-h rhythmic production of melatonin by the pineal gland is essential for coordinating circadian physiology. Melatonin production increases at night in response to the release of norepinephrine from sympathetic nerve processes which innervate the pineal gland. This signal is transduced through G-protein-coupled adrenergic receptors. Here, we found that the abundance of regulator of G-protein signaling 2 (RGS2) increases at night, that expression is increased by norepinephrine and that th...

  11. Hypoxia dysregulates the production of adiponectin and plasminogen activator inhibitor-1 independent of reactive oxygen species in adipocytes

    International Nuclear Information System (INIS)

    Low plasma levels of adiponectin (hypoadiponectinemia) and elevated circulating concentrations of plasminogen activator inhibitor (PAI)-1 are causally associated with obesity-related insulin resistance and cardiovascular disease. However, the mechanism that mediates the aberrant production of these two adipokines in obesity remains poorly understood. In this study, we investigated the effects of hypoxia and reactive oxygen species (ROS) on production of adiponectin and PAI-1 in 3T3-L1 adipocytes. Quantitative PCR and immunoassays showed that ambient hypoxia markedly suppressed adiponectin mRNA expression and its protein secretion, and increased PAI-1 production in mature adipocytes. Dimethyloxallyl glycine, a stabilizer of hypoxia-inducible factor 1α (HIF-1α), mimicked the hypoxia-mediated modulations of these two adipokines. Hypoxia caused a modest elevation of ROS in adipocytes. However, ablation of intracellular ROS by antioxidants failed to alleviate hypoxia-induced aberrant production of adiponectin and PAI-1. On the other hand, the antioxidants could reverse hydrogen peroxide (H2O2)-induced dysregulation of adiponectin and PAI-1 production. H2O2 treatment decreased the expression levels of peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer binding protein (C/EBPα), but had no effect on HIF-1α, whereas hypoxia stabilized HIF-1α and decreased expression of C/EBPα, but not PPARγ. Taken together, these data suggest that hypoxia and ROS decrease adiponectin production and augment PAI-1 expression in adipocytes via distinct signaling pathways. These effects may contribute to hypoadiponectinemia and elevated PAI-1 levels in obesity, type 2 diabetes, and cardiovascular diseases

  12. Manganese complexes with bicarbonate and sulfate in natural water

    Science.gov (United States)

    Hem, J.D.

    1963-01-01

    The association constant for the dissolved species MnHCO3+ was experimentally determined to be 63. From this value and a published constant for the species MNSO4 aq., a diagram was prepared showing per cent of dissolved manganese complexed in the presence of 10 to 10,000 p.p.m. bicarbonate and 1.0 to 10,000 p.p.m. sulfate. The rate of oxidation of Mn+2 in aerated water is greatly increased by increasing pH, and is retarded when SO4-2and HCO3- are present.

  13. Reappraisal of bicarbonate secretion by the human oesophagus

    DEFF Research Database (Denmark)

    Mertz-Nielsen, A; Hillingsø, Jens; Bukhave, K;

    1997-01-01

    with either 60 mg/day omeprazole for three days and 80 mg intravenous omeprazole before perfusion or 600 mg/day ranitidine for three days and 50 mg/h intravenously during the perfusion. Saliva and samples of aspirate from the perfused oesophagus and stomach were collected and bicarbonate concentrations were...... and thus contribute to the therapeutic efficacy of the drug in gastro-oesophageal reflux disease. SUBJECTS AND METHODS: In nine healthy volunteers, oesophageal "steady state" perfusion of a 10 cm open segment of distal oesophagus was performed twice in random order. The volunteers were pretreated...

  14. Production of xylitol by a Coniochaeta ligniaria strain tolerant of inhibitors and defective in xylose metabolism

    Science.gov (United States)

    In conversion of biomass to fuels or chemicals, inhibitory compounds arising from physical-chemical pretreatment of the feedstock can interfere with fermentation of the sugars to product. Fungal strain Coniochaeta ligniaria NRRL30616, metabolizes the furan aldehydes furfural and 5-hydroxymethylfurfu...

  15. Effect of Mucin and Bicarbonate Ion on Corrosion Behavior of AZ31 Magnesium Alloy for Airway Stents

    Directory of Open Access Journals (Sweden)

    Yongseok Jang

    2014-08-01

    Full Text Available The biodegradable ability of magnesium alloys is an attractive feature for tracheal stents since they can be absorbed by the body through gradual degradation after healing of the airway structure, which can reduce the risk of inflammation caused by long-term implantation and prevent the repetitive surgery for removal of existing stent. In this study, the effects of bicarbonate ion (HCO3− and mucin in Gamble’s solution on the corrosion behavior of AZ31 magnesium alloy were investigated, using immersion and electrochemical tests to systematically identify the biodegradation kinetics of magnesium alloy under in vitro environment, mimicking the epithelial mucus surfaces in a trachea for development of biodegradable airway stents. Analysis of corrosion products after immersion test was performed using scanning electron microscopy (SEM, energy dispersive X-ray spectroscopy (EDX and X-ray diffraction (XRD. Electrochemical impedance spectroscopy (EIS was used to identify the effects of bicarbonate ions and mucin on the corrosion behavior of AZ31 magnesium alloys with the temporal change of corrosion resistance. The results show that the increase of the bicarbonate ions in Gamble’s solution accelerates the dissolution of AZ31 magnesium alloy, while the addition of mucin retards the corrosion. The experimental data in this work is intended to be used as foundational knowledge to predict the corrosion behavior of AZ31 magnesium alloy in the airway environment while providing degradation information for future in vivo studies.

  16. Flue Gas Desulfurization by Mechanically and Thermally Activated Sodium Bicarbonate

    Directory of Open Access Journals (Sweden)

    Walawska Barbara

    2014-09-01

    Full Text Available This paper presents the results of study on structural parameters (particle size, surface area, pore volume and the sorption ability of mechanically and thermally activated sodium bicarbonate. The sorption ability of the modified sorbent was evaluated by: partial and overall SO2 removal efficiency, conversion rate, normalized stoichiometric ratio (NSR. Sodium bicarbonate was mechanically activated by various grinding techniques, using three types of mills: fluid bed opposed jet mill, fine impact mill and electromagnetic mill, differing in grinding technology. Grounded sorbent was thermally activated, what caused a significant development of surface area. During the studies of SO2 sorption, a model gas with a temperature of 300°C, of composition: sulfur dioxide at a concentration of 6292 mg/mn3, oxygen, carbon dioxide and nitrogen as a carrier gas, was used. The best development of surface area and the highest SO2 removal efficiency was obtained for the sorbent treated by electromagnetic grinding, with simultaneous high conversion rate.

  17. Pancreatic ductal bicarbonate secretion: challenge of the acinar acid load

    Directory of Open Access Journals (Sweden)

    Peter eHegyi

    2011-07-01

    Full Text Available Acinar and ductal cells of the exocrine pancreas form a close functional unit. Although most studies contain data either on acinar or ductal cells, an increasing number of evidence highlights the importance of the pancreatic acinar-ductal functional unit. One of the best examples for this functional unit is the regulation of luminal pH by both cell types. Protons co-released during exocytosis from acini cause significant acidosis, whereas, bicarbonate secreted by ductal cells cause alkalization in the lumen. This suggests that the first and probably one of the most important role of bicarbonate secretion by pancreatic ductal cells is not only to neutralize the acid chyme entering into the duodenum from the stomach, but to neutralize acidic content secreted by acinar cells. To accomplish this role, it is more than likely that ductal cells have physiological sensing mechanisms which would allow them to regulate luminal pH. To date, four different classes of acid-sensing ion channels have been identified in the gastrointestinal tract (transient receptor potential ion channels, two-pore domain potassium channel, ionotropic purinoceptor and acid-sensing ion channel, however, none of these have been studied in pancreatic ductal cells. In this mini-review, we summarize our current knowledge of these channels and urge scientists to characterize ductal acid-sensing mechanisms and also to investigate the challenge of the acinar acid load on ductal cells.

  18. Uranium release from boom clay in bicarbonate media

    International Nuclear Information System (INIS)

    The release of natural uranium from Boom Clay was studied to better understand the mechanisms governing the solid-liquid partitioning of uranium. Batch leaching experiments suggested that the portion of natural uranium released from clay is associated with colloids at a low bicarbonate concentration prevailing in Boom Clay. At increased bicarbonate concentrations, uranium was present predominantly as dissolved species indicating a formation of uranium carbonate complexes. The in situ aqueous uranium concentration, i.e., the concentration in the pore waters collected by piezometers was found to be 2 to 3 orders of magnitudes lower than the one measured by the batch techniques. These results illustrated that the batch techniques may cause a remobilization of uranium containing colloids from clay surfaces into solution when clay is suspended, agitated, and mechanically perturbed. These colloids are attributed to artefacts and are not considered to exist in situ because of the high compaction of Boom Clay. Due to the presence of colloids, a laboratory derived solid-liquid partitioning coefficient is not equivalent to and cannot simply be converted to the distribution coefficient Kd currently used in performance assessment calculations. (orig.)

  19. Regulation and roles of bicarbonate transport in cancer

    Directory of Open Access Journals (Sweden)

    Andrej eGorbatenko

    2014-04-01

    Full Text Available A unifying feature of solid tumors is a markedly altered pH profile compared to normal tissues. This reflects that solid tumors, despite completely different origins, often share several phenotypic properties with implications for intra- and extracellular pH. These include: a metabolic shift in most cancer cells towards more acid-producing pathways, reflecting both oncogenic signaling and the development of hypoxia in poorly perfused regions of the tumors; the poorly perfused and often highly dense tumor microenvironment, reducing the diffusive flux of acid equivalents compared to that in normal tissues; and the markedly altered regulation of the expression and activity of pH-regulatory transport proteins in the cancer cells. While some of these properties of tumors have been well described in recent years, the great majority of the research in this clinically important area has focused on proton transport, in particular via the Na+/H+-exchanger 1 (SLC9A1, NHE1 and various H+ ATPases. We have, however, recently demonstrated that at least under some conditions, including in vitro models of HER2 positive breast cancer, and measurements obtained directly in freshly dissected human mammary tumors, bicarbonate transporters such as the electroneutral Na+,HCO3--cotransporter (SLC4A7, NBCn1, are upregulated and play central roles in pH regulation. In this review, we summarize and discuss the current knowledge regarding the regulation and roles of bicarbonate transport in cancer.

  20. Exploration of natural product ingredients as inhibitors of human HMG-CoA reductase through structure-based virtual screening

    Directory of Open Access Journals (Sweden)

    Lin SH

    2015-06-01

    Full Text Available Shih-Hung Lin,1 Kao-Jean Huang,1,2 Ching-Feng Weng,1 David Shiuan1 1Department of Life Science and Institute of Biotechnology, National Dong Hwa University, Hualien, Taiwan, Republic of China; 2Development Center of Biotechnology, Taipei, Taiwan, Republic of China Abstract: Cholesterol plays an important role in living cells. However, a very high level of cholesterol may lead to atherosclerosis. HMG-CoA (3-hydroxy-3-methylglutaryl coenzyme A reductase is the key enzyme in the cholesterol biosynthesis pathway, and the statin-like drugs are inhibitors of human HMG-CoA reductase (hHMGR. The present study aimed to virtually screen for potential hHMGR inhibitors from natural product to discover hypolipidemic drug candidates with fewer side effects and lesser toxicities. We used the 3D structure 1HWK from the PDB (Protein Data Bank database of hHMGR as the target to screen for the strongly bound compounds from the traditional Chinese medicine database. Many interesting molecules including polyphenolic compounds, polisubstituted heterocyclics, and linear lipophilic alcohols were identified and their ADMET (absorption, disrtibution, metabolism, excretion, toxicity properties were predicted. Finally, four compounds were obtained for the in vitro validation experiments. The results indicated that curcumin and salvianolic acid C can effectively inhibit hHMGR, with IC50 (half maximal inhibitory concentration values of 4.3 µM and 8 µM, respectively. The present study also demonstrated the feasibility of discovering new drug candidates through structure-based virtual screening. Keywords: HMG-CoA reductase, virtual screening, curcumin, salvianolic acid C

  1. Lipid phosphate phosphatases regulate lysophosphatidic acid production and signaling in platelets: studies using chemical inhibitors of lipid phosphate phosphatase activity.

    Science.gov (United States)

    Smyth, Susan S; Sciorra, Vicki A; Sigal, Yury J; Pamuklar, Zehra; Wang, Zuncai; Xu, Yong; Prestwich, Glenn D; Morris, Andrew J

    2003-10-31

    Blood platelets play an essential role in ischemic heart disease and stroke contributing to acute thrombotic events by release of potent inflammatory agents within the vasculature. Lysophosphatidic acid (LPA) is a bioactive lipid mediator produced by platelets and found in the blood and atherosclerotic plaques. LPA receptors on platelets, leukocytes, endothelial cells, and smooth muscle cells regulate growth, differentiation, survival, motility, and contractile activity. Definition of the opposing pathways of synthesis and degradation that control extracellular LPA levels is critical to understanding how LPA bioactivity is regulated. We show that intact platelets and platelet membranes actively dephosphorylate LPA and identify the major enzyme responsible as lipid phosphate phosphatase 1 (LPP1). Localization of LPP1 to the platelet surface is increased by exposure to LPA. A novel receptor-inactive sn-3-substituted difluoromethylenephosphonate analog of phosphatidic acid that is a potent competitive inhibitor of LPP1 activity potentiates platelet aggregation and shape change responses to LPA and amplifies LPA production by agonist-stimulated platelets. Our results identify LPP1 as a pivotal regulator of LPA signaling in the cardiovascular system. These findings are consistent with genetic and cell biological evidence implicating LPPs as negative regulators of lysophospholipid signaling and suggest that the mechanisms involve both attenuation of lysophospholipid actions at cell surface receptors and opposition of lysophospholipid production. PMID:12909631

  2. Administration of PDE4 Inhibitors Suppressed the Pannus-Like Inflammation by Inhibition of Cytokine Production by Macrophages and Synovial Fibroblast Proliferation

    Directory of Open Access Journals (Sweden)

    Katsuya Kobayashi

    2007-01-01

    Full Text Available A marked proliferation of synovial fibroblasts in joints leads to pannus formation in rheumatoid arthritis (RA. Various kinds of cytokines are produced in the pannus. The purpose of this study is to elucidate the effects of phosphodiesterase 4 (PDE4 inhibitors in a new animal model for the evaluation of pannus formation and cytokine production in the pannus. Mice sensitized with methylated bovine serum albumin (mBSA were challenged by subcutaneous implantation of a membrane filter soaked in mBSA solution in the back of the mice. Drugs were orally administered for 10 days. The granuloma formed around the filter was collected on day 11. It was chopped into pieces and cultured in vitro for 24 hr. The cytokines were measured in the supernatants. The type of cytokines produced in the granuloma was quite similar to those produced in pannus in RA. Both PDE4 inhibitors, KF66490 and SB207499, suppressed the production of IL-1β, TNF-α, and IL-12, and the increase in myeloperoxidase activity, a marker enzyme for neutrophils and hydroxyproline content. Compared to leflunomide, PDE4 inhibitors more strongly suppressed IL-12 production and the increase in myeloperoxidase activity. PDE4 inhibitors also inhibited lipopolysaccharide-induced TNF-α and IL-12 production from thioglycolate-induced murine peritoneal macrophages and the proliferation of rat synovial fibroblasts. These results indicate this model makes it easy to evaluate the effect of drugs on various cytokine productions in a granuloma without any purification step and may be a relevant model for evaluating novel antirheumatic drugs on pannus formation in RA. PDE4 inhibitors could have therapeutic effects on pannus formation in RA by inhibition of cytokine production by macrophages and synovial fibroblast proliferation.

  3. Production of the effective sludge inhibitor for the T-1 type fuels

    International Nuclear Information System (INIS)

    Nitrogen-containing polar polymers were used as an additive to petroleum products. A new additive has been obtained by copolymerization of β-diphenylaminoethylmethacrylate with methacrylates of primary higher fatty alcohols in a solution of T-1 fuel under the action of γ-radiation. Copolymerization of the above monomers is carried out without the use of chemical initiators and at radiation source temperature of 30 deg C, which is an essential factor in ensuring the purity of the additive. 0.2 mol (56.2g) β-diphenylaminoethylmethacrylate, 0.8 mol (178.4g) methacrylate of a mixture of synthetic primary higher fatty alcohols (C7 - C12), and 100.5 g T-1 fuel (30% of total monomer weight) are placed in a glass vessel. The reaction mixture is irradiated with γ rays from a 60Co source, and complete copolymerization of the monomers is carried out at a dose of 5 x 106 rad. The copolymer yield is 100% of all the initial monomers. The product obtained, an additive, is a colourless, transparent, viscous mass with a molecular weight of 37050, refractive index etasub(D)20 = 1.4884, and nitrogen content 0.85%. With a content of this additive in T-1 fuel in concentrations up to 0.1 wt.% the amount of the insoluble residue decreases by 90% as compared with the fuel which does not contain the additive. Thus, the resulting effective additive ensures the thermal stability of T-1 fuel

  4. Structure of Trypanosoma cruzi glycosomal glyceraldehyde-3-phosphate dehydrogenase complexed with chalepin, a natural product inhibitor, at 1.95 A resolution.

    Science.gov (United States)

    Pavão, F; Castilho, M S; Pupo, M T; Dias, R L A; Correa, A G; Fernandes, J B; da Silva, M F G F; Mafezoli, J; Vieira, P C; Oliva, G

    2002-06-01

    The structure of the glycosomal glyceraldehyde-3-phosphate dehydrogenase (gGAPDH) from Trypanosoma cruzi complexed with chalepin, a natural product from Pilocarpus spicatus, has been determined by X-ray crystallography to 1.95 A resolution. The structure is in the apo form without cofactors in the subunits of the tetrameric gGAPDH in the asymmetric unit. Unequivocal density corresponding to the inhibitor was clearly identified in one monomer. The final refined model of the complex shows extensive conformational changes when compared with the native structure. The mode of binding of chalepin to gGAPDH and its implications for inhibitor design are discussed. PMID:12044862

  5. Inhibitors removal from bio-oil aqueous fraction for increased ethanol production.

    Science.gov (United States)

    Sukhbaatar, Badamkhand; Li, Qi; Wan, Caixia; Yu, Fei; Hassan, El-Barbary; Steele, Philip

    2014-06-01

    Utilization of 1,6-anhydro-β-d-glucopyranose (levoglucosan) present (11% w/v) in the water fraction of bio-oil for ethanol production will facilitate improvement in comprehensive utilization of total carbon in biomass. One of the major challenges for conversion of anhydrous sugars from the bio-oil water fraction to bio-ethanol is the presence of inhibitory compounds that slow or impede the microbial fermentation process. Removal of inhibitory compounds was first approached by n-butanol extraction. Optimal ratio of n-butanol and bio-oil water fraction was 1.8:1. Removal of dissolved n-butanol was completed by evaporation. Concentration of sugars in the bio-oil water fraction was performed by membrane filtration and freeze drying. Fermentability of the pyrolytic sugars was tested by fermentation of hydrolyzed sugars with Saccharomyces pastorianus lager yeast. The yield of ethanol produced from pyrolytic sugars in the bio-oil water fraction reached a maximum of 98% of the theoretical yield. PMID:24727698

  6. Propolis Is an Efficient Fungicide and Inhibitor of Biofilm Production by Vaginal Candida albicans.

    Science.gov (United States)

    Capoci, Isis Regina Grenier; Bonfim-Mendonça, Patrícia de Souza; Arita, Glaucia Sayuri; Pereira, Raphaela Regina de Araújo; Consolaro, Marcia Edilaine Lopes; Bruschi, Marcos Luciano; Negri, Melyssa; Svidzinski, Terezinha Inez Estivalet

    2015-01-01

    Vulvovaginal candidiasis (VVC) is one of the most common genital infections in women. The therapeutic arsenal remains restricted, and some alternatives to VVC treatment are being studied. The present study evaluated the influence of a propolis extractive solution (PES) on biofilm production by Candida albicans isolated from patients with VVC. Susceptibility testing was used to verify the minimum inhibitory concentration (MIC) of PES, with fluconazole and nystatin as controls. The biofilm formation of 29 vaginal isolates of C. albicans and a reference strain that were exposed to PES was evaluated using crystal violet staining. Colony-forming units were evaluated, proteins and carbohydrates of the matrix biofilm were quantified, and scanning electron microscopy was performed. The MIC of PES ranged from 68.35 to 546.87 μg/mL of total phenol content in gallic acid. A concentration of 546.87 μg/mL was able to cause the death of 75.8% of the isolates. PES inhibited biofilm formation by C. albicans from VVC. Besides antifungal activity, PES appears to present important antibiofilm activity on abiotic surfaces, indicating that it may have an additional beneficial effect in the treatment of VVC. PMID:25815029

  7. Propolis Is an Efficient Fungicide and Inhibitor of Biofilm Production by Vaginal Candida albicans

    Directory of Open Access Journals (Sweden)

    Isis Regina Grenier Capoci

    2015-01-01

    Full Text Available Vulvovaginal candidiasis (VVC is one of the most common genital infections in women. The therapeutic arsenal remains restricted, and some alternatives to VVC treatment are being studied. The present study evaluated the influence of a propolis extractive solution (PES on biofilm production by Candida albicans isolated from patients with VVC. Susceptibility testing was used to verify the minimum inhibitory concentration (MIC of PES, with fluconazole and nystatin as controls. The biofilm formation of 29 vaginal isolates of C. albicans and a reference strain that were exposed to PES was evaluated using crystal violet staining. Colony-forming units were evaluated, proteins and carbohydrates of the matrix biofilm were quantified, and scanning electron microscopy was performed. The MIC of PES ranged from 68.35 to 546.87 μg/mL of total phenol content in gallic acid. A concentration of 546.87 μg/mL was able to cause the death of 75.8% of the isolates. PES inhibited biofilm formation by C. albicans from VVC. Besides antifungal activity, PES appears to present important antibiofilm activity on abiotic surfaces, indicating that it may have an additional beneficial effect in the treatment of VVC.

  8. Identification of Porcine Reproductive and Respiratory Syndrome Virus Inhibitors Through an Oriented Screening on Natural Products

    Institute of Scientific and Technical Information of China (English)

    LI Wen-gui; DAI Fei-yan; CHENG Yong-xian; YIN Ge-fen; BI Jun-long; LI Dian-peng

    2013-01-01

    Porcine reproductive and respiratory syndrome(PRRS) caused by porcine reproductive and respiratory syndrome virus(PRRSV) is one of the most infectious diseases in the swine industry worldwide,causing big economic losses.Vaccines are major weapons against PRRSV,however,current available vaccines have several limitations.Developing chemical drugs as alternatives is required.On the basis of traditional medical knowledge,we purposely selected 15 natural products originated from Chinese herbs with anti-infectious effects.Their antiviral activities were evaluated by PRRSV-induced cytopathic effect(CPE) on MARC-145 cells and reverse transcription polymerase chain reaction(RT-PCR) assay.Compounds ethoxysanguinarine(EOSG) and atractylodinol were found to be the hits which could significantly reduce PRRSV-associated CPE with 50% inhibited concentration(IC50) values of 7.9 and 39.4 μmol/L,respectively.Meanwhile,compounds ethoxysanguinarine and atractylodinol significantly decreased mRNA expression of ORF7 gene in a dose-dependent manner.Study results suggest that compounds ethoxysanguinarine and atractylodinol may be useful anti-PRRSV drugs for swine industry or the hits for further lead optimization.

  9. JAK Inhibitors AG-490 and WHI-P154 Decrease IFN- γ -Induced iNOS Expression and NO Production in Macrophages

    Directory of Open Access Journals (Sweden)

    2006-01-01

    Full Text Available In inflammation, inducible nitric oxide synthase (iNOS produces nitric oxide (NO, which modulates inflammatory processes. We investigated the effects of Janus kinase (JAK inhibitors, AG-490 and WHI-P154, on iNOS expression and NO production in J774 murine macrophages stimulated with interferon- γ (IFN- γ . JAK inhibitors AG-490 and WHI-P154 decreased IFN- γ -induced nuclear levels of signal transducer and activator of transcription 1 α (STAT1 α . JAK inhibitors AG-490 and WHI-P154 decreased also iNOS protein and mRNA expression and NO production in a concentration-dependent manner. Neither of the JAK inhibitors affected the decay of iNOS mRNA when determined by actinomycin D assay. Our results suggest that the inhibition of JAK-STAT1-pathway by AG-490 or WHI-P154 leads to the attenuation of iNOS expression and NO production in IFN- γ -stimulated macrophages.

  10. Epoxidation of Alkenes with Aqueous Hydrogen Peroxide and Quaternary Ammonium Bicarbonate Catalysts

    DEFF Research Database (Denmark)

    Mielby, Jerrik Jørgen; Kegnæs, Søren

    2013-01-01

    A range of solid and liquid catalysts containing bicarbonate anions were synthesised and tested for the epoxidation of alkenes with aqueous hydrogen peroxide. The combination of bicarbonate anions and quaternary ammonium cations opens up for new catalytic systems that can help to overcome challen...

  11. 77 FR 50613 - Didecyl Dimethyl Ammonium Carbonate and Didecyl Dimethyl Ammonium Bicarbonate; Exemption From the...

    Science.gov (United States)

    2012-08-22

    ... AGENCY 40 CFR Part 180 Didecyl Dimethyl Ammonium Carbonate and Didecyl Dimethyl Ammonium Bicarbonate... Didecyl Dimethyl Ammonium Carbonate and Didecyl Dimethyl Ammonium Bicarbonate, jointly referred to as.... Background and Statutory Findings In the Federal Register of December 8, 2011 (76 FR 76674) (FRL-...

  12. EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion on the substantiation of health claims related to carbonate and bicarbonate salts of sodium and potassium and maintenance of normal bone (ID 331, 1402) pursuant to Article 13(1) of Regulation (EC) No 1924/2006

    DEFF Research Database (Denmark)

    Tetens, Inge

    claims in relation to carbonate and bicarbonate salts of sodium and potassium and maintenance of normal bone. The scientific substantiation is based on the information provided by the Member States in the consolidated list of Article 13 health claims and references that EFSA has received from Member....../base balance and bone health” and “bone density/bone health”. The target population is assumed to be the general population. In the context of the proposed wordings, the Panel assumes that the claimed effects refer to the maintenance of normal bone by maintaining acid-base balance. The Panel considers that...... maintenance of normal bone is a beneficial physiological effect. No references were provided from which conclusions could be drawn for the scientific substantiation of the claim. On the basis of the data presented, the Panel concludes that a cause and effect relationship has not been established between the...

  13. Peptic ulcer pathophysiology: acid, bicarbonate, and mucosal function

    DEFF Research Database (Denmark)

    Højgaard, L; Mertz Nielsen, A; Rune, S J

    1996-01-01

    The previously accepted role of gastric acid hypersecretion in peptic ulcer disease has been modified by studies showing no correlation between acid output and clinical outcome of ulcer disease, or between ulcer recurrence rate after vagotomy and preoperative acid secretion. At the same time......, studies have been unable to demonstrate increased acidity in the duodenal bulb in patients with duodenal ulcer, and consequently more emphasis has been given to the mucosal protecting mechanisms. The existence of an active gastric and duodenal mucosal bicarbonate secretion creates a pH gradient from...... cell removal and repair regulated by epidermal growth factor. Sufficient mucosal blood flow, including a normal acid/base balance, is important for subepithelial protection. In today's model of ulcer pathogenesis, gastric acid and H. pylori work in concert as aggressive factors, with the open question...

  14. Active transport and accumulation of bicarbonate by a unicellular cyanobacterium.

    Science.gov (United States)

    Miller, A G; Colman, B

    1980-09-01

    The rates of inorganic carbon accumulation and carbon fixation in light by the unicellular cyanobacterim Coccohloris peniocystis have been determined. Cells incubated in the light in medium containing H14CO3- were rapidly separated from the medium by centrifugation through silicone oil into a strongly basic terminating solution. Samples of these inactivated cells were assayed to determine total 14C accumulation, and acid-treated samples were assayed to determine 14C fixation. The rate of transport of inorganic into illuminated cells was faster than the rate of CO2 production in the medium from HCO3- dehydration. This evidence for HCO3- transport in these cells is in agreement with our previous results based upon measurements of photosynthetic O2 evolution. A substantial pool of inorganic carbon was bulit up within the cells presumably as HCO3- before the onset of the maximum rate of photosynthesis. Large accumulation ratios were observed, greater than 1,000 times the external HCO3- concentration. Accumulation did not occur in the dark and was greatly suppressed by the photosynthesis inhibitors 3-(3,4-dichlorophenyl)-1,1-dimethyl urea and 3-chloro-carbonylcyanide phenylhydrazone. These results indicate that the accumulation of inorganic carbon in these cells involves a light-dependent active transport process. PMID:6773925

  15. Analysis, occurrence, fate and risks of proton pump inhibitors, their metabolites and transformation products in aquatic environment: A review.

    Science.gov (United States)

    Kosma, Christina I; Lambropoulou, Dimitra A; Albanis, Triantafyllos A

    2016-11-01

    Proton pump inhibitors (PPIs) which include omeprazole, esomeprazole, lansoprazole, pantoprazole and rabeprazole, are extensively used for the relief of gastro-intestinal disorders. Despite their high worldwide consumption, PPIs are extensively metabolized in human bodies and therefore are not regularly detected in monitoring studies. Very recently, however, it has been shown that some omeprazole metabolites may enter and are likely to persist in aquatic environment. Hence, to fully assess the environmental exposures and risks associated with PPIs, it is important to better understand and evaluate the fate and behavior not only of the parent compound but also of their metabolites and their transformation products arising from biotic and abiotic processes (hydrolysis, photodegradation, biodegradation etc.) in the environment. In this light, the purpose of this review is to summarize the present state of knowledge on the introduction and behavior of these chemicals in natural and engineering systems and highlight research needs and gaps. It draws attention to their transformation, the increase contamination by their metabolites/TPs in different environmental matrices and their potential adverse effects in the environment. Furthermore, existing research on analytical developments with respect to sample treatment, separation and detection of PPIs and their metabolites/TPs is provided. PMID:27380396

  16. Involvement of CFTR in Uterine Bicarbonate Secretion and the Fertilizing Capacity of Sperm

    Institute of Scientific and Technical Information of China (English)

    WangXiao,Fei; ZhouChen-Xi; ShiQi-Xian; YuanYu-Ying; YuMei-Kuen; LouisChukwuemekaAjonuma

    2005-01-01

    Cystic fibrosis transmembrane conductance regulator (CFFR)is a cAMP-activated chloride channel expressed in a wide variety of epithelial cells,mutations of which are responsible for the hallmark defective chloride secretion observed in cystic fibrosis(CF).Although CFTR has been implicated in bicarbonate secretion,its ability to directly mediate bicarbonate secretion of any physiological significance has not been shown.We demonstrate here that endometriaI epithelial ceils possess a CFTR-mediated bicarbonate transport mechanism.Co-culture of sperm with endometrial ceils treated with antisense oligonucleotide against CFTR,or with bicarbonate secretion-defective CF epithelial cells,resulted in lower sperm capacitation and egg-fertilizing ability.These results are consistent with a critical role of CFTR in controlling uterine bicarbonate secretion and the fertilizing capacity of sperm,providing a link between defective CFTR and lower female fertility in CF.

  17. Unraveling the Reactivity of Minium toward Bicarbonate and the Role of Lead Oxides Therein.

    Science.gov (United States)

    Ayalew, Eyasu; Janssens, Koen; De Wael, Karolien

    2016-02-01

    Understanding the reactivity of (semiconductor) pigments provides vital information on how to improve conservation strategies for works of art to avoid rapid degradation of the pigments. This study focuses on the photoactivity of minium (Pb3O4), a semiconductor pigment that gives rise to strong discoloration phenomena upon exposure to various environmental conditions. For demonstrating its photoactivity, an electrochemical setup with a minium-modified graphite electrode (C|Pb3O4) was used. It is confirmed that minium is a p-type semiconductor that is photoactive during illumination and becomes inactive in the dark. Raman measurements confirm the formation of degradation products. The photoactivity of a semiconductor pigment is partly defined by the presence of lead oxide (PbO) impurities; these introduce new states in the original band gap. It will be experimentally evidenced that the presence of PbO particles in minium leads to an upward shift of the valence band that reduces the band gap. Thus, upon photoexcitation, the electron/hole separation is more easily initialized. The PbO/Pb3O4 composite electrodes demonstrate a higher reductive photocurrent compared to the photocurrent registered at pure PbO or Pb3O4-modified electrodes. Upon exposure to light with energy close to and above the band gap, electrons are excited from the valence band to the conduction band to initialize the reduction of Pb(IV) to Pb(II), resulting in the initial formation of PbO. However, in the presence of bicarbonate ions, a significantly higher photoreduction current is recorded because the PbO reacts further to form hydrocerussite. Therefore, the presence of bicarbonates in the environment stimulates the photodecomposition process of minium and plays an important role in the degradation process.

  18. Isoform of Vascular Endothelial Cell Growth Inhibitor (VEGI72-251) Increases Interleukin-2 Production by Activation of T Lymphocytes

    Institute of Scientific and Technical Information of China (English)

    Jing-Juan YAO; Min ZHANG; Xiao-Hui MIAO; Ping ZHAO; Shi-Ying ZHU; Hui DING; Zhong-Tian QI

    2006-01-01

    The objective of this study is to investigate the characteristics of the recombinant variant of human vascular endothelial cell growth inhibitor, VEGI72-251, and compare its biological activities with that of its prototype VEGI24-174. The recombinant plasmid containing the variant VEGI72-251 gene was constructed and expressed in Escherichia coli. The effects of the expressed VEGI72-251 on cell proliferations were checked in the human umbilical vein endothelial cell line and certain tumor cell lines (ECV304 and B 16). The inhibition of VEGI72-251 on angiogenesis was detected in the chorioallantoic membrane of chick embryos. In comparison with VEGI24-174, the recombinant human VEGI72-251 seems to have no effect on the proliferation of endothelial cells and the angiogenesis of the chorioallantoic membrane in vitro. An enzyme-linked immunosorbent assaybased method was used for the measurement of interleukin-2 (IL-2) production by peripheral blood monocytes (PBMCs) treated with VEGI72-251. PBMCs were pretreated with VEGI72-251 (1.25-12.50 μg/ml) for 24 h in vitro, and the IL-2 concentration in PBMC medium was increased from 354 pg/ml to 1256 pg/ml. It can be concluded that VEGI72-251 is able to increase the level of human IL-2 production by the activation of T lymphocytes. Differing from VEGI24-174 on anti-angiogenesis, VEGI72-251 may serve as an anti-cancer factor through its activation of T lymphocytes.

  19. Biohydrogen Fermentation from Sucrose and Piggery Waste with High Levels of Bicarbonate Alkalinity

    Directory of Open Access Journals (Sweden)

    Jeongdong Choi

    2015-03-01

    Full Text Available This study examined the influence of biohydrogen fermentation under the high bicarbonate alkalinity (BA and pH to optimize these critical parameters. When sucrose was used as a substrate, hydrogen was produced over a wide range of pH values (5–9 under no BA supplementation; however, BA affected hydrogen yield significantly under different initial pHs (5–10. The actual effect of high BA using raw piggery waste (pH 8.7 and BA 8.9 g CaCO3/L showed no biogas production or propionate/acetate accumulation. The maximum hydrogen production rate (0.32 L H2/g volatile suspended solids (VSS-d was observed at pH 8.95 and 3.18 g CaCO3/L. BA greater than 4 g CaCO3/L also triggered lactate-type fermentation, leading to propionate accumulation, butyrate reduction and homoacetogenesis, potentially halting the hydrogen production rate. These results highlight that the substrate with high BA need to amend adequately to maximize hydrogen production.

  20. RESEARCH ON PROTEINASE INHIBITORS OF BEANS PHASEOLUS VULGARIS TO MAKE PLANT PROTECTION PRODUCTS FROM PESTS AND DISEASES

    OpenAIRE

    Pavlovskaya, N.; Gagarina, I.; Dzumabaeva, B.; Dzangalina, E.

    2014-01-01

    An animal body and seed plants have a complex of proteolytic ferments which react in reserve protein breakdown to amino acids in food digestion and seed sprouting. At present a few hundreds of peptidohydrolases of different origin have been described. In regulation of proteolysis inhibitors of proteolytic ferments react. In a living organism they are presented by means of specific protein. Inhibitors have an ability to slow down or stop fermentation. They react in immunity apoptosis, protect ...

  1. Bicarbonate Secretion in the Murine Gallbladder - Lessons for the Treatment of Cystic Fibrosis

    Directory of Open Access Journals (Sweden)

    Cuthbert AW

    2001-07-01

    Full Text Available The epithelium lining the gallbladder of mammalian species has absorptive and secretory functions. An important function is the secretion of a bicarbonate rich fluid that helps neutralise stomach acid and provides an appropriate environment for intestinal enzymes. In cystic fibrosis (CF this secretory function is lost. This study concerns the bicarbonate secreting activity of murine gallbladders in vitro using wild type and CF mice and four main questions are considered as follows: a Does the murine gallbladder secrete bicarbonate electrogenically and is this prevented in CF? b Can the secretory activity in CF gallbladders be restored by gene therapy or pharmacologically? c How is the cystic fibrosis transmembrane conductance regulator (CFTR involved in bicarbonate secretion? d Does the data offer prospects for the treatment of CF?. Work from both the author's laboratory and the literature will be reviewed. Consideration of the currently available data indicates that the wild type murine gallbladder does secrete bicarbonate electrogenically and that this is absent in CF mice. Further it has been demonstrated that bicarbonate secretory activity can be restored by both gene therapy and by the use of drugs. The role of CFTR in bicarbonate secretion remains equivocal. Much evidence suggests that CFTR can act as a channel for HCO(3(- ions as well as Cl(- ions, while others propose a parallel arrangement of CFTR with a Cl(-/HCO(3(- exchanger is necessary. The matter is further complicated by the regulatory role of CFTR on other transporting activities. Opportunities for possible application to man are discussed.

  2. Bicarbonate Impact on U(VI) Bioreduction in a Shallow Alluvial Aquifer

    Energy Technology Data Exchange (ETDEWEB)

    Long, Philip E.; Williams, Kenneth H.; Davis, James A.; Fox, Patricia M.; Wilkins, Michael J.; Yabusaki, Steven B.; Fang, Yilin; Waichler, Scott R.; Berman, Elena S.; Gupta, Manish; Chandler, Darrell P.; Murray, Christopher J.; Peacock, Aaron D.; Giloteaux, L.; Handley, Kim M.; Lovley, Derek R.; Banfield, Jillian F.

    2015-02-01

    Field-scale biostimulation and desorption tracer experiments conducted in a uranium (U) contaminated, shallow alluvial aquifer have provided insight into the coupling of microbiology, biogeochemistry, and hydrogeology that control U mobility in the subsurface. Initial experiments successfully tested the concept that Fe-reducing bacteria such as Geobacter sp. could enzymatically reduce soluble U(VI) to insoluble U(IV) during in situ electron donor amendment (Anderson et al. 2003, Williams et al. 2011). In parallel, in situ desorption tracer tests using bicarbonate amendment demonstrated rate-limited U(VI) desorption (Fox et al. 2012). These results and prior laboratory studies underscored the importance of enzymatic U(VI)-reduction and suggested the ability to combine desorption and bioreduction of U(VI). Here we report the results of a new field experiment in which bicarbonate-promoted uranium desorption and acetate amendment were combined and compared to an acetate amendment-only experiment in the same experimental plot. Results confirm that bicarbonate amendment to alluvial aquifer desorbs U(VI) and increases the abundance of Ca-uranyl-carbonato complexes. At the same time, that the rate of acetate-promoted enzymatic U(VI) reduction was greater in the presence of added bicarbonate in spite of the increased dominance of Ca-uranyl-carbonato aqueous complexes. A model-simulated peak rate of U(VI) reduction was ~3.8 times higher during acetate-bicarbonate treatment than under acetate-only conditions. Lack of consistent differences in microbial community structure between acetate-bicarbonate and acetate-only treatments suggest that a significantly higher rate of U(VI) reduction the bicarbonate-impacted sediment may be due to a higher intrinsic rate of microbial reduction induced by elevated concentrations of the bicarbonate oxyanion. The findings indicate that bicarbonate amendment may be useful in improving the engineered bioremediation of uranium in aquifers.

  3. Bicarbonate impact on U(VI) bioreduction in a shallow alluvial aquifer

    Science.gov (United States)

    Long, Philip E.; Williams, Kenneth H.; Davis, James A.; Fox, Patricia M.; Wilkins, Michael J.; Yabusaki, Steven B.; Fang, Yilin; Waichler, Scott R.; Berman, Elena S. F.; Gupta, Manish; Chandler, Darrell P.; Murray, Chris; Peacock, Aaron D.; Giloteaux, Ludovic; Handley, Kim M.; Lovley, Derek R.; Banfield, Jillian F.

    2015-02-01

    Field-scale biostimulation and desorption tracer experiments conducted in a uranium (U) contaminated, shallow alluvial aquifer have provided insight into the coupling of microbiology, biogeochemistry, and hydrogeology that control U mobility in the subsurface. Initial experiments successfully tested the concept that Fe-reducing bacteria such as Geobacter sp. could enzymatically reduce soluble U(VI) to insoluble U(IV) during in situ electron donor amendment (Anderson et al., 2003; Williams et al., 2011). In parallel, in situ desorption tracer tests using bicarbonate amendment demonstrated rate-limited U(VI) desorption (Fox et al., 2012). These results and prior laboratory studies underscored the importance of enzymatic U(VI)-reduction and suggested the ability to combine desorption and bioreduction of U(VI). Here we report the results of a new field experiment in which bicarbonate-promoted uranium desorption and acetate amendment were combined and compared to an acetate amendment-only experiment in the same experimental plot. Results confirm that bicarbonate amendment to alluvial aquifer sediments desorbs U(VI) and increases the abundance of Ca-uranyl-carbonato complexes. At the same time, the rate of acetate-promoted enzymatic U(VI) reduction was greater in the presence of added bicarbonate in spite of the increased dominance of Ca-uranyl-carbonato aqueous complexes. A model-simulated peak rate of U(VI) reduction was ∼3.8 times higher during acetate-bicarbonate treatment than under acetate-only conditions. Lack of consistent differences in microbial community structure between acetate-bicarbonate and acetate-only treatments suggest that a significantly higher rate of U(VI) reduction in the bicarbonate-impacted sediment may be due to a higher intrinsic rate of microbial reduction induced by elevated concentrations of the bicarbonate oxyanion. The findings indicate that bicarbonate amendment may be useful in improving the engineered bioremediation of uranium in

  4. The effect of bicarbonate/fluoride dentifrices on human plaque pH.

    Science.gov (United States)

    Blake-Haskins, J C; Gaffar, A; Volpe, A R; Bánóczy, J; Gintner, Z; Dombi, C

    1997-01-01

    The acidogenic response in dental plaque after rinsing with sodium bicarbonate/fluoride dentifrice slurries was studied using three intra-oral models. In the first model, resting plaque pH was monitored in mesiobuccal plaque on upper molars and premolars in six healthy subjects after abstinence from normal oral hygiene for three days. These measurements were followed by a three-minute rinse with 10% sucrose and, following a two-minute interval, a three-minute rinse with a test dentifrice slurry. After the test dentifrice rinse, pH was monitored at regular intervals up to 60 minutes. Flow rate, pH and buffer capacity of stimulated saliva were also determined. Changes in resting pH, plaque pH minima, and maximum pH drop were calculated. A clear elevation in the resting pH was observed after bicarbonate/fluoride dentifrice rinses, and a significant increase was obtained in the pH minima. The smallest pH drop also was found after treatment with the bicarbonate/fluoride dentifrice rinse treatment (p antimony pH electrodes was used to study the effects of rinsing with increasing concentrations of sodium bicarbonate and calcium carbonate solutions, and with a fluoride dentifrice containing sodium bicarbonate. The response to these treatments was found to be rapid, dose-dependent, and was the greatest from the sodium bicarbonate. A third model used 24 subjects to assess the effects of sodium bicarbonate/fluoride dentifrice on plaque pH before and after a glucose challenge. The use of the bicarbonate/fluoride dentifrice resulted in significantly less measurable plaque acid than the fluoride dentifrice treatment. Collectively, these results indicate bicarbonate in dentifrice to be an effective buffering agent for stabilizing the pH and neutralizing plaque acids in dental plaque. PMID:9586535

  5. Xylitol production from waste xylose mother liquor containing miscellaneous sugars and inhibitors: one-pot biotransformation by Candida tropicalis and recombinant Bacillus subtilis

    OpenAIRE

    Wang, Hengwei; Li, Lijuan; Zhang, Lebin; AN, JIN; Cheng, Hairong; Deng, Zixin

    2016-01-01

    Background The process of industrial xylitol production is a massive source of organic pollutants, such as waste xylose mother liquor (WXML), a viscous reddish-brown liquid. Currently, WXML is difficult to reuse due to its miscellaneous low-cost sugars, high content of inhibitors and complex composition. WXML, as an organic pollutant of hemicellulosic hydrolysates, accumulates and has become an issue of industrial concern in China. Previous studies have focused only on the catalysis of xylose...

  6. Low risk of inhibitor formation in haemophilia A patients following en masse switch in treatment to a third generation full length plasma and albumin-free recombinant factor VIII product (ADVATE®).

    LENUS (Irish Health Repository)

    Bacon, C L

    2011-05-01

    Previous studies have suggested that development of inhibitors in previously treated patients (PTPs) may be attributable to a switch in factor VIII (FVIII) therapeutic product. Consequently, it is widely recognized that inhibitor development must be assessed in PTPs following the introduction of any new FVIII product. Following a national tender process in 2006, all patients with haemophilia A in Ireland changed their FVIII treatment product en masse to a plasma and albumin-free recombinant full-length FVIII product (ADVATE(®)). In this study, we retrospectively reviewed the case records of Irish PTPs to evaluate risk of inhibitor formation following this treatment switch. One hundred and thirteen patients participated in the study. Most patients (89%) had severe haemophilia. Only one of 96 patients with no inhibitor history developed an inhibitor. Prior to the switch in his recombinant FVIII (rFVIII) treatment of choice, this child had only experienced three exposure days (EDs). Consequently, in total he had only received 6 EDs when his inhibitor was first diagnosed. In keeping with this lack of de novo inhibitor development, we observed no evidence of any recurrent inhibitor formation in any of 16 patients with previously documented inhibitors. Similarly, following a previous en masse switch, we have previously reported that changing from a Chinese hamster ovary cell-produced to a baby hamster kidney cell-produced rFVIII was also associated with a low risk of inhibitor formation in PTPs. Our cumulative findings from these two studies clearly emphasizes that the risk of inhibitor development for PTPs following changes in commercial rFVIII product is low, at least in the Irish population.

  7. Evaluation of chloride/bicarbonate. Exchange in the human colon in vivo.

    OpenAIRE

    Davis, G R; Morawski, S. G.; Santa Ana, C A; Fordtran, J S

    1983-01-01

    During perfusion of a plasma-like solution, colonic absorption rate of chloride was much higher than the secretion rate of bicarbonate (34 vs. 3.5 meq/h, respectively). This might suggest that anion exchange (Cl/HCO3) accounts for only a small fraction of total chloride absorption. However, if the colon absorbs as well as secretes bicarbonate, this reasoning would underestimate the magnitude of the anion exchange. To see if the colon absorbs bicarbonate, we perfused a chloride-free solution (...

  8. Proximal tubular bicarbonate reabsorption and PCO2 in chronic metabolic alkalosis in the rat.

    OpenAIRE

    Maddox, D A; Gennari, F J

    1983-01-01

    Studies were undertaken to define the pattern of proximal tubular bicarbonate reabsorption and its relation to tubular and capillary PCO2 in rats with chronic metabolic alkalosis (CMA). CMA was induced by administering furosemide to rats ingesting a low electrolyte diet supplemented with NaHCO3 and KHCO3. Proximal tubular bicarbonate reabsorption and PCO2 were measured in CMA rats either 4-7 or 11-14 d after furosemide injection, in order to study a wide range of filtered bicarbonate loads. A...

  9. Sodium bicarbonate intake improves high-intensity intermittent exercise performance in trained young men

    DEFF Research Database (Denmark)

    Krustrup, Peter; Ermidis, Georgios; Mohr, Magni

    2015-01-01

    Background Sodium bicarbonate intake has been shown to improve exercise tolerance, but the effects on high-intensity intermittent exercise are less clear. Thus, the aim of the present study was to determine the effect of sodium bicarbonate intake on Yo-Yo intermittent recovery level 2 test perfor......-intensity intermittent exercise performance is improved by prior intake of sodium bicarbonate in trained young men, with concomitant elevations in blood alkalosis and peak blood lactate levels, as well as lowered rating of perceived exertion....

  10. In situ detoxification of dry dilute acid pretreated corn stover by co-culture of xylose-utilizing and inhibitor-tolerant Saccharomyces cerevisiae increases ethanol production.

    Science.gov (United States)

    Zhu, Jia-Qing; Li, Xia; Qin, Lei; Li, Wen-Chao; Li, Hui-Ze; Li, Bing-Zhi; Yuan, Ying-Jin

    2016-10-01

    Co-culture of xylose-utilizing and inhibitor-tolerant Saccharomyces cerevisiae was developed for bioethanol production from undetoxified pretreated biomass in simultaneously saccharification and co-fermentation (SSCF) process. Glucose accumulation during late fermentation phase in SSCF using xylose-utilizing strain can be eliminated by the introduction of inhibitor-tolerant strain. Effect of different ratios of two strains was investigated and xylose-utilizing strain to inhibitor-tolerant strain ratio of 10:1 (w/w) showed the best xylose consumption and the highest ethanol yield. Inoculating of xylose-utilizing strain at the later stage of SSCF (24-48h) exhibited lower ethanol yield than inoculating at early stage (the beginning 0-12h), probably due to the reduced enzymatic efficiency caused by the unconsumed xylose and oligomeric sugars. Co-culture SSCF increased ethanol concentration by 21.2% and 41.0% comparing to SSCF using individual inhibitor-tolerant and xylose-utilizing strain (increased from 48.5 and 41.7g/L to 58.8g/L), respectively, which suggest this co-culture system was very promising. PMID:27387414

  11. Impaired Pancreatic Ductal Bicarbonate Secretion in Cystic Fibrosis

    Directory of Open Access Journals (Sweden)

    Soleimani M

    2001-07-01

    Full Text Available Patients with cystic fibrosis demonstrate a defect in HCO(3(- secretion by their pancreatic duct cells. However, attempts toward understanding or correcting this defect have been hampered by a lack of knowledge regarding the cellular and molecular mechanisms mediating HCO(3(- transport in these cells. Recent functional and molecular studies indicate a major role for a basolateral electrogenically-driven Na(+:HCO(3(- cotransporter (NBC1 in mediating the transport of HCO(3(- into the duct cells. The HCO(3(- exits at the lumen predominantly via two recently discovered apical HCO(3(- transporters. cAMP, which mediates the stimulatory effect of secretin on pancreatic ductal HCO(3(- secretion, potentiates the basolateral Na(+:HCO(3(- cotransporter due to generation of a favorable electrogenic gradient as a result of membrane depolarization by Cl(--secreting cystic fibrosis transmembrane conductance regulator (CFTR. Two apical HCO(3(- transporters drive the secretion of bicarbonate into the pancreatic duct lumen. Molecular and functional studies indicate that CFTR upregulates the expression of these two apical HCO(3(- transporters. In addition, CFTR may also upregulate the expression of certain water channels and facilitate the secretion of fluid into the duct lumen. In brief, current research suggests that the defect in pancreatic HCO(3(- secretion in patients with cystic fibrosis is multifactorial and involves the alteration in the function/expression of transporters at the basolateral and luminal membrane domains of the duct cells.

  12. Suppression on plant-parasitic nematodes using a soil fumigation strategy based on ammonium bicarbonate and its effects on the nematode community

    OpenAIRE

    Lanxi Su; Yunze Ruan; Xiujuan Yang; Kang Wang; Rong Li; Qirong Shen

    2015-01-01

    Banana production is severely hindered by plant-parasitic nematodes in acidic, sandy soil. This study investigated the possibility of applying a novel fumigation agent based on ammonium bicarbonate as a strategy for controlling plant-parasitic nematodes under sealed conditions. Moreover, its effects on the nematode community in pot and field experiments were also measured using morphology and feeding-habit based classification and the PCR-DGGE method. Results showed that a mixture (LAB) of li...

  13. Effect of lignocellulose-derived inhibitors on the growth and D-lactic acid production of Sporolactobacillus inulinus YBS1-5.

    Science.gov (United States)

    Bai, Zhongzhong; Gao, Zhen; He, Bingfang; Wu, Bin

    2015-10-01

    The impact of lignocellulose-derived inhibitors on the cell growth and D-lactic production of Sporolactobacillus inulinus YBS1-5 was investigated. At high concentrations, both furans and phenolics, such as furfural, HMF, syringaldehyde and vanillin, affected cell growth and D-lactic acid production and syringaldehyde exhibited the highest. Further experiments showed that only vanillin caused cellular membrane damage. Based on the Biolog approach, in vivo studies on intact S. inulinus cells indicated that phenolics had a stronger inhibitory effect than furan derivatives on the metabolic activity of the concerned substrates related with the key enzymes of D-lactic acid fermentation. The direct in vitro inhibitory effect of the model compounds on the four key enzymes displayed similar patterns. Syringaldehyde was the strongest inhibitor. In general, comparison with published results for other microorganisms indicated that strain YBS1-5 was a robust microorganism against inhibitors of lignocellulose hydrolysate. Notably, in concentrated corn stover hydrolysate, S. inulinus YBS1-5 produced 70.7 g/L D-lactic acid, which was 87.7 % of the yield from the control experiment. However, the fermentation time was prolonged 36 h. In order to improve fermentation rate, a detoxification technology or more robust mutant to phenolics especially syringaldehyde should be developed. PMID:26216317

  14. The ethanol-induced stimulation of rat duodenal mucosal bicarbonate secretion in vivo is critically dependent on luminal Cl-.

    Directory of Open Access Journals (Sweden)

    Anna Sommansson

    Full Text Available Alcohol may induce metabolic and functional changes in gastrointestinal epithelial cells, contributing to impaired mucosal barrier function. Duodenal mucosal bicarbonate secretion (DBS is a primary epithelial defense against gastric acid and also has an important function in maintaining the homeostasis of the juxtamucosal microenvironment. The aim in this study was to investigate the effects of the luminal perfusion of moderate concentrations of ethanol in vivo on epithelial DBS, fluid secretion and paracellular permeability. Under thiobarbiturate anesthesia, a ∼30-mm segment of the proximal duodenum with an intact blood supply was perfused in situ in rats. The effects on DBS, duodenal transepithelial net fluid flux and the blood-to-lumen clearance of 51Cr-EDTA were investigated. Perfusing the duodenum with isotonic solutions of 10% or 15% ethanol-by-volume for 30 min increased DBS in a concentration-dependent manner, while the net fluid flux did not change. Pre-treatment with the CFTR inhibitor CFTRinh172 (i.p. or i.v. did not change the secretory response to ethanol, while removing Cl- from the luminal perfusate abolished the ethanol-induced increase in DBS. The administration of hexamethonium (i.v. but not capsazepine significantly reduced the basal net fluid flux and the ethanol-induced increase in DBS. Perfusing the duodenum with a combination of 1.0 mM HCl and 15% ethanol induced significantly greater increases in DBS than 15% ethanol or 1.0 mM HCl alone but did not influence fluid flux. Our data demonstrate that ethanol induces increases in DBS through a mechanism that is critically dependent on luminal Cl- and partly dependent on enteric neural pathways involving nicotinic receptors. Ethanol and HCl appears to stimulate DBS via the activation of different bicarbonate transporting mechanisms.

  15. 非PVC软袋包装碳酸氢钠注射液的可行性探讨%The Feasibility of Non-PVC bags Used for Infusion and Sodium Bicarbonate Injection

    Institute of Scientific and Technical Information of China (English)

    蔡春阳; 何玲利

    2012-01-01

    目的 研究非PVC软袋包装碳酸氢钠注射液的可行性.方法 配制碳酸氢钠注射液包装于非PVC软袋中,考察膜的透过性对碳酸氢钠注射液pH值的影响.结果 用隔离膜保护非PVC软袋装碳酸氢钠注射液,可以保持溶液pH值稳定.结论 非PVC软袋可用于碳酸氢钠注射液的包装.%Objective To study the feasibility of non-PVC bags used for infusion and sodium bicarbonate injection. Methods Sodium bicarbonate injection was prepared by the production process filled by non-PVC bags, studying the effect of pH value for sodium bicarbonate injection about leaking capability of layer. Rusults Sodium bicarbonate injection filled by non-PVC bags was protected by isolated films and the stability of the pH value could be restained. Conclusion Sodium bicarbonate injection could be installed suitably by non-PVC bags.

  16. Use of Sodium Bicarbonate in Cardiac Arrest: Current Guidelines and Literature Review.

    Science.gov (United States)

    Velissaris, Dimitrios; Karamouzos, Vassilios; Pierrakos, Charalampos; Koniari, Ioanna; Apostolopoulou, Christina; Karanikolas, Menelaos

    2016-04-01

    The aim of the review was to summarize the literature over the last 25 years regarding bicarbonate administration in out-of-hospital cardiac arrest. A PubMed search was conducted using the terms "bicarbonates" and "cardiac arrest", limited to human studies and reviews published in English (or at least with a meaningful abstract in English) in the last 25 years. Clinical and experimental data raised questions regarding the safety and effectiveness of sodium bicarbonate (SB) administration during cardiac arrest. Earlier advanced cardiac life support (ACLS) guidelines recommended routine bicarbonate administration as part of the ACLS algorithm, but recent guidelines no longer recommend its use. The debate in the literature is ongoing, but at the present time, SB administration is only recommended for cardiac arrest related to hypokalemia or overdose of tricyclic antidepressants. Several studies challenge the assumption that bicarbonate administration is beneficial for treatment of acidosis in cardiac arrest. At the present time, there is a trend against using bicarbonates in cardiac arrest, and this trend is supported by guidelines published by professional societies and organizations. PMID:26985247

  17. Identification of resveratrol oligomers as inhibitors of cystic fibrosis transmembrane conductance regulator by high-throughput screening of natural products from chinese medicinal plants.

    Science.gov (United States)

    Zhang, Yaofang; Yu, Bo; Sui, Yujie; Gao, Xin; Yang, Hong; Ma, Tonghui

    2014-01-01

    Inhibitors of cystic fibrosis transmembrane conductance regulator (CFTR) have been widely used for characterizing CFTR function in epithelial fluid transport and in diseases such as secretory diarrhea, polycystic kidney disease and cystic fibrosis. Few small molecule CFTR inhibitors have been discovered so far from combinatorial compound library. In the present study, we used a high throughput screening (HTS)-based natural product discovery strategy to identify new CFTR inhibitors from Chinese medicinal herbs. By screening 40,000 small molecule fractions from 500 herbal plants, we identified 42 positive fractions from 5 herbs and isolated two compounds that inhibited CFTR conductance from Chinese wild grapevine (Vitis amurensis Rupr). Mass spectrometry (MS) and nuclear magnetic resonance (NMR) studies determined the two active compounds as trans-ε-viniferin (TV) and r-2-viniferin (RV), respectively. Both compounds dose-dependently blocked CFTR-mediated iodide influx with IC50 around 20 μM. Further analysis by excised inside-out patch-clamp indicated strong inhibition of protein kinase A (PKA)-activated CFTR chloride currents by TV and RV. In ex vivo studies, TV and RV inhibited CFTR-mediated short-circuit Cl- currents in isolated rat colonic mucosa in a dose-dependent manner. In a closed-loop mouse model, intraluminal applications of TV (2.5 μg) and RV (4.5 μg) significantly reduced cholera toxin-induced intestinal fluid secretion. The present study identified two resveratrol oligomers as new CFTR inhibitors and validates our high-throughput screening method for discovery of bioactive compounds from natural products with complex chemical ingredients such as herbal plants.

  18. Identification of resveratrol oligomers as inhibitors of cystic fibrosis transmembrane conductance regulator by high-throughput screening of natural products from chinese medicinal plants.

    Directory of Open Access Journals (Sweden)

    Yaofang Zhang

    Full Text Available Inhibitors of cystic fibrosis transmembrane conductance regulator (CFTR have been widely used for characterizing CFTR function in epithelial fluid transport and in diseases such as secretory diarrhea, polycystic kidney disease and cystic fibrosis. Few small molecule CFTR inhibitors have been discovered so far from combinatorial compound library. In the present study, we used a high throughput screening (HTS-based natural product discovery strategy to identify new CFTR inhibitors from Chinese medicinal herbs. By screening 40,000 small molecule fractions from 500 herbal plants, we identified 42 positive fractions from 5 herbs and isolated two compounds that inhibited CFTR conductance from Chinese wild grapevine (Vitis amurensis Rupr. Mass spectrometry (MS and nuclear magnetic resonance (NMR studies determined the two active compounds as trans-ε-viniferin (TV and r-2-viniferin (RV, respectively. Both compounds dose-dependently blocked CFTR-mediated iodide influx with IC50 around 20 μM. Further analysis by excised inside-out patch-clamp indicated strong inhibition of protein kinase A (PKA-activated CFTR chloride currents by TV and RV. In ex vivo studies, TV and RV inhibited CFTR-mediated short-circuit Cl- currents in isolated rat colonic mucosa in a dose-dependent manner. In a closed-loop mouse model, intraluminal applications of TV (2.5 μg and RV (4.5 μg significantly reduced cholera toxin-induced intestinal fluid secretion. The present study identified two resveratrol oligomers as new CFTR inhibitors and validates our high-throughput screening method for discovery of bioactive compounds from natural products with complex chemical ingredients such as herbal plants.

  19. Identification of resveratrol oligomers as inhibitors of cystic fibrosis transmembrane conductance regulator by high-throughput screening of natural products from chinese medicinal plants.

    Science.gov (United States)

    Zhang, Yaofang; Yu, Bo; Sui, Yujie; Gao, Xin; Yang, Hong; Ma, Tonghui

    2014-01-01

    Inhibitors of cystic fibrosis transmembrane conductance regulator (CFTR) have been widely used for characterizing CFTR function in epithelial fluid transport and in diseases such as secretory diarrhea, polycystic kidney disease and cystic fibrosis. Few small molecule CFTR inhibitors have been discovered so far from combinatorial compound library. In the present study, we used a high throughput screening (HTS)-based natural product discovery strategy to identify new CFTR inhibitors from Chinese medicinal herbs. By screening 40,000 small molecule fractions from 500 herbal plants, we identified 42 positive fractions from 5 herbs and isolated two compounds that inhibited CFTR conductance from Chinese wild grapevine (Vitis amurensis Rupr). Mass spectrometry (MS) and nuclear magnetic resonance (NMR) studies determined the two active compounds as trans-ε-viniferin (TV) and r-2-viniferin (RV), respectively. Both compounds dose-dependently blocked CFTR-mediated iodide influx with IC50 around 20 μM. Further analysis by excised inside-out patch-clamp indicated strong inhibition of protein kinase A (PKA)-activated CFTR chloride currents by TV and RV. In ex vivo studies, TV and RV inhibited CFTR-mediated short-circuit Cl- currents in isolated rat colonic mucosa in a dose-dependent manner. In a closed-loop mouse model, intraluminal applications of TV (2.5 μg) and RV (4.5 μg) significantly reduced cholera toxin-induced intestinal fluid secretion. The present study identified two resveratrol oligomers as new CFTR inhibitors and validates our high-throughput screening method for discovery of bioactive compounds from natural products with complex chemical ingredients such as herbal plants. PMID:24714160

  20. Febuxostat, an inhibitor of xanthine oxidase, suppresses lipopolysaccharide-induced MCP-1 production via MAPK phosphatase-1-mediated inactivation of JNK.

    Directory of Open Access Journals (Sweden)

    Johji Nomura

    Full Text Available Excess reactive oxygen species (ROS formation can trigger various pathological conditions such as inflammation, in which xanthine oxidase (XO is one major enzymatic source of ROS. Although XO has been reported to play essential roles in inflammatory conditions, the molecular mechanisms underlying the involvement of XO in inflammatory pathways remain unclear. Febuxostat, a selective and potent inhibitor of XO, effectively inhibits not only the generation of uric acid but also the formation of ROS. In this study, therefore, we examined the effects of febuxostat on lipopolysaccharide (LPS-mediated inflammatory responses. Here we show that febuxostat suppresses LPS-induced MCP-1 production and mRNA expression via activating MAPK phosphatase-1 (MKP-1 which, in turn, leads to dephosphorylation and inactivation of JNK in macrophages. Moreover, these effects of febuxostat are mediated by inhibiting XO-mediated intracellular ROS production. Taken together, our data suggest that XO mediates LPS-induced phosphorylation of JNK through ROS production and MKP-1 inactivation, leading to MCP-1 production in macrophages. These studies may bring new insights into the novel role of XO in regulating inflammatory process through MAPK phosphatase, and demonstrate the potential use of XO inhibitor in modulating the inflammatory processes.

  1. An experimental study on the inhibitory effect of high concentration bicarbonate on the reduction of U(VI) in groundwater by functionalized indigenous microbial communities

    International Nuclear Information System (INIS)

    The anaerobic microcosms amended with 30 mM bicarbonate and without bicarbonate were established, respectively, and the reduction of U(VI) in the microcosms by functionalized indigenous microbial communities was investigated. Results of the chemical extraction and XANES analysis showed that the proportions of U(IV) in the microcosms amended with bicarbonate were 10 % lower than without bicarbonate at day 46. The amount of Cellulomonadaceae, Desulfovibrionaceae, Peptococcaceae and Veillonellaceae amended with bicarbonate was lower than without bicarbonate, so the reduction of U(VI) was less. The experimental results show that the high concentration bicarbonate has a significantly inhibitory effect on the reduction of U(VI). (author)

  2. Cathepsin L Plays a Major Role in Cholecystokinin Production in Mouse Brain Cortex and in Pituitary AtT-20 Cells: Protease Gene Knockout and Inhibitor Studies

    Science.gov (United States)

    Beinfeld, Margery C.; Funkelstein, Lydiane; Foulon, Thierry; Cadel, Sandrine; Kitagawa, Kouki; Toneff, Thomas; Reinheckel, Thomas; Peters, Christoph; Hook, Vivian

    2009-01-01

    Cholecystokinin (CCK) is a peptide neurotransmitter whose production requires proteolytic processing of the proCCK precursor to generate active CCK8 neuropeptide in brain. This study demonstrates the significant role of the cysteine protease cathepsin L for CCK8 production. In cathepsin L knockout (KO) mice, CCK8 levels were substantially reduced in brain cortex by an average of 75%. To evaluate the role of cathepsin L in producing CCK in the regulated secretory pathway of neuroendocrine cells, pituitary AtT-20 cells that stably produce CCK were treated with the specific cathepsin L inhibitor, CLIK-148. CLIK-148 inhibitor treatment resulted in decreased amounts of CCK secreted from the regulated secretory pathway of AtT-20 cells. CLIK-148 also reduced cellular levels of CCK9 (Arg-CCK8), consistent with CCK9 as an intermediate product of cathepsin L, shown by the decreased ratio of CCK9/CCK8. The decreased CCK0/CCK8 ratio also suggests a shift in the production to CCK8 over CCK9 during inhibition of cathepsin L. During reduction of the PC1/3 processing enzyme by siRNA, the ratio of CCK9/CCK8 was increased, suggesting a shift to the cathepsin L pathway for production of CCK9. The changes in ratios of CCK9 compared to CCK8 are consistent with dual roles of the cathepsin L protease pathway that includes aminopeptidase B to remove NH2-terminal Arg or Lys, and the PC1/3 protease pathway. These results suggest that cathepsin L functions as a major protease responsible for CCK8 production in mouse brain cortex, and participates with PC1/3 for CCK8 production in pituitary cells. PMID:19589362

  3. 发酵抑制物对葡萄糖发酵产乙醇的影响%Effects of fermentation inhibitors on ethanol production of glucose fermentation

    Institute of Scientific and Technical Information of China (English)

    李志强; 费本华; 江泽慧

    2015-01-01

    在纤维素乙醇研究中,木质纤维原料在酸性预处理过程中会产生甲酸、乙酸、乙酰丙酸、糠醛和5-羟甲基糠醛等发酵抑制物,这些发酵抑制物会影响葡萄糖发酵生产乙醇的收率。本文考察了发酵液中各种发酵抑制物含量对高温超级酿酒酵母发酵乙醇收率的影响。研究结果表明,多种发酵抑制物的协同作用对乙醇发酵的影响要高于单一种类发酵抑制物对乙醇发酵的影响。发酵液中发酵抑制物总量一般控制在3.0g/L以内时,对葡萄糖发酵生产乙醇的抑制作用不明显。%In pretreatments of lignocellulosic materials for bioethanol production,certain amount of sugars was degraded as fermentation inhibitors,and the degradation was much more severe in the acidic pretreatment.Theses fermentations inhibitors including formic acid, acetic acid, levulinic acid,furfural,and 5-hydroxymethylfurfural (HMF)which affect the conversion yield of ethanol from glucose fermentation.This paper examined the effect of the five fermentation inhibitors concentration on the ethanol yield of Saccharomyces cerevisiae glucose fermentation. The results show that, synergistic effect of various fermentation inhibitors on ethanol fermentation was higher than single fermentation inhibitor on ethanol fermentation.The total fermentation inhibitors in fermentation solutions generally controlled within 3.0g/L,which inhibitory effect on glucose fermentation for ethanol is not obvious.

  4. EFFECT OF INHIBITORS ON ENZYMATIC HYDROLYSIS AND SIMULTANEOUS SACCHARIFICATION FERMENTATION FOR LACTIC ACID PRODUCTION FROM STEAM EXPLOSION PRETREATED LESPEDEZA STALKS

    OpenAIRE

    Yue Feng; Xiang Qi,; Hong-lei Jian,; Run-cang Sun; Jian-xin Jiang

    2012-01-01

    The effects on both cellulose conversion rate and lactic acid yield were studied by adding inhibitors, including formic acid, acetic acid, furfural, and vanillin into the hydrolysate of steam-pretreated Lespedeza stalks. The results suggest that formic acid has a significant influence on the enzyme activity and poisoned bacterial cells, resulting in the reduction of cellulose conversion rate and lactic acid yield by 21% and 16.4%, respectively. Acetic acid showed a strong inhibition on simult...

  5. L655,240, acting as a competitive BACE1 inhibitor,efficiently decreases β-amyloid peptide production in HEK293-APPswe cells

    Institute of Scientific and Technical Information of China (English)

    Qin LU; Wu-yan CHEN; Zhi-yuan ZHU; Jing CHEN; Ye-chun XU; Morakot KAEWPET; Vatcharin RUKACHAISIRIKUL; Li-li CHEN; Xu SHEN

    2012-01-01

    Aim: To identify a small molecule L655,240 as a novel β-secretase (BACE1) inhibitor and to investigate its effects on β-amyloid (Aβ)generation in vitro.Methods: Fluorescence resonance energy transfer (FRET) was used to characterize the inhibitory effect of L655,240 on BACE1.Surface plasmon resonance (SPR) technology-based assay was performed to study the binding affinity of L655,240 for BACE1.The selectivity of L655,240 toward BACE1 over other aspartic proteases was determined with enzymatic assay.The effects of L655,240 on Aβ40,Aβ42,and sAPPβ production were studied in HEK293 cells stably expressing APP695 Swedish mutantK595N/M596L (HEK293-APPswe cells).The activities of BACE1,ν-secretase and α-secretase were assayed,and both the mRNA and protein levels of APP and BACE1 were evaluated using real-time PCR (RT-PCR) and Western blot analysis.Results: L655,240 was determined to be a competitive,selective BACE1 inhibitor (IC50=4.47±1.37 μmol/L),which bound to BACE1 directly (KD=17.9±0.72 μmol/L).L655,240 effectively reduced Aβ40,Aβ42,and sAPPβ production by inhibiting BACE1 without affecting the activities of y-secretase and α-secretase in HEK293-APPswe cells.L655,240 has no effect on APP and BACE1 mRNA or protein levels in HEK293-APPswe cells.Conclusion: The small molecule L655,240 is a novel BACE1 inhibitor that can effectively decreases Aβ production in vitro,thereby highlighting its therapeutic potential for the treatment of Alzheimer's disease.

  6. Avocado by-products as inhibitors of color deterioration and lipid and protein oxidation in raw porcine patties subjected to chilled storage.

    Science.gov (United States)

    Rodríguez-Carpena, J G; Morcuende, D; Estévez, M

    2011-10-01

    Processing of avocados generates an important amount of by-products such as peels and seeds that are rich in bioactive substances with proven radical suppressing activities. The objective of this study was to evaluate the effectiveness of peel and seed extracts from two avocado varieties-'Hass' and 'Fuerte'-as inhibitors of lipid and protein oxidation and color deterioration of raw porcine patties during chilled storage (4 °C/15 days). Avocado extracts significantly (pHass' extracts. Patties treated with avocado extracts had significantly lower amounts of TBA-RS than control ones throughout the storage. 'Hass' avocado extracts significantly inhibited the formation of protein carbonyls in chilled patties at day 15. The present results highlight the potential usage of extracts from avocado by-products as ingredients for the production of muscle foods with enhanced quality traits.

  7. Ability of sat-1 to transport sulfate, bicarbonate, or oxalate under physiological conditions.

    Science.gov (United States)

    Krick, Wolfgang; Schnedler, Nina; Burckhardt, Gerhard; Burckhardt, Birgitta C

    2009-07-01

    Tubular reabsorption of sulfate is achieved by the sodium-dependent sulfate transporter, NaSi-1, located at the apical membrane, and the sulfate-anion exchanger, sat-1, located at the basolateral membrane. To delineate the physiological role of rat sat-1, [(35)S]sulfate and [(14)C]oxalate uptake into sat-1-expressing oocytes was determined under various experimental conditions. Influx of [(35)S]sulfate was inhibited by bicarbonate, thiosulfate, sulfite, and oxalate, but not by sulfamate and sulfide, in a competitive manner with K(i) values of 2.7 +/- 1.3 mM, 101.7 +/- 9.7 microM, 53.8 +/- 10.9 microM, and 63.5 +/- 38.7 microM, respectively. Vice versa, [(14)C]oxalate uptake was inhibited by sulfate with a K(i) of 85.9 +/- 9.5 microM. The competitive type of inhibition indicates that these compounds are most likely substrates of sat-1. Physiological plasma bicarbonate concentrations (25 mM) reduced sulfate and oxalate uptake by more than 75%. Simultaneous application of sulfate, bicarbonate, and oxalate abolished sulfate as well as oxalate uptake. These data and electrophysiological studies using a two-electrode voltage-clamp device provide evidence that sat-1 preferentially works as an electroneutral sulfate-bicarbonate or oxalate-bicarbonate exchanger. In kidney proximal tubule cells, sat-1 likely completes sulfate reabsorption from the ultrafiltrate across the basolateral membrane in exchange for bicarbonate. In hepatocytes, oxalate extrusion is most probably mediated either by an exchange for sulfate or bicarbonate. PMID:19369292

  8. Diapocynin, a dimer of the NADPH oxidase inhibitor apocynin, reduces ROS production and prevents force loss in eccentrically contracting dystrophic muscle.

    Directory of Open Access Journals (Sweden)

    Hesham M Ismail

    Full Text Available Elevation of intracellular Ca2+, excessive ROS production and increased phospholipase A2 activity contribute to the pathology in dystrophin-deficient muscle. Moreover, Ca2+, ROS and phospholipase A2, in particular iPLA2, are thought to potentiate each other in positive feedback loops. NADPH oxidases (NOX have been considered as a major source of ROS in muscle and have been reported to be overexpressed in muscles of mdx mice. We report here on our investigations regarding the effect of diapocynin, a dimer of the commonly used NOX inhibitor apocynin, on the activity of iPLA2, Ca2+ handling and ROS generation in dystrophic myotubes. We also examined the effects of diapocynin on force production and recovery ability of isolated EDL muscles exposed to eccentric contractions in vitro, a damaging procedure to which dystrophic muscle is extremely sensitive. In dystrophic myotubes, diapocynin inhibited ROS production, abolished iPLA2 activity and reduced Ca2+ influx through stretch-activated and store-operated channels, two major pathways responsible for excessive Ca2+ entry in dystrophic muscle. Diapocynin also prevented force loss induced by eccentric contractions of mdx muscle close to the value of wild-type muscle and reduced membrane damage as seen by Procion orange dye uptake. These findings support the central role played by NOX-ROS in the pathogenic cascade leading to muscular dystrophy and suggest diapocynin as an effective NOX inhibitor that might be helpful for future therapeutic approaches.

  9. Cerebroventricular calcitonin gene-related peptide inhibits rat duodenal bicarbonate secretion by release of norepinephrine and vasopressin.

    OpenAIRE

    Lenz, H. J.; Brown, M R

    1990-01-01

    Proximal duodenal bicarbonate secretion is an important factor in humans and animals protecting the mucosa against acid-peptic damage. This study examined the mechanisms responsible for the central nervous system regulation of duodenal bicarbonate secretion by calcitonin gene-related peptide (CGRP) in unrestrained rats. Cerebroventricular administration of rat CGRP significantly inhibited basal duodenal bicarbonate secretion as well as the stimulatory effects of vasoactive intestinal peptide,...

  10. Conservation of functional domain structure in bicarbonate-regulated “soluble” adenylyl cyclases in bacteria and eukaryotes

    OpenAIRE

    Kobayashi, Mime; Buck, Jochen; Levin, Lonny R.

    2004-01-01

    Soluble adenylyl cyclase (sAC) is an evolutionarily conserved bicarbonate sensor. In mammals, it is responsible for bicarbonate-induced, cAMP-dependent processes in sperm required for fertilization and postulated to be involved in other bicarbonate- and carbon dioxide-dependent functions throughout the body. Among eukaryotes, sAC-like cyclases have been detected in mammals and in the fungi Dictyostelium; these enzymes display extensive similarity extending through two cyclase catalytic domain...

  11. Evidence for Bicarbonate Secretion by Ameloblasts in a Novel Cellular Model.

    Science.gov (United States)

    Bori, E; Guo, J; Rácz, R; Burghardt, B; Földes, A; Kerémi, B; Harada, H; Steward, M C; Den Besten, P; Bronckers, A L J J; Varga, G

    2016-05-01

    Formation and growth of hydroxyapatite crystals during amelogenesis generate a large number of protons that must be neutralized, presumably by HCO3 (-)ions transported from ameloblasts into the developing enamel matrix. Ameloblasts express a number of transporters and channels known to be involved in HCO3 (-)transport in other epithelia. However, to date, there is no functional evidence for HCO3 (-)transport in these cells. To address questions related to HCO3 (-)export from ameloblasts, we have developed a polarized 2-dimensional culture system for HAT-7 cells, a rat cell line of ameloblast origin. HAT-7 cells were seeded onto Transwell permeable filters. Transepithelial resistance was measured as a function of time, and the expression of transporters and tight junction proteins was investigated by conventional and quantitative reverse transcription polymerase chain reaction. Intracellular pH regulation and HCO3 (-)transport were assessed by microfluorometry. HAT-7 cells formed epithelial layers with measureable transepithelial resistance on Transwell permeable supports and expressed claudin-1, claudin-4, and claudin-8-key proteins for tight junction formation. Transport proteins previously described in maturation ameloblasts were also present in HAT-7 cells. Microfluorometry showed that the HAT-7 cells were polarized with a high apical membrane CO2permeability and vigorous basolateral HCO3 (-)uptake, which was sensitive to Na(+)withdrawal, to the carbonic anhydrase inhibitor acetazolamide and to H2DIDS inhibition. Measurements of transepithelial HCO3 (-)transport showed a marked increase in response to Ca(2+)- and cAMP-mobilizing stimuli. Collectively, 2-dimensional HAT-7 cell cultures on permeable supports 1) form tight junctions, 2) express typical tight junction proteins and electrolyte transporters, 3) are functionally polarized, and 4) can accumulate HCO3 (-)ions from the basolateral side and secrete them at the apical membrane. These studies provide

  12. [Sodium bicarbonate infusion for intoxication with tricyclic antidepressives: recommended inspite of lack of scientific evidence].

    Science.gov (United States)

    Vrijlandt, P J; Bosch, T M; Zijlstra, J G; Tulleken, J E; Ligtenberg, J J; van der Werf, T S

    2001-09-01

    Sodium bicarbonate infusion is widely recommended in textbooks for patients who present with self-poisoning from tricyclic antidepressives. Cardiac conduction disorders could also be treated or prevented by means of such an infusion. The scientific basis for these recommendations was investigated by using Medline to search for publications about clinical studies that supported the use of sodium carbonate; 111 articles were scrutinized. Observational studies and case reports mention a rapid improvement in hypotension and cardiac arrhythmias following the administration of sodium bicarbonate. Results from animal experiments are contentious; it is not clear whether alkalinisation or the administration of extra sodium causes the effect. Randomized studies in patients have not been carried out. As the toxicity of sodium bicarbonate is low, and its potential benefit appears to be high, we recommend its use, despite the lack of scientific evidence. No recommendations concerning dosing, concentration and the length of the therapy can be provided on the basis of the literature. PMID:11561485

  13. Application Research on Mould Inhibitors Production of Beauveria bassiana%白僵菌生产中防霉剂的应用研究

    Institute of Scientific and Technical Information of China (English)

    缪东; 舒燕; 邬里洋; 周映华; 王升平; 高书锋; 周小玲; 曾发娇

    2016-01-01

    In order to solve the problem of Beauveria bassiana vulnerable to mould contamination in solid culture, the corn borer Beauveria bassiana ABUV-3 and the pine caterpillars Beauveria bassiana DBUV-7 as for the tested strains, a series of studies of 40%Kejunling and other ifve kinds of mould inhibitors were conducted. The results showed that the ifve kinds of mould inhibitors on spores and bacteria of Mucor, Trichoderma, Rhizopus, green mould and Aspergillus lfavus all have inhibitory effect, in which the inhibitory effects, the 70% of soluble Junjuesha and Lvmeiba powder was the best; although the direct action of the 5 mould inhibitors will bring inhibited effect on the spore germination ofBeauveria bassiana, there was no inhibitory effect on spore production and germination by adding a certain amount of mould inhibitor when producing spore in solid culture. Therefore, it is suggested that in the process of production ofBeauveria bassiana, in solid culture medium added with 500 times liquid of 70% Junjuesha and Lvmeiba powder (equivalent dose for 2 mg / mL) to inhibit mould contamination.%为了解决白僵菌固体培养时易遭受霉菌污染问题,以玉米螟白僵菌ABUV–3和松毛虫白僵菌DBUV–7为供试菌株,对40%克菌灵等5种防霉剂进行了系列研究。结果表明:5种防霉剂对毛霉菌、木霉菌、根霉菌、绿霉菌和黄曲霉菌的孢子和菌体均有抑制作用,其中以70%菌绝杀可溶性和绿霉霸粉剂的抑制效果最好;虽然5种防霉剂直接作用时会对白僵菌的孢子萌发产生抑制作用,但在固体培养生产孢子时添加一定量的防霉剂,对孢子产量及其萌发并没有抑制作用。因此,建议在白僵菌生产过程中,在固体培养基中添加70%菌决杀和绿霉霸粉剂500倍液(折合剂量为2 mg/mL),用以抑制霉菌的污染。

  14. [Bicarbonate instead of lactate buffered substitution solution for continuous hemofiltration in intensive care].

    Science.gov (United States)

    Olbricht, C J; Huxmann-Nägeli, D; Bischoff, H

    1990-04-01

    The substitution fluids applied in continuous haemofiltration contain 40 mmol/l of lactate. This is unphysiological, since administration of large amounts of lactate lowers the phosphorylation potential and increases catabolism. With bicarbonate-buffered fluid three problems may arise: 1. Precipitation of calcium carbonate and magnesium carbonate; 2. pH is usually 8.4; 3. evaporation of CO2 increases pH. To solve these problems we applied a two-component system consisting of a glass bottle with 160 ml sodium bicarbonate 8.4% and a bag with 4.5 l of acidic solution. Prior to use, the bicarbonate was infused into the bag. The values of Ca++, Mg++, bicarbonate, and pH in this final substitution solution were constant during a 24 hr period after mixing. Precipitation of Ca++ and Mg++ carbonate was prevented by 3 mmol/l of lactic acid in the solution. The pH was 7.37. Evaporation of CO2 was prevented by bags made of special plastic sheeting. The solution was then applied in 7 intensive-care patients suffering from acute renal failure treated by continuous arteriovenous haemofiltration. No side effects of the solution were observed during six days of treatment. The values of Ca++, bicarbonate, pH, and pCO2 remained constant under clinical routine conditions. Hence, bicarbonate-buffered substitution solution is recommended for continuous haemofiltration. Continuous haemofiltration is now also available for patients with impaired liver function and increased lactate levels. PMID:2360710

  15. Electroencephalogram investigations of the disequilibrium syndrome during bicarbonate and acetate dialysis.

    Science.gov (United States)

    Hampl, H; Klopp, H W; Michels, N; Mahiout, A; Schilling, H; Wolfgruber, M; Schiller, R; Hanefeld, F; Kessel, M

    1983-01-01

    Continuous long-time electroencephalographic (EEG) monitoring was performed during acetate and bicarbonate dialysis in 20 patients. Persisting normal basic activity of the EEG without neurological symptoms was found only during the course of bicarbonate dialysis. However, in acetate dialysis, during the decrease of arterial CO2 tension (PaCO2), we registered EEG disturbances with moderate to severe slowing, dysrhythmic activity and high voltage discharges. The decrease in PaCO2 and the deterioration in EEG activity in the patients during acetate dialysis was concomitant with severe neurological alterations, e.g. the typical symptoms of so-called 'disequilibrium' causing a cessation of dialysis in three patients.

  16. Decreased cerebral blood flow after administration of sodium bicarbonate in the distressed newborn infant

    DEFF Research Database (Denmark)

    Lou, H C; Lassen, N A; Fris-Hansen, B

    1978-01-01

    In the course of our studies on cerebral blood flow in newborn infants, we have observed a striking depressing effect of sodium bicarbonate infusion on cerebral blood flow which in some cases may severely aggravate cerebral ischemia. We measured cerebral blood flow before and after the treatment...... with 1 to 8 meqs of sodium bicarbonate in seven distressed newborn infants. The 133 Xe clearance technique was used. The results showed in six of the seven cases a decrease in cerebral blood flow, which in most cases was reduced to 14 to 22 ml/100 g/min, which is about half the value prior to the...

  17. Highly efficient hydrogen storage system based on ammonium bicarbonate/formate redox equilibrium over palladium nanocatalysts.

    Science.gov (United States)

    Su, Ji; Yang, Lisha; Lu, Mi; Lin, Hongfei

    2015-03-01

    A highly efficient, reversible hydrogen storage-evolution process has been developed based on the ammonium bicarbonate/formate redox equilibrium over the same carbon-supported palladium nanocatalyst. This heterogeneously catalyzed hydrogen storage system is comparable to the counterpart homogeneous systems and has shown fast reaction kinetics of both the hydrogenation of ammonium bicarbonate and the dehydrogenation of ammonium formate under mild operating conditions. By adjusting temperature and pressure, the extent of hydrogen storage and evolution can be well controlled in the same catalytic system. Moreover, the hydrogen storage system based on aqueous-phase ammonium formate is advantageous owing to its high volumetric energy density.

  18. The activation/depassivation of nickel–chromium–molybdenum alloys in bicarbonate solution: Part I

    International Nuclear Information System (INIS)

    Electrochemical and surface analytical techniques (X-ray photoelectron and Auger spectroscopies) were used to characterize the influence of potential on the properties of the oxide film formed on the Hybrid BC-1 (a Ni–Cr–Mo) alloy in chloride solutions containing bicarbonate. In the passive region the film possesses the expected bilayer structure with a Cr(III)-dominated barrier layer containing mixed oxidation states of Mo and an outer dominantly-hydroxide layer. At more positive potentials the Cr/Mo content of the film decreases when bicarbonate is present and the alloy becomes covered by a thick (>100 nm), and only partially protective, Ni(OH)2 layer

  19. EFFECT OF INHIBITORS ON ENZYMATIC HYDROLYSIS AND SIMULTANEOUS SACCHARIFICATION FERMENTATION FOR LACTIC ACID PRODUCTION FROM STEAM EXPLOSION PRETREATED LESPEDEZA STALKS

    Directory of Open Access Journals (Sweden)

    Yue Feng,

    2012-06-01

    Full Text Available The effects on both cellulose conversion rate and lactic acid yield were studied by adding inhibitors, including formic acid, acetic acid, furfural, and vanillin into the hydrolysate of steam-pretreated Lespedeza stalks. The results suggest that formic acid has a significant influence on the enzyme activity and poisoned bacterial cells, resulting in the reduction of cellulose conversion rate and lactic acid yield by 21% and 16.4%, respectively. Acetic acid showed a strong inhibition on simultaneous saccharification fermentation (SSF process, but little effect on enzymatic hydrolysis. Hydrolysis and SSF were less affected by furfural and vanillin compared with weak acids. The lactic acid yield of Lespedeza stalks rinsed with water increased from 64.0% to 89.4%, and the time to reach the maximum concentration was shortened from 96 hours to 48 hours when compared with the unwashed materials.

  20. Treatment with a Small Molecule Mutant IDH1 Inhibitor Suppresses Tumorigenic Activity and Decreases Production of the Oncometabolite 2-Hydroxyglutarate in Human Chondrosarcoma Cells.

    Directory of Open Access Journals (Sweden)

    Luyuan Li

    Full Text Available Chondrosarcomas are malignant bone tumors that produce cartilaginous matrix. Mutations in isocitrate dehydrogenase enzymes (IDH1/2 were recently described in several cancers including chondrosarcomas. The IDH1 inhibitor AGI-5198 abrogates the ability of mutant IDH1 to produce the oncometabolite D-2 hydroxyglutarate (D-2HG in gliomas. We sought to determine if treatment with AGI-5198 would similarly inhibit tumorigenic activity and D-2HG production in IDH1-mutant human chondrosarcoma cells. Two human chondrosarcoma cell lines, JJ012 and HT1080 with endogenous IDH1 mutations and a human chondrocyte cell line C28 with wild type IDH1 were employed in our study. Mutation analysis of IDH was performed by PCR-based DNA sequencing, and D-2HG was detected using tandem mass spectrometry. We confirmed that JJ012 and HT1080 harbor IDH1 R132G and R132C mutation, respectively, while C28 has no mutation. D-2HG was detectable in cell pellets and media of JJ012 and HT1080 cells, as well as plasma and urine from an IDH-mutant chondrosarcoma patient, which decreased after tumor resection. AGI-5198 treatment decreased D-2HG levels in JJ012 and HT1080 cells in a dose-dependent manner, and dramatically inhibited colony formation and migration, interrupted cell cycling, and induced apoptosis. In conclusion, our study demonstrates anti-tumor activity of a mutant IDH1 inhibitor in human chondrosarcoma cell lines, and suggests that D-2HG is a potential biomarker for IDH mutations in chondrosarcoma cells. Thus, clinical trials of mutant IDH inhibitors are warranted for patients with IDH-mutant chondrosarcomas.

  1. Cross-talk between human mast cells and bronchial epithelial cells in plasminogen activator inhibitor-1 production via transforming growth factor-β1.

    Science.gov (United States)

    Cho, Seong H; Lee, Sun H; Kato, Atsushi; Takabayashi, Tetsuji; Kulka, Marianna; Shin, Soon C; Schleimer, Robert P

    2015-01-01

    Previous reports suggest that plasminogen activator inhibitor-1 (PAI-1) promotes airway remodeling and that human and mouse mast cells (MCs) are an important source of PAI-1. In the present study we investigated MC-epithelial cell (EC) interactions in the production of PAI-1. We stimulated the human MC line LAD2 with IgE-receptor cross-linking and collected the supernatants. We incubated the human bronchial EC line BEAS-2B with the LAD2 supernatants and measured the level of PAI-1. When the supernatants from IgE-stimulated LAD2 were added to BEAS-2B, there was a significant enhancement of PAI-1 production by BEAS-2B. When we treated the MC supernatants with a transforming growth factor (TGF)-β1 neutralizing antibody, the MC-derived induction of PAI-1 from BEAS-2B was completely abrogated. Although TGF-β1 mRNA was constitutively expressed in resting LAD2, it was not highly induced by IgE-mediated stimulation. Nonetheless, active TGF-β1 protein was significantly increased in LAD2 after IgE-mediated stimulation. Active TGF-β1 produced by primary cultured human MCs was significantly reduced in the presence of a chymase inhibitor, suggesting a role of MC chymase as an activator of latent TGF-β1. This study indicates that stimulation of human MCs by IgE receptor cross-linking triggers activation of TGF-β1, at least in part via chymase, which in turn induces the production of PAI-1 by bronchial ECs. Our data suggest that human MCs may play an important role in airway remodeling in asthma as a direct source of PAI-1 and by activating bronchial ECs to produce further PAI-1 via a TGF-β1-mediated activation pathway. PMID:24987792

  2. BIOKID: Randomized controlled trial comparing bicarbonate and lactate buffer in biocompatible peritoneal dialysis solutions in children [ISRCTN81137991

    Directory of Open Access Journals (Sweden)

    Misselwitz Joachim

    2004-10-01

    Full Text Available Abstract Background Peritoneal dialysis (PD is the preferred dialysis modality in children. Its major drawback is the limited technique survival due to infections and progressive ultrafiltration failure. Conventional PD solutions exert marked acute and chronic toxicity to local tissues. Prolonged exposure is associated with severe histopathological alterations including vasculopathy, neoangiogenesis, submesothelial fibrosis and a gradual loss of the mesothelial cell layer. Recently, more biocompatible PD solutions containing reduced amounts of toxic glucose degradation products (GDPs and buffered at neutral pH have been introduced into clinical practice. These solutions contain lactate, bicarbonate or a combination of both as buffer substance. Increasing evidence from clinical trials in adults and children suggests that the new PD fluids may allow for better long-term preservation of peritoneal morphology and function. However, the relative importance of the buffer in neutral-pH, low-GDP fluids is still unclear. In vitro, lactate is cytotoxic and vasoactive at the concentrations used in PD fluids. The BIOKID trial is designed to clarify the clinical significance of the buffer choice in biocompatible PD fluids. Methods/design The objective of the study is to test the hypothesis that bicarbonate based PD solutions may allow for a better preservation of peritoneal transport characteristics in children than solutions containing lactate buffer. Secondary objectives are to assess any impact of the buffer system on acid-base status, peritoneal tissue integrity and the incidence and severity of peritonitis. After a run-in period of 2 months during which a targeted cohort of 60 patients is treated with a conventional, lactate buffered, acidic, GDP containing PD fluid, patients will be stratified according to residual renal function and type of phosphate binding medication and randomized to receive either the lactate-containing Balance solution or the

  3. Simultaneous blood-tissue exchange of oxygen, carbon dioxide, bicarbonate, and hydrogen ion.

    Science.gov (United States)

    Dash, Ranjan K; Bassingthwaighte, James B

    2006-07-01

    A detailed nonlinear four-region (red blood cell, plasma, interstitial fluid, and parenchymal cell) axially distributed convection-diffusion-permeation-reaction-binding computational model is developed to study the simultaneous transport and exchange of oxygen (O2) and carbon dioxide (CO2) in the blood-tissue exchange system of the heart. Since the pH variation in blood and tissue influences the transport and exchange of O2 and CO2 (Bohr and Haldane effects), and since most CO2 is transported as HCO3(-) (bicarbonate) via the CO2 hydration (buffering) reaction, the transport and exchange of HCO3(-) and H+ are also simulated along with that of O2 and CO2. Furthermore, the model accounts for the competitive nonlinear binding of O2 and CO2 with the hemoglobin inside the red blood cells (nonlinear O2-CO2 interactions, Bohr and Haldane effects), and myoglobin-facilitated transport of O2 inside the parenchymal cells. The consumption of O2 through cytochrome-c oxidase reaction inside the parenchymal cells is based on Michaelis-Menten kinetics. The corresponding production of CO2 is determined by respiratory quotient (RQ), depending on the relative consumption of carbohydrate, protein, and fat. The model gives a physiologically realistic description of O2 transport and metabolism in the microcirculation of the heart. Furthermore, because model solutions for tracer transients and steady states can be computed highly efficiently, this model may be the preferred vehicle for routine data analysis where repetitive solutions and parameter optimization are required, as is the case in PET imaging for estimating myocardial O2 consumption. PMID:16775761

  4. Ergogenic effects of caffeine and sodium bicarbonate supplementation on intermittent exercise performance preceded by intense arm cranking exercise

    DEFF Research Database (Denmark)

    Marriott, Matthaus; Krustrup, Peter; Mohr, Magni

    2015-01-01

    intermittent exercise performance and metabolic markers under exercise-induced acidification, intense arm-cranking exercise was performed prior to intense intermittent running after intake of placebo, caffeine and sodium bicarbonate. METHODS: Male team-sports athletes (n = 12) ingested sodium bicarbonate (Na...

  5. Regulation of mitogen-stimulated human T-cell proliferation, interleukin-2 production, and interleukin-2 receptor expression by protein kinase C inhibitor, H-7

    Energy Technology Data Exchange (ETDEWEB)

    Atluru, D.; Polam, S.; Atluru, S. (Kansas State Univ., Manhattan (United States)); Woloschak, G.E. (Argonne National Lab., IL (United States))

    1990-01-01

    Recently published reports suggest that the activation of protein kinase C (PKC) plays an important role in the activation pathway of many cell types. In this study, the authors examined the role of PKC in human T-cell proliferation, IL-2 production, and IL-2R expression, when cultured with the mitogen PHA, the PKC inhibitor H-7, and H-7 control HA1004. H-7 inhibited the PHA-simulated ({sup 3}H)thymidine uptake, IL-2production, and IL-2R expression in a dose-related manner. Further, they found H-7 inhibited T-cell proliferation, IL-2 production, and IL-2mRNA from PHA plus PMA-stimulated cultures. They also found that H-7 inhibited the early-stage activation of PHA-stimulated cells. The presence of exogenous purified human IL-2 or rIL-4 partly reversed the immunosuppression caused by H-7. In contrast, HA1004 had no effect on cell proliferation, IL-2 production, or IL-2R expression. The results demonstrate that PKC activation is one major pathway through which T-cells become activated.

  6. CO2 absorption in carbonate/bicarbonate solutions : The Danckwerts-criterion revisited

    NARCIS (Netherlands)

    Cents, A. H. G.; Brilman, D. W. F.; Versteeg, G. F.

    2005-01-01

    In industrial applications CO2 is frequently removed from gas streams at elevated pressures by absorption and subsequent chemical reaction in carbonate/bicarbonate solutions (e.g. Benfield process). The criterion that determines whether or not this reaction can be regarded as pseudo-first order is g

  7. Control of blue mold of apple by combining controlled atmosphere, antagonist mixtures and sodium bicarbonate

    Science.gov (United States)

    'Golden Delicious' apples were wound-inoculated with Penicillium expansum, treated with various combinations of sodium bicarbonate and two antagonists, and stored in air or controlled atmosphere (1.4% O2, 3% CO2). The fruit were stored for 2 or 4 months at 1°C. The antagonists survived and their p...

  8. 21 CFR 862.1160 - Bicarbonate/carbon dioxide test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Bicarbonate/carbon dioxide test system. 862.1160 Section 862.1160 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry...

  9. Association of erosive esophagitis with Helicobacter pylori eradication: a role of salivary bicarbonate and glycoprotein secretion.

    Science.gov (United States)

    Namiot, D B; Namiot, Z; Markowski, A R; Leszczyńska, K; Bucki, R; Kemona, A; Gołebiewska, M

    2009-01-01

    In some populations, Helicobacter pylori eradication is associated with development of erosive esophagitis. The aim of this study was to evaluate the contribution of salivary bicarbonate and glycoprotein secretion to the pathogenesis of erosive esophagitis developing after H. pylori eradication. Gastroscopy and saliva collection were performed at recruitment and 12 months after completion of eradication therapy. Eighty-eight patients with duodenal ulcer were recruited to the study. Erosive esophagitis was found in 13 patients (grade A, 8 patients; grade B, 4 patients; grade C, 1 patient). Among the 74 subjects who completed the study, erosive esophagitis was detected in 21 patients (grade A, 15 patients; grade B, 6 patients); they all were successfully eradicated. Bicarbonate and glycoprotein secretion was not found to differ significantly between the subjects with and without erosive esophagitis both before and 1 year after H. pylori eradication. However, it was lower in H. pylori-infected (baseline) than in H. pylori-noninfected erosive esophagitis subjects (1 year after successful eradication) (bicarbonate 2.34 [1.29-3.40)]vs. 3.64 [2.70-4.58]micromol/min and glycoprotein 0.23 [0.15-0.31]vs. 0.35 [0.28-0.43] mg/min, P= 0.04 and P= 0.04, respectively). We conclude that changes in salivary bicarbonate and glycoprotein secretion related to H. pylori eradication do not promote the development of erosive esophagitis in duodenal ulcer patients. PMID:19222537

  10. Internal Active Thermal Control System (IATCS) Sodium Bicarbonate/Carbonate Buffer in an Open Aqueous Carbon Dioxide System and Corollary Electrochemical/Chemical Reactions Relative to System pH Changes

    Science.gov (United States)

    Stegman, Thomas W.; Wilson, Mark E.; Glasscock, Brad; Holt, Mike

    2014-01-01

    The International Space Station (ISS) Internal Active Thermal Control System (IATCS) experienced a number of chemical changes driven by system absorption of CO2 which altered the coolant’s pH. The natural effects of the decrease in pH from approximately 9.2 to less than 8.4 had immediate consequences on system corrosion rates and corrosion product interactions with specified coolant constituents. The alkalinity of the system was increased through the development and implementation of a carbonate/bicarbonate buffer that would increase coolant pH to 9.0 – 10.0 and maintain pH above 9.0 in the presence of ISS cabin concentrations of CO2 up to twenty times higher than ground concentrations. This paper defines how a carbonate/bicarbonate buffer works in an open carbon dioxide system and summarizes the analyses performed on the buffer for safe and effective application in the on-orbit system. The importance of the relationship between the cabin environment and the IATCS is demonstrated as the dominant factor in understanding the system chemistry and pH trends before and after addition of the carbonate/bicarbonate buffer. The paper also documents the corollary electrochemical and chemical reactions the system has experienced and the rationale for remediation of these effects with the addition of the carbonate/bicarbonate buffer.

  11. Sodium bicarbonate supplementation prevents skilled tennis performance decline after a simulated match

    Directory of Open Access Journals (Sweden)

    Huang Ming-Hsiang

    2010-10-01

    Full Text Available Abstract The supplementation of sodium bicarbonate (NaHCO3 could increase performance or delay fatigue in intermittent high-intensity exercise. Prolonged tennis matches result in fatigue, which impairs skilled performance. The aim of this study was to investigate the effect of NaHCO3 supplementation on skilled tennis performance after a simulated match. Nine male college tennis players were recruited for this randomized cross-over, placebo-controlled, double-blind study. The participants consumed NaHCO3 (0.3 g. kg-1 or NaCl (0.209 g. kg-1 before the trial. An additional supplementation of 0.1 g. kg-1 NaHCO3 or 0.07 g. kg-1 NaCl was ingested after the third game in the simulated match. The Loughborough Tennis Skill Test was performed before and after the simulated match. Post-match [HCO3-] and base excess were significantly higher in the bicarbonate trial than those in the placebo trial. Blood [lactate] was significantly increased in the placebo (pre: 1.22 ± 0.54; post: 2.17 ± 1.46 mM and bicarbonate (pre: 1.23 ± 0.41; post: 3.21 ± 1.89 mM trials. The match-induced change in blood [lactate] was significantly higher in the bicarbonate trial. Blood pH remained unchanged in the placebo trial (pre: 7.37 ± 0.32; post: 7.37 ± 0.14 but was significantly increased in the bicarbonate trial (pre: 7.37 ± 0.26; post: 7.45 ± 0.63, indicating a more alkaline environment. The service and forehand ground stroke consistency scores were declined significantly after the simulated match in the placebo trial, while they were maintained in the bicarbonate trial. The match-induced declines in the consistency scores were significantly larger in the placebo trial than those in the bicarbonate trial. This study suggested that NaHCO3 supplementation could prevent the decline in skilled tennis performance after a simulated match.

  12. EFFECTS OF SODIUM BICARBONATE INGESTION ON SWIM PERFORMANCE IN YOUTH ATHLETES

    Directory of Open Access Journals (Sweden)

    Jozef Langfort

    2009-03-01

    Full Text Available The purpose of this study was to evaluate the effect of oral administration of sodium bicarbonate (300 mg·kg-1 b.w. on swim performance in competitive, (training experience of 6.6 ± 0.6 years youth, (15.1 ± 0.6 years male swimmers. The subjects completed a test trial, in a double blind fashion, on separate days, consisting of 4 x 50m front crawl swims with a 1st minute passive rest interval twice, on two occasions: after ingestion of bicarbonate or placebo, 72 hours apart, at the same time of the day. Blood samples were drawn from the finger tip three times during each trial; upon arrival to the laboratory, 60 min after ingestion of placebo or the sodium bicarbonate solution and after the 4 x 50m test, during the 1st min of recovery. Plasma lactate concentration, blood pH, standard bicarbonate and base excess were evaluated. The total time of the 4 x 50 m test trial improved from 1.54.28 to 1.52.85s, while statistically significant changes in swimming speed were recorded only during the first 50m sprint (1.92 vs. 1.97 m·s-1, p < 0.05. Resting blood concentration of HCO-3 increased following the ingestion of sodium bicarbonate from 25.13 to 28.49 mM (p < 0.05. Sodium bicarbonate intake had a statistically significant effect on resting blood pH (7.33 vs. 7.41, p < .05 as well as on post exercise plasma lactate concentration (11.27 vs. 13.06 mM, p < 0.05. Collectively, these data demonstrate that the ingestion of sodium bicarbonate in youth athletes is an effective buffer during high intensity interval swimming and suggest that such a procedure can be used in youth athletes to increase training intensity as well as swimming performance in competition at distances from 50 to 200 m

  13. Effects of fibril- or fixed-collagen on matrix metalloproteinase-1and tissue inhibitor of matrix metalloproteinase-1 production in the human hepatocyte cell line HLE

    Institute of Scientific and Technical Information of China (English)

    Makoto Nakamuta; Kazuhiro Kotoh; Munechika Enjoji; Hajime Nawata

    2005-01-01

    AIM: Matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) are central to the spontaneous resolution of liver fibrosis. The mechanisms involved have been investigated in hepatic steilate cells (ISC), but not in hepatocytes. We investigated the effects of fibril- and fixed-collagen on MMP-1 and TIMP-1 production in hepatocytes, using the HLE cell line.METHODS: Fibril type T and Ⅳ collagen were prepared by HCl digestion of type T and Ⅳ collagen, respectively.For fixed-collagen, culture dishes were coated with fibril type Ⅰ or Ⅳ collagen and fixed by ultraviolet. Type Ⅰcollagenase activity was measured using fluorescein isothiocyanate-labeled type Ⅰ collagen. MMP-1 and TIMP-1 in HLE cells were measured by a one-step sandwich enzyme immunoassay.RESULTS: Both fibril type Ⅰand Ⅳ collagen significantly increased type Ⅰ coilagenase activity about two-fold compared with no fibril collagen. The effects of the fibril collagen were not affected by the coating condition. There was no significant difference in the effects on collagenase activity between cells cultured in medium containing fibril type Ⅰ collagen and those cultured in the presence of type Ⅳ collagen. Both types of fibril collagen significantly increased MMP-1 production, and showed more than 10-fold higher levels of MMP-1 than the control. The enhanced MMP-1 production by fibril collagens was unaffected by the coating condition. By contrast, TIMP-1 production was not changed by the addition of fibril type Ⅰ or Ⅳ collagen,and neither was it affected by the coating conditions.Coating with type Ⅰ collagen significantly suppressed MMP-1production by almost one-tenth compared with no coating.By contrast, lIMP-1 production was not affected by either the absence of a collagen coat or by increasing the concentration of the coating collagen.CONCLUSION: These results indicated that, in HLE cells,fibril- and fixed-collagen have opposite effects on MMP-1

  14. "One-shot" analysis of PDE-5 inhibitors and analogues in counterfeit herbal natural products using an LC-DAD-QTOF system.

    Science.gov (United States)

    Bortolini, Claudio; Pivato, Antonio; Bogialli, Sara; Pastore, Paolo

    2015-08-01

    A highly selective and robust method for simultaneous screening and confirmation of target and non-target phosphodiesterase type 5 (PDE-5) inhibitor analogues within a single chromatographic run in counterfeit herbal products was developed. The protocol, based on an easy and rapid extraction with a water/acetonitrile 1 % formic acid solution, followed by sonication and centrifugation, exploits an LC-diode array detector-quadrupole-time-of-flight (DAD-QTOF) system. The extraction method was optimized both at high concentrations and at trace levels. These two situations are typically encountered in pharmaceutical formulations and herbal food supplements. Carryover effects, never reported before and occurring mainly for vardenafil, were overcome using a polymer-based column. An in-house validation was carried out using five blanks of different bulk matrices spiked with seven standard analytes, namely yohimbine, sildenafil, vardenafil, tadalafil, homosildenafil, pseudovardenafil and hydroxyhomovardenafil. Reliable quantitation was possible using a conventional standard solution for all the pharmaceutical and herbal samples considered, as matrix effects were eliminated. Accuracy ranged from 80.9 to 108.1 % with overall relative standard deviation (RSD) non-target analysis. Among the 26 samples of dietary supplements and herbal remedies bulk marketed for erectile dysfunctions, three samples were found to be contaminated with both registered and unregistered synthetic PDE-5 inhibitors, i.e. yohimbine, sildenafil, dimethylsildenafil and thiodimethylsildenafil or thiomethisosildenafil. The occurrence of such contaminations, both at trace levels and at pharmaceutical dosage, indicates the illicit use of synthetic PDE-5 analogues. Graphical Abstract Examples of pharmaceutical formulations and herbal natural products marketed for the erectile dysfunction. PMID:26072210

  15. "One-shot" analysis of PDE-5 inhibitors and analogues in counterfeit herbal natural products using an LC-DAD-QTOF system.

    Science.gov (United States)

    Bortolini, Claudio; Pivato, Antonio; Bogialli, Sara; Pastore, Paolo

    2015-08-01

    A highly selective and robust method for simultaneous screening and confirmation of target and non-target phosphodiesterase type 5 (PDE-5) inhibitor analogues within a single chromatographic run in counterfeit herbal products was developed. The protocol, based on an easy and rapid extraction with a water/acetonitrile 1 % formic acid solution, followed by sonication and centrifugation, exploits an LC-diode array detector-quadrupole-time-of-flight (DAD-QTOF) system. The extraction method was optimized both at high concentrations and at trace levels. These two situations are typically encountered in pharmaceutical formulations and herbal food supplements. Carryover effects, never reported before and occurring mainly for vardenafil, were overcome using a polymer-based column. An in-house validation was carried out using five blanks of different bulk matrices spiked with seven standard analytes, namely yohimbine, sildenafil, vardenafil, tadalafil, homosildenafil, pseudovardenafil and hydroxyhomovardenafil. Reliable quantitation was possible using a conventional standard solution for all the pharmaceutical and herbal samples considered, as matrix effects were eliminated. Accuracy ranged from 80.9 to 108.1 % with overall relative standard deviation (RSD) non-target analysis. Among the 26 samples of dietary supplements and herbal remedies bulk marketed for erectile dysfunctions, three samples were found to be contaminated with both registered and unregistered synthetic PDE-5 inhibitors, i.e. yohimbine, sildenafil, dimethylsildenafil and thiodimethylsildenafil or thiomethisosildenafil. The occurrence of such contaminations, both at trace levels and at pharmaceutical dosage, indicates the illicit use of synthetic PDE-5 analogues. Graphical Abstract Examples of pharmaceutical formulations and herbal natural products marketed for the erectile dysfunction.

  16. Sphingosine kinase inhibitor suppresses IL-18-induced interferon-gamma production through inhibition of p38 MAPK activation in human NK cells

    International Nuclear Information System (INIS)

    Natural killer (NK) cells play an important role in the innate immune response. Interleukin-18 (IL-18) is a well-known interferon-gamma (IFN-γ inducing factor, which stimulates immune response in NK and T cells. Sphingosine kinase (SPHK) catalyzes the formation of sphingosine 1-phosphate (S1P), which acts as a second messenger to function as an anti-apoptotic factor and proliferation stimulator of immune cells. In this study, to elucidate whether SPHK is involved in IL-18-induced IFN-γ production, we measured IL-18-induced IFN-γ production after pre-treatment with SPHK inhibitor (SKI) in NK-92MI cells. We found that IL-18-induced IFN-γ expression was blocked by SKI pre-treatment in both mRNA and protein levels. In addition, the increased IFN-γ production by stimulation with IL-18 is mediated through both SPHK and p38 MAPK. To determine the upstream signals of SKI and p38 MAPK in IL-18-induced IFN-γ production, phosphorylation levels of p38 MAPK was measured after SKI pre-treatment. As a result, inhibition of SPHK by SKI blocked phosphorylation of p38 MAPK, showing that SPHK activation by IL-18 is an upstream signal of p38 MAPK activation. Inhibition of SPHK by SKI also inhibited IL-18-induced IFN-γ production in human primary NK cells. In conclusion, SPHK activation is an essential factor for IL-18-induced IFN-γ production via p38 MAPK

  17. Sodium bicarbonate-based hydration prevents contrast-induced nephropathy: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Tamhane Umesh

    2009-05-01

    Full Text Available Abstract Background Contrast-induced nephropathy is the leading cause of in-hospital acute renal failure. This side effect of contrast agents leads to increased morbidity, mortality, and health costs. Ensuring adequate hydration prior to contrast exposure is highly effective at preventing this complication, although the optimal hydration strategy to prevent contrast-induced nephropathy still remains an unresolved issue. Former meta-analyses and several recent studies have shown conflicting results regarding the protective effect of sodium bicarbonate. The objective of this study was to assess the effectiveness of normal saline versus sodium bicarbonate for prevention of contrast-induced nephropathy. Methods The study searched MEDLINE, EMBASE, Cochrane databases, International Pharmaceutical Abstracts database, ISI Web of Science (until 15 December 2008, and conference proceedings for randomized controlled trials that compared normal saline with sodium bicarbonate-based hydration regimen regarding contrast-induced nephropathy. Random-effects models were used to calculate summary odds ratios. Results A total of 17 trials including 2,633 subjects were pooled. Pre-procedural hydration with sodium bicarbonate was associated with a significant decrease in the rate of contrast-induced nephropathy (odds ratios 0.52; 95% confidence interval 0.34–0.80, P = 0.003. Number needed to treat to prevent one case of contrast-induced nephropathy was 16 (95% confidence interval 10–34. No significant differences in the rates of post-procedure hemodialysis (P = 0.20 or death (P = 0.53 was observed. Conclusion Sodium bicarbonate-based hydration was found to be superior to normal saline in prevention of contrast-induced nephropathy in this updated meta-analysis.

  18. Effect of artemisinin/artesunate as inhibitors of hepatitis B virus production in an "in vitro" replicative system.

    Science.gov (United States)

    Romero, Marta R; Efferth, Thomas; Serrano, Maria A; Castaño, Beatriz; Macias, Rocio I R; Briz, Oscar; Marin, Jose J G

    2005-11-01

    The antiviral effect against hepatitis B virus (HBV) of artemisinin, its derivative artesunate and other compounds highly purified from traditional Chinese medicine remedies, were investigated. HBV production by permanently transfected HepG2 2.2.15 cells was determined by measuring the release of surface protein (HBsAg) and HBV-DNA after drug exposure (0.01-100 microM) for 21 days. The forms of HBV-DNA released were investigated by Southern-blotting. Neutral Red retention test was used to evaluate drug-induced toxicity on host cells. The compounds were classified according to their potential interest as follows: (i) none: they had no effect on viral production (daidzein, daidzin, isonardosinon, nardofuran, nardosinon, tetrahydronardosinon and quercetin); (ii) low: they were able to markedly reduce viral production, but also induced toxicity on host cells (berberine and tannic acid) or they had no toxic effect on host cells but only had a moderate ability to reduce viral production (curcumin, baicalein, baicalin, bufalin, diallyl disulphide, glycyrrhizic acid and puerarin); (iii) high: they induced strong inhibition of viral production at concentrations at which host cell viability was not affected (artemisinin and artesunate). Moreover, artesunate in conjunction with lamivudine had synergic anti-HBV effects, which warrants further evaluation of artemisinin/artesunate as antiviral agents against HBV infection.

  19. Organization and alternate splice products of the gene encoding nuclear inhibitor of protein phosphatase-1 (NIPP-1).

    Science.gov (United States)

    Van Eynde, A; Pérez-Callejón, E; Schoenmakers, E; Jacquemin, M; Stalmans, W; Bollen, M

    1999-04-01

    Nuclear inhibitor of protein phosphatase-1 (NIPP-1) is one of two major regulatory subunits of protein phosphatase-1 in mammalian nuclei. We report here the cloning and structural characterization of the human NIPP-1 genes, designated PPP1R8P and PPP1R8 in human gene nomenclature. PPP1R8P (1.2 kb) is a processed pseudogene and was localized by in situ hybridization to chromosome 1p33-32. PPP1R8 is an authentic NIPP-1 gene and was localized to chromosome 1p35. PPP1R8 (25.2 kb) is composed of seven exons and encodes four different transcripts, as determined from cDNA library screening, reverse transcriptase-PCR (RT-PCR) and/or EST (expressed sequence tag) database search analysis. NIPP-1alpha mRNA represents the major transcript in human tissues and various cell lines, and encodes a polypeptide of 351 residues that only differs from the previously cloned calf thymus NIPP-1 by a single residue. The other transcripts, termed NIPP-1beta, gamma and delta, are generated by alternative 5'-splice site usage, by exon skipping and/or by alternative polyadenylation. The NIPP-1beta/delta and NIPP-1gamma mRNAs are expected to encode fragments of NIPP-1alpha that differ from the latter by the absence of the first 142 and 224 residues, respectively. NIPP-1gamma corresponds to 'activator of RNA decay-1' (Ard-1) which, unlike NIPP-1alpha, displays in vitro and endoribonuclease activity and lacks an RVXF consensus motif for interaction with protein phosphatase-1. While the NIPP-1alpha/beta/delta-transcripts were found to be present in various human tissues, the NIPP-1gamma transcript could only be detected in human transformed B-lymphocytes. PMID:10103062

  20. A scalable low-cost cGMP process for clinical grade production of the HIV inhibitor 5P12-RANTES in Pichia pastoris.

    Science.gov (United States)

    Cerini, Fabrice; Gaertner, Hubert; Madden, Knut; Tolstorukov, Ilya; Brown, Scott; Laukens, Bram; Callewaert, Nico; Harner, Jay C; Oommen, Anna M; Harms, John T; Sump, Anthony R; Sealock, Robert C; Peterson, Dustin J; Johnson, Scott K; Abramson, Stephan B; Meagher, Michael; Offord, Robin; Hartley, Oliver

    2016-03-01

    In the continued absence of an effective anti-HIV vaccine, approximately 2 million new HIV infections occur every year, with over 95% of these in developing countries. Calls have been made for the development of anti-HIV drugs that can be formulated for topical use to prevent HIV transmission during sexual intercourse. Because these drugs are principally destined for use in low-resource regions, achieving production costs that are as low as possible is an absolute requirement. 5P12-RANTES, an analog of the human chemokine protein RANTES/CCL5, is a highly potent HIV entry inhibitor which acts by achieving potent blockade of the principal HIV coreceptor, CCR5. Here we describe the development and optimization of a scalable low-cost production process for 5P12-RANTES based on expression in Pichia pastoris. At pilot (150 L) scale, this cGMP compliant process yielded 30 g of clinical grade 5P12-RANTES. As well as providing sufficient material for the first stage of clinical development, this process represents an important step towards achieving production of 5P12-RANTES at a cost and scale appropriate to meet needs for topical HIV prevention worldwide.

  1. Imbalance between HAT and HDAC activities in the PBMCs of patients with ankylosing spondylitis or rheumatoid arthritis and influence of HDAC inhibitors on TNF alpha production.

    Directory of Open Access Journals (Sweden)

    Eric Toussirot

    Full Text Available OBJECTIVE: Acetylation or deacetylation of histone proteins may modulate cytokine gene transcription such as TNF alpha (TNF. We evaluated the balance between histone deacetytlase (HDAC and histone acetyltransferase (HAT in patients with rheumatoid arthritis (RA or ankylosing spondylitis (AS compared to healthy controls (HC and determined the influence of HDAC inhibitors (trichostatin A -TSA- or Sirtinol -Sirt- on these enzymatic activities and on the PBMC production of TNF. METHODS: 52 patients with RA, 21 with AS and 38 HC were evaluated. HAT and HDAC activities were measured on nuclear extracts from PBMC using colorimetric assays. Enzymatic activities were determined prior to and after ex vivo treatment of PBMC by TSA or Sirt. TNF levels were evaluated in PBMC culture supernatants in the absence or presence of TSA or Sirt. RESULTS: HAT and HDAC activities were significantly reduced in AS, while these activities reached similar levels in RA and HC. Ex vivo treatment of PBMC by HDACi tended to decrease HDAC expression in HC, but Sirt significantly reduced HAT in RA. TNF production by PBMC was significantly down-regulated by Sirt in HC and AS patients. CONCLUSION: HAT and HDAC were disturbed in AS while no major changes were found in RA. HDACi may modulate HDAC and HAT PBMC expression, especially Sirt in RA. Sirtinol was able to down regulate TNF production by PBMC in HC and AS. An imbalance between HAT and HDAC activities might provide the rationale for the development of HDACi in the therapeutic approach to inflammatory rheumatic diseases.

  2. Cholinesterase inhibitors from botanicals

    Directory of Open Access Journals (Sweden)

    Faiyaz Ahmed

    2013-01-01

    Full Text Available Alzheimer′s disease (AD is a progressive neurodegenerative disease, wherein a progressive loss of cholinergic synapses occurs in hippocampus and neocortex. Decreased concentration of the neurotransmitter, acetylcholine (ACh, appears to be critical element in the development of dementia, and the most appropriate therapeutic approach to treat AD and other form of dementia is to restore acetylcholine levels by inhibiting both major form of cholinesterase: Acetylcholinesterase (AChE and butyrylcholinesterase (BChE. Consequently, researches have focused their attention towards finding cholinesterase inhibitors from natural products. A large number of such inhibitors have been isolated from medicinal plants. This review presents a comprehensive account of the advances in field of cholinesterase inhibitor phytoconstituents. The structures of some important phytoconstituents (collected through www.Chemspider.com are also presented and the scope for future research is discussed.

  3. Total synthesis and structural confirmation of the marine natural product Dysinosin A: a novel inhibitor of thrombin and Factor VIIa.

    Science.gov (United States)

    Hanessian, Stephen; Margarita, Roberto; Hall, Adrian; Johnstone, Shawn; Tremblay, Martin; Parlanti, Luca

    2002-11-13

    The structure and absolute configuration of the marine antithrombotic product dysinosin A was confirmed by total synthesis. The strategy involved disconnections to three subunits, of which two were synthesized from the readily available l-glutamic acid, d-leucine, and d-mannitol. The Grubbs olefin metathesis carbocyclization reaction was utilized to prepare two intermediates. PMID:12418860

  4. Potential inhibitors from wet oxidation of wheat straw and their effect on ethanol production of Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Klinke, H.B.; Olsson, L.; Thomsen, A.B.;

    2003-01-01

    in concentrations of 50-100 times the concentration found in the hydrolysate for their effect on fermentation by yeast. At these high concentrations (10 mM), 4-hydroxy-benzaldehyde, vanillin, 4-hydroxyacetophenone and acetovanillone caused a 53-67% decrease in the volumetric ethanol productivity in S. cerevisiae...

  5. Development of Fourth Generation ABC Inhibitors from Natural Products: A Novel Approach to Overcome Cancer Multidrug Resistance.

    Science.gov (United States)

    Karthikeyan, Subburayan; Hoti, Sugeerappa Laxmanappa

    2015-01-01

    Multidrug resistance (MDR) in cancer caused due to overexpression of ABC drug transporters is a major problem in modern chemotherapy. Molecular investigations on MDR have revealed that the resistance is due to various transport proteins of the ABC superfamily which include Phosphoglycoprotein (P-gp/MDR1/ ABCB1), multidrug resistance-associated protein-1 (MRP1), and the breast cancer resistance protein (BCRP). They have been characterized functionally and are considered as major players in the development of MDR in cancer cells. These ATP-dependent transporter proteins cause MDR either by decreased uptake of the drug or increased efflux of the drug from the target organelles. Several MDR-reversing agents are being developed and are in various stages of clinical trials. The first three generations of ABC modulators such as quinine, verapamil, cyclosporine-A, tariquitor, PSC 833, LY335979, and GF120918 required to be administered in high doses to reverse MDR and were associated with adverse effects. Additionally, these modulators non-selectively inhibit ABC and adversely accumulate chemotherapeutic drugs in brain and kidney. Currently, research has stepped up towards reversing MDR by using natural products which exhibitted potential as chemosensitizers. Globally, there is a rich biodiversity of natural products which can be sourced for developing drugs. These products may provide more lead compounds with superior activity, foremost to the development of more effective therapies for MDR cancer cells. Here, we briefly review the status of natural products for reversing MDR modulators, and discuss the long term goal of MDR strategies in current clinical settings. PMID:25584696

  6. Adaptation and transcriptome analysis of Aureobasidium pullulans in corncob hydrolysate for increased inhibitor tolerance to malic acid production.

    Directory of Open Access Journals (Sweden)

    Xiang Zou

    Full Text Available Malic acid is a dicarboxylic acid widely used in the food industry, and is also a potential C4 platform chemical. Corncob is a low-cost renewable feedstock from agricultural industry. However, side-reaction products (furfural, 5-hydroxymethylfurfural (HMF, formic acid, and acetic acid that severely hinder fermentation are formed during corncob pretreatment. The process for producing malic acid from a hydrolysate of corncob was investigated with a polymalic acid (PMA-producing Aureobasidium pullulans strain. Under the optimal hydrolysate sugar concentration 110 g/L, A. pullulans was further adapted in an aerobic fibrous bed bioreactor (AFBB by gradually increasing the sugar concentration of hydrolysate. After nine batches of fermentation, the production and productivity of malic acid reached 38.6 g/L and 0.4 g/L h, respectively, which was higher than that in the first batch (27.6 g/L and 0.29 g/L h, respectively. The adapted strain could grow under the stress of 0.5 g/L furfural, 3 g/L HMF, 2g/L acetic acid, and 0.5 g/L formic acid, whereas the wild type did not. Transcriptome analysis revealed that the differentially expressed genes were related to carbohydrate transport and metabolism, lipid transport and metabolism, signal transduction mechanism, redox metabolism, and energy production and conversion under 0.5 g/L furfural and 3 g/L HMF stress conditions. In total, 42 genes in the adapted strain were upregulated by 15-fold or more, and qRT-PCR also confirmed that the expression levels of key genes (i.e. SIR, GSS, CYS, and GSR involved in sulfur assimilation pathway were upregulated by over 10-fold in adapted strain for cellular protection against oxidative stress.

  7. Characterization of forced degradation products and in silico toxicity prediction of Sofosbuvir: A novel HCV NS5B polymerase inhibitor.

    Science.gov (United States)

    Swain, Debasish; Samanthula, Gananadhamu; Bhagat, Shweta; Bharatam, P V; Akula, Venkatakrishna; Sinha, Barij N

    2016-02-20

    Sofosbuvir is a direct acting antiviral medication used to treat Hepatitis C viral infection. The present study focuses on the degradation behavior of the drug under various stress conditions (hydrolysis, oxidative, thermal and photolytic) as per International Conference on Harmonization (ICH Q1A (R2)) guidelines. A high performance liquid chromatographic system (HPLC) was used to develop a selective, precise and accurate method for separating all the degradation products. The separation was achieved on a Sunfire™ C18 (150mm×4.6mm×5μm) stationary phase with a mobile phase of 10mM ammonium acetate (pH 5.0) buffer and acetonitrile in gradient elution mode. A quadrupole-time of flight mass analyzer equipped with an electrospray ionization technique was used to propose the structural information based on the MS/MS and accurate mass measurements. Seven degradation products were identified and characterised by LC-ESI-QTOF-MS/MS. In silico toxicity of the drug and its degradation products was determined using TOPKAT and DEREK toxicity prediction softwares. The proposed method was validated as per the ICH Q2 guidelines. PMID:26771133

  8. Effects of sodium bicarbonate and 1,25-dihydroxy-cholecalciferol on calcium and phosphorus balances in the rat

    International Nuclear Information System (INIS)

    Metabolic balance studies were undertaken to determine whether sodium bicarbonate (NaHCO3) supplements (4.5 mmol/day) altered 7-day cumulative calcium (Ca) phosphorus (P) balances in growing rats consuming either a basal diet providing 0.6% Ca and 0.3% P, or this diet plus 1,25-dihydroxycholecalciferol [40 ng 1,25(OH)2D3/day]. Feeding bicarbonate lowered urinary Ca but raised fecal Ca so that Ca balance became less positive. However, 1,25(OH)2D3 increased net absorption of Ca and P to the same degree when given to control rats and rats consuming bicarbonate. Nevertheless, bicarbonate-fed rats had lower net Ca absorption than controls, even when treated with high doses of 1,25(OH)2D3. Changes in net Ca absorption induced by bicarbonate may occur at a point in the gut distal to the duodenum since duodenal 45Ca absorption was decreased by bicarbonate feeding. The present results show that bicarbonate consumption depressed net Ca absorption in the rat. The effect appears to be independent of changes in 1,25(OH)2D3 metabolism because it is manifest in animals receiving high doses of 1,25(OH)2D3, which stimulate alimentary Ca absorption maximally, and because bicarbonate-fed rats are able to respond normally to exogenous 1,25(OH)2D3 by increasing their net absorption of Ca and P. In view of this demonstration that NaHCO3 supplements elevate fecal Ca loss in the rat, it is suggested that studies should be undertaken to determine whether bicarbonate exerts similar adverse effects on Ca balance in humans

  9. Prevention of contrast induced nephropathy with sodium bicarbonate (the PROMEC study

    Directory of Open Access Journals (Sweden)

    John Fredy Nieto-Ríos

    2014-09-01

    Full Text Available Introduction: Contrast-induced nephropathy is a common complication of radiographic procedures. Different measures have been used to avoid this damage, but the evidence is controversial. New investigations are required to clarify it. We investigated the efficacy and safety of sodium bicarbonate solution compared with sodium chloride solution to prevent contrast induced nephropathy in patients with or at risk of renal dysfunction. Methods: A prospective, single-center, randomized clinical trial conducted from May 1, 2007 to February 8, 2008. Inpatients in a tertiary center, scheduled to undergo a procedure with the nonionic radiographic contrast agent iohexol. There were 220 patients with serum creatinine levels of at least 1.2 mg/dL (106.1 µmol/L and/or type 2 diabetics, who were randomized to receive an infusion of sodium chloride (n = 113 or sodium bicarbonate (n = 107 before and after contrast dye administration. The intervention were "A" group received 1 ml/kg/hour of normal saline solution, starting 12 hours before and continuing 12 hours after iohexol contrast. "B" group received 3 ml/kg of sodium bicarbonate solution (150 mEq/L one hour prior to procedure and then drip rate was decreased to 1 ml/kg/hour until 6 hours post procedure. Our main outcome measure was change in serum creatinine. Results: The mean creatinine value after the procedure was 1.26 mg/dL in the saline group and 1.22 mg/dL in the bicarbonate group (mean difference: 0.036; CI 95%: -0.16 to 0.23, p = 0.865. The diagnosis of contrast-induced nephropathy, defined by increase in serum creatinine on 25% or more within 2 days after administration of radiographic contrast, was done in twelve patients (12% in the bicarbonate group and eighth patients (7.1% in the saline group (RR: 1.68, CI 95%: 0.72 to 3.94. Conclusion: Our investigation showed that there were no differences between normal saline solution (extended infusion vs. bicarbonate solution for nephroprotection.

  10. Sodium Bicarbonate Treatment during Transient or Sustained Lactic Acidemia in Normoxic and Normotensive Rats

    Science.gov (United States)

    Valenza, Franco; Pizzocri, Marta; Salice, Valentina; Chevallard, Giorgio; Fossali, Tommaso; Coppola, Silvia; Froio, Sara; Polli, Federico; Gatti, Stefano; Fortunato, Francesco; Comi, Giacomo P.; Gattinoni, Luciano

    2012-01-01

    Introduction Lactic acidosis is a frequent cause of poor outcome in the intensive care settings. We set up an experimental model of lactic acid infusion in normoxic and normotensive rats to investigate the systemic effects of lactic acidemia per se without the confounding factor of an underlying organic cause of acidosis. Methodology Sprague Dawley rats underwent a primed endovenous infusion of L(+) lactic acid during general anesthesia. Normoxic and normotensive animals were then randomized to the following study groups (n = 8 per group): S) sustained infusion of lactic acid, S+B) sustained infusion+sodium bicarbonate, T) transient infusion, T+B transient infusion+sodium bicarbonate. Hemodynamic, respiratory and acid-base parameters were measured over time. Lactate pharmacokinetics and muscle phosphofructokinase enzyme's activity were also measured. Principal Findings Following lactic acid infusion blood lactate rose (P<0.05), pH (P<0.05) and strong ion difference (P<0.05) drop. Some rats developed hemodynamic instability during the primed infusion of lactic acid. In the normoxic and normotensive animals bicarbonate treatment normalized pH during sustained infusion of lactic acid (from 7.22±0.02 to 7.36±0.04, P<0.05) while overshoot to alkalemic values when the infusion was transient (from 7.24±0.01 to 7.53±0.03, P<0.05). When acid load was interrupted bicarbonate infusion affected lactate wash-out kinetics (P<0.05) so that blood lactate was higher (2.9±1 mmol/l vs. 1.0±0.2, P<0.05, group T vs. T+B respectively). The activity of phosphofructokinase enzyme was correlated with blood pH (R2 = 0.475, P<0.05). Conclusions pH decreased with acid infusion and rose with bicarbonate administration but the effects of bicarbonate infusion on pH differed under a persistent or transient acid load. Alkalization affected the rate of lactate disposal during the transient acid load. PMID:23029373

  11. Recombinant VP1, an Akt inhibitor, suppresses progression of hepatocellular carcinoma by inducing apoptosis and modulation of CCL2 production.

    Directory of Open Access Journals (Sweden)

    Tai-An Chen

    Full Text Available BACKGROUND: The application of viral elements in tumor therapy is one facet of cancer research. Recombinant capsid protein VP1 (rVP1 of foot-and-mouth disease virus has previously been demonstrated to induce apoptosis in cancer cell lines. Here, we aim to further investigate its apoptotic mechanism and possible anti-metastatic effect in murine models of hepatocellular carcinoma (HCC, one of the most common human cancers worldwide. METHODOLOGY/PRINCIPAL FINDINGS: Treatment with rVP1 inhibited cell proliferation in two murine HCC cell lines, BNL and Hepa1-6, with IC₅₀ values in the range of 0.1-0.2 µM. rVP1 also induced apoptosis in these cells, which was mediated by Akt deactivation and dissociation of Ku70-Bax, and resulted in conformational changes and mitochondrial translocation of Bax, leading to the activation of caspases-9, -3 and -7. Treatment with 0.025 µM rVP1, which did not affect the viability of normal hepatocytes, suppressed cell migration and invasion via attenuating CCL2 production. The production of CCL2 was modulated by Akt-dependent NF-κB activation that was decreased after rVP1 treatment. The in vivo antitumor effects of rVP1 were assessed in both subcutaneous and orthotopic mouse models of HCC in immune-competent BALB/c mice. Intratumoral delivery of rVP1 inhibited subcutaneous tumor growth as a result of increased apoptosis. Intravenous administration of rVP1 in an orthotopic HCC model suppressed tumor growth, inhibited intra-hepatic metastasis, and prolonged survival. Furthermore, a decrease in the serum level of CCL2 was observed in rVP1-treated mice. CONCLUSIONS/SIGNIFICANCE: The data presented herein suggest that, via inhibiting Akt phosphorylation, rVP1 suppresses the growth, migration, and invasion of murine HCC cells by inducing apoptosis and attenuating CCL2 production both in vitro and in vivo. Recombinant protein VP1 thus has the potential to be developed as a new therapeutic agent for HCC.

  12. Recent Developments in the Use of Sodium Bicarbonate as an Ergogenic Aid.

    Science.gov (United States)

    McNaughton, Lars R; Gough, Lewis; Deb, Sanjoy; Bentley, David; Sparks, S Andy

    2016-01-01

    This review examines the current status of sodium bicarbonate as an ergogenic aid. It builds on previous reviews in the area. Current research would suggest that as an ergogenic aid, a 300 mg·kg dose of NaHCO3 can improve high-intensity exercise, within a range of exercise modalities, such as a single bout of supramaximal exercise, high-intensity intermittent activity, and skill-based sports. In particular, these benefits seem to be present to a greater extent within trained individuals. Despite this, there appears to exist a high intraindividual variability in response to NaHCO3, and therefore, the ergogenic benefits may not be induced during every exercise bout. Current thinking also suggests that athletes need to individualize their ingestion timings to maximize peak pH or blood bicarbonate to effectively maximize the performance effect, and this may allow individuals to attain the ergogenic benefits of NaHCO3 more consistently. PMID:27399820

  13. Influence of bicarbonate ions and redox conditions on the surface composition of a leached borosilicate glass

    International Nuclear Information System (INIS)

    A serie of short leaching tests have been performed on a borosilicate glass (I117) up to a maximum of 40 days. The tests were performed in a closed system in oxic and anoxic conditions and in presence of bicarbonate ions. The bicarbonate ions do not influence the mass losses while the oxic condition gives rise to an higher mass losses. Surface analysis was performed on the surface layer for the elements uranium and iron. Uranium is always depleted at the surface of the samples. It appears that adsorption and diffusion in the layer play an important part in the uranium released. Iron on the contrary is enriched so that solubility of the formed species are responsible of its concentration

  14. Caffeine, but not bicarbonate, improves 6 min maximal performance in elite rowers

    DEFF Research Database (Denmark)

    Christensen, Peter Møller; Petersen, Mads H; Friis, Signe N;

    2014-01-01

    This study examined the ergogenic effects in a 6 min maximal performance test (PT) on 12 elite rowers: 6 open-weight (mean ± SD; 25 ± 1 years, and 92 ± 3 kg) and 6 light-weight (25 ± 3 years, and 73 ± 6 kg), following supplementation with caffeine (CAF), sodium bicarbonate (SB), and the combination.......05) than in open-weight rowers (0.3% ± 0.8%; P > 0.05). No difference between interventions was observed for readiness and stomach comfort before PT and perceived exertion during PT. This study demonstrates that caffeine ingestion does improve performance in elite rowing. In contrast sodium bicarbonate...... does not appear to be ergogenic, but it does not abolish the ergogenic effect of caffeine....

  15. Accelerating the dissolution of enteric coatings in the upper small intestine: evolution of a novel pH 5.6 bicarbonate buffer system to assess drug release.

    Science.gov (United States)

    Varum, Felipe J O; Merchant, Hamid A; Goyanes, Alvaro; Assi, Pardis; Zboranová, Veronika; Basit, Abdul W

    2014-07-01

    Despite rapid dissolution in compendial phosphate buffers, gastro resistant (enteric coated) products can take up to 2 h to disintegrate in the human small intestine, which clearly highlights the inadequacy of the in vitro test method to predict in vivo behaviour of these formulations. The aim of this study was to establish the utility of a novel pH 5.6 bicarbonate buffer, stabilized by an Auto pH™ System, as a better surrogate of the conditions of the proximal small intestine to investigate the dissolution behaviour of standard and accelerated release enteric double coating formulations. Prednisolone tablets were coated with 3 or 5 mg/cm(2) of partially neutralized EUDRAGIT(®) L 30 D-55, HP-55 or HPMC adjusted to pH 6 or 8. An outer layer of EUDRAGIT(®) L 30 D-55 was applied at 5mg/cm(2). For comparison purposes, a standard single layer of EUDRAGIT(®) L 30 D-55 was applied to the tablets. Dissolution was carried out using USP II apparatus in 0.1 M HCl for 2 h, followed by pH 5.6 bicarbonate buffer. EUDRAGIT(®) L 30 D-55 single-coated tablets showed a slow drug release with a lag time of 75 min in buffer, whereas release from the EUDRAGIT(®) L 30 D-55 double-coated tablets was accelerated. These in vitro lag times closely match the in vivo disintegration times for these coated tablets reported previously. Drug release was further accelerated from modified double coatings, particularly in the case of coatings with a thinner inner layer of HP-55 or HPMC (pH 8 and KH2PO4). This study confirms that the pH 5.6 bicarbonate buffer system offers significant advantages during the development of dosage forms designed to release the drug in the upper small intestine.

  16. The Consumption of Bicarbonate-Rich Mineral Water Improves Glycemic Control

    OpenAIRE

    Shinnosuke Murakami; Yasuaki Goto; Kyo Ito; Shinya Hayasaka; Shigeo Kurihara; Tomoyoshi Soga; Masaru Tomita; Shinji Fukuda

    2015-01-01

    Hot spring water and natural mineral water have been therapeutically used to prevent or improve various diseases. Specifically, consumption of bicarbonate-rich mineral water (BMW) has been reported to prevent or improve type 2 diabetes (T2D) in humans. However, the molecular mechanisms of the beneficial effects behind mineral water consumption remain unclear. To elucidate the molecular level effects of BMW consumption on glycemic control, blood metabolome analysis and fecal microbiome analysi...

  17. Acid-base analysis: a critique of the Stewart and bicarbonate-centered approaches.

    Science.gov (United States)

    Kurtz, Ira; Kraut, Jeffrey; Ornekian, Vahram; Nguyen, Minhtri K

    2008-05-01

    When approaching the analysis of disorders of acid-base balance, physical chemists, physiologists, and clinicians, tend to focus on different aspects of the relevant phenomenology. The physical chemist focuses on a quantitative understanding of proton hydration and aqueous proton transfer reactions that alter the acidity of a given solution. The physiologist focuses on molecular, cellular, and whole organ transport processes that modulate the acidity of a given body fluid compartment. The clinician emphasizes the diagnosis, clinical causes, and most appropriate treatment of acid-base disturbances. Historically, two different conceptual frameworks have evolved among clinicians and physiologists for interpreting acid-base phenomena. The traditional or bicarbonate-centered framework relies quantitatively on the Henderson-Hasselbalch equation, whereas the Stewart or strong ion approach utilizes either the original Stewart equation or its simplified version derived by Constable. In this review, the concepts underlying the bicarbonate-centered and Stewart formulations are analyzed in detail, emphasizing the differences in how each approach characterizes acid-base phenomenology at the molecular level, tissue level, and in the clinical realm. A quantitative comparison of the equations that are currently used in the literature to calculate H(+) concentration ([H(+)]) is included to clear up some of the misconceptions that currently exist in this area. Our analysis demonstrates that while the principle of electroneutrality plays a central role in the strong ion formulation, electroneutrality mechanistically does not dictate a specific [H(+)], and the strong ion and bicarbonate-centered approaches are quantitatively identical even in the presence of nonbicarbonate buffers. Finally, our analysis indicates that the bicarbonate-centered approach utilizing the Henderson-Hasselbalch equation is a mechanistic formulation that reflects the underlying acid-base phenomenology. PMID

  18. Plasma exchange successfully treats central pontine myelinolysis after acute hypernatremia from intravenous sodium bicarbonate therapy

    OpenAIRE

    Chang, Kyung Yoon; Lee, In-Hee; Kim, Gi Jun; Cho, Kangwon; Park, Hoon Suk; Kim, Hyung Wook

    2014-01-01

    Background Osmotic demyelination syndrome (ODS) primarily occurs after rapid correction of severe hyponatremia. There are no proven effective therapies for ODS, but we describe the first case showing the successful treatment of central pontine myelinolysis (CPM) by plasma exchange, which occurred after rapid development of hypernatremia from intravenous sodium bicarbonate therapy. Case presentation A 40-year-old woman presented with general weakness, hypokalemia, and metabolic acidosis. The p...

  19. Evaluation of different sodium bicarbonate regimens for the prevention of contrast medium-induced nephropathy

    OpenAIRE

    Abouzeid, Sameh; Mosbah, Osama

    2016-01-01

    Introduction The rapid decline in renal function caused by radiographic contrast agents usually is transient, but it can result in chronic kidney disease. The pathophysiology of contrast-induced nephropathy (CIN) is poorly understood, but it may include acute hypoxia-induced oxidative stress and free radicals generated within the acid environment of the renal medulla. Thus, the alkalization of urine by sodium bicarbonate has been regarded as resulting in the reduction of CIN. The aim of this ...

  20. SODIUM BICARBONATE INFUSION: TO PREVENT CARDIAC SURGERY - ASSOCIATED ACUTE KIDNEY INJURY

    Directory of Open Access Journals (Sweden)

    Ramesh

    2015-02-01

    Full Text Available OBJECTIVES: The incidence of cardiac surgery – associated acute kidney injury is 50% of patients and is associated with increased mortality and morbidity. This study aimed to determine if perioperative urinary and plasma alkalization with sodium bicarbonate infusion re duces the incidence of cardiac surgery – associated acute kidney injury. SETTING AND DESIGN: This study is double blind randomized control trial conducted at U N Mehta Institute of Cardiology and Research Center , India. METHOD S AND RESULT: A total of 140 pat ients scheduled to undergo elective cardiac surgery , who were at increased risk of development of cardiac surgery – associated acute kidney injury using recognized risk factors. Patients were randomly allocated to receive either sodium bicarbonate (n = 70 o r sodium chloride (n = 70 infusion , commencing at the start of anesthesia , in a dose of 4 mmol/kg over 24 hour. The primary outcome measure was the number of patients with development of CSA - AKI , defined as an increase in creatinine greater than 25% from baseline to peak value within the first three postoperative days. Significant differences among the groups in both plasma and urinary pH were achieved 6 hours after commencement of the infusion , and these changes persisted for more than 24 hours. A total o f 7 out of 70(10% patients in the sodium bicarbonate group and 16 out of 70(22.85% patients in the sodium chloride group developed acute kidney injury within the first three postoperative days with p value of 0.06 which is statistically not significant . There were also no significant differences in ventilation hours , ICU or hospital length of stay , or mortality. CONCLUSIONS: Perioperative alkalization of blood and urine using an infusion of sodium bicarbonate did not result in a decrease in the incidence of acute kidney injury in patients undergoing cardiac surgery. KEYWORDS: Acute kidney injury; Cardiac surgery; Cardiopulmonary bypass; Creatinine

  1. Bicarbonate and Ca(2+) Sensing Modulators Activate Photoreceptor ROS-GC1 Synergistically.

    Science.gov (United States)

    Duda, Teresa; Pertzev, Alexandre; Makino, Clint L; Sharma, Rameshwar K

    2016-01-01

    Photoreceptor ROS-GC1, a prototype subfamily member of the membrane guanylate cyclase family, is a central component of phototransduction. It is a single transmembrane-spanning protein, composed of modular blocks. In rods, guanylate cyclase activating proteins (GCAPs) 1 and 2 bind to its juxtamembrane domain (JMD) and the C-terminal extension, respectively, to accelerate cyclic GMP synthesis when Ca(2+) levels are low. In cones, the additional expression of the Ca(2+)-dependent guanylate cyclase activating protein (CD-GCAP) S100B which binds to its C-terminal extension, supports acceleration of cyclic GMP synthesis at high Ca(2+) levels. Independent of Ca(2+), ROS-GC1 activity is also stimulated directly by bicarbonate binding to the core catalytic domain (CCD). Several enticing molecular features of this transduction system are revealed in the present study. In combination, bicarbonate and Ca(2+)-dependent modulators raised maximal ROS-GC activity to levels that exceeded the sum of their individual effects. The F(514)S mutation in ROS-GC1 that causes blindness in type 1 Leber's congenital amaurosis (LCA) severely reduced basal ROS-GC1 activity. GCAP2 and S100B Ca(2+) signaling modes remained functional, while the GCAP1-modulated mode was diminished. Bicarbonate nearly restored basal activity as well as GCAP2- and S100B-stimulated activities of the F(514)S mutant to normal levels but could not resurrect GCAP1 stimulation. We conclude that GCAP1 and GCAP2 forge distinct pathways through domain-specific modules of ROS-GC1 whereas the S100B and GCAP2 pathways may overlap. The synergistic interlinking of bicarbonate to GCAPs- and S100B-modulated pathways intensifies and tunes the dependence of cyclic GMP synthesis on intracellular Ca(2+). Our study challenges the recently proposed GCAP1 and GCAP2 "overlapping" phototransduction model (Peshenko et al., 2015b). PMID:26858600

  2. Impact of Bicarbonate, Ammonium Chloride, and Acetazolamide on Hepatic and Renal SLC26A4 Expression

    OpenAIRE

    Alesutan, Ioana; Daryadel, Arezoo; Mohebbi, Nilufar; Pelzl, Lisann; Leibrock, Christina; Voelkl, Jakob; Bourgeois, Soline; Dossena, Silvia; Nofziger, Charity; Paulmichl, Markus; Carsten A Wagner; Lang, Florian

    2011-01-01

    SLC26A4 encodes pendrin, a transporter exchanging anions such as chloride, bicarbonate, and iodide. Loss of function mutations of SLC26A4 cause Pendred syndrome characterized by hearing loss and enlarged vestibular aqueducts as well as variable hypothyroidism and goiter. In the kidney, pendrin is expressed in the distal nephron and accomplishes HCO(3)(-) secretion and Cl(-) reabsorption. Renal pendrin expression is regulated by acid-base balance. The liver contributes to acid-base regulation ...

  3. Ammonium Bicarbonate Transport in Anion Exchange Membranes for Salinity Gradient Energy

    KAUST Repository

    Geise, Geoffrey M.

    2013-09-17

    Many salinity gradient energy technologies such as reverse electrodialysis (RED) rely on highly selective anion transport through polymeric anion exchange membranes. While there is considerable interest in using thermolytic solutions such as ammonium bicarbonate (AmB) in RED processes for closed-loop conversion of heat energy to electricity, little is known about membrane performance in this electrolyte. The resistances of two commercially available cation exchange membranes in AmB were lower than their resistances in NaCl. However, the resistances of commercially available anion exchange membranes (AEMs) were much larger in AmB than in NaCl, which would adversely affect energy recovery. The properties of a series of quaternary ammonium-functionalized poly(phenylene oxide) and Radel-based AEMs were therefore examined to understand the reasons for increased resistance in AmB to overcome this performance penalty due to the lower mobility of bicarbonate, 4.59 × 10-4 cm2/(V s), compared to chloride, 7.90 × 10-4 cm2/(V s) (the dilute aqueous solution mobility ratio of HCO3 - to Cl- is 0.58). Most membrane resistances were generally consistent with the dilute solution mobilities of the anions. For a few key samples, however, increased water uptake in AmB solution reduced the ionic resistance of the polymer compared to its resistance in NaCl solution. This increased water uptake was attributed to the greater hydration of the bicarbonate ion compared to the chloride ion. The increased resistance due to the use of bicarbonate as opposed to chloride ions in AEMs can therefore be mitigated by designing polymers that swell more in AmB compared to NaCl solutions, enabling more efficient energy recovery using AmB thermolytic solutions in RED. © 2013 American Chemical Society.

  4. Umami Receptor Activation Increases Duodenal Bicarbonate Secretion via Glucagon-Like Peptide-2 Release in Rats

    OpenAIRE

    Wang, Joon-Ho; Inoue, Takuya; Higashiyama, Masaaki; Guth, Paul H.; Engel, Eli; Kaunitz, Jonathan D.; Akiba, Yasutada

    2011-01-01

    Luminal nutrient chemosensing during meal ingestion is mediated by intestinal endocrine cells, which regulate secretion and motility via the release of gut hormones. We have reported that luminal coperfusion of l-Glu and IMP, common condiments providing the umami or proteinaceous taste, synergistically increases duodenal bicarbonate secretion (DBS) possibly via taste receptor heterodimers, taste receptor type 1, member 1 (T1R1)/R3. We hypothesized that glucose-dependent insulinotropic peptide...

  5. Content of CYP3A4 inhibitors, naringin, naringenin and bergapten in grapefruit and grapefruit juice products.

    Science.gov (United States)

    Ho, P C; Saville, D J; Coville, P F; Wanwimolruk, S

    2000-04-01

    The flavonoids, naringin and naringenin and the furanocoumarin, bergapten (5-methoxypsoralen), were detected in some fresh grapefruit and commercial grapefruit juices but were not detected in other fruit juices tested (orange; orange with apple base; dark grape; orange and mango with apple base; orange, peach, passion fruit juice). The contents of these three grapefruit constituents in commercial juice and fresh grapefruit varied from brand to brand and also from lot to lot. Juice was prepared from the fresh fruit via different methods (by hand, squeezer or blender). The naringin content, after hand-squeeze, ranged from 115 to 384 mg/l. With hand-squeeze juice production, bergapten was not detected (less than 0.5 mg/l) in two varieties of grapefruit, and naringenin was usually not in detectable levels (less than 2 mg/l) in three varieties. All three constituents were present in New Zealand grapefruit preparations (including juice by hand-squeeze) and different lots showed variation in content (1.5-, 2.3- and 4.7-fold for naringin, naringenin and bergapten, respectively). Differences in the concentrations of these three constituents, which have potential for drug interaction, may contribute to the variability in pharmacokinetics of CYP3A4 drugs and some contradictory results of drug interaction studies with grapefruit juice. PMID:10812937

  6. Bicarbonate-induced activation of H₂O₂ for metal-free oxidative desulfurization.

    Science.gov (United States)

    Bokare, Alok D; Choi, Wonyong

    2016-03-01

    Efficient oxidative desulfurization (ODS) of model oil containing dibenzothiophene (DBT) and aromatic thiophenic derivatives has been achieved at room temperature using hydrogen peroxide activation by inorganic bicarbonate (HCO3(-)). Using in-situ formation of peroxymonocarbonate as oxidant, the transformation of main model substrate DBT to corresponding DBT-sulfone was easily accomplished in biphasic reaction conditions. In the presence of water-acetonitrile polar phase, increasing the water content upto 50% decreased the extraction capacity more than 3 times, but ∼ 90% DBT oxidation was still achieved. The oxidizing capacity of bicarbonate catalyst was maintained during repeated ODS cycles, but DBT removal efficiency was critically dependent on the extraction capacity of the polar phase. Under heterogeneous reaction conditions, bicarbonate-modified ion-exchange resin achieved similar ODS activity compared to the homogeneous catalytic system. Additionally, the efficient formation of peroxymonocarbonate using gaseous CO2 precursor in alkaline conditions was also utilized for DBT oxidation. The present study proposes the NaHCO3/H2O2 catalytic system as an efficient and cheap metal-free alternative for the oxidative removal of aromatic sulfur compounds from fuel oil. PMID:26561755

  7. The role of perioperative sodium bicarbonate infusion affecting renal function after Cardiothoracic Surgery

    Directory of Open Access Journals (Sweden)

    Katja Regina Turner

    2014-06-01

    Full Text Available Cardiac surgery associated acute kidney injury (CSA-AKI is associated with poor outcomes including increased mortality, length of hospital stay and cost. The incidence of acute kidney injury (AKI is reported to be between 3-30% depending on the definition of AKI. We designed a multicenter randomized controlled trial to test our hypothesis that a perioperative infusion of sodium bicarbonate during cardiac surgery will attenuate the postoperative rise in creatinine indicating renal injury when compared to a perioperative infusion with normal saline. An interim analysis was performed after data was available on the first 120 participants. A similar number of patients in the two treatment groups developed acute kidney injury (AKI, defined as an increase in serum creatinine the first 48 hours after surgery of 0.3 mg/dl or more. Specifically 14 patients (24% who received sodium chloride (SC and 17 patients (27% who received sodium bicarbonate (SB were observed to develop AKI post surgery, resulting in a relative risk of AKI of 1.1 (95% CI: 0.6-2.1, chi-square p-value=0.68 for patients receiving SB compared to those who received SC . The data safety monitoring board for the trial recommended closing the study early as there was only a 12% probability that the null hypothesis would be rejected. We therefore concluded that a perioperative infusion of sodium bicarbonate failed to attenuate the risk of CSA-AKI.

  8. Repeated High Intensity Bouts with Long Recovery: Are Bicarbonate or Carbohydrate Supplements an Option?

    Directory of Open Access Journals (Sweden)

    Thomas Stöggl

    2014-01-01

    Full Text Available The effects of varying recovery modes and the influence of preexercise sodium bicarbonate and carbohydrate ingestion on repeated high intensity performance, acid-base response, and recovery were analyzed in 12 well-trained males. They completed three repeated high intensity running bouts to exhaustion with intervening recovery periods of 25 min under the following conditions: sodium bicarbonate, active recovery (BIC; carbohydrate ingestion, active recovery (CHO; placebo ingestion, active recovery (ACTIVE; placebo ingestion, passive recovery (PASSIVE. Blood lactate (BLa, blood gases, heart rate, and time to exhaustion were collected. The three high intensity bouts had a duration of 138±9, 124±6, and 121±6 s demonstrating a decrease from bout 1 to bout 3. Supplementation strategy had no effect on performance in the first bout, even with differences in pH and bicarbonate (HCO3-. Repeated sprint performance was not affected by supplementation strategy when compared to ACTIVE, while PASSIVE resulted in a more pronounced decrease in performance compared with all other interventions. BIC led to greater BLa, pH, and HCO3- values compared with all other interventions, while for PASSIVE the opposite was found. BLa recovery was lowest in PASSIVE; recovery in pH, and HCO3- was lower in PASSIVE and higher in BIC.

  9. In vivo predictive dissolution: transport analysis of the CO2 , bicarbonate in vivo buffer system.

    Science.gov (United States)

    Krieg, Brian J; Taghavi, Seyed Mohammad; Amidon, Gordon L; Amidon, Gregory E

    2014-11-01

    Development of an oral in vivo predictive dissolution medium for acid drugs with a pKa in the physiological range (e.g., Biopharmaceutics Classification System Class IIa) requires transport analysis of the complex in vivo CO2 /bicarbonate buffering system. In this report, we analyze this buffer system using hydrodynamically defined rotating disk dissolution. Transport analysis of drug flux was predicted using the film model approach of Mooney et al based on equilibrium assumptions as well as accounting for the slow hydration reaction, CO2 + H2 O → H2 CO3 . The accuracy of the models was compared with experimentally determined results using the rotating disk dissolution of ibuprofen, indomethacin, and ketoprofen. The equilibrium and slow hydration reaction rate models predict significantly different dissolution rates. The experimental results are more accurately predicted by accounting for the slow hydration reaction under a variety of pH and hydrodynamic conditions. Although the complex bicarbonate buffering system requires further consideration given its dynamic nature in vivo, a simplifying irreversible reaction (IRR) transport analysis accurately predicts in vitro rotating disk dissolution rates of several carboxylic acid drugs. This IRR transport model provides further insight into bicarbonate buffer and can be useful in developing more physiologically relevant buffer systems for dissolution testing.

  10. Effects of angiotensin II and ionomycin on fluid and bicarbonate absorption in the rat proximal tubule

    Energy Technology Data Exchange (ETDEWEB)

    Chatsudthipong, V.; Chan, Y.L.

    1986-03-01

    Microperfusion of proximal convoluted tubule(PCT) and peritubular capillaries was performed to examine the effects of angiotensin II(Ang II) and ionomycin on fluid and bicarbonate absorption. Bicarbonate was determined by microcalorimetry and C-14 inulin was used as a volume marker. The rates of bicarbonate absorption (JHCO/sub 3/) was 143 peq/min x mm and fluid absorption(Jv) was 2.70 nl/min x mm, when PCT and capillary perfusate contained normal Ringer solution. Addition of Ang II (10/sup -6/M) to the capillary perfusate caused reductions of JHCO/sub 3/ and Jv by 35%. A similar effect was observed when ionomycin was added to the capillary perfusate. Ang II antagonist, (Sar/sup 1/, Ile/sup 8/)-Angiotensin II(10/sup -6/M), completely blocked the inhibitory effect of Ang II on Jv and JHCO/sub 3/. Removal of calcium from both luminal and capillary perfusate did not change the effect of Ang II on Jv and JHCO/sub 3/. Our results indicate that Ang II inhibits the sodium-hydrogen exchanger in the proximal tubule via interacting with angiotensin receptor. The mechanism of Ang II action may involve mobilization of intracellular calcium.

  11. Effects of Bicarbonate and High pH Conditions on Zinc and Other Nutrients Absorption in Rice

    Institute of Scientific and Technical Information of China (English)

    LU Zhong-xian; MENG Fan-hua; S. VILLAREAL; WEI You-zhang; YU Xiao-ping; YANG Xiao-e; K. L. HEONG; LIN Jian-jun; HU Cui; LIU Jian-xiang

    2004-01-01

    Zinc deficiency was widely observed in calcareous soil where bicarbonate and high pH were always related with low zinc availability. In a hydroponic experiment, one zinc-efficient rice (IR36) and one zinc-inefficient rice (IR26) genotypes were employed to investigate the effects of bicarbonate and high pH conditions on absorption, transport of zinc and other nutrients (P, K, Ca, Mg,Fe, Cu, Mn) in rice. As compared with the control, high pH inhibited absorption, translocation and accumulation of zinc and other nutrients in both rice genotypes. Bicarbonate had minor effect on zinc-efficient rice genotype (IR36) whereas it could decrease zinc and other nutrient absorption in zinc-inefficient rice genotype (IR26). These results implied that increasing rice tolerance to bicarbonate is one of the most important strategies to improve rice adaptation for zinc-deficit calcareous soil.

  12. Bicarbonate secretion in vivo by rat distal tubules during alkalosis induced by dietary chloride restriction and alkali loading.

    OpenAIRE

    Levine, D Z; Iacovitti, M; Harrison, V

    1991-01-01

    To examine in vivo the separate effects on distal tubule JtCO2, of dietary chloride restriction, bicarbonate loading, and changes in luminal chloride concentration, we microperfused distal tubules at a physiologic flow rate (8 nl/min) with solutions containing either 45 or 0 mM chloride (after gluconate substitution). Rats were fed a diet containing zero, minimal, or normal amounts of chloride, while drinking either water or a solution of 0.15 M sodium bicarbonate. Neither extracellular fluid...

  13. No effect of bicarbonate treatment on insulin sensitivity and glucose control in non-diabetic older adults

    OpenAIRE

    Harris, Susan S.; Dawson-Hughes, Bess

    2010-01-01

    Chronic mild metabolic acidosis is common among older adults, and limited evidence suggests that it may contribute to insulin resistance and type-2 diabetes. This analysis was conducted to determine whether bicarbonate supplementation, an alkalinizing treatment, improves insulin sensitivity or glucose control in non-diabetic older adults. Fasting blood glucose and insulin were measured in stored samples from subjects who had completed a 3-month clinical trial of bicarbonate supplementation to...

  14. Speciation of technetium(IV) in bicarbonate media.

    Science.gov (United States)

    Alliot, Isabelle; Alliot, Cyrille; Vitorge, Pierre; Fattahi, Massoud

    2009-12-15

    The technetium isotope (99)Tc is a major fission product from nuclear reactors. Ultimately it is disposed of as radioactive waste since it has few applications outside of scientific research. Geochemical modeling of the dissolution of nuclear waste and of the solubility and speciation of the dissolved radionuclides in groundwater is an important part of the Performance Assessment for the safety of nuclear waste repositories. It relies on the availability of a critically assessed thermodynamic database. The potential of the Tc(VII)/Tc(IV) redox couple is measured here under various chemical conditions to verify the stoichiometries of Tc complexes and determine their stabilities: (i) -log(10)[H(+)] in the range 7.0-10.0, for 0.3, 0.6, and 0.7 M [CO(3)](total); (ii) [CO(3)](total) in the range 0.01-0.6 M at -log(10)[H(+)] approximately 8.6; and (iii) [Tc(VII)]/[Tc(IV] ratios of (6.02 10(-5) M)/(10(-6) M) and (6.02 10(-5) M)/(6.02 10(-5) M) at -log(10)[H(+)] = -9.1 and [CO(3)](total) = 1 M. Assuming that Tc(VII), TcO(4)(-) is the only species which exists under all the above chemical conditions, the potentiometric results can be interpreted by considering the presence of two hydroxide-carbonate monomeric complexes. The hydrolysis equilibrium between these two complexes is Tc(CO(3))(OH)(2) + H(2)O Tc(CO(3))(OH)(3)(-) + H(+) with -log(10)[H(+)](1/2) = 8.69 +/- 0.20, which is consistent with the -8.3 +/- 0.6 corresponding hydrolysis constant of the NEA TDB review. 733 +/- 44 mV/SHE and 575 +/- 60 mV/SHE are measured for the standard potentials of the TcO(4)(-)/Tc(CO(3))(OH)(2), and for the TcO(4)(-)/Tc(CO(3))(OH)(3)(-) redox couples respectively. The corresponding formation constants from TcO(OH)(2) are log(10)K(1,2) = 19.8 +/- 0.5 and log(10)K(1,3) = 10.5 +/- 0.5, to be compared with the 19.3 +/- 0.3 and 11.0 +/- 0.6 values proposed by the NEA TDB review. Note that these values have been converted for the formation reactions described here, thus the given values are not

  15. Sunflower trypsin inhibitor-1.

    Science.gov (United States)

    Korsinczky, Michael L J; Schirra, Horst Joachim; Craik, David J

    2004-10-01

    SFTI-1 is a bicyclic 14 amino acid peptide that was originally isolated from the seeds of the sunflower Helianthus annuus. It is a potent inhibitor of trypsin, with a sub-nanomolar K(i) value and is homologous to the active site region of the well-known family of serine protease inhibitors known as the Bowman-Birk trypsin inhibitors. It has a cyclic backbone that is cross-braced by a single disulfide bridge and a network of hydrogen bonds that result in a well-defined structure. SFTI-1 is amenable to chemical synthesis, allowing for the creation of synthetic variants. Alterations to the structure such as linearising the backbone or removing the disulfide bridge do not reduce the potency of SFTI-1 significantly, and minimising the peptide to as few as nine residues results in only a small decrease in reactivity. The creation of linear variants of SFTI-1 also provides a tool for investigating putative linear precursor peptides. The mechanism of biosynthesis of SFTI-1 is not yet known but it seems likely that it is a gene-coded product that has arisen from a precursor protein that may be evolutionarily related to classic Bowman-Birk inhibitors. PMID:15544530

  16. Specific and efficient targeting of cyanobacterial bicarbonate transporters to the inner envelope membrane of chloroplasts in Arabidopsis

    Directory of Open Access Journals (Sweden)

    Susumu eUehara

    2016-02-01

    Full Text Available Installation of cyanobacterial bicarbonate transporters to the inner envelope membrane (IEM of chloroplasts in C3 plants has been thought to improve photosynthetic performance. However, the method to deliver cyanobacterial bicarbonate transporters to the chloroplast IEM remains to be established. In this study, we provide evidence that the cyanobacterial bicarbonate transporters, BicA and SbtA, can be specifically installed into the chloroplast IEM using the chloroplast IEM targeting signal in conjunction with the transit peptide. We fused the transit peptide and the mature portion of Cor413im1, whose targeting mechanism to the IEM has been characterized in detail, to either BicA or SbtA isolated from Synechocystis sp. PCC6803. Among the seven chimeric constructs tested, we confirmed that four chimeric bicarbonate transporters, designated as BicAI, BicAII, SbtAII, and SbtAIII, were expressed in Arabidopsis. Furthermore, these chimeric transporters were specifically targeted to the chloroplast IEM. They were also resistant to alkaline extraction but can be solubilized by Triton X-100, indicating that they are integral membrane proteins in the chloroplast IEM. One of the transporters, BicA, could reside in the chloroplast IEM even after removal of the IEM targeting signal. Taken together, our results indicate that the addition of IEM targeting signal, as well as the transit peptide, to bicarbonate transporters allows us to efficiently target nuclear-encoded chimeric bicarbonate transporters to the chloroplast IEM.

  17. Production of tissue inhibitors of metalloproteinases (TIMPs) by pig ovarian cells in vivo and the effect of TIMP-1 on steroidogenesis in vitro.

    Science.gov (United States)

    Shores, E M; Hunter, M G

    2000-09-01

    Precisely which ovarian cells produce tissue inhibitors of metalloproteinases (TIMPs) is unclear. Although granulosa cells are reported to produce TIMPs, thecal TIMP production has not been investigated nor has the influence of TIMPs on theca cells. Furthermore, although periovulatory follicles have been examined, little is known about smaller ovarian follicles. Follicles >/= 2 mm in diameter were collected from Large White hybrid gilts on the day before predicted oestrus (n = 3) or after hCG treatment (n = 3) and divided into 1 mm size classes. Small (2 to /= 5 mm were separated into follicular fluid, granulosa and theca cell compartments. After homogenization, TIMP-1, -2 and -3 were detected by reverse zymography. Theca cells (50 x 10(3) per well) were cultured with TIMP-1 (10, 100 or 200 ng ml(-1) with or without long-R3 insulin-like growth factor I (IGF-I)) in a serum-free system to investigate the effect on steroidogenesis and the number of cells. Both large and small pig follicles produced TIMPs and TIMP-1, -2 and -3 were detected in follicular fluid, granulosa and theca cell samples. There was a phase x tissue type interaction for the presence of both TIMP-1 and -2 (P 0.05), and the highest concentrations occurred in the theca tissue. There were tissue type x follicle size interactions for the presence of both TIMP-1 and -2 (P < 0.001). In vitro, TIMP-1 increased thecal steroidogenesis after 144 h (oestradiol, P < 0.05, progesterone, P < 0.001) but reduced the number of viable cells (P < 0.001). In conclusion, TIMP-1, -2 and -3 were present in large and small pig follicles and were produced by both granulosa and theca cells, although concentrations differed with the type of tissue. Production was regulated by factors including follicle size and phase of the oestrous cycle. In addition to controlling tissue remodelling, TIMP-1 may also regulate steroidogenesis. PMID:11006148

  18. Effects of Nitric Oxide Production Inhibitor Named, NG-Nitro-L-Arginine Methyl Ester (L-NAME, on Rat Mesenchymal Stem Cells Differentiation

    Directory of Open Access Journals (Sweden)

    E Arfaei

    2010-04-01

    Full Text Available Introduction & Objectives: Recently, the findings of some studies have shown that, nitric oxide (NO probably has an important role in differentiation of mesenchymal stem cells to osteoblasts. The aim of the present investigation was to study the effects of nitric oxide production inhibitor named, NG-nitro-L-arginine methyl ester (L-NAME, on rat mesenchymal stem cells differentiation to osteoblasts in vitro. Materials & Methods: This was an experimental study conducted at Hamedan University of Medical Sciences in 2009, in which rat bone marrow stem cells were isolated in an aseptic condition and cultured in vitro. After third passage, the cells were cultured in osteogenic differentiation medium. To study the effects of L-NAME on osteogenic differentiation, the L-NAME was added to the culture medium at a concentration of 125, 250, and 500 μM in some culture plates. During the culture procedure, the media were replaced with fresh ones, with a three days interval. After 28 days of culturing the mineralized matrix was stained using Alizarian red staining method. The gathered data were analyzed by SPSS software version 12 using one way ANOVA. Results: The findings of this study showed that in the presence of L-NAME, differentiation of bone marrow mesenchymal stem cells to osteoblasts was disordered and matrix mineralization significantly decreased in a dose dependent manner. Conclusion: This study revealed that, inhibition of nitric oxide production using L-NAME can prevent the differentiation of rat bone marrow mesenchymal stem cells to osteoblast. The results imply that NO is an important constituent in differentiation of mesenchymal stem cell to osteoblasts.

  19. The influencing factors of Sodium Bicarbonate Injection and the controlling measures%影响碳酸氢钠注射液质量的因素与控制措施

    Institute of Scientific and Technical Information of China (English)

    冯燕

    2015-01-01

    To study the factors that affect the quality of Sodium Bicarbonate Injection from the producing procedure;To discuss and analyze the stability problems and the existance of visible foreign matters confronted in the procedure of Sodium Bicarbonate Injection producing. To raise the improving measures,ensure and improve product quality.%从制剂生产过程探讨影响碳酸氢钠质量的影响因素及改进措施。对碳酸氢钠注射液生产中常面临的稳定性问题、可见异物问题进行分析讨论,提出改进措施,保证和提高产品质量。

  20. Suppression on plant-parasitic nematodes using a soil fumigation strategy based on ammonium bicarbonate and its effects on the nematode community.

    Science.gov (United States)

    Su, Lanxi; Ruan, Yunze; Yang, Xiujuan; Wang, Kang; Li, Rong; Shen, Qirong

    2015-12-01

    Banana production is severely hindered by plant-parasitic nematodes in acidic, sandy soil. This study investigated the possibility of applying a novel fumigation agent based on ammonium bicarbonate as a strategy for controlling plant-parasitic nematodes under sealed conditions. Moreover, its effects on the nematode community in pot and field experiments were also measured using morphology and feeding-habit based classification and the PCR-DGGE method. Results showed that a mixture (LAB) of lime (L) and ammonium bicarbonate (AB) in suitable additive amounts (0.857 g kg(-1) of L and 0.428 g kg(-1) of AB) showed stronger nematicidal ability than did the use of AB alone or the use of ammonium hydroxide (AH) and calcium cyanamide (CC) with an equal nitrogen amount. The nematode community was altered by the different fumigants, and LAB showed an excellent plant-parasitic nematicidal ability, especially for Meloidogyne and Rotylenchulus, as revealed by morphology and feeding-habit based classification, and for Meloidogyne, as revealed by the PCR-DGGE method. Fungivores and omnivore-predators were more sensitive to the direct effects of the chemicals than bacterivores. This study explored a novel fumigation agent for controlling plant-parasitic nematodes based on LAB and provides a potential strategy to ensure the worldwide development of the banana industry.

  1. Comparison of the Kinetic Rate Law Parameters for the Dissolution of Natural and Synthetic Autunite in the Presence of Aqueous Bicarbonate Ions

    Energy Technology Data Exchange (ETDEWEB)

    Gudavalli, Ravi; Katsenovich, Yelena; Wellman, Dawn M.; Idarraga, Melina; Lagos, Leonel; Tansel, Berrin

    2013-08-02

    Bicarbonate is one of the most significant components within the uranium geochemical cycle. In aqueous solutions, bicarbonate forms strong complexes with uranium. As such, aqueous bicarbonate may significantly increase the rate of uranium release from uranium minerals. Quantifying the relationship of aqueous bicarbonate concentration to the rate of uranium release during dissolution is critical to understanding the long-term fate of uranium within the environment. Single-pass flow-through (SPTF) experiments were conducted to estimate the rate of uranium release from Na meta-autunite as a function of bicarbonate (0.0005-0.003 M) under the pH range of 6-11 and a temperature range of 5-60oC. Consistent with the results of previous investigation, the rate of uranium release exhibited minimal dependency on temperature; but were strongly dependent on pH. Increasing aqueous bicarbonate concentrations afforded comparable increases in the rate of release of uranium. Most notably under low pH conditions the aqueous bicarbonate resulted in up to 370 fold increases in the rate of uranium release in relative to the rate of uranium release in the absence of bicarbonate. However, the effect of aqueous bicarbonate on the release of uranium was significantly less under higher pH conditions. It is postulated that at high pH values, surface sites are saturated with carbonate, thus the addition of more bicarbonate would have less effect on uranium release.

  2. Physical and chemical properties of a durably efficacious ammonium bicarbonate as a fertilizer and its yield-increasing mechanism

    Institute of Scientific and Technical Information of China (English)

    张志明; 李继云; 冯元琦; 毕庶春; 伍蔚民

    1997-01-01

    A new fertilizer of cocrystal type,known as durably efficacious ammonium bicarbonate (DEAB),has been developed by adding a certain amount of dicyandiamide (DCD) as an ammonia-stabilizing agent to ammonium bearbenate(AB)during the process of its production.As compared with AB,DEAB was found to have a reduction of direct volatilization loss by 53%,a fertilizer availability period prolonged from 35-45 to 90-110 d,and an increase in the rate of nitrogen in fertilizer being utilized by 5.9%-10.2%,and a saving of the amount of fertilizer to be ap-phed by 20%-30% for the same level of yield,or an increase of the crop yield by over 10% for the same level of ni-tregen fertilization;in addition,it was found to show usually a function of promoting the crop to early mature.It can be apptied as basal dressing all in one time to soil and thus also used as a labour-saving and crop yield-increasing fertil-izer for is non-mtertillage,plastics film covering and water-saving agriculture

  3. Chemical Fixation of CO2 in Coal Combustion Products and Recycling through Biosystems

    Energy Technology Data Exchange (ETDEWEB)

    C. Henry Copeland; Paul Pier; Samantha Whitehead; David Behel

    2001-09-30

    This Annual Technical Progress Report presents the principle results in enhanced growth of algae using coal combustion products as a catalyst to increase bicarbonate levels in solution. A co-current reactor is present that increases the gas phase to bicarbonate transfer rate by a factor of five to nine. The bicarbonate concentration at a given pH is approximately double that obtained using a control column of similar construction. Algae growth experiments were performed under laboratory conditions to obtain baseline production rates and to perfect experimental methods. The final product of this initial phase in algae production is presented.

  4. Quantification of Kinetic Rate Law Parameters of Uranium Release from Sodium Autunite as a Function of Aqueous Bicarbonate Concentrations

    Energy Technology Data Exchange (ETDEWEB)

    Gudavalli, Ravi; Katsenovich, Yelena; Wellman, Dawn M.; Lagos, Leonel; Tansel, Berrin

    2013-09-05

    ABSTRACT: Hydrogen carbonate is one of the most significant components within the uranium geochemical cycle. In aqueous solutions, hydrogen carbonate forms strong complexes with uranium. As such, aqueous bicarbonate may significantly increase the rate of uranium release from uranium minerals. Quantifying the relationship of aqueous hydrogen carbonate solutions to the rate of uranium release during dissolution is critical to understanding the long-term fate of uranium within the environment. Single-pass flow-through (SPTF) experiments were conducted to estimate the rate of uranium release from Na meta-autunite as a function of bicarbonate solutions (0.0005-0.003 M) under the pH range of 6-11 and temperatures of 5-60oC. Consistent with the results of previous investigation, the rate of uranium release from sodium autunite exhibited minimal dependency on temperature; but were strongly dependent on pH and increasing concentrations of bicarbonate solutions. Most notably at pH 7, the rate of uranium release exhibited 370 fold increases relative to the rate of uranium release in the absence of bicarbonate. However, the effect of increasing concentrations of bicarbonate solutions on the release of uranium was significantly less under higher pH conditions. It is postulated that at high pH values, surface sites are saturated with carbonate, thus the addition of more bicarbonate would have less effect on uranium release. Results indicate the activation energies were unaffected by temperature and bicarbonate concentration variations, but were strongly dependent on pH conditions. As pH increased from 6 to 11, activation energy values were observed to decrease from 29.94 kJ mol-1 to 13.07 kJ mol-1. The calculated activation energies suggest a surface controlled dissolution mechanism.

  5. Tumor necrosis factor-α promotes cholestasis-induced liver fibrosis in the mouse through tissue inhibitor of metalloproteinase-1 production in hepatic stellate cells.

    Directory of Open Access Journals (Sweden)

    Yosuke Osawa

    Full Text Available Tumor necrosis factor (TNF-α, which is a mediator of hepatotoxicity, has been implicated in liver fibrosis. However, the roles of TNF-α on hepatic stellate cell (HSC activation and liver fibrosis are complicated and remain controversial. To explore this issue, the role of TNF-α in cholestasis-induced liver fibrosis was examined by comparing between TNF-α(-/- mice and TNF-α(+/+ mice after bile duct ligation (BDL. Serum TNF-α levels in mice were increased by common BDL combined with cystic duct ligation (CBDL+CDL. TNF-α deficiency reduced liver fibrosis without affecting liver injury, inflammatory cell infiltration, and liver regeneration after CBDL+CDL. Increased expression levels of collagen α1(I mRNA, transforming growth factor (TGF-β mRNA, and α-smooth muscle actin (αSMA protein by CBDL+CDL in the livers of TNF-α(-/- mice were comparable to those in TNF-α(+/+ mice. Exogenous administration of TNF-α decreased collagen α1(I mRNA expression in isolated rat HSCs. These results suggest that the reduced fibrosis in TNF-α(-/- mice is regulated in post-transcriptional level. Tissue inhibitor of metalloproteinase (TIMP-1 plays a crucial role in the pathogenesis of liver fibrosis. TIMP-1 expression in HSCs in the liver was increased by CBDL+CDL, and the induction was lower in TNF-α(-/- mice than in TNF-α(+/+ mice. Fibrosis in the lobe of TIMP-1(-/- mice with partial BDL was also reduced. These findings indicate that TNF-α produced by cholestasis can promote liver fibrosis via TIMP-1 production from HSCs. Thus, targeting TNF-α and TIMP-1 may become a new therapeutic strategy for treating liver fibrosis in cholestatic liver injury.

  6. Bicarbonate and Ca2+ sensing modulators activate photoreceptor ROS-GC1 synergistically

    Directory of Open Access Journals (Sweden)

    Teresa eDuda

    2016-01-01

    Full Text Available Photoreceptor ROS-GC1, a prototype subfamily member of the membrane guanylate cyclase family, is a central component of phototransduction. It is a single transmembrane-spanning protein, composed of modular blocks. In rods, guanylate cyclase activating proteins (GCAPs 1 and 2 bind to its juxtamembrane domain and the C-terminal extension, respectively, to accelerate cyclic GMP synthesis when Ca2+ levels are low. In cones, the additional expression of the Ca2+-dependent guanylate cyclase activating protein (CD-GCAP S100B which binds to its C-terminal extension, supports acceleration of cyclic GMP synthesis at high Ca2+ levels. Independent of Ca2+, ROS-GC1 activity is also stimulated directly by bicarbonate binding to the core catalytic domain. Several enticing molecular features of this transduction system are revealed in the present study. In combination, bicarbonate and Ca2+-dependent modulators raised maximal ROS-GC activity to levels that exceeded the sum of their individual effects. The F514S mutation in ROS-GC1 that causes blindness in type 1 Leber’s congenital amaurosis severely reduced basal ROS-GC1 activity. GCAP2 and S100B Ca2+ signaling modes remained functional, while the GCAP1-modulated mode was diminished. Bicarbonate nearly restored basal activity as well as GCAP2- and S100B-stimulated activities of the F514S mutant to normal levels but could not resurrect GCAP1 stimulation. We conclude that GCAP1 and GCAP2 forge distinct pathways through domain-specific modules of ROS-GC1 whereas the S100B and GCAP2 pathways may overlap. The synergistic interlinking of bicarbonate to GCAPs- and S100B-modulated pathways intensifies and tunes the dependence of cyclic GMP synthesis on intracellular Ca2+. Our study challenges the recently proposed GCAP1 and GCAP2 overlapping phototransduction model (Peshenko, I.V., Olshevskaya, and Dizhoor, A. M. (2015 J Biol. Chem 290, 6913-6924.

  7. Sodium Bicarbonate Prevents Contrast-Induced Nephropathy in Addition to Theophylline: A Randomized Controlled Trial.

    Science.gov (United States)

    Huber, Wolfgang; Huber, Toni; Baum, Stephan; Franzen, Michael; Schmidt, Christian; Stadlbauer, Thomas; Beitz, Analena; Schmid, Roland M; Schmid, Sebastian

    2016-05-01

    In this study, we investigated whether hydration with sodium bicarbonate is superior to hydration with saline in addition to theophylline (both groups) in the prophylaxis of contrast-induced nephropathy (CIN). It was a prospective, randomized, double-blinded study in a university hospital on 2 general intensive care units (63% of investigations) and normal wards.After approval of the local ethics committee and informed consent 152 patients with screening serum creatinine ≥1.1 mg/dL and/or at least 1 additional risk factor for CIN undergoing intravascular contrast media (CM) exposure were randomized to receive a total of 9 mL/kg bicarbonate 154 mmol/L (group B; n = 74) or saline 0.9% (group S; n = 78) hydration within 7 h in addition to intravenous application of 200 mg theophylline. Serum creatinine was determined immediately before, 24 and 48 h after CM exposure. As primary endpoint we investigated the incidence of CIN (increase of serum creatinine ≥0.5 mg/dL and/or ≥25% within 48 h of CM).Both groups were comparable regarding baseline characteristics. Incidence of CIN was significantly less frequent with bicarbonate compared to sodium hydration (1/74 [1.4%] vs 7/78 [9.0%]; P = 0.035). Time course of serum creatinine was more favorable in group B with decreases in serum creatinine after 24 h (-0.084 mg/dL [95% confidence interval: -0.035 to -0.133 mg/dL]; P = 0.008) and 48 h (-0.093 mg/dL (-0.025 to -0.161 mg/dL); P = 0.007) compared to baseline which were not observed in group S.In patients at increased risk of CIN receiving prophylactic theophylline, hydration with sodium bicarbonate reduces contrast-induced renal impairment compared to hydration with saline. PMID:27227933

  8. CRACK2. Modelling calcium carbonate deposition from bicarbonate solutions in cracks in concrete

    DEFF Research Database (Denmark)

    Brodersen, Knud Erik

    2003-01-01

    by diffusion in pore systems in columns of cementitious materials. The hydroxyl is precipitating calcite from a flow of bicarbonate solution in a crack connecting the ends of a row of such columns. Thecementitious material is simulated as calcium hydroxide mixed with inert material but with sodium hydroxide...... and on the composition of the outflowing solution, which can be compared directly with experimental results.Leaching behavior of sodium can be used to tune the model to experimental observations. The calcite is mostly precipitated on top of the original crack surface and may under certain circumstances fill the crack...

  9. The burden of inhibitors in haemophilia patients.

    Science.gov (United States)

    Walsh, Christopher E; Jiménez-Yuste, Víctor; Auerswald, Guenter; Grancha, Salvador

    2016-08-31

    The burden of disease in haemophilia patients has wide ranging implications for the family and to society. There is evidence that having a current inhibitor increases the risk of morbidity and mortality. Morbidity is increased by the inability to treat adequately and its consequent disabilities, which then equates to a poor quality of life compared with non-inhibitor patients. The societal cost of care, or `burden of inhibitors', increases with the ongoing presence of an inhibitor. Therefore, it is clear that successful eradication of inhibitors by immune tolerance induction (ITI) is the single most important milestone one can achieve in an inhibitor patient. The type of factor VIII (FVIII) product used in ITI regimens varies worldwide. Despite ongoing debate, there is in vitro and retrospective clinical evidence to support the use of plasma-derived VWF-containing FVIII concentrates in ITI regimens in order to achieve early and high inhibitor eradication success rates. PMID:27528280

  10. Association between serum bicarbonate and pH with depression, cognition and sleep quality in hemodialysis patients.

    Science.gov (United States)

    Afsar, Baris; Elsurer, Rengin

    2015-07-01

    Metabolic acidosis is a common feature in chronic renal failure patients, worsening progressively as renal function declines. There are conflicting data in hemodialysis (HD) patients with regard to acidosis, alkalosis and mortality. In HD patients, cognitive impairment, depression, sleep disorders and impaired quality of life are very common. Besides, these conditions are related with increased morbidity and mortality. However, no previous study investigated the relationship between pH, venous bicarbonate and anion gap with depression, sleep problems and cognitive function in HD patients. In this study we investigated these relationships. In total, 65 HD patients were included. The demographic parameters and laboratory parameters including bicarbonate, pH and anion gap was measured for all patients. Depressive symptoms, sleep quality and cognitive function, were measured by Beck depression inventory, The Pittsburgh Sleep Quality Index and by Mini Mental State Examination, respectively. We found that, sleep quality but not cognitive function or depression was independently related with venous pH and bicarbonate. Anion gap has no independent relationship with sleep quality, cognitive function and depression. In conclusion, metabolic acidosis and bicarbonate levels were independently related with sleep quality in HD patients. However, there was no association between metabolic acidosis and bicarbonate levels with cognitive function and depression.

  11. Association between serum bicarbonate and pH with depression, cognition and sleep quality in hemodialysis patients.

    Science.gov (United States)

    Afsar, Baris; Elsurer, Rengin

    2015-07-01

    Metabolic acidosis is a common feature in chronic renal failure patients, worsening progressively as renal function declines. There are conflicting data in hemodialysis (HD) patients with regard to acidosis, alkalosis and mortality. In HD patients, cognitive impairment, depression, sleep disorders and impaired quality of life are very common. Besides, these conditions are related with increased morbidity and mortality. However, no previous study investigated the relationship between pH, venous bicarbonate and anion gap with depression, sleep problems and cognitive function in HD patients. In this study we investigated these relationships. In total, 65 HD patients were included. The demographic parameters and laboratory parameters including bicarbonate, pH and anion gap was measured for all patients. Depressive symptoms, sleep quality and cognitive function, were measured by Beck depression inventory, The Pittsburgh Sleep Quality Index and by Mini Mental State Examination, respectively. We found that, sleep quality but not cognitive function or depression was independently related with venous pH and bicarbonate. Anion gap has no independent relationship with sleep quality, cognitive function and depression. In conclusion, metabolic acidosis and bicarbonate levels were independently related with sleep quality in HD patients. However, there was no association between metabolic acidosis and bicarbonate levels with cognitive function and depression. PMID:25894326

  12. Effect of vasoactive intestinal polypeptide and somatostatin on secretion of epidermal growth factor and bicarbonate from Brunner's glands

    DEFF Research Database (Denmark)

    Poulsen, Steen Seier

    1984-01-01

    The effect of VIP and somatostatin on secretion of epidermal growth factor and bicarbonate from Brunner's glands was investigated in the rat. Vasoactive intestinal polypeptide infused in doses of 10 and 100 ng/kg/h significantly increased epidermal growth factor and bicarbonate output, but the co......The effect of VIP and somatostatin on secretion of epidermal growth factor and bicarbonate from Brunner's glands was investigated in the rat. Vasoactive intestinal polypeptide infused in doses of 10 and 100 ng/kg/h significantly increased epidermal growth factor and bicarbonate output......, but the concentrations did not change. Somatostatin infused at doses of 1, 10, 100 and 1000 ng/kg/h against a background of VIP 100 ng/kg/h inhibited in dose-dependent fashion the stimulated epidermal growth factor and bicarbonate outputs from rat Brunner's gland pouches. Also basal secretion was inhibited...... by somatostatin. Infusion of antisomatostatin serum stimulated Brunner's gland secretion. By immunohistochemical studies of rat duodena, it was found that epidermal growth factor, is almost exclusively present in the secretory cells of Brunner's glands. It is concluded that VIP stimulates secretion of epidermal...

  13. Quantified pH imaging with hyperpolarized 13C‐bicarbonate

    DEFF Research Database (Denmark)

    Scholz, David Johannes; Janich, Martin A.; Köllisch, Ulrich;

    2015-01-01

    Because pH plays a crucial role in several diseases, it is desirable to measure pH in vivo noninvasively and in a spatially localized manner. Spatial maps of pH were quantified in vitro, with a focus on method‐based errors, and applied in vivo. In vitro and in vivo 13C mapping were performed...... for various flip angles for bicarbonate (BiC) and CO2 with spectral‐spatial excitation and spiral readout in healthy Lewis rats in five slices. Acute subcutaneous sterile inflammation was induced with Concanavalin A in the right leg of Buffalo rats. pH and proton images were measured 2 h after induction....... After optimizing the signal to noise ratio of the hyperpolarized 13C‐bicarbonate, error estimation of the spectral‐spatial excited spectrum reveals that the method covers the biologically relevant pH range of 6 to 8 with low pH error (pH maps shows negligible impact...

  14. Integrated control of Penicillium digitatum by the predacious yeast Saccharomycopsis crataegensis and sodium bicarbonate on oranges

    Directory of Open Access Journals (Sweden)

    R. S. Pimenta

    2010-06-01

    Full Text Available Our investigation of integrated biological control (IBC started with an assay testing activity of the predacious yeast Saccharomycopsis crataegensis UFMG-DC19.2 against Penicillium digitatum LCP 4354, a very aggressive fungus that causes postharvest decay in oranges. Under unfavourable environmental conditions, the yeast showed a high potential for control (39.9% disease severity reduction of this fungus. This result was decisive for the next step, in which S. crataegensis was tested in association with sodium bicarbonate salt, a generally regarded as safe (GRAS substance. The yeast was able to survive at different concentrations of the salt (1%, 2% and 5%, and continued to grow for a week at the wound site, remaining viable at high population for 14 days on the fruit surface. The yeast alone reduced the severity of decay by 41.7% and sodium bicarbonate alone reduced severity of decay by 19.8%, whereas the application of both led to a delay in the development of symptoms from 2 to 10 days. Ingredients of the formulations were not aggressive to fruits since no lesions were produced in control experiments.

  15. CRACK2 - Modelling calcium carbonate deposition from bicarbonate solution in cracks in concrete

    Energy Technology Data Exchange (ETDEWEB)

    Brodersen, K

    2003-03-01

    The numerical CRACK2 model simulates precipitation of calcite from calcium bicarbonate solution (e.g. groundwater) passing through cracks in concrete or other cementitious materials. A summary of experimental work is followed by a detailed description of the model. Hydroxyl ions are transported by diffusion in pore systems in columns of cementitious materials. The hydroxyl is precipitating calcite from a flow of bicarbonate solution in a crack connecting the ends of a row of such columns. The cementitious material is simulated as calcium hydroxide mixed with inert material but with sodium hydroxide dissolved in the pore solution. Diffusive migration of cesium as radioactive isotope is also considered. Electrical interaction of the migrating ions is taken into account. Example calculations demonstrate effects of parameter variations on distribution of precipitated calcite in the crack and on the composition of the outflowing solution, which can be compared directly with experimental results. Leaching behavior of sodium can be used to tune the model to experimental observations. The calcite is mostly precipitated on top of the original crack surface and may under certain circumstances fill the crack. The produced thin layers of low porosity calcite act as a diffusion barrier limiting contact between cement and solution. Pore closure mechanisms in such layers are discussed. Implications for safety assessment of radioactive waste disposal are shortly mentioned. The model is also relevant for conventional uses of concrete. (au)

  16. Bicarbonate correction of ketoacidosis alters host-pathogen interactions and alleviates mucormycosis.

    Science.gov (United States)

    Gebremariam, Teclegiorgis; Lin, Lin; Liu, Mingfu; Kontoyiannis, Dimitrios P; French, Samuel; Edwards, John E; Filler, Scott G; Ibrahim, Ashraf S

    2016-06-01

    Patients with diabetic ketoacidosis (DKA) are uniquely predisposed to mucormycosis, an angioinvasive fungal infection with high mortality. Previously, we demonstrated that Rhizopus invades the endothelium via binding of fungal CotH proteins to the host receptor GRP78. Here, we report that surface expression of GRP78 is increased in endothelial cells exposed to physiological concentrations of β-hydroxy butyrate (BHB), glucose, and iron that are similar to those found in DKA patients. Additionally, expression of R. oryzae CotH was increased within hours of incubation with DKA-associated concentrations of BHB, glucose, and iron, augmenting the ability of R. oryzae to invade and subsequently damage endothelial cells in vitro. BHB exposure also increased fungal growth and attenuated R. oryzae neutrophil-mediated damage. Further, mice given BHB developed clinical acidosis and became extremely susceptible to mucormycosis, but not aspergillosis, while sodium bicarbonate reversed this susceptibility. BHB-related acidosis exerted a direct effect on both GRP78 and CotH expression, an effect not seen with lactic acidosis. However, BHB also indirectly compromised the ability of transferrin to chelate iron, as iron chelation combined with sodium bicarbonate completely protected endothelial cells from Rhizopus-mediated invasion and damage. Our results dissect the pathogenesis of mucormycosis during ketoacidosis and reinforce the importance of careful metabolic control of the acidosis to prevent and manage this infection. PMID:27159390

  17. Bicarbonate transporters in corals point towards a key step in the evolution of cnidarian calcification

    KAUST Repository

    Zoccola, Didier

    2015-06-04

    The bicarbonate ion (HCO3−) is involved in two major physiological processes in corals, biomineralization and photosynthesis, yet no molecular data on bicarbonate transporters are available. Here, we characterized plasma membrane-type HCO3− transporters in the scleractinian coral Stylophora pistillata. Eight solute carrier (SLC) genes were found in the genome: five homologs of mammalian-type SLC4 family members, and three of mammalian-type SLC26 family members. Using relative expression analysis and immunostaining, we analyzed the cellular distribution of these transporters and conducted phylogenetic analyses to determine the extent of conservation among cnidarian model organisms. Our data suggest that the SLC4γ isoform is specific to scleractinian corals and responsible for supplying HCO3− to the site of calcification. Taken together, SLC4γ appears to be one of the key genes for skeleton building in corals, which bears profound implications for our understanding of coral biomineralization and the evolution of scleractinian corals within cnidarians.

  18. Patterns in the Parathyroid Response to Sodium Bicarbonate Infusion Test in Healthy Volunteers

    Directory of Open Access Journals (Sweden)

    Theodossis S. Papavramidis

    2014-01-01

    Full Text Available Background. The sodium bicarbonate infusion test evaluates the function of the parathyroid glands. The present study aims to evaluate the range of parathyroid response in healthy individuals and the potential influence of various factors. Methods. Fifty healthy volunteers were subjected to the test. Levels of vitamin D, calcium, albumin, and PTH were measured before infusion. PTH was measured at 3, 5, 10, 30, and 60 minutes after infusion. Results. A curve describing the response of parathyroids to the test was drawn. Twenty percent of the subjects had blunted PTH response. No significant difference was observed between normal and blunted responders concerning age, BMI, baseline PTH, or calcium levels. Nonetheless, there was a significant difference in vitamin D levels (P=0.024. Interpretation. The test is easy to perform and may be used for everyday screening. It has to be clarified whether our observations are, at least partly, produced due to the presence of individuals with a constitutively blunted response or if low levels of vitamin D decrease the ability of the parathyroids to respond. Whichever the case, PTH response of normal individuals to sodium bicarbonate infusion test is more varied than previously thought and vitamin D levels influence it.

  19. Catalytic scavenging of peroxynitrite by lactoperoxidase in the absence and presence of bicarbonate.

    Science.gov (United States)

    Gebicka, Lidia; Didik, Joanna; Gebicki, Jerzy L

    2010-02-01

    The kinetics of the reaction of lactoperoxidase with peroxynitrite was studied under neutral and acidic pH. Lactoperoxidase catalyses peroxynitrite decay with the rate constant, k(c), increasing with decreasing pH. The values of k(c) obtained at pH 7.1, 6.1 and 5.1 are (1.9+/-0.1)x10(6), (5.0+/-0.1)x10(6) and (8.5+/-0.2)x10(6) M(-1)s(-1), respectively. This tendency means that peroxynitrous acid is the species involved in the reaction with the catalytic centre of lactoperoxidase. Lactoperoxidase is also able to scavenge peroxynitrite in the presence of bicarbonate with the rate constant identical, within experimental error, to that measured in the absence of bicarbonate. It is thus concluded that CO(3)-(.)/(.)NO(.2) radicals formed in the system do not inactivate LPO. The mechanism of the catalytic scavenging of peroxynitrite by LPO is proposed. The physiological relevance of this reaction is discussed.

  20. Effect of carbohydrate or sodium bicarbonate ingestion on performance during a validated basketball simulation test.

    Science.gov (United States)

    Afman, Gregg; Garside, Richard M; Dinan, Neal; Gant, Nicholas; Betts, James A; Williams, Clyde

    2014-12-01

    Current recommendations for nutritional interventions in basketball are largely extrapolated from laboratory-based studies that are not sport-specific. We therefore adapted and validated a basketball simulation test relative to competitive basketball games using well-trained basketball players (n = 10), then employed this test to evaluate the effects of two common preexercise nutritional interventions on basketball-specific physical and skilled performance. Specifically, in a randomized and counterbalanced order, participants ingested solutions providing either 75 g carbohydrate (sucrose) 45 min before exercise (Study A; n = 10) or 2 × 0.2 g · kg(-1) sodium bicarbonate (NaHCO3) 90 and 20 min before exercise (Study B; n = 7), each relative to appropriate placebos (H2O and 2 × 0.14 g · kg(-1) NaCl, respectively). Heart rate, sweat rate, pedometer count, and perceived exertion did not systematically differ between the 60-min basketball simulation test and competitive basketball, with a strong positive correlation in heart rate response (r = .9, p basketball simulation test provides a valid reflection of physiological demands in competitive basketball and is sufficiently sensitive to detect meaningful changes in physical and skilled performance. While there are benefits of preexercise carbohydrate or sodium bicarbonate ingestion, these should be balanced against potential negative side effects.

  1. HDAC Inhibitors.

    Science.gov (United States)

    Olzscha, Heidi; Bekheet, Mina E; Sheikh, Semira; La Thangue, Nicholas B

    2016-01-01

    Lysine acetylation in proteins is one of the most abundant posttranslational modifications in eukaryotic cells. The dynamic homeostasis of lysine acetylation and deacetylation is dictated by the action of histone acetyltransferases (HAT) and histone deacetylases (HDAC). Important substrates for HATs and HDACs are histones, where lysine acetylation generally leads to an open and transcriptionally active chromatin conformation. Histone deacetylation forces the compaction of the chromatin with subsequent inhibition of transcription and reduced gene expression. Unbalanced HAT and HDAC activity, and therefore aberrant histone acetylation, has been shown to be involved in tumorigenesis and progression of malignancy in different types of cancer. Therefore, the development of HDAC inhibitors (HDIs) as therapeutic agents against cancer is of great interest. However, treatment with HDIs can also affect the acetylation status of many other non-histone proteins which play a role in different pathways including angiogenesis, cell cycle progression, autophagy and apoptosis. These effects have led HDIs to become anticancer agents, which can initiate apoptosis in tumor cells. Hematological malignancies in particular are responsive to HDIs, and four HDIs have already been approved as anticancer agents. There is a strong interest in finding adequate biomarkers to predict the response to HDI treatment. This chapter provides information on how to assess HDAC activity in vitro and determine the potency of HDIs on different HDACs. It also gives information on how to analyze cellular markers following HDI treatment and to analyze tissue biopsies from HDI-treated patients. Finally, a protocol is provided on how to detect HDI sensitivity determinants in human cells, based on a pRetroSuper shRNA screen upon HDI treatment. PMID:27246222

  2. STUDY & EVALUATE THE COMPARISON OF PLAIN LIGNOCAINE AND LIGNACAINE WITH SODIUM BICARBONATE EFFECTS IN SUPRACLAVICULAR BRACHIAL PLEXUS BLOCK

    Directory of Open Access Journals (Sweden)

    Vijetha

    2015-08-01

    Full Text Available BACKGROUND & AIMS : supraclavicular brachial plexus block is usually used to anaesthetize the upper limb for the purpose of upper limb surgeries. Drugs like Lignocaine , Bupiv a caine are used for this block and some additives are added to prolong the duration and quality of bl ockade. The present study is aimed to evaluate the comparison of plain lignocaine and lign o caine with sodium bicarbonate in supraclavicular brachial plexus block by means of the onset time of sensory and motor blockade, the quality of sensory and motor blo ckade , and the duration of blockade . METHODS : Sixty patients aged between 18 and 60 years of physical status ASA 1 and 2 undergoing upper limb surgeries lasting more than 30 minutes were included in the study. The patients were randomly allocated into two groups. Supraclavicular brachial plexus block was performed after eliciting paraesthesia. The patients in Group I (n=30 received 25ml of 1% plain lignocaine (prepared by adding 12.5ml of distilled water to 12.5ml of 2% plain lignocaine. The patients in th e Group II (study group received 25ml of 1% alkalinized lignocaine (prepared by adding 3ml of 7.5% sodium bicarbonate and 9.5ml of distilled water to 12.5ml of 2% plain lignocaine. RESULTS : The present study entitled Comparison of effects of plain lignoc aine and lignocaine with sodium bicarbonate on brachial plexus block concludes that, the onset time of sensory and motor blockade is lesser with sodium bicarbonate added lignocaine (4.13, 11.1minutes when compared to plain lignocaine(9.73, 21.1minutes in supraclavicular brachial plexus block, the quality of sensory and motor blockade is better with sodium bicarbonate added lignocaine, the duration of motor and sensory blockade was significantly prolonged when lignocaine with sodium bicarbonate was used in supraclavicular brachial plexus block

  3. 透明质酸钠预防术后硬功夫膜外瘢痕粘连性疼痛的研究%Study on sodium hyaluronate product as inhibitor of pain due to epidural cicatrization

    Institute of Scientific and Technical Information of China (English)

    孟国良; 刘文俊; 刘启明

    2002-01-01

    Objective To evaluate the clinical effect of sodium hyaluronate product(SHP) used as inhibitor to preventing the formation of epidural scar.Method 160 patients suffering from lumbar intervertebral disc herniation were treated by operation,during which SHP was daubed around dura matter as obstruct to prevent epidural scar formation.Result No adverse reaction was observed.Pain was relieved and VAS was decreassed from 8.35 to 0.42 in mean.Using SHP got better curative effect than control group did.The cure and mend rate is 100% .No relapse occurs.Less scar formation was proved by CT in some cases.Conclusion SHP is ideal material used as inhibitor of epidural cicatrization.

  4. The synthesis technology of aminoguanidine bicarbonate%氨基胍重碳酸盐的合成工艺研究

    Institute of Scientific and Technical Information of China (English)

    梁吉连; 吴广文; 解世伟

    2011-01-01

    以水合肼、石灰氮、硫酸、碳酸氢铵为原料合成氨基胍重碳酸盐.考察了原料比、水的用量、pH、反应温度等影响因素,优化了反应条件.实验结果表明,较佳的反应条件为:用水量100 mL,反应温度45℃,n(水合肼)∶n(石灰氮)=1∶2,pH7.2~ 7.5,70℃保温3h;结晶反应的较佳条件为:结晶温度10℃,结晶时间4h.在此条件下,产品收率高达96.07%,产品纯度达98%.%Aminoguanidine bicarbonate was synthesized using hydrazine hydrate, lime nitrogen, sulfuric acid and ammonium bicarbonate as raw materials. Factors were investigated including the material ratio( hydrazine hydrate;lime nitrogen) ,water consumption,pH value and reaction temperature. The results show that optimum reaction conditions; is follow;the dose of water is 100 mL,reaction temperature is 451 ,the mole ratio of hydrazine hydrate to lime nitrogen is 1:2, pH value is 7. 2 - 7. 5, heat for three hours at 70T. The optimum conditions of crystallization are the crystallization temperature of 10℃ and the crystallization time of 4 hours. In this condition, the yield of products is 96. 07% and the product purity is 98% .

  5. The dipeptidyl peptidase IV inhibitor vildagliptin suppresses endogenous glucose production and enhances islet function after single-dose administration in type 2 diabetic patients

    DEFF Research Database (Denmark)

    Balas, Bogdan; Baig, Muhammad R; Watson, Catherine;

    2007-01-01

    AIMS/HYPOTHESIS: Vildagliptin is a selective dipeptidyl peptidase IV inhibitor that augments meal-stimulated levels of biologically active glucagon-like peptide-1. Chronic vildagliptin treatment decreases postprandial glucose levels and reduces hemoglobin A1c in type 2 diabetic patients. However,...

  6. Development of an on-line high performance liquid chromatography detection system for human cytochrome P450 1A2 inhibitors in extracts of natural products

    NARCIS (Netherlands)

    Jeurissen, S.M.F.; Claassen, F.W.; Havlik, J.; Bouwmans, E.; Cnubben, N.H.P.; Sudhölter, E.J.R.; Rietjens, I.M.C.M.; Beek, van T.A.

    2007-01-01

    An on-line HPLC screening method for detection of inhibitors of human cytochrome P450 1A2 in extracts was developed. HPLC separation of extracts is connected to a continuous methoxyresorufin-O-demethylation (MROD) assay in which recombinant human P450 1A2 converts methoxyresorufin to its fluorescent

  7. Studies on aldose reductase inhibitors from natural products. IV. Constituents and aldose reductase inhibitory effect of Chrysanthemum morifolium, Bixa orellana and Ipomoea batatas.

    Science.gov (United States)

    Terashima, S; Shimizu, M; Horie, S; Morita, N

    1991-12-01

    The hot water extracts of Chrysanthemum morifolium, Bixa orellana and Ipomoea batatas, were found to have potent inhibitory activity towards lens aldose reductase (AR). Ellagic acid (4) was isolated from C. morifolium and I. batatas, isoscutellarein (7) from B. orellana and 3,5-dicaffeoylquinic acid (10) from I. batatas, respectively, as potent inhibitors. PMID:1814628

  8. Biocatalysts with enhanced inhibitor tolerance

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Shihui; Linger, Jeffrey; Franden, Mary Ann; Pienkos, Philip T.; Zhang, Min

    2015-12-08

    Disclosed herein are biocatalysts for the production of biofuels, including microorganisms that contain genetic modifications conferring tolerance to growth and fermentation inhibitors found in many cellulosic feedstocks. Methods of converting cellulose-containing materials to fuels and chemicals, as well as methods of fermenting sugars to fuels and chemicals, using these biocatalysts are also disclosed.

  9. Optimizing the Processing Technology to Prepare Sodium Bicarbonate with Rhubarb by Orthogonal Test%正交试验法优选小苏打制大黄的炮制工艺

    Institute of Scientific and Technical Information of China (English)

    刘波; 徐常本

    2013-01-01

    Objective: To optimize the best processing technology for preparing Rhubarb with Sodium Bicarbonate. Methods:The main ingredients of Rhubarb are determined by HPLC, such as rhein, emodin, chrysophanol, aloe emodin ether. With its ingredients as the index, the impact of the three key factors of processing technology: the concentration of Sodium Bicarbonate solution (A) ,the amount of Sodium Bicarbonate solution ( B)and the cooked temperature (C) ,on the quality of the finished product were studied and evaluated. Thus, the optimized technology parameters for making Rhubarb by Sodium Bicarbonate were obtained. Results : A and C had a significant effect on the result and B had no significant effect. According to the degree of their effect they can be put in the following order; A > C > B. Conclusion:The best processing technology is A2B1C2. Rhubarb Pieces are put in Sodium Bicarbonate solution(concentration; 15% ;amount:10% of that of Rhubarb Pieces)and mixed well. When the solution is exhausted, they will be fried dry,removed and cooled.%目的:优选小苏打制大黄的最佳炮制工艺.方法:HPLC测定大黄的主要成分大黄酸、大黄素、大黄酚、芦荟大黄素和大黄素甲醚,以其成分含量为指标综合评判,研究炮制工艺的3个关键因素即小苏打溶液浓度(A)、小苏打溶液用量(B)和炮制温度(C)对成品质量的影响,优选小苏打制大黄工艺的技术参数.结果:小苏打溶液浓度和炮制温度对结果有显著影响,小苏打溶液用量对结果无显著影响,影响程度大小顺序为A>C>B.结论:最佳炮制工艺为A2BIC2:取净大黄饮片,加入浓度为15%、用量为药材重量10%的小苏打溶液拌匀,闷润至液体被吸尽后,120℃炒干,取出,晾凉.

  10. Update on Aromatase Inhibitors

    Directory of Open Access Journals (Sweden)

    Seifert-Klauss V

    2015-01-01

    Full Text Available Aromatase inhibitors (AI block the last phase of estrogen production in many types of tissues which express the enzym aromatase, among them muscle, liver, adrenal, brain and fat. The enzyme catalyzes the last step of the biosynthesis of the estrogens, i. e. the aromatisation of testosterone to estradiol and of androstendion to estrone. Aromatase is localized in the membrane of the endoplasmatic reticulum and is also produced in the placenta and the gonads. Mutations in the gene CYP19A1, which codes for aromatase, can lead either to lack or excess of aromatase. Gene polymorphisms also influence the amount of bioavailable estrogen and bone density.br Indications: AI are approved for the treatment of postmenopausal women with hormone receptor positive breast cancer, both in the adjuvant setting as well as after recurrence and in progressive disease. In premenopausal and in perimenopausal women AI cause an increased sensitivity of the ovaries to follicle stimulating hormone (FSH and can thereby lead to a boosted estrogen answer – this effect is particularly pronounced in early perimenopausal women – so that these situations demand a combination with GnRH-analogue if AI treatment is to be initiated. Alternatively, tamoxifene may be used in premenopausal patients, with or without GnRH analogues. Treatment of premenopausal patients with hormone receptor positive breast cancer with aromatase inhibiting therapy alone constitutes an absolute contraindication. Aromatase inhibitors do not lead to estrogen receptor downregulation or block the receptor such as tamoxifene. An exceptional application is the application in reproductive medicine in women who do not have hormone receptor positive breast cancer: because of the higher sensitivity induced by AI-co-therapy, FSH-doses and -costs for assisted reproduction are reduced, and ovarian hyperstimulation syndrome (OHSS may be avoided. For premenopausal diseases which are said to be positively affected by

  11. Effect of Sodium bicarbonate on Fire behaviour of tilled E- Glass Reinforced Epoxy Composites

    Science.gov (United States)

    Girish, S.; Devendra, K.; Bharath, K. N.

    2016-09-01

    Composites such as fibre reinforced polymers give us the good mechanical properties, but their fire behaviour is not appreciable and needs to be improved. In this work, E- glass fiber is used as a reinforcement material and Epoxy resin is used as a matrix with particulate sodium bi-carbonate (NaHCO3) is used as additive. The hand lay-up technique is adopted for the development of composites by varying percentage of additive. All the tests were conducted according to ASTM standards to study the Fire behaviour of the developed composites. The different fire properties like Ignition time, mass loss rate and flame propagation rate of Fiber Reinforced Polymers (FRP) with NaHCO3 are compared with neat FRPs. It is found that the ignition time increases as the percentage of additive is increased.

  12. Effects of Glycine, Water, Ammonia, and Ammonium Bicarbonate on the Oligomerization of Methionine

    Science.gov (United States)

    Huang, Rui; Furukawa, Yoshihiro; Otake, Tsubasa; Kakegawa, Takeshi

    2016-09-01

    The abiotic oligomerization of amino acids may have created primordial, protein-like biological catalysts on the early Earth. Previous studies have proposed and evaluated the potential of diagenesis for the amino acid oligomerization, simulating the formation of peptides that include glycine, alanine, and valine, separately. However, whether such conditions can promote the formation of peptides composed of multiple amino acids remains unclear. Furthermore, the chemistry of pore water in sediments should affect the oligomerization and degradation of amino acids and oligomers, but these effects have not been studied extensively. In this study, we investigated the effects of water, ammonia, ammonium bicarbonate, pH, and glycine on the oligomerization and degradation of methionine under high pressure (150 MPa) and high temperature conditions (175 °C) for 96 h. Methionine is more difficult to oligomerize than glycine and methionine dimer was formed in the incubation of dry powder of methionine. Methionine oligomers as long as trimers, as well as methionylglycine and glycylmethionine, were formed under every condition with these additional compounds. Among the compounds tested, the oligomerization reaction rate was accelerated by the presence of water and by an increase in pH. Ammonia also increased the oligomerization rate but consumed methionine by side reactions and resulted in the rapid degradation of methionine and its peptides. Similarly, glycine accelerated the oligomerization rate of methionine and the degradation of methionine, producing water, ammonia, and bicarbonate through its decomposition. With Gly, heterogeneous dimers (methionylglycine and glycylmethionine) were formed in greater amounts than with other additional compounds although smaller amount of these heterogeneous dimers were formed with other additional compounds. These results suggest that accelerated reaction rates induced by water and co-existing reactive compounds promote the oligomerization

  13. Effect of Beta alanine and sodium bicarbonate supplementation on repeated-sprint performance.

    Science.gov (United States)

    Ducker, Kagan J; Dawson, Brian; Wallman, Karen E

    2013-12-01

    This study aimed to investigate if combining beta alanine (BA) and sodium bicarbonate (NaHCO3) supplementation could lead to enhanced repeated-sprint performance in team-sport athletes, beyond what is possible with either supplement alone. Participants (n = 24) completed duplicate trials of a repeated-sprint test (3 sets; 6 × 20 m departing every 25 seconds, 4 minutes active recovery between sets) and were then allocated into 4 groups as follows: BA only (n = 6; 28 days BA, acute sodium chloride placebo); NaHCO3 only (n = 6; 28 days glucose placebo, acute NaHCO3); BA/NaHCO3 (n = 6; 28 days BA, acute NaHCO3); placebo only (n = 6; 28 days glucose placebo, acute sodium chloride placebo), then completed duplicate trials postsupplementation. Sodium bicarbonate alone resulted in moderate effect size (d = 0.40-0.71) and "likely" and "very likely" benefit for overall total sprint times (TST) and for each individual set and for first sprint (sets 2 and 3) and best sprint time (sets 2 and 3). Combining BA and NaHCO3 resulted in "possible" to "likely" benefits for overall TST and for sets 2 and 3. First sprint (set 3) and best sprint time (sets 2 and 3) also showed "likely" benefit after this trial. The BA and placebo groups showed no differences in performance after supplementation. In conclusion, these results indicate that supplementation with acute NaHCO3 improved repeated-sprint performance more than either a combination of NaHCO3 and BA or BA alone.

  14. Caffeine, but not bicarbonate, improves 6 min maximal performance in elite rowers.

    Science.gov (United States)

    Christensen, Peter M; Petersen, Mads H; Friis, Signe N; Bangsbo, Jens

    2014-09-01

    This study examined the ergogenic effects in a 6 min maximal performance test (PT) on 12 elite rowers: 6 open-weight (mean ± SD; 25 ± 1 years, and 92 ± 3 kg) and 6 light-weight (25 ± 3 years, and 73 ± 6 kg), following supplementation with caffeine (CAF), sodium bicarbonate (SB), and the combination of both, in a double-blind randomized placebo (PLA) controlled design. PT was executed on 4 occasions, on separate days within a week, and in a non-fasted state, with standardized training being performed the day before PT. Protocols were as follows: (i) CAF, 3 mg/kg, 45 min prior to PT + calcium as SB-PLA; (ii) SB, 0.3 g/kg, 75 min prior to PT + dextrose as CAF-PLA; (iii) CAF + SB; and (iv) PLA; CAF-PLA + SB-PLA. The total distance in the CAF (1878 ± 97 m) and CAF + SB (1877 ± 97 m) was longer than in the PLA (1865 ± 104 m; P PLA (393 ± 61 W; P PLA in the last half (4-6 min) of PT. Trials with CAF were more effective in light-weight rowers (1.0% ± 0.8% improvement in distance; P 0.05). No difference between interventions was observed for readiness and stomach comfort before PT and perceived exertion during PT. This study demonstrates that caffeine ingestion does improve performance in elite rowing. In contrast sodium bicarbonate does not appear to be ergogenic, but it does not abolish the ergogenic effect of caffeine. PMID:24999004

  15. Chemical equilibrium of hydrogen and aqueous solutions of 1 : 1 bicarbonate and formate salts with a common cation

    NARCIS (Netherlands)

    Engel, D.C.; Versteeg, G.F.; Swaaij, W.P.M. van

    1997-01-01

    The chemical equilibrium of hydrogen and aqueous solutions of 1:1 bicarbonate and formate salts with a common cation has been investigated in an intensively stirred batch reactor: MHCO3(aq) + H2(aq) ↔ MOOCH(aq) + H2O(l) This was accomplished for the sodium (M = Na), potassium (M = K) and ammonium (M

  16. Bicarbonate utilization and pH polarity. The response of photosynthetic electron transport to carbon limitation in Potamogeton lucens leaves

    NARCIS (Netherlands)

    van Ginkel, LC; Prins, HBA

    1998-01-01

    By the process of pH polarity, several submersed angiosperms can use bicarbonate as carbon source for photosynthesis. Under conditions of relatively high light intensity and low CO2 availability, the pH of the apoplast and unstirred layer becomes acid at one side of the leaf and alkaline at the othe

  17. Control of blue mold decay of apple during commercial controlled atmosphere storage with yeast antagonists and sodium bicarbonate

    Science.gov (United States)

    A mixture of two yeast antagonists, Metschnikowia pulcherrima and Cryptococcus laurentii, originally isolated from apples and having superior biocontrol activity against blue mold of apple over individual application of these yeasts, were used in combination with sodium bicarbonate (SBC) in a pilot ...

  18. Effects of rapid versus slow infusion of sodium bicarbonate on cerebral hemodynamics and oxygenation in preterm infants.

    NARCIS (Netherlands)

    Velden, A.A.E.M. van der; Hopman, J.C.W.; Klaessens, J.H.G.M.; Feuth, A.B.; Sengers, R.C.A.; Liem, K.D.

    2006-01-01

    BACKGROUND: Sodium bicarbonate (NaHCO3) is often used for correction of metabolic acidosis in preterm infants. The effects of NaHCO3 administration on cerebral hemodynamics and oxygenation are not well known. Furthermore, there is no consensus on infusion rate of NaHCO3. OBJECTIVES: To evaluate the

  19. No effect of bicarbonate treatment on insulin sensitivity and glucose control in non-diabetic older adults

    Science.gov (United States)

    Chronic mild metabolic acidosis is common among older adults, and limited evidence suggests that it may contribute to insulin resistance and type 2 diabetes. This analysis was conducted to determine whether bicarbonate supplementation, an alkalinizing treatment, improves insulin sensitivity or gluco...

  20. Analysis of ammonia-oxidizing bacteria dominating in lab-scale bioreactors with high ammonium bicarbonate loading

    NARCIS (Netherlands)

    Vejmelkova, D.; Sorokin, D.Y.; Abbas, B.; Kovaleva, O.L.; Kleerebezem, R.; Kampschreur, M.J.; Muyzer, G.; Van Loosdrecht, M.C.M.

    2011-01-01

    The ammonia-oxidizing bacterial community (AOB) was investigated in two types of laboratory-scale bioreactors performing partial oxidation of ammonia to nitrite or nitrate at high (80 mM) to extremely high (428 mM) concentrations of ammonium bicarbonate. At all conditions, the dominant AOB was affil

  1. Analysis of ammonia-oxidizing bacteria dominating in lab-scale bioreactors with high ammonium bicarbonate loading

    NARCIS (Netherlands)

    D. Vejmelkova; D.Y. Sorokin; B. Abbas; O.L. Kovaleva; R. Kleerebezem; M.J. Kampschreur; G. Muyzer; M.C.M. van Loosdrecht

    2012-01-01

    The ammonia-oxidizing bacterial community (AOB) was investigated in two types of laboratory-scale bioreactors performing partial oxidation of ammonia to nitrite or nitrate at high (80 mM) to extremely high (428 mM) concentrations of ammonium bicarbonate. At all conditions, the dominant AOB was affil

  2. The interaction of quinones, herbicides and bicarbonate with their binding environment and the acceptor side of photosystem II in photosynthesis

    NARCIS (Netherlands)

    Vermaas, W.

    1984-01-01

    In this thesis experiments are described which are directed towards a further characterization of the interaction of the native bound plastoquinone Q B , artificial quinones, herbicides and bicarbonate with their binding environment at the acceptor side of Photosystem II in the thylakoid

  3. Mechanisms of CFTR functional variants that impair regulated bicarbonate permeation and increase risk for pancreatitis but not for cystic fibrosis.

    Directory of Open Access Journals (Sweden)

    Jessica LaRusch

    2014-07-01

    Full Text Available CFTR is a dynamically regulated anion channel. Intracellular WNK1-SPAK activation causes CFTR to change permeability and conductance characteristics from a chloride-preferring to bicarbonate-preferring channel through unknown mechanisms. Two severe CFTR mutations (CFTRsev cause complete loss of CFTR function and result in cystic fibrosis (CF, a severe genetic disorder affecting sweat glands, nasal sinuses, lungs, pancreas, liver, intestines, and male reproductive system. We hypothesize that those CFTR mutations that disrupt the WNK1-SPAK activation mechanisms cause a selective, bicarbonate defect in channel function (CFTRBD affecting organs that utilize CFTR for bicarbonate secretion (e.g. the pancreas, nasal sinus, vas deferens but do not cause typical CF. To understand the structural and functional requirements of the CFTR bicarbonate-preferring channel, we (a screened 984 well-phenotyped pancreatitis cases for candidate CFTRBD mutations from among 81 previously described CFTR variants; (b conducted electrophysiology studies on clones of variants found in pancreatitis but not CF; (c computationally constructed a new, complete structural model of CFTR for molecular dynamics simulation of wild-type and mutant variants; and (d tested the newly defined CFTRBD variants for disease in non-pancreas organs utilizing CFTR for bicarbonate secretion. Nine variants (CFTR R74Q, R75Q, R117H, R170H, L967S, L997F, D1152H, S1235R, and D1270N not associated with typical CF were associated with pancreatitis (OR 1.5, p = 0.002. Clones expressed in HEK 293T cells had normal chloride but not bicarbonate permeability and conductance with WNK1-SPAK activation. Molecular dynamics simulations suggest physical restriction of the CFTR channel and altered dynamic channel regulation. Comparing pancreatitis patients and controls, CFTRBD increased risk for rhinosinusitis (OR 2.3, p<0.005 and male infertility (OR 395, p<<0.0001. WNK1-SPAK pathway-activated increases in

  4. Three genes expressing Kunitz domains in the epididymis are related to genes of WFDC-type protease inhibitors and semen coagulum proteins in spite of lacking similarity between their protein products

    Directory of Open Access Journals (Sweden)

    Lilja Hans

    2011-10-01

    Full Text Available Abstract Background We have previously identified a locus on human chromosome 20q13.1, encompassing related genes of postulated WFDC-type protease inhibitors and semen coagulum proteins. Three of the genes with WFDC motif also coded for the Kunitz-type protease inhibitor motif. In this report, we have reinvestigated the locus for homologous genes encoding Kunitz motif only. The identified genes have been analyzed with respect to structure, expression and function. Results We identified three novel genes; SPINT3, SPINT4 and SPINT5, and the structure of their transcripts were determined by sequencing of DNA generated by rapid amplification of cDNA ends. Each gene encodes a Kunitz domain preceded by a typical signal peptide sequence, which indicates that the proteins of 7.6, 8.7, and 9.7 kDa are secreted. Analysis of transcripts in 26 tissues showed that the genes predominantly are expressed in the epididymis. The recombinantly produced proteins could not inhibit the amidolytic activity of trypsin, chymotrypsin, plasmin, thrombin, coagulation factor Xa, elastase, urokinase and prostate specific antigen, whereas similarly made bovine pancreatic trypsin inhibitor (BPTI had the same bioactivity as the protein isolated from bovine pancreas. Conclusions The similar organization, chromosomal location and site of expression, suggests that the novel genes are homologous with the genes of WFDC-type protease inhibitors and semen coagulum proteins, despite the lack of similarity in primary structure of their protein products. Their restricted expression to the epididymis suggests that they could be important for male reproduction. The recombinantly produced proteins are presumably bioactive, as demonstrated with similarly made BPTI, but may have a narrower spectrum of inhibition, as indicated by the lacking activity against eight proteases with differing specificity. Another possibility is that they have lost the protease inhibiting properties, which is

  5. Assessment of the in vitro and in vivo properties of a {sup 99m}Tc-labeled inhibitor of the multidrug resistant gene product P-glycoprotein

    Energy Technology Data Exchange (ETDEWEB)

    Bergmann, R. E-mail: R.Bergmann@fz-rossendorf.de; Brust, P.; Scheunemann, M.; Pietzsch, H.-J.; Seifert, S.; Roux, F.; Johannsen, B

    2000-02-01

    Overexpression of P-glycoprotein (Pgp), which is present in the plasma membrane of various tumor cells and in several normal cell types, contributes to the multidrug resistance (MDR) phenotype of many human cancers. As a prerequisite for therapy, the expression of Pgp must be studied. The available clinical radiopharmaceuticals for studying the expression of Pgp include the lipophilic {sup 99m}Tc cations (sestamibi, tetrofosmin) as well as [{sup 99m}Tc]Q57, [{sup 99m}Tc]Q58, and [{sup 99m}Tc]Q63. Here we describe the in vitro and in vivo properties of the structurally different complex (3-thiapentane-1,5-dithiolato)[[N-(3-phenylpropyl)-N-2(3-quinazoline-2,4 -dionyl)-ethyl]amino-ethylthiolato] oxotechnetium(V) ({sup 99/99m}Tc1) as a potential inhibitor of Pgp. {sup 99}Tc1 enhances the net cell accumulation of Pgp substrates [{sup 3}H]vinblastine, [{sup 3}H]vincristine, [{sup 3}H]colchicine, [{sup 99m}Tc]sestamibi, and [{sup 99m}Tc]tetrofosmin in rat brain endothelial cells (RBE4), an immortalized endothelial cell line that expresses Pgp. In addition, the cell accumulation of {sup 99m}Tc1 could be increased by verapamil and reserpine, which are known Pgp inhibitors. A multitracer approach was used to study the side effects of {sup 99}Tc1 on cell metabolism. The cells were simultaneously incubated with [{sup 99m}Tc]sestamibi, 2-[{sup 18}F]fluoro-2-deoxyglucose ([{sup 18}F]FDG), and various {sup 3}H-labeled tracers. Two-dimensional scatter plots of [{sup 99m}Tc]sestamibi uptake/[{sup 18}F]FDG uptake show typical changes of known Pgp inhibitors including {sup 99}Tc1. The effects of {sup 99}Tc1 on the in vivo distribution of [{sup 99m}Tc]sestamibi and [{sup 18}F]FDG in rats also are comparable with the effects of verapamil, an established Pgp inhibitor and calcium channel blocker. We conclude that {sup 99/99m}Tc1 is a transport substrate and a potential inhibitor of Pgp. Our approach may be useful in the design of further radiotracers with specificity to Pgp.

  6. Enhanced U(VI) release from autunite mineral by aerobic Arthrobacter sp. in the presence of aqueous bicarbonate

    Energy Technology Data Exchange (ETDEWEB)

    Katsenovich, Yelena; Carvajal, Denny A.; Wellman, Dawn M.; Lagos, Leonel

    2012-04-20

    The bacterial effect on U(VI) leaching from the autunite mineral (Ca[(UO{sub 2})(PO{sub 4})]{sub 2} {center_dot} 3H{sub 2}O) was investigated to provide a more comprehensive understanding into important microbiological processes affecting autunite stability within subsurface bicarbonate-bearing environments. Experiments were performed in a culture of G975 Arthrobacter oxydans strain, herein referred to as G975, a soil bacterium previously isolated from Hanford Site soil. 91 mg of autunite powder and 50 mL of phosphorus-limiting sterile media were amended with bicarbonate ranging between 1-10 mM in glass reactor bottles and inoculated with G975 strain after the dissolution of autunite was at steady state. SEM observations indicated G975 formed a biofilm on the autunite surface and penetrated the mineral cleavages. The mineral surface colonization by bacteria tended to increase concomitantly with bicarbonate concentrations. Additionally, a sterile cultureware with inserts was used in non-contact bioleaching experiments where autunite and bacteria cells were kept separately. The data suggest the G975 bacteria is able to enhance U(VI) leaching from autunite without the direct contact with the mineral. In the presence of bicarbonate, the damage to bacterial cells caused by U(VI) toxicity was reduced, yielding similar values for total organic carbon (TOC) degradation and cell density compared to U(VI)-free controls. The presence of active bacterial cells greatly enhanced the U(VI) bioleaching from autunite in bicarbonate-amended media.

  7. Enhanced U(VI) release from autunite mineral by aerobic Arthrobacter sp. in the presence of aqueous bicarbonate

    Energy Technology Data Exchange (ETDEWEB)

    Katsenovich, Yelena P.; Carvajal, Denny A.; Wellman, Dawn M.; Lagos, Leonel E.

    2012-05-01

    The bacterial effect on U(VI) release from the autunite mineral (Ca[(UO2)(PO4)]2•3H2O) was investigated to provide a more comprehensive understanding of the important microbiological processes affecting autunite stability within subsurface bicarbonate-bearing environments. Experiments were performed in a culture of the Arthrobacter oxydans G975 strain, herein referred to as G975, a soil bacterium previously isolated from Hanford Site soil. 91 mg of autunite powder and 50 mL of phosphorous-limiting sterile media were amended with bicarbonate (ranging between 1 and 10 mM) in glass reactor bottles and inoculated with the G975 strain after the dissolution of autunite was at steady state. SEM observations indicated that G975 formed a biofilm on the autunite surface and penetrated the mineral cleavages. The mineral surface colonization by bacteria tended to increase concomitantly with bicarbonate concentrations. Additionally, a sterile culture-ware with inserts was used in non-contact dissolution experiments where autunite and bacteria cells were kept separately. The data suggest that G975 bacteria is able to enhance the release of U(VI) from autunite without direct contact with the mineral. In the presence of bicarbonate, the damage to bacterial cells caused by U(VI) toxicity was reduced, yielding similar values for total organic carbon (TOC) degradation and cell density compared to U(VI)-free controls. The presence of active bacterial cells greatly enhanced the release of U(VI) from autunite in bicarbonate-amended media.

  8. Lack of the sodium-driven chloride bicarbonate exchanger NCBE impairs visual function in the mouse retina.

    Directory of Open Access Journals (Sweden)

    Gerrit Hilgen

    Full Text Available Regulation of ion and pH homeostasis is essential for normal neuronal function. The sodium-driven chloride bicarbonate exchanger NCBE (Slc4a10, a member of the SLC4 family of bicarbonate transporters, uses the transmembrane gradient of sodium to drive cellular net uptake of bicarbonate and to extrude chloride, thereby modulating both intracellular pH (pH(i and chloride concentration ([Cl(-](i in neurons. Here we show that NCBE is strongly expressed in the retina. As GABA(A receptors conduct both chloride and bicarbonate, we hypothesized that NCBE may be relevant for GABAergic transmission in the retina. Importantly, we found a differential expression of NCBE in bipolar cells: whereas NCBE was expressed on ON and OFF bipolar cell axon terminals, it only localized to dendrites of OFF bipolar cells. On these compartments, NCBE colocalized with the main neuronal chloride extruder KCC2, which renders GABA hyperpolarizing. NCBE was also expressed in starburst amacrine cells, but was absent from neurons known to depolarize in response to GABA, like horizontal cells. Mice lacking NCBE showed decreased visual acuity and contrast sensitivity in behavioral experiments and smaller b-wave amplitudes and longer latencies in electroretinograms. Ganglion cells from NCBE-deficient mice also showed altered temporal response properties. In summary, our data suggest that NCBE may serve to maintain intracellular chloride and bicarbonate concentration in retinal neurons. Consequently, lack of NCBE in the retina may result in changes in pH(i regulation and chloride-dependent inhibition, leading to altered signal transmission and impaired visual function.

  9. Identification of wild soybean (Glycine soja) TIFY family genes and their expression profiling analysis under bicarbonate stress.

    Science.gov (United States)

    Zhu, Dan; Bai, Xi; Luo, Xiao; Chen, Qin; Cai, Hua; Ji, Wei; Zhu, Yanming

    2013-02-01

    Wild soybean (Glycine soja L. G07256) exhibits a greater adaptability to soil bicarbonate stress than cultivated soybean, and recent discoveries show that TIFY family genes are involved in the response to several abiotic stresses. A genomic and transcriptomic analysis of all TIFY genes in G. soja, compared with G. max, will provide insight into the function of this gene family in plant bicarbonate stress response. This article identified and characterized 34 TIFY genes in G. soja. Sequence analyses indicated that most GsTIFY proteins had two conserved domains: TIFY and Jas. Phylogenetic analyses suggested that these GsTIFY genes could be classified into two groups. A clustering analysis of all GsTIFY transcript expression profiles from bicarbonate stress treated G. soja showed that there were five different transcript patterns in leaves and six different transcript patterns in roots when the GsTIFY family responds to bicarbonate stress. Moreover, the expression level changes of all TIFY genes in cultivated soybean, treated with bicarbonate stress, were also verified. The expression comparison analysis of TIFYs between wild and cultivated soybeans confirmed that, different from the cultivated soybean, GsTIFY (10a, 10b, 10c, 10d, 10e, 10f, 11a, and 11b) were dramatically up-regulated at the early stage of stress, while GsTIFY 1c and 2b were significantly up-regulated at the later period of stress. The frequently stress responsive and diverse expression profiles of the GsTIFY gene family suggests that this family may play important roles in plant environmental stress responses and adaptation.

  10. Proton pump inhibitors

    Science.gov (United States)

    Proton pump inhibitors (PPIs) are medicines that work by reducing the amount of stomach acid made by ... Proton pump inhibitors are used to: Relieve symptoms of acid reflux, or gastroesophageal reflux disease (GERD). This ...

  11. Carbon dioxide metabolism by Actinomyces viscosus: pathways for succinate and aspartate production.

    OpenAIRE

    Brown, A T; Breeding, L C

    1980-01-01

    14C-labeled bicarbonate was incorporated into trichloroacetic acid-insoluble material by cell suspensions of A. viscosus strain M100 and also into the four-carbon fermentation product, succinate, but not into the three-carbon fermentation product, lactate. The initial step in the conversion of 14C-labeled bicarbonate into both trichloroacetic acid-insoluble material and succinate was catalyzed by the enzyme phosphoenolypyruvate carboxylase, which served to convert the glycolytic intermediate,...

  12. Measurement of energy expenditure in healthy male adults using [14C] bicarbonate

    International Nuclear Information System (INIS)

    Full text: The use of double-labelled water (3HH 18O) to measure total energy expenditure (TEE) in free-living humans is expensive and requires access to a mass spectrometer. A 48-hour infusion of [14C]-bicarbonate with the measurement of [14C]-carbon dioxide (14CO2) after urease digestion of the urine, has been shown to produce comparable results to whole body calorimetry. We have used [14C]-bicarbonate to measure TEE and determined (i) it's comparability with the Schofield equation and (ii) the reproducibility of repeated measurements within an individual. On two occasions ∼ 14 days apart, measurements of TEE, resting metabolic rate (RMR), respiratory quotient (RQ), energy intake, food quotient (FQ) and physical activity were made in eight healthy men (age 50 ± 3 yrs, wt 79 ± 3 kg, BMI 26 ± 1 kg/m2, fat mass 22.7 ± 2.5 kg, lean mass 56.5 ± 2.4 kg). Samples of each subjects' urine (collected for two consecutive 24 hour periods) were assayed in triplicate. RMR and RQ were determined by indirect calorimetry. Diet and activity patterns were recorded for four days during the infusion, and were analysed to determine energy intake and activity levels. There were no significant differences in any of the variables on the two study days. Data are expressed as mean ± SE. The coefficient of variation (CV) for the 14CO2 assay (within-assay CV) was 4.1 ± 0.4% (range 1.7 - 7.5%). The variation for the subjects between study days was 5.1 ± 0.9% (range 0.9 - 9.2%). TEE measured by 14CO2 (16,200 ± 780 KJ/day; range 13,400 - 19,387 KJ/day) was greater (14.7 ± 9% (% mean absolute difference ranged from -24.6 to 0.8%)) than the Schofield estimate of TEE (13,800 ± 710 KJ/day; range 12,100-15,500 KJ/day); the group means were significantly different (95% limits of agreement, T = 3.8, P = 0.007). Energy intake was 10,700 ± 535 KJ/day (range 7,970 - 12,600 KJ/day). Fasting RQ was 0.81 ± 0.01 (range 0.78 - 0.88), FQ was 0.84 ± 0.01 (range 0.78 - 0.87), and RQ/FQ was 0.97

  13. 2′-Deoxyriboguanylurea, the primary breakdown product of 5-aza-2′-deoxyribocytidine, is a mutagen, an epimutagen, an inhibitor of DNA methyltransferases and an inducer of 5-azacytidine-type fragile sites

    Science.gov (United States)

    Lamparska, Katarzyna; Clark, Jarrod; Babilonia, Gail; Bedell, Victoria; Yip, Wesley; Smith, Steven S.

    2012-01-01

    5-Aza-2′-deoxycytidine (5azaC-dR) has been employed as an inhibitor of DNA methylation, a chemotherapeutic agent, a clastogen, a mutagen, an inducer of fragile sites and a carcinogen. However, its effects are difficult to quantify because it rapidly breaks down in aqueous solution to the stable compound 2′-deoxyriboguanylurea (GuaUre-dR). Here, we used a phosphoramidite that permits the introduction of GuaUre-dR at defined positions in synthetic oligodeoxynucleotides to demonstrate that it is a potent inhibitor of human DNA methyltransferase 1 (hDNMT1) and the bacterial DNA methyltransferase (M.EcoRII) and that it is a mutagen that can form productive base pairs with either Guanine or Cytosine. Pure GuaUre-dR was found to be an effective demethylating agent and was able to induce 5azaC-dR type fragile sites FRA1J and FRA9E in human cells. Moreover, we report that demethylation associated with C:G → G:C transversion and C:G → T:A transition mutations was observed in human cells exposed to pure GuaUre-dR. The data suggest that most of the effects attributed to 5azaC-dR are exhibited by its stable primary breakdown product. PMID:22850746

  14. Telescoped Process to Manufacture 6,6,6-Trifluorofucose via Diastereoselective Transfer Hydrogenation: Scalable Access to an Inhibitor of Fucosylation Utilized in Monoclonal Antibody Production.

    Science.gov (United States)

    Achmatowicz, Michal M; Allen, John G; Bio, Matthew M; Bartberger, Michael D; Borths, Christopher J; Colyer, John T; Crockett, Richard D; Hwang, Tsang-Lin; Koek, Jan N; Osgood, Stephen A; Roberts, Scott W; Swietlow, Aleksander; Thiel, Oliver R; Caille, Seb

    2016-06-01

    IgG1 monoclonal antibodies with reduced glycan fucosylation have been shown to improve antibody-dependent cellular cytotoxicity (ADCC) by allowing more effective binding of the Fc region of these proteins to T cells receptors. Increased in vivo efficacy in animal models and oncology clinical trials has been associated with the enhanced ADCC provided by these engineered mAbs. 6,6,6-Trifluorofucose (1) is a new inhibitor of fucosylation that has been demonstrated to allow the preparation of IgG1 monoclonal antibodies with lower fucosylation levels and thus improve the ADCC of these proteins. A new process has been developed to support the preparation of 1 on large-scale for wide mAb manufacture applications. The target fucosylation inhibitor (1) was synthesized from readily available d-arabinose in 11% overall yield and >99.5/0.5 dr (diastereomeric ratio). The heavily telescoped process includes seven steps, two crystallizations as purification handles, and no chromatography. The key transformation of the sequence involves the diastereoselective preparation of the desired trifluoromethyl-bearing alcohol in >9/1 dr from a trimethylsilylketal intermediate via a ruthenium-catalyzed tandem ketal hydrolysis-transfer hydrogenation process. PMID:27152753

  15. An optimized micro-assay of myosin Ⅱ ATPase activity based on the molybdenum blue method and its application in screening natural product inhibitors

    Institute of Scientific and Technical Information of China (English)

    CHEN Hong-Lin; ZHAO Jing; ZHANG Guan-Jun; KOU Jun-Ping; YU Bo-Yang

    2016-01-01

    Myosin Ⅱ plays multiple roles in physiological and pathological functions through its ATPase activity.The present study was designed to optimize a micro-assay of myosin Ⅱ ATPase activity based on molybdenum blue method,using a known myosin Ⅱ ATPase inhibitor,blebbistatin.Several parameters were observed in the enzymatic reaction procedure,including the concentrations of the substrate (ATP) and calcium chloride,pH,and the reaction and incubation times.The proportion of coloration agent was also investigated.The sensitivity of this assay was compared with the malachite green method and bioluminescence method.Additionally,20 natural compounds were studied for myosin Ⅱ ATPase inhibitory activity using the optimized method.Our results showed that ATP at the concentration of 5 mmol·L-1 and ammonium molybdate:stannous chloride at the ratio of 15 ∶ 1 could greatly improve the sensitivity of this method.The IC50 of blebbistatin obtained by this method was consistent with literature.Compound 8 was screened with inhibitory activity on myosin Ⅱ ATPase.The optimized method showed similar accuracy,lower detecting limit,and wider linear range,which could be a promising approach to screening myosin Ⅱ ATPase inhibitors in vitro.

  16. An optimized micro-assay of myosin II ATPase activity based on the molybdenum blue method and its application in screening natural product inhibitors.

    Science.gov (United States)

    Chen, Hong-Lin; Zhao, Jing; Zhang, Guan-Jun; Kou, Jun-Ping; Yu, Bo-Yang

    2016-06-01

    Myosin II plays multiple roles in physiological and pathological functions through its ATPase activity. The present study was designed to optimize a micro-assay of myosin II ATPase activity based on molybdenum blue method, using a known myosin II ATPase inhibitor, blebbistatin. Several parameters were observed in the enzymatic reaction procedure, including the concentrations of the substrate (ATP) and calcium chloride, pH, and the reaction and incubation times. The proportion of coloration agent was also investigated. The sensitivity of this assay was compared with the malachite green method and bioluminescence method. Additionally, 20 natural compounds were studied for myosin II ATPase inhibitory activity using the optimized method. Our results showed that ATP at the concentration of 5 mmol·L(-1) and ammonium molybdate : stannous chloride at the ratio of 15 : 1 could greatly improve the sensitivity of this method. The IC50 of blebbistatin obtained by this method was consistent with literature. Compound 8 was screened with inhibitory activity on myosin II ATPase. The optimized method showed similar accuracy, lower detecting limit, and wider linear range, which could be a promising approach to screening myosin II ATPase inhibitors in vitro. PMID:27473959

  17. Beneficial effect of sulphate-bicarbonate-calcium water on gallstone risk and weight control

    Science.gov (United States)

    Corradini, Stefano Ginanni; Ferri, Flaminia; Mordenti, Michela; Iuliano, Luigi; Siciliano, Maria; Burza, Maria Antonella; Sordi, Bruno; Caciotti, Barbara; Pacini, Maria; Poli, Edoardo; Santis, Adriano De; Roda, Aldo; Colliva, Carolina; Simoni, Patrizia; Attili, Adolfo Francesco

    2012-01-01

    AIM: To investigate the effect of drinking sulphate-bicarbonate-calcium thermal water (TW) on risk factors for atherosclerosis and cholesterol gallstone disease. METHODS: Postmenopausal women with functional dyspepsia and/or constipation underwent a 12 d cycle of thermal (n = 20) or tap (n = 20) water controlled drinking. Gallbladder fasting volume at ultrasound, blood vitamin E, oxysterols (7-β-hydroxycholesterol and 7-ketocholesterol), bile acid (BA), triglycerides, total/low density lipoprotein and high density lipoprotein cholesterol were measured at baseline and at the end of the study. Food consumption, stool frequency and body weight were recorded daily. RESULTS: Blood lipids, oxysterols and vitamin E were not affected by either thermal or tap water consumption. Fasting gallbladder volume was significantly (P < 0.005) smaller at the end of the study than at baseline in the TW (15.7 ± 1.1 mL vs 20.1 ± 1.7 mL) but not in the tap water group (19.0 ± 1.4 mL vs 19.4 ± 1.5 mL). Total serum BA concentration was significantly (P < 0.05) higher at the end of the study than at baseline in the TW (5.83 ± 1.24 μmol vs 4.25 ± 1.00 μmol) but not in the tap water group (3.41 ± 0.46 μmol vs 2.91 ± 0.56 μmol). The increased BA concentration after TW consumption was mainly accounted for by glycochenodeoxycholic acid. The number of pasta (P < 0.001), meat (P < 0.001) and vegetable (P < 0.005) portions consumed during the study and of bowel movements per day (P < 0.05) were significantly higher in the TW than in the tap water group. Body weight did not change at the end of the study as compared to baseline in both groups. CONCLUSION: Sulphate-bicarbonate-calcium water consumption has a positive effect on lithogenic risk and intestinal transit and allows maintenance of a stable body weight despite a high food intake. PMID:22408352

  18. Beneficial effect of sulphate-bicarbonate-calcium water on gallstone risk and weight control

    Institute of Scientific and Technical Information of China (English)

    Stefano Ginanni Corradini; Edoardo Poli; Adriano De Santis; Aldo Roda; Carolina Colliva; Patrizia Simoni; Adolfo Francesco Attili; Flaminia Ferri; Michela Mordenti; Luigi Iuliano; Maria Siciliano; Maria Antonella Burza; Bruno Sordi; Barbara Caciotti; Maria Pacini

    2012-01-01

    AIM:To investigate the effect of drinking sulphate-bicarbonate-calcium thermal water (TW) on risk factors for atherosclerosis and cholesterol gallstone disease.METHODS:Postmenopausal women with functional dyspepsia and/or constipation underwent a 12 d cycle of thermal (n =20) or tap (n =20) water controlled drinking.Gallbladder fasting volume at ultrasound,blood vitamin E,oxysterols (7-β-hydroxycholesterol.and 7-ketocholesterol),bile acid (BA),triglycerides,total/low density lipoprotein and high density lipoprotein cholesterol were measured at baseline and at the end of the study.Food consumption,stool frequency and body weight were recorded daily.RESULTS:Blood lipids,oxysterols and vitamin E were not affected by either thermal or tap water consumption.Fasting gallbladder volume was significantly (P <0.005) smaller at the end of the study than at baseline in the TW (15.7 ± 1.1 mL vs 20.1 ± 1.7 mL) but not in the tap water group (19.0 ± 1.4 mL vs 19.4 ± 1.5 mL).Total serum BA concentration was significantly (P <0.05) higher at the end of the study than at baseline in the TW (5.83-1.24 μmol vs 4.25 ± 1.00 μmol) but not in the tap water group (3.41 ± 0.46 μmol vs 2.91 ± 0.56 μmol).The increased BA concentration after TW consumption was mainly accounted for by glycochenodeoxycholic acid.The number of pasta (P < 0.001),meat (P < 0.001) and vegetable (P < 0.005) portions consumed during the study and of bowel movements per day (P < 0.05) were significantly higher in the TW than in the tap water group.Body weight did not change at the end of the study as compared to baseline in both groups.CONCLUSION:Sulphate-bicarbonate-calcium water consumption has a positive effect on lithogenic risk and intestinal transit and allows maintenance of a stable body weight despite a high food intake.

  19. Variability of Acid-Base Status in Acetate-Free Biofiltration 84% versus Bicarbonate Dialysis

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    Harzallah Kais

    2008-01-01

    Full Text Available The ultimate goal of hemodialysis (HD treatment is to achieve the highest level of efficacy in the presence of maximal clinical tolerance. With an aim to offer good hemodynamic stability, as observed during the acetate-free biofiltration 14% (AFB 14% to patients who are intolerant to bicarbonate dialysis (BD and with less cost, we have developed since June 1994, a new HD technique, namely AFB 84%. This study was carried out to analyze acid-base variations during the AFB 84% in comparison to BD in hemodynamically stable patients on regular HD. This was a prospective randomized crossover study carried out on 12 patients (6 males and 6 females for a total of 144 HD sessions (72 BD and 72 AFB 84%. Patients with decompensated cardiomyopathy, respiratory diseases or uncontrolled hypertension were not included in the trial. All the patients were treated with BD or AFB 84%; the latter is characterized by the absence of acetate in the dialysate and a complete correction of buffer balance by post-dilutional infusion of bicarbonate-based replacement solution. The comparison of pre-dialysis arterial acid-base and blood-gas parameters revealed no significant differences of pH, HCO 3 - and paCO 2 levels between the two techniques. Analysis of post-dialysis parameters showed that, among patients dialyzed with BD, there was over correction of metabolic acidosis with a tendency towards metabolic alkalosis. In contrast, in patients dialyzed with AFB 84%, we observed a significant improvement in pH and HCO 3 - levels but the increase in paCO2 level was not significant. A comparison of these parameters between the two techniques showed statistically significant difference in pH, HCO3 - and paCO2 levels, but not for paO2 level. AFB 84% can offer some important advantages with the complete absence of acetate from the substitution fluids, and permits a better correction of metabolic acidosis than BD, without causing alkalosis.

  20. Bicarbonate enhances expression of the endocarditis and biofilm associated pilus locus, ebpR-ebpABC, in Enterococcus faecalis

    Directory of Open Access Journals (Sweden)

    Thomson L Charlene

    2010-01-01

    Full Text Available Abstract Background We previously identified ebpR, encoding a potential member of the AtxA/Mga transcriptional regulator family, and showed that it is important for transcriptional activation of the Enterococcus faecalis endocarditis and biofilm associated pilus operon, ebpABC. Although ebpR is not absolutely essential for ebpABC expression (100-fold reduction, its deletion led to phenotypes similar to those of an ebpABC mutant such as absence of pili at the cell surface and, consequently, reduced biofilm formation. A non-piliated ebpABC mutant has been shown to be attenuated in a rat model of endocarditis and in a murine urinary tract infection model, indicating an important participation of the ebpR-ebpABC locus in virulence. However, there is no report relating to the environmental conditions that affect expression of the ebpR-ebpABC locus. Results In this study, we examined the effect of CO2/HCO3-, pH, and the Fsr system on the ebpR-ebpABC locus expression. The presence of 5% CO2/0.1 M HCO3- increased ebpR-ebpABC expression, while the Fsr system was confirmed to be a weak repressor of this locus. The mechanism by which the Fsr system repressed the ebpR-ebpABC locus expression appears independent of the effects of CO2- bicarbonate. Furthermore, by using an ebpA::lacZ fusion as a reporter, we showed that addition of 0.1 M sodium bicarbonate to TSBG (buffered at pH 7.5, but not the presence of 5% CO2, induced ebpA expression in TSBG broth. In addition, using microarray analysis, we found 73 genes affected by the presence of sodium bicarbonate (abs(fold > 2, P ebpA mRNA levels under the conditions tested. Conclusions This study reports that the ebp locus expression is enhanced by the presence of bicarbonate with a consequential increase in the number of cells producing pili. Although the molecular basis of the bicarbonate effect remains unclear, the pathway is independent of the Fsr system. In conclusion, E. faecalis joins the growing family of

  1. Preventive and therapeutic effects of sodium bicarbonate on melamine-induced bladder stones in mice.

    Science.gov (United States)

    Ren, Shu-Ting; Du, Yun-Xia; Xu, Chang-Fu; Zhang, Jiao-Jiao; Mo, Li-Ping; Sun, Ying; Gao, Xiao-Li

    2014-10-01

    The actual preventive and therapeutic effects of alkalinizing urine on melamine-induced bladder stones (cystolith) are not completely known. Using an ideal model, two experiments were conducted in Balb/c mice. The mice were fed a normal diet in controls and a melamine diet in the other groups. The first day was set as experiment-day 1. In "Experiment 1", either low-/mid-/high-dose sodium bicarbonate (SB) or sterile water was administered by intragastric perfusion (once daily) to the mice for 14 days. Relative to the model group, the mean pH of the urine in the SB groups was significantly elevated at 3 h after SB administration, with a significant decrease in cystolith incidence on experiment-day 14. In "Experiment 2", on experiment-day 12, the melamine diet was replaced by a normal diet in 4 groups with melamine withdrawal (MW). Meanwhile, either mid-/high-dose SB or sterile water was administered by intragastric perfusion (once) to the mice in the corresponding groups. On experiment-day 12, after an additional 8 h, the cystolith incidence was significantly reduced in the high-SB, MW + mid-SB and MW + high-SB groups than in the model group. In conclusion, low urinary pH is one of the main determinants of the formation of melamine-associated stones, urinary alkalinization can be achieved by a proper dose of oral SB, and SB acts to prevent and treat melamine-induced cystoliths in mice.

  2. Does bicarbonated mineral water rich in sodium change insulin sensitivity of postmenopausal women?

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    S. Schoppen

    2007-10-01

    Full Text Available Aim: To study the effects of drinking 0.5 L of two sodium-rich bicarbonated mineral waters (BMW-1 and 2, with a standard meal, on postprandial insulin and glucose changes. And to determine, if the effects vary depending on insulin resistance, measured by homeostasis model assessment (HOMA. Methods: In a 3-way randomized crossover study, 18 healthy postmenopausal women consumed two sodiumrich BMWs and a low-mineral water (LMW with a standard fat-rich meal. Fasting and postprandial blood samples were taken at 30, 60 and 120 min. Serum glucose, insulin, cholesterol and triacylglycerols were determined. Insulin resistance was estimated by HOMA and insulin sensitivity was calculated by quantitative insulin sensitivity check index (QUICKY. Results: Glucose levels did not change. HOMA and QUICKY values were highly inversely correlated (r = -1,000; p < 0.0001. Insulin concentrations showed a significant time effect (p < 0.0001 and a significant water x time interaction (p < 0.021. At 120 min insulin levels with BMW-1 were significantly lower than with LMW (p = 0.022. Postprandial insulin concentrations showed significantly different patterns of mineral water intake depending on HOMA n-tiles (p = 0.016. Conclusion: Results suggests an increase in insulin sensitivity after BMWs consumption. This effect is more marked in the women, who have higher HOMA values. These waters should be considered part of a healthy diet in order to prevent insulin resistance and cardiovascular disease.

  3. Stress corrosion cracking tests on electron beam welded carbon steel specimens in carbonate-bicarbonate solution

    International Nuclear Information System (INIS)

    Stress corrosion cracking tests have been performed on tapered carbon steel test pieces containing electron beam welds with a view to defining susceptibility to such cracking in a carbonate-bicarbonate solution at 90 C and an appropriate electrode potential. The tests involved applying cyclic loads to the specimens and it is shown that the threshold stress for cracking reduces linearly with increase in the magnitude of the cyclic load component. Extrapolation of these trends to zero fluctuating stress indicates static load threshold stresses in the vicinity of the yield stress (i.e. about 300 N/mm2 for parent plate without a weld, 400 N/mm2 for specimens with welds on one side only and 600 N/mm2 for specimens having welds penetrating through the thickness of the specimen). The averages of the maximum crack velocities observed were least for parent plate material and greatest for weld metal, the former being essentially intergranular in morphology and the latter mostly transgranular, with heat affected zone material being intermediate between these extremes. (author)

  4. The Consumption of Bicarbonate-Rich Mineral Water Improves Glycemic Control

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    Shinnosuke Murakami

    2015-01-01

    Full Text Available Hot spring water and natural mineral water have been therapeutically used to prevent or improve various diseases. Specifically, consumption of bicarbonate-rich mineral water (BMW has been reported to prevent or improve type 2 diabetes (T2D in humans. However, the molecular mechanisms of the beneficial effects behind mineral water consumption remain unclear. To elucidate the molecular level effects of BMW consumption on glycemic control, blood metabolome analysis and fecal microbiome analysis were applied to the BMW consumption test. During the study, 19 healthy volunteers drank 500 mL of commercially available tap water (TW or BMW daily. TW consumption periods and BMW consumption periods lasted for a week each and this cycle was repeated twice. Biochemical tests indicated that serum glycoalbumin levels, one of the indexes of glycemic controls, decreased significantly after BMW consumption. Metabolome analysis of blood samples revealed that 19 metabolites including glycolysis-related metabolites and 3 amino acids were significantly different between TW and BMW consumption periods. Additionally, microbiome analysis demonstrated that composition of lean-inducible bacteria was increased after BMW consumption. Our results suggested that consumption of BMW has the possible potential to prevent and/or improve T2D through the alterations of host metabolism and gut microbiota composition.

  5. 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.

  6. In situ and laboratory toxicity of coalbed natural gas produced waters with elevated sodium bicarbonate

    Science.gov (United States)

    Farag, Aida M.; Harper, David D.; Skaar, Don

    2014-01-01

    Some tributaries in the Powder River Structural Basin, USA, were historically ephemeral, but now contain water year round as a result of discharge of coalbed natural gas (CBNG)-produced waters. This presented the opportunity to study field sites with 100% effluent water with elevated concentrations of sodium bicarbonate. In situ experiments, static renewal experiments performed simultaneously with in situ experiments, and static renewal experiments performed with site water in the laboratory demonstrated that CBNG-produced water reduces survival of fathead minnow (Pimephales promelas) and pallid sturgeon (Scaphirhynchus albus). Age affected survival of fathead minnow, where fish 2 d posthatch (dph) were more sensitive than 6 dph fish, but pallid sturgeon survival was adversely affected at both 4 and 6 dph. This may have implications for acute assays that allow for the use of fish up to 14 dph. The survival of early lifestage fish is reduced significantly in the field when concentrations of NaHCO3 rise to more than 1500 mg/L (also expressed as >1245 mg HCO3 (-) /L). Treatment with the Higgin's Loop technology and dilution of untreated water increased survival in the laboratory. The mixing zones of the 3 outfalls studied ranged from approximately 800 m to 1200 m below the confluence. These experiments addressed the acute toxicity of effluent waters but did not address issues related to the volumes of water that may be added to the watershed.

  7. Putative interaction of brush cells with bicarbonate secreting cells in the proximal corpus mucosa

    Directory of Open Access Journals (Sweden)

    Julia Anna-Maria Eberle

    2013-07-01

    Full Text Available The gastric epithelium is protected from the highly acidic luminal content by alkaline mucus which is secreted from specialized epithelial cells. In the stomach of mice strong secretion of alkaline fluid was observed at the gastric groove, the border between corpus and fundus mucosa. Since this region is characterized by numerous brush cells it was proposed that these cells might secrete alkaline solution as suggested for brush cells in the bile duct. In fact, it was found that in this region multiple cells express elements which are relevant for the secretion of bicarbonate, including carbonic anhydrase (CAII, the cystic fibrosis transmembrane conductance regulator (CFTR and the Na+/H+ exchanger (NHE1. However, this cell population was distinct from brush cells which express the TRP-channel TRPM5 and are considered as putative sensory cells. The location of both cell populations in close proximity implies the possibility for a paracrine interaction. This view was substantiated by the finding that brush cells express prostaglandin synthase-1 (COX-1 and the neighbouring cells a specific receptor type for prostaglandins. The notion that brush cells may be able to sense a local acidification was supported by the observation that they express the channel PKD1L3 which contributes to the acid responsiveness of gustatory sensory cells. The results support the concept that brush cells may sense the luminal content and influence via prostaglandins the secretion of alkaline solution.

  8. In situ and laboratory toxicity of coalbed natural gas produced waters with elevated sodium bicarbonate.

    Science.gov (United States)

    Farag, Aïda M; Harper, David D; Skaar, Don

    2014-09-01

    Some tributaries in the Powder River Structural Basin, USA, were historically ephemeral, but now contain water year round as a result of discharge of coalbed natural gas (CBNG)-produced waters. This presented the opportunity to study field sites with 100% effluent water with elevated concentrations of sodium bicarbonate. In situ experiments, static renewal experiments performed simultaneously with in situ experiments, and static renewal experiments performed with site water in the laboratory demonstrated that CBNG-produced water reduces survival of fathead minnow (Pimephales promelas) and pallid sturgeon (Scaphirhynchus albus). Age affected survival of fathead minnow, where fish 2 d posthatch (dph) were more sensitive than 6 dph fish, but pallid sturgeon survival was adversely affected at both 4 and 6 dph. This may have implications for acute assays that allow for the use of fish up to 14 dph. The survival of early lifestage fish is reduced significantly in the field when concentrations of NaHCO(3) rise to more than 1500 mg/L (also expressed as >1245 mg HCO(3) (-) /L). Treatment with the Higgin's Loop technology and dilution of untreated water increased survival in the laboratory. The mixing zones of the 3 outfalls studied ranged from approximately 800 m to 1200 m below the confluence. These experiments addressed the acute toxicity of effluent waters but did not address issues related to the volumes of water that may be added to the watershed. PMID:24909548

  9. Evaluating Battery-like Reactions to Harvest Energy from Salinity Differences using Ammonium Bicarbonate Salt Solutions.

    Science.gov (United States)

    Kim, Taeyoung; Rahimi, Mohammad; Logan, Bruce E; Gorski, Christopher A

    2016-05-10

    Mixing entropy batteries (MEBs) are a new approach to generate electricity from salinity differences between two aqueous solutions. To date, MEBs have only been prepared from solutions containing chloride salts, owing to their relevance in natural salinity gradients created from seawater and freshwater. We hypothesized that MEBs could capture energy using ammonium bicarbonate (AmB), a thermolytic salt that can be used to convert waste heat into salinity gradients. We examined six battery electrode materials. Several of the electrodes were unstable in AmB solutions or failed to produce expected voltages. Of the electrode materials tested, a cell containing a manganese oxide electrode and a metallic lead electrode produced the highest power density (6.3 mW m(-2) ). However, this power density is still low relative to previously reported NaCl-based MEBs and heat recovery systems. This proof-of-concept study demonstrated that MEBs could indeed be used to generate electricity from AmB salinity gradients. PMID:27030080

  10. Alleviating versus stimulating effects of bicarbonate on the growth of Vallisneria natans under ammonia stress.

    Science.gov (United States)

    Dou, Yanyan; Wang, Baozhong; Chen, Liangyan; Yin, Daqiang

    2013-08-01

    Bicarbonate plays a crucial role in limiting the growth of submersed aquatic macrophytes in eutrophic lakes, and high ammonia is often toxic to macrophytes. In order to evaluate the combined effect of HCO3 (-) and total ammonia (i.e., the total of NH3 and NH4 (+)) on submersed macrophytes Vallisneria natans, the growth and physiological response of V. natans in the presence of HCO3 (-) and ammonia were studied. The results showed that with the increase of ammonia, morphological parameters of V. natans declined. In contrast, increased HCO3 (-) concentration stimulated the growth of V. natans, especially when the NH4 (+)-N/NO3 (-)-N ratio was 1:7. High ammonia concentration induced excess free amino acids (FAA) accumulation and soluble carbohydrates (SC) depletion in plant tissues. However, the elevated HCO3 (-) promoted the synthesis of SC and rendered the decrease of FAA/SC ratio. The results also suggested that HCO3 (-) could partially alleviate the stress of ammonia, as evidenced by the decrease of FAA/SC ratio and the growth enhancement of V. natans when the ammonia concentration was 0.58 mg L(-1). Given the fact that HCO3 (-) is probably the dominant available carbon source in most eutrophic lakes, the ability of V. natans to use HCO3 (-) for SC synthesis may explain the alleviating effect of HCO3 (-) on V. natans under ammonia stress. PMID:23381797

  11. Kinase Inhibitors from Marine Sponges

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    Ana Zivanovic

    2011-10-01

    Full Text Available Protein kinases play a critical role in cell regulation and their deregulation is a contributing factor in an increasing list of diseases including cancer. Marine sponges have yielded over 70 novel compounds to date that exhibit significant inhibitory activity towards a range of protein kinases. These compounds, which belong to diverse structural classes, are reviewed herein, and ordered based upon the kinase that they inhibit. Relevant synthetic studies on the marine natural product kinase inhibitors have also been included.

  12. ZD6474, an inhibitor of vascular endothelial growth factor receptor tyrosine kinase, inhibits growth of experimental lung metastasis and production of malignant pleural effusions in a non-small cell lung cancer model.

    Science.gov (United States)

    Matsumori, Yuka; Yano, Seiji; Goto, Hisatsugu; Nakataki, Emiko; Wedge, Stephen R; Ryan, Anderson J; Sone, Saburo

    2006-01-01

    ZD6474 is a novel, orally active inhibitor of vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase, with some additional activity against epidermal growth factor receptor (EGFR) tyrosine kinase. The purpose of this study was to determine the potential of ZD6474 in the control of established experimental lung metastasis and pleural effusions produced by human non-small cell lung cancer (NSCLC) cells. PC14PE6 (adenocarcinoma) and H226 (squamous cell carcinoma) cells express high levels of EGFR and only PC14PE6 cells overexpress VEGF. Neither ZD6474 nor the EGFR tyrosine kinase inhibitor gefitinib inhibit proliferation of PC14PE6 or H226 cells in vitro. Both PC14PE6 and H226 cells inoculated intravenously into nude mice induced multiple lung nodules after 5-7 weeks. In addition, PC14PE6 cells produced bloody pleural effusions. Daily oral treatment with ZD6474 did not reduce the number of lung nodules produced by PC14PE6 or H226 cells, but did reduce the lung weight and the size of lung nodules. ZD6474 also inhibited the production of pleural effusions by PC14PE6 cells. Histological analyses of lung lesions revealed that ZD6474 treatment inhibited activation of VEGFR-2 and reduced tumor vascularization and tumor cell proliferation. Therapeutic effects of ZD6474 were considered likely to be due to inhibition of VEGFR-2 tyrosine kinase because gefitinib was inactive in this model. These results indicate that ZD6474, an inhibitor of VEGFR-2, may be useful in controlling the growth of established lung metastasis and pleural effusions by NSCLC. PMID:16783964

  13. Online coupling solid-phase ligand-fishing with high-performance liquid chromatography-diode array detector-tandem mass spectrometry for rapid screening and identification of xanthine oxidase inhibitors in natural products.

    Science.gov (United States)

    Peng, Mi-Jun; Shi, Shu-Yun; Chen, Lin; Zhang, Shui-Han; Cai, Ping; Chen, Xiao-Qing

    2016-09-01

    Screening and analysis of bioactive compounds from natural products is challenging work due to their complexity. This study presents the first report on hyphenation of solid-phase ligand-fishing using immobilized xanthine oxidase microcolumn (IXOM) and high-performance liquid chromatography-diode array detector-tandem mass spectrometry (HPLC-DAD-MS/MS) for screening and identification of XO inhibitors from complex mixtures. Solid-phase ligand-fishing system was hyphenated with the HPLC system via four-port switching valve and a six-port injection valve as an interface for transferring effluents from IXOM to HPLC, and collecting chromatograms from LFMC (ligand-fishing microextraction column) and C18 column in a run by only one DAD. Mixtures containing allopurinol (positive control) and tryptophane (negative control) were analyzed in order to verify the specificity and reproducibility of the approach. Subsequently, the newly developed system was applied to screening and identification of XO inhibitors from L. macranthoides and its human microsomal metabolites. Six prototype compounds (3-caffeoylquinic acid, 5-caffeoylquinic acid, 4-caffeoylquinic acid, 3,4-dicaffeoylquinic acid, 3,5-dicaffeoylquinic acid, 4,5-dicaffeoylquinic acid) and three metabolites (3-caffeoyl-epi-quinic acid, 5-caffeoyl-epi-quinic acid, 4-caffeoyl-epi-quinic acid) with XO binding affinities were identified. The XO inhibition activities of six prototype compounds were evaluated and confirmed using in vitro enzymatic assay. With the online system developed here, we present a feasible, selective, and effective strategy for rapid screening and identification of enzyme inhibitors from complex mixtures. PMID:27438719

  14. Infusing sodium bicarbonate suppresses hydrogen peroxide accumulation and superoxide dismutase activity in hypoxic-reoxygenated newborn piglets.

    Directory of Open Access Journals (Sweden)

    Jiang-Qin Liu

    Full Text Available BACKGROUND: The effectiveness of sodium bicarbonate (SB has recently been questioned although it is often used to correct metabolic acidosis of neonates. The aim of the present study was to examine its effect on hemodynamic changes and hydrogen peroxide (H(2O(2 generation in the resuscitation of hypoxic newborn animals with severe acidosis. METHODS: Newborn piglets were block-randomized into a sham-operated control group without hypoxia (n = 6 and two hypoxia-reoxygenation groups (2 h normocapnic alveolar hypoxia followed by 4 h room-air reoxygenation, n = 8/group. At 10 min after reoxygenation, piglets were given either i.v. SB (2 mEq/kg, or saline (hypoxia-reoxygenation controls in a blinded, randomized fashion. Hemodynamic data and blood gas were collected at specific time points and cerebral cortical H(2O(2 production was continuously monitored throughout experimental period. Plasma superoxide dismutase and catalase and brain tissue glutathione, superoxide dismutase, catalase, nitrotyrosine and lactate levels were assayed. RESULTS: Two hours of normocapnic alveolar hypoxia caused cardiogenic shock with metabolic acidosis (PH: 6.99 ± 0.07, HCO(3(-: 8.5 ± 1.6 mmol/L. Upon resuscitation, systemic hemodynamics immediately recovered and then gradually deteriorated with normalization of acid-base imbalance over 4 h of reoxygenation. SB administration significantly enhanced the recovery of both pH and HCO(3- recovery within the first hour of reoxygenation but did not cause any significant effect in the acid-base at 4 h of reoxygenation and the temporal hemodynamic changes. SB administration significantly suppressed the increase in H(2O(2 accumulation in the brain with inhibition of superoxide dismutase, but not catalase, activity during hypoxia-reoxygenation as compared to those of saline-treated controls. CONCLUSIONS: Despite enhancing the normalization of acid-base imbalance, SB administration during resuscitation did not provide any beneficial

  15. POST-EXERCISE LACTATE PRODUCTION AND METABOLISM IN THREE SPECIES OF AQUATIC AND TERRESTRIAL DECAPOD CRUSTACEANS

    Science.gov (United States)

    Walsh

    1994-01-01

    Aquatic and terrestrial crustaceans are dependent on both aerobic and anaerobic metabolism for energy production during exercise. Anaerobic energy production is marked by an accumulation of lactate in both muscle tissue and haemolymph, but the metabolic fate of lactate is not clear. Lactate recycling via gluconeogenesis and the potential role of carbonic anhydrase (CA) in supplying bicarbonate for the carboxylation of pyruvate were investigated in three species of decapod crustaceans: Callinectes sapidus (aquatic), Cardisoma guanhumi (semi-terrestrial) and Gecarcinus lateralis (terrestrial). CA activity was found in mitochondria and cytoplasmic fractions of gill, hepatopancreas and muscle of all three species. Significant activities of key enzymes of gluconeogenesis (e.g. pyruvate carboxylase, phosphoenolpyruvate carboxykinase and fructose bisphosphatase), however, could not be detected. Exercise to exhaustion produced a species-specific pattern of accumulation and clearance of lactate in tissue and haemolymph, indicating a differential degree of reliance on anaerobic energy production. Treatment with acetazolamide, a CA inhibitor, did not significantly alter the pattern of lactate dynamics in animals given repeated bouts of exhaustive exercise interspersed with periods of recovery. Injection of [U-14C]lactate resulted in the appearance of label in both muscle glycogen and excreted carbon dioxide, suggesting multiple metabolic fates for lactate. Lactate turnover rates for G. lateralis were similar to those reported for fish. In these animals, gluconeogenesis possibly proceeds via the reversal of pyruvate kinase, or via the typical Cori cycle but so slowly that the uncatalysed supply of bicarbonate is sufficient to keep pace with the low activities of pyruvate carboxylase and the subsequent low rates of pyruvate carboxylation.

  16. The Effect of Bicarbonate on the Microbial Dissolution of Autunite Mineral in the Presence of Gram-Positive Bacteria

    Energy Technology Data Exchange (ETDEWEB)

    Sepulveda-Medina, Paola; Katsenovich, Yelena; Wellman, Dawn M.; Lagos, Leonel

    2015-06-01

    Bacteria are key players in the processes that govern fate and transport of contaminants. The uranium release from Na and Ca-autunite by Arthrobacter oxydans strain G968 was evaluated in the presence of bicarbonate ions. This bacterium was previously isolated from Hanford Site soil and in earlier prescreening tests demonstrated low tolerance to U(VI) toxicity compared to other A.oxydans isolates. Experiments were conducted using glass serum bottles as mixed bioreactors and sterile 6-well cell culture plates with inserts separating bacteria cells from mineral solids. Reactors containing phosphorus-limiting media were amended with bicarbonate ranging between 0-10 mM and metaautunite solids to provide a U(VI) concentration of 4.4 mmol/L. Results showed that in the presence of bicarbonate, A.oxydans G968 was able to enhance the release of U(VI) from Na and Ca autunite at the same capacity as other A.oxydans isolates with relatively high tolerance to U(VI). The effect of bacterial strains on autunite dissolution decreases as the concentration of bicarbonate increases. The results illustrate that direct interaction between the bacteria and the mineral is not necessary to result in U (VI) biorelease from autunite. The formation of secondary calcium-phosphate mineral phases on the surface of the mineral during the dissolution can ultimately reduce the natural autunite mineral contact area, which bacterial cells can access. This thereby reduces the concentration of uranium released into the solution. This study provides a better understanding of the interactions between meta-autunite and microbes in conditions mimicking arid and semiarid subsurface environments of western U.S.

  17. Sodium bicarbonate for the prevention of contrast induced nephropathy: A meta-analysis of published clinical trials

    International Nuclear Information System (INIS)

    Background: Contrast induced nephropathy (CIN) is a serious but rare complication following contrast based procedures. Sodium bicarbonate (NaHCO3) has been postulated to prevent CIN by various mechanisms. However, the outcomes following sodium bicarbonate administration to prevent CIN have been inconsistent. Methods: A meta-analysis of published randomized clinical trials to determine if the administration of sodium bicarbonate is superior to sodium chloride among patients with chronic renal failure undergoing catheterization and interventional procedures in preventing CIN was performed. Results: Data were combined across seven published clinical trials consisting of 1734 patients. There were no significant differences in the baseline characteristics between the NaHCO3 and NaCl groups except patients in the bicarbonate group were heavier (P = 0.04). The odds ratio (OR) for the development of contrast nephropathy for NaHCO3 versus NaCl was 0.33 (95% confidence interval [CI] 0.16-0.69; P = 0.003). Heterogeneity and publication bias were detectable with P-values 0.01 and 0.0005 respectively. There was no difference between the NaHCO3 group and the NaCl group in the occurrence of death [OR 0.6; 95% CI (0.26-1.41); P = 0.24], congestive heart failure [OR 0.85; 95% CI (0.32-2.24); P = 0.74] and the requirement for renal replacement therapy [OR 0.56; 95% CI (0.22-1.41); P = 0.22]. Conclusion: This meta-analysis demonstrates that based on currently available randomized trials, the administration of NaHCO3 is superior to the administration of NaCl alone in the prevention of CIN among patients with moderate to severe chronic kidney disease. However, further controlled clinical trials are needed due to significant study heterogeneity and publication bias.

  18. Sodium bicarbonate for the prevention of contrast induced nephropathy: A meta-analysis of published clinical trials

    Energy Technology Data Exchange (ETDEWEB)

    Kunadian, Vijayalakshmi, E-mail: kunadianvijay@aol.com [Cardiothoracic Centre, Freeman Hospital, Newcastle upon Tyne Hospitals, NHS Foundation Trust/Newcastle University, Newcastle upon Tyne (United Kingdom); Zaman, Azfar, E-mail: Azfar.Zaman@nuth.nhs.uk [Cardiothoracic Centre, Freeman Hospital, Newcastle upon Tyne Hospitals, NHS Foundation Trust/Newcastle University, Newcastle upon Tyne (United Kingdom); Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne (United Kingdom); Spyridopoulos, Ioakim [Cardiothoracic Centre, Freeman Hospital, Newcastle upon Tyne Hospitals, NHS Foundation Trust/Newcastle University, Newcastle upon Tyne (United Kingdom); Institute of Human Genetics, Newcastle University, Newcastle upon Tyne (United Kingdom); Qiu, Weiliang [Channing Laboratory, Department of Medicine, Brigham and Women' s Hospital/Harvard Medical School, Boston, MA, United States of America (United States)

    2011-07-15

    Background: Contrast induced nephropathy (CIN) is a serious but rare complication following contrast based procedures. Sodium bicarbonate (NaHCO{sub 3}) has been postulated to prevent CIN by various mechanisms. However, the outcomes following sodium bicarbonate administration to prevent CIN have been inconsistent. Methods: A meta-analysis of published randomized clinical trials to determine if the administration of sodium bicarbonate is superior to sodium chloride among patients with chronic renal failure undergoing catheterization and interventional procedures in preventing CIN was performed. Results: Data were combined across seven published clinical trials consisting of 1734 patients. There were no significant differences in the baseline characteristics between the NaHCO{sub 3} and NaCl groups except patients in the bicarbonate group were heavier (P = 0.04). The odds ratio (OR) for the development of contrast nephropathy for NaHCO{sub 3} versus NaCl was 0.33 (95% confidence interval [CI] 0.16-0.69; P = 0.003). Heterogeneity and publication bias were detectable with P-values 0.01 and 0.0005 respectively. There was no difference between the NaHCO{sub 3} group and the NaCl group in the occurrence of death [OR 0.6; 95% CI (0.26-1.41); P = 0.24], congestive heart failure [OR 0.85; 95% CI (0.32-2.24); P = 0.74] and the requirement for renal replacement therapy [OR 0.56; 95% CI (0.22-1.41); P = 0.22]. Conclusion: This meta-analysis demonstrates that based on currently available randomized trials, the administration of NaHCO{sub 3} is superior to the administration of NaCl alone in the prevention of CIN among patients with moderate to severe chronic kidney disease. However, further controlled clinical trials are needed due to significant study heterogeneity and publication bias.

  19. Effects of iron on Vitamin C/copper-induced hydroxyl radical generation in bicarbonate-rich water.

    Science.gov (United States)

    Jansson, Patric J; Del Castillo, Urko; Lindqvist, Christer; Nordström, Tommy

    2005-05-01

    The aim of this study was to evaluate whether iron, like copper, could support Vitamin C mediated hydroxyl radical formation in bicarbonate-rich water. By using the hydroxyl radical indicator coumarin-3-carboxylic acid, we found that iron, in contrast to copper, was not capable to support Vitamin C induced hydroxyl radical formation. However, when 0.2 mg/l iron and 0.1 mg/l copper were both added to bicarbonate supplemented Milli-Q water, the Vitamin C induced formation of 7-hydroxycoumarin, as measured by HPLC analysis, was inhibited by 47.5%. The inhibition of hydroxyl radical formation by iron was also evident in the experiments performed on copper contaminated bicarbonate-rich household drinking water samples. In the presence of 0.2 mg/l of ferric iron the ascorbic acid induced hydroxyl radical formation was inhibited by 36.0-44.6%. This inhibition was even more significant, 47.0-59.2%, when 0.8 mg/l of ferric iron was present. None of the other redox-active metals, e.g. manganese, nickel or cobalt, could support ascorbic acid induced hydroxyl radical formation and did not have any impact on the ascorbic acid/copper-induced hydroxyl radical generation. Our results show, that iron cannot by itself produce hydroxyl radicals in bicarbonate rich water but can significantly reduce Vitamin C/copper-induced hydroxyl radical formation. These findings might partly explain the mechanism for the iron-induced protective effect on various copper related degenerative disorders that earlier has been observed in animal model systems. PMID:16036332

  20. Mechanisms of CFTR functional variants that impair regulated bicarbonate permeation and increase risk for pancreatitis but not for cystic fibrosis.

    OpenAIRE

    Jessica LaRusch; Jinsei Jung; General, Ignacio J.; Lewis, Michele D; Hyun Woo Park; Brand, Randall E.; Andres Gelrud; Anderson, Michelle A.; Banks, Peter A; Darwin Conwell; Christopher Lawrence; Joseph Romagnuolo; John Baillie; Samer Alkaade; Gregory Cote

    2014-01-01

    CFTR is a dynamically regulated anion channel. Intracellular WNK1-SPAK activation causes CFTR to change permeability and conductance characteristics from a chloride-preferring to bicarbonate-preferring channel through unknown mechanisms. Two severe CFTR mutations (CFTRsev ) cause complete loss of CFTR function and result in cystic fibrosis (CF), a severe genetic disorder affecting sweat glands, nasal sinuses, lungs, pancreas, liver, intestines, and male reproductive system. We hypothesize tha...

  1. A randomized, crossover pharmacodynamic study of immediate-release omeprazole/sodium bicarbonate and delayed-release lansoprazole in healthy adult volunteers.

    Science.gov (United States)

    Pratha, Vijayalakshmi S; McGraw, Thomas; Tobin, William

    2016-06-01

    Proton pump inhibitors (PPIs) effectively block gastric acid secretion and are the treatment of choice for heartburn. PPIs differ, however, in onset of action and bioavailability. In this single-center, open-label, three-way crossover study, onset of action of immediate-release omeprazole 20 mg/sodium bicarbonate 1100 mg (IR-OME) and delayed-release (DR) lansoprazole 15 mg was evaluated in 63 healthy fasting adults. Subjects were randomized to once daily IR-OME, or DR-lansoprazole, or no treatment for 7 days. The primary efficacy endpoint was the earliest time where a statistically significant difference was observed between IR-OME and DR-lansoprazole in median intragastric pH scores for three consecutive 5-min intervals on day 7. Secondary endpoints compared effects of active treatments on days 1 and 7 (e.g., time to sustained inhibition, percentage of time with pH >4). A significant difference in median intragastric pH favoring IR-OME was observed on day 7 starting at the 10- to 15-min interval postdosing (P = 0.024) and sustaining through the 115- to 120-min interval (P = 0.017). On day 1, IR-OME achieved sustained inhibition of intragastric acidity significantly faster than DR-lansoprazole. IR-OME maintained pH >4 significantly longer than DR-lansoprazole over a 24-h period (P = 0.007) on day 7. Overall, results of this study demonstrate IR-OME is safe and well tolerated and that treatment with IR-OME results in significantly faster onset of action and better gastric acid suppression at steady state than DR-lansoprazole. PMID:27433347

  2. Plant Protein Intake Is Associated with Fibroblast Growth Factor 23 and Serum Bicarbonate in Patients with CKD: The Chronic Renal Insufficiency Cohort Study

    Science.gov (United States)

    Scialla, Julia J.; Appel, Lawrence J; Wolf, Myles; Yang, Wei; Zhang, Xiaoming; Sozio, Stephen M.; Miller, Edgar R.; Bazzano, Lydia A.; Cuevas, Magdalena; Glenn, Melanie J.; Lustigova, Eva; Kallem, Radhakrishna R.; Porter, Anna C.; Townsend, Raymond R.; Weir, Matthew R.; Anderson, Cheryl A.M.

    2012-01-01

    Background Protein from plant, as opposed to animal, sources may be preferred in chronic kidney disease (CKD), due to lower bioavailability of phosphate and lower nonvolatile acid load. Study Design Observational cross-sectional study. Setting & Participants 2938 participants with chronic kidney disease and information on dietary intake at the baseline visit in the Chronic Renal Insufficiency Cohort Study. Predictors Percentage of total protein from plant sources (% plant protein) was determined by scoring individual food items from the National Cancer Institute Diet History Questionnaire (DHQ). Outcomes Metabolic parameters, including serum phosphate, bicarbonate (HCO3), potassium, and albumin, plasma fibroblast growth factor 23 (FGF23), and parathyroid hormone (PTH), and hemoglobin. Measurements We modeled the association between % plant protein and metabolic parameters using linear regression. Models were adjusted for age, sex, race, diabetes, body mass index, eGFR, income, smoking, total energy intake, total protein intake, 24 hour urinary sodium, use of angiotensin converting enzyme inhibitors/angiotensin receptor blockers and use of diuretics. Results Higher % plant protein was associated with lower FGF23 (p=0.05) and higher HCO3 (p=0.01), but not with serum phosphate or PTH (p=0.9 and 0.5, respectively). Higher % plant protein was not associated with higher serum potassium (p=0.2), lower serum albumin (p=0.2) or lower hemoglobin (p=0.3). The associations of % plant protein with FGF23 and HCO3 did not differ by diabetes status, sex, race, CKD stage (2/3 vs. 4/5) or total protein intake (≤ 0.8 g/kg/d vs. >0.8 g/kg/d) (p-interaction > 0.10 for each). Limitations Cross-sectional study; Determination of % plant protein using the DHQ has not been validated. Conclusions Consumption of a higher percentage of protein from plant sources may lower FGF23 and raise HCO3 in patients with CKD. PMID:22480598

  3. Intestinal GPS: bile and bicarbonate control cyclic di-GMP to provide Vibrio cholerae spatial cues within the small intestine.

    Science.gov (United States)

    Koestler, Benjamin J; Waters, Christopher M

    2014-01-01

    The second messenger cyclic di-GMP (c-di-GMP) regulates numerous phenotypes in response to environmental stimuli to enable bacteria to transition between different lifestyles. Here we discuss our recent findings that the human pathogen Vibrio cholerae recognizes 2 host-specific signals, bile and bicarbonate, to regulate intracellular c-di-GMP. We have demonstrated that bile acids increase intracellular c-di-GMP to promote biofilm formation. We have also shown that this bile-mediated increase of intracellular c-di-GMP is negated by bicarbonate, and that this interaction is dependent on pH, suggesting that V. cholerae uses these 2 environmental cues to sense and adapt to its relative location in the small intestine. Increased intracellular c-di-GMP by bile is attributed to increased c-di-GMP synthesis by 3 diguanylate cyclases (DGCs) and decreased expression of one phosphodiesterase (PDE) in the presence of bile. The molecular mechanisms by which bile controls the activity of the 3 DGCs and the regulators of bile-mediated transcriptional repression of the PDE are not yet known. Moreover, the impact of varying concentrations of bile and bicarbonate at different locations within the small intestine and the response of V. cholerae to these cues remains unclear. The native microbiome and pharmaceuticals, such as omeprazole, can impact bile and pH within the small intestine, suggesting these are potential unappreciated factors that may alter V. cholerae pathogenesis. PMID:25621620

  4. Role of the bicarbonate-responsive soluble adenylyl cyclase in pH sensing and metabolic regulation

    Directory of Open Access Journals (Sweden)

    Jung-Chin eChang

    2014-02-01

    Full Text Available The evolutionarily conserved soluble adenylyl cyclase (sAC, adcy10 was recently identified as a unique source of cAMP in the cytoplasm and the nucleus. Its activity is regulated by bicarbonate and fine-tuned by calcium. As such, and in conjunction with carbonic anhydrase (CA, sAC constitutes an HCO3-/CO¬2/pH sensor. In both alpha-intercalated cells of the collecting duct and the clear cells of the epididymis, sAC is expressed at significant level and involved in pH homeostasis via apical recruitment of vacuolar H+-ATPase (VHA in a PKA-dependent manner. In addition to maintenance of pH homeostasis, sAC is also involved in metabolic regulation such as coupling of Krebs cycle to oxidative phosphorylation via bicarbonate/CO2 sensing. Additionally, sAC also regulates CFTR channel and plays an important role in regulation of barrier function and apoptosis. These observations suggest that sAC, via bicarbonate-sensing, plays an important role in maintaining homeostatic status of cells against fluctuations in their microenvironment.

  5. Current Status of Sodium Bicarbonate in Coronary Angiography: An Updated Comprehensive Meta-Analysis and Systematic Review

    Directory of Open Access Journals (Sweden)

    Sadegh Ali-Hassan-Sayegh

    2015-01-01

    Full Text Available This systematic review with meta-analysis sought to determine comparison of efficacy and safety of hydration with sodium bicarbonate versus sodium chloride on contrast induced nephropathy and clinical outcomes. We searched major electronic databases for studies in randomized controlled trials. A value of P50% indicated significant heterogeneity between the studies. Literature search of all databases retrieved 650 studies. 29 studies enrolled in meta-analysis. Pooled analysis indicated about the incidence of CIN (OR of 0.718; 95% CI: 0.60 to 0.85; P=0.000, requirement of hemodialysis (OR of 1.00; 95% CI: 0.49 to 2.01; P=0.9, mean changes of serum creatinine (WMD of 2.321; 95% CI: 1.995 to 2.648; P=0.000, length of hospital stays (WMD of −0.774; 95% CI: −1.65 to 0.10; P=0.08, major adverse cardiovascular events (OR = 1.075, 95% CI: 0.59 to 1.95; P=0.8, and mortality (OR of 0.73; 95% CI: 0.42 to 1.26; P=0.2. Overall, hydration with sodium bicarbonate could significantly reduce CIN and the length of hospital stay compared to sodium chloride. In addition NAC added as a supplement to sodium bicarbonate could increase prophylactic effects against nephropathy.

  6. Effect of sodium bicarbonate air abrasive polishing on resistance to sliding during tooth alignment and leveling: An in vitro study

    Directory of Open Access Journals (Sweden)

    Jorge C. B. L. Filho

    2012-01-01

    Full Text Available Objective: The aim of this in vitro study was to evaluate the Resistance to Sliding (RS provided by metallic brackets and 3 types of orthodontic wires (TMA, SS and NiTi, before and after the use of sodium bicarbonate airborne particle abrasion, in an experimental model with 3 non leveled brackets. Materials and Methods: The bicarbonate airborne abrasion was applied perpendicularly to the bracket slots at a distance of 2 mm, for 5 seconds (T2 and 10 seconds (T3 on each bracket slot. In a universal testing machine, the wires were pulled through a set of 3 non leveled brackets at a cross head speed of 50 mm/min for a distance of 10 mm, and static and kinetic friction readings were registered at T1 (no airborne abrasion, T2 and T3. Results: For all tested wires, a significant RS increase between T1 and T3 (P<0.001 was seen. For SS and TMA wires, there was a statistically significant RS increase between T1 and T2 (P<0.001. Between T2 and T3, RS increase was significant for TMA (P<0.001 and NiTiwires (P<0.05. Conclusions: Sodium bicarbonate air abrasive polishing during orthodontic treatment is not recommended, once this procedure promoted a significant RS increase between the metallic brackets and all the three types of wires tested.

  7. Topology mapping to characterize cyanobacterial bicarbonate transporters: BicA (SulP/SLC26 family) and SbtA.

    Science.gov (United States)

    Price, G Dean; Howitt, Susan M

    2014-09-01

    This mini-review addresses advances in understanding the transmembrane topologies of two unrelated, single-subunit bicarbonate transporters from cyanobacteria, namely BicA and SbtA. BicA is a Na(+)-dependent bicarbonate transporter that belongs to the SulP/SLC26 family that is widespread in both eukaryotes and prokaryotes. Topology mapping of BicA via the phoA/lacZ fusion reporter method identified 12 transmembrane helices with an unresolved hydrophobic region just beyond helix 8. Re-interpreting this data in the light of a recent topology study on rat prestin leads to a consensus topology of 14 transmembrane domains with a 7+7 inverted repeat structure. SbtA is also a Na(+)-dependent bicarbonate transporter, but of considerably higher affinity (Km 2-5 μM versus >100 μM for BicA). Whilst SbtA is widespread in cyanobacteria and a few bacteria, it appears to be absent from eukaryotes. Topology mapping of SbtA via the phoA/lacZ fusion reporter method identified 10 transmembrane helices. The topology consists of a 5+5 inverted repeat, with the two repeats separated by a large intracellular loop. The unusual location of the N and C-termini outside the cell raises the possibility that SbtA forms a novel fold, not so far identified by structural and topological studies on transport proteins.

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

    Science.gov (United States)

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

    2016-09-01

    The sodium bicarbonate cotransporter (NBCe2, aka NBC4) was originally isolated from the human testis and heart (Pushkin et al. IUBMB Life 50:13-19, 2000). Subsequently, NBCe2 was found in diverse locations where it plays a role in regulating sodium and bicarbonate transport, influencing intracellular, extracellular, interstitial, and ultimately plasma pH (Boron et al. J Exp Biol. 212:1697-1706, 2009; Parker and Boron, Physiol Rev. 93:803-959, 2013; Romero et al. Mol Asp Med. 34:159-182, 2013). NBCe2 is located in human and rodent renal-collecting duct and proximal tubule. While much is known about the two electrogenic sodium bicarbonate cotransporters, NBCe1 and NBCe2, in the regulation of sodium homeostasis and pH balance in the rodent kidney, little is known about their roles in human renal physiology. NBCe2 is located in the proximal tubule Golgi apparatus under basal conditions and then disperses throughout the cell, but particularly into the apical membrane microvilli, during various maneuvers that increase intracellular sodium. This review will summarize our current understanding of the distribution and function of NBCe2 in the human kidney and how genetic variants of its gene, SLC4A5, contribute to salt sensitivity of blood pressure. PMID:27628629

  9. Natural Product Total Synthesis in the Organic Laboratory: Total Synthesis of Caffeic Acid Phenethyl Ester (CAPE), a Potent 5-Lipoxygenase Inhibitor from Honeybee Hives

    Science.gov (United States)

    Touaibia, Mohamed; Guay, Michel

    2011-01-01

    Natural products play a critical role in modern organic synthesis and learning synthetic techniques is an important component of the organic laboratory experience. In addition to traditional one-step organic synthesis laboratories, a multistep natural product synthesis is an interesting experiment to challenge students. The proposed three-step…

  10. Natural product inhibitors of fatty acid biosynthesis: synthesis of the marine microbial metabolites pseudopyronines A and B and evaluation of their anti-infective activities

    DEFF Research Database (Denmark)

    Giddens, Anna C.; Nielsen, Lone; Boshoff, Helena I.;

    2007-01-01

    Total syntheses of the title natural products, pseudopyronines A (1) and B (2), have been achieved using methyl β-oxo carboxylic ester starting materials. The natural products and a small set of structurally related compounds were evaluated for growth inhibitory activity against a range of pathog...

  11. Influences of Inhibitors on S-adenosyl-L-methionine Production Employing Pichia and the Mechanisms%抑制剂对Pichia生产S-腺苷甲硫氨酸的作用及机制

    Institute of Scientific and Technical Information of China (English)

    胡晓清; 储炬; 张嗣良; 庄英萍; 王永红

    2012-01-01

    S-腺苷甲硫氨酸(S-adenosyl-L-methionine,SAM)是市场前景广阔的高价值氨基酸.为通过削弱胞内SAM消耗而进一步提高其积累量,作者在诱导型和组成型P.pastoris发酵后期添加3种抑制剂.首先考察其作用并比较其差异,然后分析其机制.结果显示,添加S-腺苷高半胱氨酸水解酶抑制剂Aristeromycin有助于SAM积累,但比较而言,其在诱导型酵母中最适添加质量浓度更低,很可能因为甲醇代谢导致的氧化胁迫使细胞对甲基化作用依赖性增强.添加多胺合成抑制剂DFMA有利于SAM积累,但添加过多对细胞生长和抗氧化不利.组成型酵母中添加7.5 g/L乙酸可通过抑制多胺生成而增强SAM积累.3种抑制剂均可有效提高P.pastoris中SAM产量.%S-adenosyl-L-methionine (SAM) was high-value amino acid that had great market potential. To enhance SAM accumulation by inhibiting its consumption,three inhibitors were added during the late fermentation stage of inducible Pichia and constitutive Pichia. Firstly, their influences were investigated,and the differences were compared,and finally,the mechanisms were analyzed. The results showed that addition of Aristeromycin,an inhibitor of 5-adenosyl-L-homocysteine hydrolase,contributed to SAM accumulation,but comparatively speaking,the optimum addition level for inducible Pichia was lower,likely because the oxidative stress resulting from methanol metabolism strengthened the dependence of Pichia cell on transmethylation reaction. Supplement of DFMA,an inhibitor of polyamine synthesis,improved SAM accumulation,while the excessive amount of DFMA led to reduction of cell growth and anti-oxidation ability. Addition of acetic acid at 7.5 g/L improved SAM accumulation, through reducing polyamine formation. The three inhibitors mentioned above were proved effective for improvement of SAM production.

  12. Therapeutic Potential of Monoacylglycerol Lipase Inhibitors

    OpenAIRE

    Mulvihill, Melinda M.; Nomura, Daniel K.

    2012-01-01

    Marijuana and aspirin have been used for millennia to treat a wide range of maladies including pain and inflammation. Both cannabinoids, like marijuana, that exert anti-inflammatory action through stimulating cannabinoid receptors, and cyclooxygenase (COX) inhibitors, like aspirin, that suppress pro-inflammatory eicosanoid production have shown benefitial outcomes in mouse models of neurodegenerative diseases and cancer. Both cannabinoids and COX inhibitors, however, have untoward effects tha...

  13. Successful recovery from iatrogenic severe hypernatremia and severe metabolic acidosis resulting from accidental use of inappropriate bicarbonate concentrate for hemodialysis treatment

    OpenAIRE

    Bhosale, Guruprasad P; Veena R Shah

    2015-01-01

    Bicarbonate dialysis is the treatment modality of choice for correction of metabolic acidosis in chronic renal failure. However, improper selection of dialysate concentrate can result in life-threatening human errors. We report a case of iatrogenic severe hypernatremia (sodium 207 mEq/L) and severe metabolic acidosis (pH 6.65) that resulted due to accidental use of inappropriate bicarbonate concentrate for hemodialysis treatment. There was successful recovery in this patient with no neurologi...

  14. The chronic toxicity of sodium bicarbonate, a major component of coal bed natural gas produced waters

    Science.gov (United States)

    Farag, Aida M.; Harper, David D.

    2014-01-01

    Sodium bicarbonate (NaHCO3) is the principal salt in coal bed natural gas produced water from the Powder River Structural Basin, Wyoming, USA, and concentrations of up to 3000 mg NaHCO3/L have been documented at some locations. No adequate studies have been performed to assess the chronic effects of NaHCO3 exposure. The present study was initiated to investigate the chronic toxicity and define sublethal effects at the individual organism level to explain the mechanisms of NaHCO3 toxicity. Three chronic experiments were completed with fathead minnows (Pimephales promelas), 1 with white suckers (Catostomus commersoni), 1 with Ceriodaphnia dubia, and 1 with a freshwater mussel, (Lampsilis siliquoidea). The data demonstrated that approximately 500 mg NaHCO3/L to 1000 mg NaHCO3/L affected all species of experimental aquatic animals in chronic exposure conditions. Freshwater mussels were the least sensitive to NaHCO3 exposure, with a 10-d inhibition concentration that affects 20% of the sample population (IC20) of 952 mg NaHCO3/L. The IC20 for C. dubia was the smallest, at 359 mg NaHCO3/L. A significant decrease in sodium–potassium adenosine triphosphatase (Na+/K+ ATPase) together with the lack of growth effects suggests that Na+/K+ ATPase activity was shut down before the onset of death. Several histological anomalies, including increased incidence of necrotic cells, suggested that fish were adversely affected as a result of exposure to >450 mg NaHCO3/L.

  15. Preventive and therapeutic effects of sodium bicarbonate on melamine-induced bladder stones in mice.

    Science.gov (United States)

    Ren, Shu-Ting; Du, Yun-Xia; Xu, Chang-Fu; Zhang, Jiao-Jiao; Mo, Li-Ping; Sun, Ying; Gao, Xiao-Li

    2014-10-01

    The actual preventive and therapeutic effects of alkalinizing urine on melamine-induced bladder stones (cystolith) are not completely known. Using an ideal model, two experiments were conducted in Balb/c mice. The mice were fed a normal diet in controls and a melamine diet in the other groups. The first day was set as experiment-day 1. In "Experiment 1", either low-/mid-/high-dose sodium bicarbonate (SB) or sterile water was administered by intragastric perfusion (once daily) to the mice for 14 days. Relative to the model group, the mean pH of the urine in the SB groups was significantly elevated at 3 h after SB administration, with a significant decrease in cystolith incidence on experiment-day 14. In "Experiment 2", on experiment-day 12, the melamine diet was replaced by a normal diet in 4 groups with melamine withdrawal (MW). Meanwhile, either mid-/high-dose SB or sterile water was administered by intragastric perfusion (once) to the mice in the corresponding groups. On experiment-day 12, after an additional 8 h, the cystolith incidence was significantly reduced in the high-SB, MW + mid-SB and MW + high-SB groups than in the model group. In conclusion, low urinary pH is one of the main determinants of the formation of melamine-associated stones, urinary alkalinization can be achieved by a proper dose of oral SB, and SB acts to prevent and treat melamine-induced cystoliths in mice. PMID:25092435

  16. Bacteriostatic effect of human milk and bovine colostrum on Escherichia coli: importance of bicarbonate.

    Science.gov (United States)

    Griffiths, E; Humphreys, J

    1977-01-01

    At pH 7.4 and in the presence of NaHCO3, human milk and bovine colostrum inhibited the growth of Escherichia coli O111. Adding sufficient iron to saturate the iron-binding capacity of the lactoferrin present in the milk or colostrum prevented bacteriostasis. At pH 6.8 neither molk nor colostrum inhibited E. coli 0111. Adjusting the pH to 7.4 with NaHCO3 resulted in the development of bacteriostatic activity. Adjusting the pH to 7.4 with NaOH was ineffective. Dialyzed colostrum and milk inhibited bacterial growth at pH 6.8 in the absence of added NaHCO3; addition of citrate or iron abolished bacteriostasis. The chromatographic elution profile of tyrosyl-transfer ribonucleic acid (tRNA) from iron-replete E. coli differs significantly from that of tyrosyl-tRNA from iron-deficient organisms. Examination of the elution profile tyrosyl-tRNA from E. coli 0111 growing in colostrum without added NaHCO3 showed that such bacteria were fully replete in iron. The nature of the elution profile of tyrosyl-tRNA also showed that iron was freely available to the bacteria when citrate was added to dialyzed colostrum but not available in its absence, even at pH 6.8. Results support the idea that the bacteriostatic action of milk and colostrum, due to the combined action of antibody and lactoferrin, depends on the addition of bicarbonate to counteract the iron-mobilizing effect of the citrate normally present in these secretions. PMID:14890

  17. Thermal Care of Functional Dyspepsia Based on Bicarbonate-Sulphate-Calcium Water: A Sequential Clinical Trial

    Directory of Open Access Journals (Sweden)

    Giuseppe Rocca

    2007-01-01

    Full Text Available Drug treatment of functional dyspepsia is often unsatisfactory. We assessed the efficacy of a bicarbonate-sulphate-calcium thermal water cycle of 12 days, in patients with functional dyspepsia. Patients with functional dyspepsia were sent by their general practitioners to 12 days of treatment with thermal water, 200–400 ml in the morning, at temperature of 33°C (91.4 F and were evaluated on a strict intention to treat basis. Four efficacy endpoints were analyzed as follows: (i reduction of the global symptoms score, (ii reduction of intensity to a level not interfering with everyday activities, (iii specific efficacy on ulcer-like or dysmotility-like dyspepsia and (iv esophageal or abdominal-associated symptoms. Statistical significance was reached for all three primary outcomes after the first 29 consecutive patients. Thermal water reduced the global symptom score, reduced intensity of symptoms to a level not interfering with everyday activity, but was unable to completely suppress all symptoms. A parallel effect emerged for ulcer-like and dyspepsia-like subgroups. The effect on heartburn and abdominal symptoms was not significant, suggesting a specific effect of the water on the gastric and duodenal wall. The Roma II criteria identify a natural kind of dyspepsia that improves with thermal water. Ulcer-like and dysmotility-like are not therapeutically distinguishable subgroups. Patients with dominant esophageal or abdominal symptoms should receive a different therapy. Sequential methods are very effective for the evaluation of traditional care practices and should be considered preliminary and integrative to randomized controlled trials in this context.

  18. Thermal Care of Functional Dyspepsia Based on Bicarbonate-Sulphate-Calcium Water: A Sequential Clinical Trial

    Science.gov (United States)

    Dioni, Federico; Rocca, Nadia; Oliveri, Filippo; Brunetto, Maurizia R; Bonino, Ferruccio

    2007-01-01

    Drug treatment of functional dyspepsia is often unsatisfactory. We assessed the efficacy of a bicarbonate-sulphate-calcium thermal water cycle of 12 days, in patients with functional dyspepsia. Patients with functional dyspepsia were sent by their general practitioners to 12 days of treatment with thermal water, 200–400 ml in the morning, at temperature of 33°C (91.4 F) and were evaluated on a strict intention to treat basis. Four efficacy endpoints were analyzed as follows: (i) reduction of the global symptoms score, (ii) reduction of intensity to a level not interfering with everyday activities, (iii) specific efficacy on ulcer-like or dysmotility-like dyspepsia and (iv) esophageal or abdominal-associated symptoms. Statistical significance was reached for all three primary outcomes after the first 29 consecutive patients. Thermal water reduced the global symptom score, reduced intensity of symptoms to a level not interfering with everyday activity, but was unable to completely suppress all symptoms. A parallel effect emerged for ulcer-like and dyspepsia-like subgroups. The effect on heartburn and abdominal symptoms was not significant, suggesting a specific effect of the water on the gastric and duodenal wall. The Roma II criteria identify a natural kind of dyspepsia that improves with thermal water. Ulcer-like and dysmotility-like are not therapeutically distinguishable subgroups. Patients with dominant esophageal or abdominal symptoms should receive a different therapy. Sequential methods are very effective for the evaluation of traditional care practices and should be considered preliminary and integrative to randomized controlled trials in this context. PMID:17965771

  19. The Effect of Sodium Bicarbonate in Sports Drink on the Metabolism of Athletes

    Directory of Open Access Journals (Sweden)

    Yanchun Liu

    2015-05-01

    Full Text Available It is known that sodium bicarbonate (NaHCO3 is used by athletes before exercise to delay fatigue and improve performance based on the knowledge that it removes H+ ions from the body through the creation of a metabolic alkalosis state. In this study, the effects of 0.3 g/kg NaHCO3 given orally to athletes and non-athletes before a 600 m race were compared. After resting for 48 h, 0.3 g/kg NaHCO3 was given orally as a 500 mL fruit juice and the same determinations made under the same conditions 2 h later. In the study, the time taken to complete race after the administration of NaHCO3 fell compared to that before its administration in the athletes. The level of HCO3- before the administration of NaHCO3 in the athletes was observed to be higher than after the administration of NaHCO3. A rise in the HLa levels was observed after exercising following the administration of NaHCO3 ’ in the athletes. The differences in the other parameters apart from that in pH were not statistically significant (p<0.01, (p<0.05. In conclusion, it can be said that, use of NaHCO3 at doses low enough not to cause gastrointestinal disturbances is one of the factors that positively affect anaerobic performance in athletes, but this effect is lower than that observed in individuals leading sedentary lives.

  20. Expectancy of ergogenicity from sodium bicarbonate ingestion increases high-intensity cycling capacity.

    Science.gov (United States)

    Higgins, Matthew F; Shabir, Akbar

    2016-04-01

    This study examined whether expectancy of ergogenicity of a commonly used nutritional supplement (sodium bicarbonate; NaHCO3) influenced subsequent high-intensity cycling capacity. Eight recreationally active males (age, 21 ± 1 years; body mass, 75 ± 8 kg; height, 178 ± 4 cm; WPEAK = 205 ± 22 W) performed a graded incremental test to assess peak power output (WPEAK), one familiarisation trial and two experimental trials. Experimental trials consisted of cycling at 100% WPEAK to volitional exhaustion (TLIM) 60 min after ingesting either a placebo (PLA: 0.1 g·kg(-1) sodium chloride (NaCl), 4 mL·kg(-1) tap water, and 1 mL·kg(-1) squash) or a sham placebo (SHAM: 0.1 g·kg(-1) NaCl, 4 mL·kg(-1) carbonated water, and 1 mL·kg(-1) squash). SHAM aimed to replicate the previously reported symptoms of gut fullness (GF) and abdominal discomfort (AD) associated with NaHCO3 ingestion. Treatments were administered double blind and accompanied by written scripts designed to remain neutral (PLA) or induce expectancy of ergogenicity (SHAM). After SHAM mean TLIM increased by 9.5% compared to PLA (461 ± 148 s versus 421 ± 150 s; P = 0.048, d = 0.3). Ratings of GF and AD were mild but ~1 unit higher post-ingestion for SHAM. After 3 min TLIM overall ratings of perceived exertion were 1.4 ± 1.3 units lower for SHAM compared to PLA (P = 0.020, d = 0.6). There were no differences between treatments for blood lactate, blood glucose, or heart rate. In summary, ergogenicity after NaHCO3 ingestion may be influenced by expectancy, which mediates perception of effort during subsequent exercise. The observed ergogenicity with SHAM did not affect our measures of cardiorespiratory physiology or metabolic flux. PMID:26863442

  1. Changes in plasma levels of vasoactive peptides during sequential bicarbonate hemodialysis.

    Science.gov (United States)

    Hegbrant, J; Thysell, H; Mårtensson, L; Ekman, R; Boberg, U

    1993-01-01

    The hemodynamic response to isolated ultrafiltration (IUF) is characterized by a vasoconstriction, while there is no significant change in peripheral vascular resistance during isovolemic bicarbonate hemodialysis (IVHD). The present investigation was designed to study the plasma levels of vasoactive regulatory peptides together with noradrenaline (NA) and plasma renin activity (PRA) in 11 patients during sequential hemodialysis (SQHD) - IUF for 60 min, followed by IVHD for 210 min. During IUF, the vasoconstrictors arginine vasopressin (AVP), gamma 2-melanocyte-stimulating hormone (gamma 2-MSH), neuropeptide Y (NPY), NA and PRA increased. During IVHD, NPY and PRA remained unchanged on a higher level. A decrease in AVP below the baseline and in gamma 2-MSH and NA to the baseline levels occurred during IVHD. In the case of vasodilators, there were no changes in calcitonin gene-related peptide or motilin during SQHD. An increase in beta-endorphin (beta-END) occurred during IUF, followed by a decrease during IVHD. Substance P and vasoactive intestinal peptide were unchanged during IUF but decreased during IVHD. We conclude that SQHD is characterized by an increase in all the measured vasoconstrictors during IUF in response to loss of fluid, and by a decrease in some vasoconstrictors (AVP, gamma 2-MSH, NA) during IVHD. With the exception of beta-END, there were no changes or only minor ones in vasodilators during SQHD. There are changes in plasma levels of vasoactive substances during SQHD but the importance of these changes for the hemodynamic adaptation to ultrafiltration and dialysis needs to be studied further.

  2. Thermal analysis of modified sodium bicarbonate%碳酸氢钠的改性及其热分析

    Institute of Scientific and Technical Information of China (English)

    曹贤武; 张轶钧; 伍巍; 吴鹏君

    2012-01-01

    考察了不同目数下碳酸氢钠的热分解温度;采用熔融法和溶液法,使用硬脂酸、芥酸酰胺等5种改性剂对碳酸氢钠进行改性,利用DSC和TG评价其改性效果。结果表明:碳酸氢钠的目数对其热分解温度有一定影响;采用有机包覆改性碳酸氢钠的方法能够有效提高其分解温度,缩短分解区间,提高分解速率,从而应用于泡沫塑料加工;当NaHCO3∶硬脂酸的质量比为1∶0.5时,采用熔融法所得的改性碳酸氢钠的起始分解温度由115℃提高至178℃,分解区间由61℃缩短至25℃;改性前后碳酸氢钠的热分解反应都符合"成核与核增长"机理中的Avrami-Erofeev方程,改性剂的添加会导致核成长因子n的增加,改性碳酸氢钠的活化能Ea也有所提高。%The decomposition temperature of sodium bicarbonate with different mesh number was studied.Five modifiers,including stearic acid and erucamide,were used to modify sodium bicarbonate by melting method and solution method.The effects of modification were evaluated by differential scanning calorimetry(DSC) and thermal gravimetric analysis(TGA).The results showed that the mesh number of sodium bicarbonate has influence on its decomposition temperature.The organic coating and modification of sodium bicarbonate can increase the initial decomposition temperature,narrow the range of decomposition temperature and improve the decomposition rate.All of these can be used in the processing of foam plastic.Sodium bicarbonate was modified by melting-method with a mass ratio of 1∶0.5 obtained in the optimized condition,in which its initial decomposition temperature is increased from 115 ℃ to 178 ℃,and its decomposition temperature range is narrowed from 61 ℃ to 25 ℃.The most probable mechanism functions of the thermal decomposition of sodium bicarbonate and modified sodium bicarbonate agree with Avrami-Erofeev equations.The addition of modifiers can increase the nucleation growth

  3. [Direct oral thrombin inhibitor, "dabigatran"].

    Science.gov (United States)

    Yasaka, Masahiro

    2013-01-01

    Dabigatran is an oral, direct, and competitive inhibitor of thrombin, which is administered to patients with non-valvular atrial fibrillation for prevention of stroke at a dose of 110 mg twice daily or 150 mg twice daily. Anticoagulation by dabigatran is "hybrid anticoagulation", consisting of action of both dabigatran and physiological coagulation inhibitors because warfarin inhibits production of protein C and protein S but dabigatran does not. Management of dabigatran is easier than that of warfarin because food restriction is unnecessary, drug interaction is small, and absorption time is short and serum concentration corresponds to the anticoagulatory effect in dabigatran treatment. The RE-LY trial confirmed effectiveness and safety of both doses of dabigatran for prevention of stroke and both doses of dabigatran had much lower risks of intracranial bleeding compared with warfarin. Compliance to guidance of dabigatran treatment is essential for avoidance of severe hemorrhagic complications. PMID:23631181

  4. Potential inhibitors from wet oxidation of wheat straw and their effect on ethanol production of Saccharomyces cerevisiae: Wet oxidation and fermentation by yeast

    DEFF Research Database (Denmark)

    Klinke, Helene Bendstrup; Olsson, Lisbeth; Thomsen, A.B.;

    2003-01-01

    in concentrations of 50-100 times the concentration found in the hydrolysate for their effect on fermentation by yeast. At these high concentrations (10 mM), 4-hydroxy-benzaldehyde, vanillin, 4-hydroxyacetophenone and acetovanillone caused a 53-67% decrease in the volumetric ethanol productivity in S. cerevisiae...

  5. Cellulosic Ethanol Production from Xylose-extracted Corncob Residue by SSF Using Inhibitor- and Thermal-tolerant Yeast Clavispora NRRL Y-50339

    Science.gov (United States)

    Xylose-extracted corncob residue, a byproduct of the xylose-producing industry using corncobs, is an abundant potential energy resource for cellulosic ethanol production. Simultaneous saccharification and fermentation (SSF) is considered an ideal one-step process for conversion of lignocellulosic b...

  6. Sodium bicarbonate induces crystalline wax generation, activates host-resistance, and increases imazalil level in rind wounds of oranges, improving the control of green mold during storage.

    Science.gov (United States)

    Dore, Antonio; Molinu, Maria Giovanna; Venditti, Tullio; D'Hallewin, Guy

    2010-06-23

    Imazalil (IMZ) was quantified in the flavedo and albedo (Citrus fruits outer and inner tissue of the exocarp) of wounded and unwounded Valencia L. Olinda oranges following a 2 min immersion at 25 degrees C in 50, 100, or 250 microg mL(-1) of the fungicide mixture with or without 3% sodium bicarbonate (SBC). The addition of SBC significantly reduced the decay incidence throughout 30 d of storage at 10 degrees C with 95% RH and 6 d of simulated marketing period at 25 degrees C and 75% RH. In unwounded oranges, IMZ uptake was not changed by the coapplication of SBC, and the fungicide was predominantly recovered in the flavedo. To the contrary, in the albedo of wounded fruit, the residue level increased by about 6-fold when the fungicide was applied with SBC. When SBC was coapplied to wounded fruit, the phytoalexin scoparone was induced in the albedo and the accumulation was not affected by IMZ. When fruit was treated with SBC, scanning electron microscopy observations evidenced a production of crystalline wax patches with branched stripes and the magnitude was positively correlated to the salt concentration in the mixture. The generation as fast as 24 h post-treatment, and the different morphology of the new wax suggests a displacement of intracuticular waxes which can affect the fungicide sorption and diffusion coefficient into the rind. PMID:20486661

  7. Net primary productivity collected from New Horizon in Gulf of California and North Pacific Ocean from 2004-07-14 to 2008-08-06 (NCEI Accession 0130076)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Net primary productivity determined from 13C-labeled in situ incubations. Water collected via Niskin bottle was incubated with labeled bicarbonate for 24 hours at...

  8. The role of sodium bicarbonate in the nucleation of noctilucent clouds

    Directory of Open Access Journals (Sweden)

    J. M. C. Plane

    Full Text Available It is proposed that a component of meteoric smoke, sodium bicarbonate (NaHCO3, provides particularly effective condensation nuclei for noctilucent clouds. This assertion is based on three conditions being met. The first is that NaHCO3 is present at sufficient concentration (±104 cm-3 in the upper mesosphere between 80 and 90 km. It is demonstrated that there is strong evidence for this based on recent laboratory measurements coupled with atmospheric modelling. The second condition is that the thermodynamics of NaHCO3(H2On cluster formation allow spontaneous nucleation to occur under mesospheric conditions at temperatures below 140 K. The Gibbs free energy changes for forming clusters with n = 1 and 2 were computed from quantum calculations using hybrid density functional/Hartree-Fock (B3LYP theory and a large basis set with added polarization and diffuse functions. The results were then extrapolated to higher n using an established dependence of the free energy on cluster size and the free energy for the sublimation of H2O to bulk ice. A 1-dimensional model of sodium chemistry was then employed to show that spontaneous nucleation to form ice particles (n >100 should occur between 84 and 89 km in the high-latitude summer mesosphere. The third condition is that other metallic components of meteoric smoke are less effective condensation nuclei, so that the total number of potential nuclei is small relative to the amount of available H2O. Quantum calculations indicate that this is probably the case for major constituents such as Fe(OH2, FeO3 and MgCO3.

    Key words: Atmospheric composition and structure (aerosols and particles; cloud physics and chemistry; middle atmosphere · composition and chemistry

  9. Efficiency of two nitrification inhibitors (dicyandiamide and 3, 4-dimethypyrazole phosphate) on soil nitrogen transformations and plant productivity: a meta-analysis.

    Science.gov (United States)

    Yang, Ming; Fang, Yunting; Sun, Di; Shi, Yuanliang

    2016-01-01

    Dicyandiamide (DCD) and 3, 4-dimethypyrazole phosphate (DMPP) are often claimed to be efficient in regulating soil N transformations and influencing plant productivity, but the difference of their performances across field sites is less clear. Here we applied a meta-analysis approach to compare effectiveness of DCD and DMPP across field trials. Our results showed that DCD and DMPP were equally effective in altering soil inorganic N content, dissolve inorganic N (DIN) leaching and nitrous oxide (N2O) emissions. DCD was more effective than DMPP on increasing plant productivity. An increase of crop yield by DMPP was generally only observed in alkaline soil. The cost and benefit analysis (CBA) showed that applying fertilizer N with DCD produced additional revenues of $109.49 ha(-1) yr(-1) for maize farms, equivalent to 6.02% increase in grain revenues. In comparisons, DMPP application produced less monetary benefit of $15.67 ha(-1) yr(-1). Our findings showed that DCD had an advantage of bringing more net monetary benefit over DMPP. But this may be weakened by the higher toxicity of DCD than DMPP especially after continuous DCD application. Alternatively, an option related to net monetary benefit may be achieved through applying DMPP in alkaline soil and reducing the cost of purchasing DMPP products. PMID:26902689

  10. Screening New Drugs for Immunotoxic Potential: II. Assessment of the Effects of Selective and Nonselective COX-2 Inhibitors on Complement Activation, Superoxide Anion Production and Leukocyte Chemotaxis and Migration Through Endothelial Cells.

    Science.gov (United States)

    Furst, Sylvia M; Khan, K Nasir; Komocsar, Wendy J; Fan, Lian; Mennear, John

    2005-04-01

    Results from earlier experiments in our laboratories revealed that both selective and nonselective inhibitors of cyclooxygenase-2 possess little potential for decreasing in vitro phagocytosis by rat macrophages or canine neutrophils and no potential for decreasing in vivo phagocytosis by the intact murine immune system. We now report the results of studies to assess in vitro and ex vivo effects of the drugs on 1) canine complement activation, 2) generation of superoxide anion and hydrogen peroxide (oxidative burst) by canine neutrophils, and 3) leukocytic chemotaxis and transmigration through endothelial cell monolayers. In vitro concentrations of naproxen sodium, SC-236, SC-245, and SC-791 ranging from 0.1 to 10 muM were tested for their abilities to inhibit canine complement-mediated hemolysis of opsonized sheep erythrocytes and to block phorbol myristate acetate-induced oxidative burst in canine neutrophils. Both models responded to known inhibitory agents, leupeptin in the complement activation test and staurosporine in the superoxide anion assay. In contrast, tested nonsteroidal anti-inflammatory drugs produced only trivial changes in complement activation and superoxide anion production. Experiments on plasma and neutrophils isolated from dogs administered an experimental selective COX-2 inhibitor during a 28-day toxicology study revealed no evidence of drug-associated changes in complement activation or formation of superoxide anion. SC-791 reduced chemotaxis of canine leukocytes toward zymosan-activated dog plasma, but not toward leukotriene B(4). None of the other drugs tested significantly affected leukocytic chemotaxis. Ibuprofen, SC-245 and SC-791 but not SC-236, reduced transmigration of canine leukocytes through endothelial cell monolayers. Based on the results of these experiments and our earlier studies we have concluded that, although high (suprapharmacologic) concentrations of the drugs may induce in vitro evidence of apparent immunomodulation of

  11. Inhibition of human CYP19 by azoles used as antifungal agents and aromatase inhibitors, using a new LC-MS/MS method for the analysis of estradiol product formation

    International Nuclear Information System (INIS)

    Azoles are used as fungicides in agriculture or antifungal drugs in medicine. Their therapeutic activity is based on the inhibition of fungal lanosterol-14α-demethylase (CYP51). Azoles are also used for the treatment of estrogen-dependent diseases, e.g. in breast cancer therapy. Inhibition of CYP19 (aromatase) is the working principle for tumor therapy, but is an unwanted side effect of azoles used as fungicides or antifungal drugs. The inhibition of recombinant human CYP19 by 21 azoles in use for the three different purposes was investigated using the natural substrate testosterone. Estradiol product formation was measured by a newly developed and fully validated analytical method based on liquid chromatography-tandem mass spectrometry utilizing photospray ionization (APPI). Potency of enzyme inhibition was expressed in terms of IC5 concentrations. The two cytostatic drugs fadrozole and letrozole were the most potent inhibitors. However, azoles used as fungicides, e.g. prochloraz, or as antifungal drugs, e.g. bifonazole, were almost as potent inhibitors of aromatase as the drugs used in tumor therapy. Comparison of plasma concentrations that may be reached in antifungal therapy do not allow for large safety factors for bifonazole and miconazole. The IC5 values were compared to data obtained with other substrates, such as the pseudo-substrate dibenzylfluorescein (DBF). A high correlation was found, indicating that the fluorescence assay with DBF can well be used for potency ranking and screening of chemicals for aromatase inhibition. The data for antifungal drugs show that side effects on steroid hormone synthesis in humans due to inhibition of aromatase should be considered

  12. Fate of nitrogen in soil-crop system by nuclear techniques. Effects of applied rate of ammonium bicarbonate

    International Nuclear Information System (INIS)

    The experiment was conducted with 15N tracing techniques in Shijiazhuang from 1994 to 1995. Three nitrogen rates, including optimum rate (150 kg/hm2) based on the recommendation of local farmers, above 50% of optimum rate (225 kg/hm2) and below 50% of optimum rate (75 kg/hm2), were selected to study the effect of application rates of ammonium bicarbonate on yield of winter wheat and fate of applied nitrogen under local management and irrigated condition. The results showed that nitrogen uptake and grain yield of wheat under fertilized treatments were higher than those in unfertilized treatment (except 225 kg/hm2 treatment). The highest yield and top dry mater weight (grain 6.80 t/hm2, top 14.70 t/hm2) were obtained in optimum N applied treatment (150 kg/hm2), while the highest nitrogen recovery efficiency (38.5%) of ammonium bicarbonate by winter wheat was found in below 50% of optimum rate treatment (75 kg/hm2) due to the relatively high basic fertility of the field. However, nitrogen recovery efficiency of ammonium bicarbonate decreased with the increasing N application rate. The highest residue of fertilizer N was found in 225 kg/hm2 treatment, and 46% of the residue existed in the top layer of the soil (0∼50 cm). The unaccounted N from fertilizer were 30.20%, 36.56%, 31.25% in 75 kg/hm2, 150 kg/hm2, 225 kg/hm2 treatments respectively according to 15N balance calculation in soil-plant system. The effect of residue N in soil on the next crop, maize, in 225 kg/hm2 treatment was best in three fertilized treatments, suggesting the possibilities of nitrate leaching down in 225 kg/hm2 treatment. (15 tabs.)

  13. Sodium bicarbonate protects uranium-induced acute nephrotoxicity through uranium-decorporation by urinary alkalinization in rats

    OpenAIRE

    Ohmachi, Yasushi; Imamura, Tomomi; Ikeda, Mizuyo; Shishikura, Eriko; Kim, Eunjoo; Kurihara, Osamu; Sakai, Kazuo

    2015-01-01

    To evaluate the effectiveness of sodium bicarbonate (SB) in removing uranium and protecting animals from uranium toxicity, we intramuscularly administered 1 mg/kg of uranyl nitrate to 8-wk-old male SD rats, and 20 min after administration of uranyl nitrate, the animals were given a single oral administration of SB at 0.1, 0.3 or 1 g/kg. The SB treatment at a dose of 0.3 g/kg or more raised the pH of the rats’ urine until 4 h after treatment, and it significantly reduced the uranium amounts in...

  14. Effect of Electrochemical Treatment in Aqueous Ammonium Bicarbonate on Surface Properties of PAN-based Carbon Fibers

    Institute of Scientific and Technical Information of China (English)

    曹海琳; 黄玉东; 张志谦; 孙举涛

    2004-01-01

    The surface properties of PAN-based carbon fibers electrochemically treated in aqueous ammonium bicarbonate before and after treatment were characterized by X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM) and Dynamic Contact Angle Analysis (DCAA). The results of characterization indicated that the oxygen and nitrogen contents in carbon fiber surface were significantly increased by electrochemical treatment, and amide groups was introduced onto it, which was related with the electrolyte. The AFM photographs illustrated that the roughness of the fiber surface was also increased. The wettibality of the fibers was improved after treatment because the surface energy especially the polar part of it was increased.

  15. Effect of ambient temperature and sodium bicarbonate supplementation on water and electrolyte balances in dry and lactating Holstein cows

    OpenAIRE

    Khelil-Arfa, Hajer; Faverdin, Philippe; Boudon, Anne

    2014-01-01

    The aim of this study was to quantify the effect of the interaction between 2 constant ambient temperatures [thermoneutrality (TN; 15°C) and high temperature (HT; 28°C)] and 2 levels of Na bicarbonate supplementation [calculated to provide diet Na contents of 0.20% DM (Na(-)) and 0.50% DM (Na(+))] on water partitioning in dairy cows. Treatments were compared on 4 dry and 4 mid-lactation Holstein cows according to 2 Latin squares (1 for each physiological stage) over the course of 4 periods of...

  16. Using a simple HPLC approach to identify the enzymatic products of UTL-5g, a small molecule TNF-α inhibitor, from porcine esterase and from rabbit esterase

    OpenAIRE

    Swartz, Kenneth; ZHANG, YIGUAN; Valeriote, Frederick; Chen, Ben; SHAW, JIAJIU

    2013-01-01

    UTL-5g is a novel small-molecule chemoprotector that lowers hepatotoxicity, nephrotoxicity, and myelotoxicity induced by cisplatin through TNF-α inhibition among other factors. As a prelude to investigating the metabolites of UTL-5g, we set out to identify the enzymatic products of UTL-5g under the treatment of both porcine liver esterase (PLE) and rabbit liver esterase (RLE). First, a number of mixtures made by UTL-5g and PLE were incubated at 25 °C. At predetermined time points, individual ...

  17. Profiling acylated homoserine lactones in Yersinia ruckeri and influence of exogenous acyl homoserine lactones and known quorum-sensing inhibitors on protease production

    DEFF Research Database (Denmark)

    Kastbjerg, Vicky Gaedt; Nielsen, Kristian Fog; Dalsgaard, Inger;

    2007-01-01

    produced at least eight different acylated homoserine lactones (AHLs) with N-(3-oxooctanoyl)-l-homoserine lactone (3-oxo-C8-HSL) being the dominant molecule. Also, some uncommon AHL, N-(3-oxoheptanoyl)-l-homoserine lactone (3-oxo-C7-HSL) and N-(3-oxononanoyl)-l-homoserine lactone (3-oxo-C9-HSL), were...... produced. 3-oxo-C8-HSL was detected in organs from fish infected with Y. ruckeri. Protease production was significantly lower at temperatures above 23 degrees C than below although growth was faster at the higher temperatures. Neither addition of sterile filtered high-density Y. ruckeri culture supernatant...

  18. LC-MS-MS Characterization of Forced Degradation Products of Fidarestat, a Novel Aldose Reductase Inhibitor: Development and Validation of a Stability-Indicating RP-HPLC Method.

    Science.gov (United States)

    Talluri, M V N Kumar; Khatoon, Lubna; Kalariya, Pradipbhai D; Chavan, Balasaheb B; Ragampeta, Srinivas

    2015-10-01

    An accurate, precise, robust and selective stability-indicating liquid chromatographic (LC) method has been developed for the monitoring of fidarestat in the presence of its forced degradants. The drug was subjected to hydrolysis (acid, alkali and neutral degradation), oxidation, photolysis and thermal stress conditions. The drug degraded significantly under hydrolytic (basic, acidic and neutral) and oxidative stress conditions, whereas it was found to be stable in photolytic and thermal conditions. The chromatographic separation was achieved on a Grace C18, (250 mm × 4.6 mm × 5 μm) column using gradient mobile phase system consisting of 10 mM of ammonium acetate buffer at pH 4 and acetonitrile at a flow rate of 1 mL/min with UV detection at 283 nm. The developed method was extended to liquid chromatography quadrupole time-of-flight tandem mass spectrometry (LC-QTOF-MS-MS) for characterization of all the degradation products. A total of five new degradation products were identified and characterized by LC-QTOF-MS-MS. The developed LC method was validated as per ICH guideline Q2 (R1). The proposed method was found to be successively applied for the quality control of fidarestat in bulk drug analysis. PMID:26014964

  19. Milk alkali syndrome induced by calcitriol and calcium bicarbonate in a patient with hypoparathyroidism

    Directory of Open Access Journals (Sweden)

    Eda Altun

    2013-01-01

    Full Text Available The milk-alkali syndrome (MAS was a common cause of hypercalcemia, metabolic alkalosis, and renal failure in the early 20 th century. This syndrome was first recognized secondary to treatment of peptic ulcer disease with milk and absorbable alkali. Its incidence fell after the introduction of H2-blocker and proton pump inhibitor. Persistent ingestion of calcium carbonate and vitamin D caused MAS. We report a patient presenting with a triad of hypercalcemia, metabolic alkalosis and renal failure secondary to treatment of idiopathic hypoparathyroidism.

  20. Effects of sodium bicarbonate concentration on growth, photosynthesis, and carbonic anhydrase activity of macroalgae Gracilariopsis lemaneiformis, Gracilaria vermiculophylla, and Gracilaria chouae (Gracilariales, Rhodophyta).

    Science.gov (United States)

    Zhou, Wei; Sui, Zhenghong; Wang, Jinguo; Hu, Yiyi; Kang, Kyoung Ho; Hong, Hye Ran; Niaz, Zeeshan; Wei, Huihui; Du, Qingwei; Peng, Chong; Mi, Ping; Que, Zhou

    2016-06-01

    There is potential for bicarbonate to improve crop yields and economic efficiency of marine algae. However, few studies have focused on the effect of bicarbonate on the growth, photosynthesis, and enzyme activity associated with carbon utilization, especially in commercial macroalgae. Here, the addition of bicarbonate (up to 420 mg L(-1)) to macroalgal cultures has been evaluated for Gracilariopsis lemaneiformis, Gracilaria vermiculophylla, and Gracilaria chouae with respect to growth rate, photosynthetic activity, carbonic anhydrase activity, and biochemical composition. The results showed that the effects of NaHCO3 on growth, chlorophyll a, phycoerythrin, photosynthetic oxygen evolution, photochemical parameters of PSI and PSII, carbonic anhydrase activity, and nitrogen content were significant (P 336 mg L(-1) for Gp. lemaneiformis and >420 mg L(-1) for the other two species). Moreover, species-specific differences induced by supplementation with bicarbonate were discovered during culture. Optimal concentrations of NaHCO3 used in this study were 252 mg L(-1) for Gp. lemaneiformis and 336 mg L(-1) for G. vermiculophylla and G. chouae. These results suggest that an adequate supplementation of sodium bicarbonate is a viable strategy for promoting growth and photosynthetic activity in some macroalgae as well as for improving biochemical composition. The study will help to accelerate the growth rate of algae and improve the quality of thalli, and will also be useful for enhancing the understanding of carbon utilization in macroalgae.

  1. Gastric bicarbonate secretion and release of prostaglandin E2 are increased in duodenal ulcer patients, but not in Helicobacter pylori positive healthy subjects

    DEFF Research Database (Denmark)

    A, Mertz-Nielsen; Hillingsø, Jens; Frøkiær, Hanne;

    1996-01-01

    Background: Duodenal ulcer (DU) patients have impaired proximal duodenal mucosal bicarbonate secretion at rest and in response to luminal acid with higher acid-stimulated mucosal release of prostaglandin (PG) E(2) than healthy subjects. Our purpose was to determine whether this abnormality was pr...... be responsible for the abnormally high gastric secretion of bicarbonate in inactive DU patients. Th; defective duodenal secretion of bicarbonate observed in these patients may be a consequence of previous ulceration rather than the mere presence of H. pylori infection.......Background: Duodenal ulcer (DU) patients have impaired proximal duodenal mucosal bicarbonate secretion at rest and in response to luminal acid with higher acid-stimulated mucosal release of prostaglandin (PG) E(2) than healthy subjects. Our purpose was to determine whether this abnormality...... was present also in the stomach of DU patients. Methods: Simultaneous determinations of gastric and duodenal bicarbonate secretion and luminal release of PGE(2) were performed in 16 healthy volunteers (5 Helicobacter pylori-positive) and 8 inactive DU patients (all H. pylori-positivr). Results: In healthy...

  2. Gastric bicarbonate secretion and release of prostaglandin E2 are increased in duodenal ulcer patients but not in Helicobacter pylori-positive healthy subjects

    DEFF Research Database (Denmark)

    Mertz-Nielsen, A; Hillingsø, Jens; Frøkiaer, H;

    1996-01-01

    BACKGROUND: Duodenal ulcer (DU) patients have impaired proximal duodenal mucosal bicarbonate secretion at rest and in response to luminal acid with higher acid-stimulated mucosal release of prostaglandin (PG) E2 than healthy subjects. Our purpose was to determine whether this abnormality was pres...... for the abnormally high gastric secretion of bicarbonate in inactive DU patients. The defective duodenal secretion of bicarbonate observed in these patients may be a consequence of previous ulceration rather than the mere presence of H. pylori infection.......BACKGROUND: Duodenal ulcer (DU) patients have impaired proximal duodenal mucosal bicarbonate secretion at rest and in response to luminal acid with higher acid-stimulated mucosal release of prostaglandin (PG) E2 than healthy subjects. Our purpose was to determine whether this abnormality...... was present also in the stomach of DU patients. METHODS: Simultaneous determinations of gastric and duodenal bicarbonate secretion and luminal release of PGE2 were performed in 16 healthy volunteers (5 Helicobacter pylori-positive) and 8 inactive DU patients (all H. pylori-positive). RESULTS: In healthy...

  3. Evaluation of antifungal activity of carbonate and bicarbonate salts alone or in combination with biocontrol agents in control of citrus green mold.

    Science.gov (United States)

    Zamani, M; Sharifi Tehrani, A; Ali Abadi, A Alizadeh

    2007-01-01

    The aim of this research was to determine if the attacks of green mold on orange could be reduced by edible salts alone or in combination with biocontrol agent. For this purpose toxicity to Pantoea digitatum and practical use of sodium carbonate (SC), sodium bicarbonate (SBC) and potassium carbonate, and potassium bicarbonate alone or in combination with antagonistic bacteria (Pseudomonas fluorescens isolate PN, Bacillus subtilis isolate VHN, Pantoea agglomerans isolate CA) to control green mold were determined. All were fungistatic. SC and SBC were equal and superior to the other salts for control of green mold on oranges inoculated 6h before treatment and were chosen for subsequent trails under cold storage conditions. The biocontrol agents were found completely tolerant to 3% sodium bicarbonate and sodium carbonate at room temperature; although their culturability was reduced by > 1000-fold after 60 min in 1% other salt solutions. Satisfactory results were also obtained with the combined treatment for control of green mold. A significant increase in biocontrol activity of all isolate was observed when combined with sodium carbonate and sodium bicarbonate. The treatments comprising CA combined with SB was as effective as fungicide treatment. Thus, use of sodium bicarbonate treatment at 3% followed by the antagonist P. agglomerans CA could be an alternative to chemical fungicides for control of green mold on oranges. PMID:18396809

  4. Effects of sodium bicarbonate concentration on growth, photosynthesis, and carbonic anhydrase activity of macroalgae Gracilariopsis lemaneiformis, Gracilaria vermiculophylla, and Gracilaria chouae (Gracilariales, Rhodophyta).

    Science.gov (United States)

    Zhou, Wei; Sui, Zhenghong; Wang, Jinguo; Hu, Yiyi; Kang, Kyoung Ho; Hong, Hye Ran; Niaz, Zeeshan; Wei, Huihui; Du, Qingwei; Peng, Chong; Mi, Ping; Que, Zhou

    2016-06-01

    There is potential for bicarbonate to improve crop yields and economic efficiency of marine algae. However, few studies have focused on the effect of bicarbonate on the growth, photosynthesis, and enzyme activity associated with carbon utilization, especially in commercial macroalgae. Here, the addition of bicarbonate (up to 420 mg L(-1)) to macroalgal cultures has been evaluated for Gracilariopsis lemaneiformis, Gracilaria vermiculophylla, and Gracilaria chouae with respect to growth rate, photosynthetic activity, carbonic anhydrase activity, and biochemical composition. The results showed that the effects of NaHCO3 on growth, chlorophyll a, phycoerythrin, photosynthetic oxygen evolution, photochemical parameters of PSI and PSII, carbonic anhydrase activity, and nitrogen content were significant (P 336 mg L(-1) for Gp. lemaneiformis and >420 mg L(-1) for the other two species). Moreover, species-specific differences induced by supplementation with bicarbonate were discovered during culture. Optimal concentrations of NaHCO3 used in this study were 252 mg L(-1) for Gp. lemaneiformis and 336 mg L(-1) for G. vermiculophylla and G. chouae. These results suggest that an adequate supplementation of sodium bicarbonate is a viable strategy for promoting growth and photosynthetic activity in some macroalgae as well as for improving biochemical composition. The study will help to accelerate the growth rate of algae and improve the quality of thalli, and will also be useful for enhancing the understanding of carbon utilization in macroalgae. PMID:26960545

  5. Calcineurin inhibitors suppress cytokine production from memory T cells and differentiation of naive T cells into cytokine-producing mature T cells.

    Directory of Open Access Journals (Sweden)

    Kenshiro Tsuda

    Full Text Available T cells have been classified as belonging to the Th1 or Th2 subsets according to the production of defining cytokines such as IFN-γ and IL-4. The discovery of the Th17 lineage and regulatory T cells shifted the simple concept of the Th1/Th2 balance into a 4-way mechanistic pathway of local and systemic immunological activity. Clinically, the blockage of cytokine signals or non-specific suppression of cytokine predominance by immunosuppressants is the first-line treatment for inflammatory T cell-mediated disorders. Cyclosporine A (CsA and Tacrolimus (Tac are commonly used immunosuppressants for the treatment of autoimmune disease, psoriasis, and atopic disorders. Many studies have shown that these compounds suppress the activation of the calcium-dependent phosphatase calcineurin, thereby inhibiting T-cell activation. Although CsA and Tac are frequently utilized, their pharmacological mechanisms have not yet been fully elucidated.In the present study, we focused on the effects of CsA and Tac on cytokine secretion from purified human memory CD4(+T cells and the differentiation of naïve T cells into cytokine-producing memory T cells. CsA or Tac significantly inhibited IFN-γ, IL-4, and IL-17 production from memory T cells. These compounds also inhibited T cell differentiation into the Th1, Th2, and Th17 subsets, even when used at a low concentration. This study provided critical information regarding the clinical efficacies of CsA and Tac as immunosuppressants.

  6. 自噬抑制剂3-MA抑制EV71病毒颗粒的产生与释放%Autophagy inhibitor 3-MA decreases the production and release of infections enterovirus 71 particles

    Institute of Scientific and Technical Information of China (English)

    张晓延; 郗雪艳; 赵振东

    2011-01-01

    目的 通过研究肠道病毒71型(Enterovirus 71,EV71)感染引起细胞的自噬及抑制自噬对病毒滴度的影响,为进一步明确EV71的致病机制提供基础.方法 利用Western Blot检测EV71感染后RD-A细胞内源性LC3的型别转换和P62的降解来指示细胞发生自噬的水平,通过测定染毒细胞培养上清中EV71病毒CCID50来观察抑制自噬后细胞释放EV71感染性病毒颗粒的变化.结果 EV71的感染促进了细胞LC3的型别转换和F62的降解,诱导了细胞发生自噬;3-MA抑制细胞自噬后,EV71染毒细胞产生的感染性EV71病毒颗粒数量减少.结论 EV71可以诱导细胞发生自噬,细胞自噬可能促进EV71感染性病毒颗粒的产生和释放.%Objective To determine whether or not enterovirus 71 ( enteroviurs 71, EV71) may induce autophagy and affect the production and release of EV71 after the treatment of autophagy inhibitor. Methods Western blots were performed to examine the conversion of LC3- Ⅰ to LC3-Ⅱ and the degradation of P62 after the RD-A cells were infected with EV71. CCID50 was determined by checking the virus titer in the supernatant of cells that treated with autophagy inhibitor 3-MA. Results EV71 infection enhances the type conversion of LC3 and degradation of P62. The infectious virus particles were decreased after the treatment of 3-MA. Conclusion EV71 infection could induce cell autophagy and the autophagy might contribute to the production and release of infectious EV71 particles.

  7. Paraffin wax deposits and chemical inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Mendell, J.L.

    1970-01-01

    Solutions to this problem becomes necessary with the advent of extremely deep production, offshore production, and the probability of ocean-floor completions. The reasons for paraffin-wax accumulations are many and difficult to pinpoint. Inhibition of these paraffin deposits appears to be the best solution. Paraffin solvents and inhibitors are as follows: solvents, wetting agents, dispersants, and crystal modifiers. Solvents are effective, but can harm a refinery catalyst and create health hazards. Wetting agents and dispersants comprise the majority of chemicals used as paraffin wax inhibitors. Crystal modifiers are relatively new and may provide the most efficient means of reducing deposition. Evaluations of chemical paraffin inhibitors are outlined. Field test results which consider the various chemicals tested may give satisfactory results in determining which particular chemical can solve the problem of the particular situation. (38 refs.)

  8. Evaluation of flow fields on bubble removal and system performance in an ammonium bicarbonate reverse electrodialysis stack

    KAUST Repository

    Hatzell, Marta C.

    2013-11-01

    Ammonium bicarbonate has recently been demonstrated to be an excellent thermolytic solution for energy generation in reverse electrodialysis (RED) stacks. However, operating RED stacks at room temperatures can promote gaseous bubble (CO2, NH3) accumulation within the stack, reducing overall system performance. The management and minimization of bubbles formed in RED flow fields is an important operational issue which has yet to be addressed. Flow fields with and without spacers in RED stacks were analyzed to determine how both fluid flow and the buildup and removal of bubbles affected performance. In the presence of a spacer, the membrane resistance increased by ~50Ω, resulting in a decrease in power density by 30% from 0.140Wm-2 to 0.093Wm-2. Shorter channels reduced concentration polarization affects, and resulted in 3-23% higher limiting current density. Gas accumulation was minimized through the use of short vertically aligned channels, and consequently the amount of the membrane area covered by bubbles was reduced from ~20% to 7% which caused a 12% increase in power density. As ammonium bicarbonate RED systems are scaled up, attention to channel aspect ratio, length, and alignment will enable more stable performance. © 2013 Elsevier B.V.

  9. Avaliação do uso de inibidores de etileno sobre a produção de compostos voláteis e de mangiferina em manga Evaluation of the use of ethylene inhibitors on production of volatile compounds and mangiferin in mango fruit

    Directory of Open Access Journals (Sweden)

    Kirley Marques Canuto

    2010-01-01

    Full Text Available Effects of two ethylene inhibitors, 1-methylcylopropene (1-MCP and aminoethoxyvinylglycine (AVG, on production of volatile compounds and mangiferin (a bioactive xanthone in 'Tommy Atkins' mango fruit were investigated. Volatile composition and mangiferin content, in treated and untreated fruits at three maturity, stages were determined by SPME-GC-MS and HPLC, respectively. These chromatographical analysis revealed that the volatile profiles and mangiferin concentrations were not significantly different, suggesting that the use of ethylene inhibitors does not affect the mango aroma and functional properties relative to this xanthone. Moreover, a simple, precise and accurate HPLC method was developed for quantifying mangiferin in mango pulp.

  10. sbmC, a stationary-phase induced SOS Escherichia coli gene, whose product protects cells from the DNA replication inhibitor microcin B17.

    Science.gov (United States)

    Baquero, M R; Bouzon, M; Varea, J; Moreno, F

    1995-10-01

    Microcin B17 (MccB17) is a ribosomally synthesized peptide antibiotic of 43 amino acids that induces double-strand breaking of DNA in a DNA gyrase-dependent reaction. As a consequence, the SOS regulon is induced and massive DNA degradation occurs. In this work we have characterized an Escherichia coli gene, sbmC, that in high copy number determines high cell resistance to MccB17. sbmC encodes a cytoplasmic polypeptide of 157 amino acids (M(r), 18,095) that has been visualized in SDS-polyacrylamide gels. The gene is located at min 44 of the E. coli genetic map, close to the sbcB gene. sbmC expression is induced by DNA-damaging agents and, also, by the entry of cells into the stationary growth phase. A G-->T transversion at the fifth nucleotide of the quasicanonical LexA-box preceding the gene makes recA cells 16-fold more resistant to exogenous MccB17. The gene product, SbmC, also blocks MccB17 export from producing cells. Altogether, our results suggest that SbmC recognizes and sequesters MccB17 in a reversible way.

  11. Evaluation of a pilot-scaled paddle dryer for the production of ethanol from lignocellulose including inhibitor removal and high-solids enzymatic hydrolysis

    Directory of Open Access Journals (Sweden)

    Egidio Viola

    2016-03-01

    Full Text Available The advantage of using paddle dryers (PD in the production of sugars and 2nd generation ethanol from pretreated wheat straw was investigated. This machinery was employed in order to detoxify steam-exploded substrates and to mix different slurries in the hydrolysis step. The obtained hydrolysate was fermented by the yeast Saccharomyces cerevisiae. Acetic acid and furfural were reduced up to 11 and 26 fold respectively in the detoxified substrate. When fermentation was carried out at low solid suspension, the use of PD was as effective as water extraction in detoxifying exploded biomass, giving ethanol yields of 90% at 0.05 solid/liquid ratio (S/L and 80% at 0.10 S/L. Moreover, by using PD the cellulose conversion yield was significantly improved in the hydrolysis step: when operating at higher S/L (0.4, the hydrolysis efficiency was twice the one achieved by using a bioreactor with a Rushton stirrer.

  12. Endogenous angiogenesis inhibitors and their therapeutic implications.

    Science.gov (United States)

    Cao, Y

    2001-04-01

    A number of endogenous inhibitors targeting the tumor vasculature have recently been identified using in vitro and in vivo antiangiogenesis models. While many of these angiogenesis inhibitors display a broad spectrum of biological actions on several systems in the body, several inhibitors including angiostatin, endostatin, and serpin antithrombin seem to act specifically on the proliferating endothelial cell compartment of the newly formed blood vessels. The discovery of these specific endothelial inhibitors not only increases our understanding of the functions of these molecules in the regulation of physiological and pathological angiogenesis, but may also provide an important therapeutic strategy for the treatment of cancer and other angiogenesis dependent diseases, including diabetic retinopathy and chronic inflammations. Systemic administration of these angiogenesis inhibitors in animals significantly suppresses the growth of a variety of tumors and their metastases. However, their production as functional recombinant proteins has been proven to be difficult. In addition, high dosages of these inhibitors are required to suppress tumor growth in animal studies. Other disadvantages of the antiangiogenic protein therapy include repeated injections, prolonged treatment, transmission of toxins and infectious particles, and high cost for manufacturing large amounts of protein molecules. Thus, alternative strategies need to be developed in order to improve the clinical settings of antiangiogenic therapy. Developments of these strategies are ongoing and they include identification of more potent inhibitors, antiangiogenic gene therapy, improvement of protein/compound half-lives in the circulation, increase of their concentrations at the disease location, and combinatorial therapies with approaches including chemotherapy, radiotherapy, and immunotherapy. Despite the above-mentioned disadvantages, a few inhibitors have entered into the early stages of clinical trials and

  13. Molecular mechanisms of calcium-sensing receptor-mediated calcium signaling in the modulation of epithelial ion transport and bicarbonate secretion.

    Science.gov (United States)

    Xie, Rui; Dong, Xiao; Wong, Chase; Vallon, Volker; Tang, Bo; Sun, Jun; Yang, Shiming; Dong, Hui

    2014-12-12

    Epithelial ion transport is mainly under the control of intracellular cAMP and Ca(2+) signaling. Although the molecular mechanisms of cAMP-induced epithelial ion secretion are well defined, those induced by Ca(2+) signaling remain poorly understood. Because calcium-sensing receptor (CaSR) activation results in an increase in cytosolic Ca(2+) ([Ca(2+)]cyt) but a decrease in cAMP levels, it is a suitable receptor for elucidating the mechanisms of [Ca(2+)]cyt-mediated epithelial ion transport and duodenal bicarbonate secretion (DBS). CaSR proteins have been detected in mouse duodenal mucosae and human intestinal epithelial cells. Spermine and Gd(3+), two CaSR activators, markedly stimulated DBS without altering duodenal short circuit currents in wild-type mice but did not affect DBS and duodenal short circuit currents in cystic fibrosis transmembrane conductance regulator (CFTR) knockout mice. Clotrimazole, a selective blocker of intermediate conductance Ca(2+)-activated K(+) channels but not chromanol 293B, a selective blocker of cAMP-activated K(+) channels (KCNQ1), significantly inhibited CaSR activator-induced DBS, which was similar in wild-type and KCNQ1 knockout mice. HCO3 (-) fluxes across epithelial cells were activated by a CFTR activator, but blocked by a CFTR inhibitor. CaSR activators induced HCO3 (-) fluxes, which were inhibited by a receptor-operated channel (ROC) blocker. Moreover, CaSR activators dose-dependently raised cellular [Ca(2+)]cyt, which was abolished in Ca(2+)-free solutions and inhibited markedly by selective CaSR antagonist calhex 231, and ROC blocker in both animal and human intestinal epithelial cells. Taken together, CaSR activation triggers Ca(2+)-dependent DBS, likely through the ROC, intermediate conductance Ca(2+)-activated K(+) channels, and CFTR channels. This study not only reveals that [Ca(2+)]cyt signaling is critical to modulate DBS but also provides novel insights into the molecular mechanisms of CaSR-mediated Ca(2+)-induced

  14. 酶解丝素蛋白制备ACE抑制肽的研究%Enzymatic Hydrolysis of Silk Fibroin for Production of ACE Inhibitors

    Institute of Scientific and Technical Information of China (English)

    吴晖; 罗美琪; 唐语谦; 肖性龙; 袁坤; 李晓凤

    2011-01-01

    Silk fibroin was hydrolyzed by Alcalase to produce the peptide with high ACE-inhibition activity. The effects of several influential factors on the enzymatic hydrolysis were investigated and the optimum reaction conditions were determined as follows: pH 8.5, temperature 60 "C, substrate concentration 5%, enzyme dosage 1000 U/g protein, and reaction time 240 min, under which the DH. ACE-inhibition rate, peptide yield and protein recovery of the product were 17.12%, 74.07%, 50.31% and 77.37%, respectively. MALDI-TOF mass spectrometry of the hydrolysate showed that the molecular weight of (he peptides was below 2.4kDa.%本研究首次探讨利用Alcalase酶解丝素蛋白制备高活性ACE抑制肽.以水解度为主要评价指标,研究了温度、浓度、pH、加酶量以及反应时间对酶解反应的影响.分析了不同水解度下的酶解产物与ACE体外抑制活性、肽得率和蛋白回收率的关系.确定了制备ACE抑制肽的最佳酶解反应DH值为17.12%,此时所得丝素蛋白肽的肽得率为50.31%,蛋白回收率为77.37%,ACE抑制率可达74.07%.基质辅助激光解吸电离-飞行时间质谱仪(MALDI-TOF)分析表明,所制备的丝素蛋白肽的分子量小于2.4 kDa.

  15. Bicarbonate as tracer for plant assimilated C and homogeneity of 14C and 15N distribution in ryegrass and white clover tissue by alternative labeling approaches

    DEFF Research Database (Denmark)

    Rasmussen, Jim; Kusliene, Gedrime; Jacobsen, Ole Stig;

    2013-01-01

    parts with high and low 14C activity were separated and analyzed for 15N enrichment. Results Bicarbonate applied by leaf-labeling efficiently introduced 14C into both white clover and ryegrass, although the 14C activity in particular for white clover was found predominantly in the labeled leaf. Using 14...... that 15N also had a heterogeneous distribution (up to two orders of magnitude). Conclusion Bicarbonate can efficiently be used to introduce 14C or 13C into plant via the leaf-labeling method. Both 14C and 15N showed heterogeneous distribution in the plant, although the distribution of 15N was more even...

  16. Successful recovery from iatrogenic severe hypernatremia and severe metabolic acidosis resulting from accidental use of inappropriate bicarbonate concentrate for hemodialysis treatment

    Directory of Open Access Journals (Sweden)

    Guruprasad P Bhosale

    2015-01-01

    Full Text Available Bicarbonate dialysis is the treatment modality of choice for correction of metabolic acidosis in chronic renal failure. However, improper selection of dialysate concentrate can result in life-threatening human errors. We report a case of iatrogenic severe hypernatremia (sodium 207 mEq/L and severe metabolic acidosis (pH 6.65 that resulted due to accidental use of inappropriate bicarbonate concentrate for hemodialysis treatment. There was successful recovery in this patient with no neurological sequelae. To the best of our knowledge, this is the first case report in adults of severe hypernatremia along with severe metabolic acidosis due to error in the preparation of dialysis fluid.

  17. Np(V) and Np(VI) in bicarbonate/carbonate aqueous solutions; Np(V) et Np(VI) en solution aqueuse bicarbonate/carbonate

    Energy Technology Data Exchange (ETDEWEB)

    Vitorge, P.; Capdevila, H

    1998-12-31

    Formation constants for NpO{sub 2}(CO{sub 3}){sub i}{sup l2i} (i = 1, 2 and 3), NaNpO{sub 2}CO{sub 3(s)} and Na{sub 3}NpO{sub 2}(CO{sub 3}){sub 2(s)} are deduced from Simakin`s et al. (1977), Maya`s (1983), and Vitorge`s et al. data, who also found evidence for a mixed Np(V)-OH-CO{sub 3} soluble complex. Simakin (1977) found NpO{sub 2}(CO{sub 3}){sub 3}{sup -4}, it was confirmed by Riglet (1989), and by Offerle, Capdevilla and Vittorge (1995). Temperature influence was studied by Ullman and Schreiner (1988), and by Offerle, Capdevila and Vittorge (1995). Grenthe, Riglet and Vitorge (1986 and 1989) proved the existence of the trinuclear species (NpO{sub 2}){sub 3}(CO{sub 3}){sub 6}{sup -6}. Maya (1984) mis-interpreted his data; nevertheless they show evidence of a new polynuclear mixed species, certainly (NpO{sub 2}){sub 2}(OH){sub 3}CO{sub 3}{sup -1}, as initially proposed by Maya. No other Np(V) or Np(VI) soluble complex could be detected, the proposed ones quantitatively account for all published works. Unpublished data allowed to estimate the stability of intermediary mononuclear complexes and NpO{sub 2}CO{sub 3(s)} solubility product. M{sub 4}NpO{sub 2}(CO{sub 3}){sub 3(s)} (M{sup +} = K{sup +} or NH{sub 4}{sup +}) ones are deduced from Gorbenko-Germanov and Klimov (1966), and Moskvin (1975) data as respectively interpreted and reinterpreted by this review. Thermodynamic data determined in this report are under discussion within OECD-NEA-TDB. (author)

  18. Relationship of proton motive force and the F(0)F (1)-ATPase with bio-hydrogen production activity of Rhodobacter sphaeroides: effects of diphenylene iodonium, hydrogenase inhibitor, and its solvent dimethylsulphoxide.

    Science.gov (United States)

    Hakobyan, Lilit; Gabrielyan, Lilit; Trchounian, Armen

    2012-08-01

    Rhodobacter sphaeroides MDC 6521 was able to produce bio-hydrogen (H(2)) in anaerobic conditions under illumination. In this study the effects of the hydrogenase inhibitor-diphenylene iodonium (Ph(2)I) and its solvent dimethylsulphoxide (DMSO) on growth characteristics and H(2) production by R. sphaeroides were investigated. The results point out the concentration dependent DMSO effect: in the presence of 10 mM DMSO H(2) yield was ~6 fold lower than that of the control. The bacterium was unable to produce H(2) in the presence of Ph(2)I. In order to examine the mediatory role of proton motive force (∆p) or the F(0)F(1)-ATPase in H(2) production by R. sphaeroides, the effects of Ph(2)I and DMSO on ∆p and its components (membrane potential (∆ψ) and transmembrane pH gradient), and ATPase activity were determined. In these conditions ∆ψ was of -98 mV and the reversed ∆pH was +30 mV, resulting in ∆p of -68 mV. Ph(2)I decreased ∆ψ in concentrations of 20 μM and higher; lower concentrations of Ph(2)I as DMSO had no valuable effect on ∆ψ. The R. sphaeroides membrane vesicles demonstrated significant ATPase activity sensitive to N,N'-dicyclohexylcarbodiimide. The 10-20 μM Ph(2)I did not affect the ATPase activity, whereas 40 μM Ph(2)I caused a marked inhibition (~2 fold) in ATPase activity. The obtained results provide novel evidence on the involvement of hydrogenase and the F(0)F(1)-ATPase in H(2) production by R. sphaeroides. Moreover, these data indicate the role of hydrogenase and the F(0)F(1)-ATPase in ∆p generation. In addition, DMSO might increase an interaction of nitrogenase with CO(2), decreasing nitrogenase activity and affecting H(2) production.

  19. / production

    Indian Academy of Sciences (India)

    François Arleo; Pol-Bernard Gossiaux; Thierry Gousset; Jörg Aichelin

    2003-04-01

    For more than 25 years /Ψ production has helped to sharpen our understanding of QCD. In proton induced reaction some observations are rather well understood while others are still unclear. The current status of the theory of /Ψ production will be sketched, paying special attention to the issues of formation time and /Ψ re-interaction in a nuclear medium.

  20. [Prospects for the design of new therapeutically significant protease inhibitors based on knottins and sunflower seed trypsin inhibitor (SFTI 1)].

    Science.gov (United States)

    Kuznetsova, S S; Kolesanova, E F; Talanova, A V; Veselovsky, A V

    2016-05-01

    Plant seed knottins, mainly from the Cucurbitacea family, and sunflower seed trypsin inhibitor (SFTI 1) are the most low-molecular canonical peptide inhibitors of serine proteases. High efficiency of inhibition of various serine proteases, structure rigidity together with the possibility of limited variations of amino acid sequences, high chemical stability, lack of toxic properties, opportunity of production by either chemical synthesis or use of heterologous expression systems make these inhibitors attractive templates for design of new compounds for regulation of therapeutically significant serine protease activities. Hence the design of such compounds represents a prospective research field. The review considers structural characteristics of these inhibitors, their properties, methods of preparation and design of new analogs. Examples of successful employment of natural serine protease inhibitors belonging to knottin family and SFTI 1 as templates for the design of highly specific inhibitors of certain proteases are given. PMID:27562989

  1. Proteasome inhibitor treatment in alcoholic liver disease

    Institute of Scientific and Technical Information of China (English)

    Fawzia Bardag-Gorce

    2011-01-01

    Oxidative stress, generated by chronic ethanol consumption, is a major cause of hepatotoxicity and liver injury. Increased production of oxygen-derived free radicals due to ethanol metabolism by CYP2E1 is principally located in the cytoplasm and in the mitochondria, which does not only injure liver cells, but also other vital organs, such as the heart and the brain. Therefore, there is a need for better treatment to enhance the antioxidant response elements. To date, there is no established treatment to attenuate high levels of oxidative stress in the liver of alcoholic patients. To block this oxidative stress, proteasome inhibitor treatment has been found to significantly enhance the antioxidant response elements of hepatocytes exposed to ethanol. Recent studies have shown in an experimental model of alcoholic liver disease that proteasome inhibitor treatment at low dose has cytoprotective effects against ethanol-induced oxidative stress and liver steatosis. The beneficial effects of proteasome inhibitor treatment against oxidative stress occurred because antioxidant response elements (glutathione peroxidase 2, superoxide dismutase 2, glutathione synthetase, glutathione reductase, and GCLC) were upregulated when rats fed alcohol were treated with a low dose of PS-341 (Bortezomib, Velcade(r)). This is an important finding because proteasome inhibitor treatment up-regulated reactive oxygen species removal and glutathione recycling enzymes, while ethanol feeding alone down-regulated these antioxidant elements. For the first time, it was shown that proteasome inhibition by a highly specific and reversible inhibitor is different from the chronic ethanol feeding-induced proteasome inhibition. As previously shown by our group, chronic ethanol feeding causes a complex dysfunction in the ubiquitin proteasome pathway, which affects the proteasome system, as well as the ubiquitination system. The beneficial effects of proteasome inhibitor treatment in alcoholic liver disease

  2. Effect of Cl- on photosynthetic bicarbonate uptake in two cyanobacteria Microcystis aeruginosa and Synechocystis PCC6803

    Institute of Scientific and Technical Information of China (English)

    CHEN Zhen; CHENG HuiMin; CHEN XiongWen

    2009-01-01

    Photosynthetic inorganic carbon utilization was investigated in two cyanobacteria Microcystis aeruginosa and Synechocystis PCC6803 grown in standing culture. Photosynthetic rates for the two algae reached about 10 times the theoretical CO2 supply rate at low dissolved inorganic carbon (DIC) of 100 μmol/L, and the rates were unaffected by the addition of 20 mmol/L Na+, indicating that the two algae possessed Na+-independent HCO3- utilization for photosynthesis under low DIC. Their photo-synthetic rates at low DIC were inhibited by higher Cl-and the degrees of inhibition were increased with the rise of Cl- concentration, and in the presence of Diphenylamine-2-carboxylate (DPC), a reported Cl-channel inhibitor, the rates decreased by 74%-82%, implying that putative DPC-sensitive Cl- channels participate In Na+-indepandent HCO3- uptake for photosynthesis. The experiment of intracellular 14C-DIC accumulation for photosynthesis showed that internal DIC pools decreased by about 80% with 200 pmol/L DPC and by 64%-70% with 100 mmol/L Cl-. The experiment of chlorophyll a fluorescence quenching showed that initial rates and extents of fluorescence quenching obviously decreased with 200 μmol/L DPC or 100 mmol/L Cl-. The two experiments gave further evidence that putative DPC-sen-sitive Cl- channels participate in Na+-independent HCO3- uptake for photosynthesis in the two algae grown in standing culture.

  3. CFTR mediates bicarbonate-dependent activation of miR-125b in preimplantation embryo development

    Institute of Scientific and Technical Information of China (English)

    Yong Chao Lu; Alvin Chun Hang Ma; Anskar Yu Hung Leung; He Feng Huang; Hsiao Chang Chan; Hui Chen; Kin Lam Fok; Lai Ling Tsang; Mei Kuen Yu; Xiao Hu Zhang; Jing Chen; Xiaohua Jiang; Yiu Wa Chung

    2012-01-01

    Although HCO3-is known to be required for early embryo development,its exact role remains elusive.Here we report that HCO3-acts as an environmental cue in regulating miR-125b expression through CFTR-mediated influx during preimplantation embryo development.The results show that the effect of HCO3-on preimplantation embryo development can be suppressed by interfering the function of a HCO3--conducting channel,CFTR,by a specific inhibitor or gene knockout.Removal of extracellular HCO3-or inhibition of CFTR reduces miR-125b expression in 2 cell-stage mouse embryos.Knockdown of miR-125b mimics the effect of HCO3-removal and CFTR inhibition,while injection of miR-125b precursor reverses it.Downregulation of miR-125b upregulates p53 cascade in both human and mouse embryos.The activation of miR-125b is shown to be mediated by sAC/PKA-dependent nuclear shuttling of NF-KB.These results have revealed a critical role of CFTR in signal transduction linking the environmental HCO3-to activation of miR-125b during preimplantation embryo development and indicated the importance of ion channels in regulation of miRNAs.

  4. Contemporary reliance on bicarbonate acquisition predicts increased growth of seagrass Amphibolis antarctica in a high-CO2 world.

    Science.gov (United States)

    Burnell, Owen W; Connell, Sean D; Irving, Andrew D; Watling, Jennifer R; Russell, Bayden D

    2014-01-01

    Rising atmospheric CO2 is increasing the availability of dissolved CO2 in the ocean relative to HCO3 (-). Currently, many marine primary producers use HCO3 (-) for photosynthesis, but this is energetically costly. Increasing passive CO2 uptake relative to HCO3 (-) pathways could provide energy savings, leading to increased productivity and growth of marine plants. Inorganic carbon-uptake mechanisms in the seagrass Amphibolis antarctica were determined using the carbonic anhydrase inhibitor acetazolamide (AZ) and the buffer tris(hydroxymethyl)aminomethane (TRIS). Amphibolis antarctica seedlings were also maintained in current and forecasted CO2 concentrations to measure their physiology and growth. Photosynthesis of A. antarctica was significantly reduced by AZ and TRIS, indicating utilization of HCO3 (-)-uptake mechanisms. When acclimated plants were switched between CO2 treatments, the photosynthetic rate was dependent on measurement conditions but not growth conditions, indicating a dynamic response to changes in dissolved CO2 concentration, rather than lasting effects of acclimation. At forecast CO2 concentrations, seedlings had a greater maximum electron transport rate (1.4-fold), photosynthesis (2.1-fold), below-ground biomass (1.7-fold) and increase in leaf number (2-fold) relative to plants in the current CO2 concentration. The greater increase in photosynthesis (measured as O2 production) compared with the electron transport rate at forecasted CO2 concentration suggests that photosynthetic efficiency increased, possibly due to a decrease in photorespiration. Thus, it appears that the photosynthesis and growth of seagrasses reliant on energetically costly HCO3 (-) acquisition, such as A. antarctica, might increase at forecasted CO2 concentrations. Greater growth might enhance the future prosperity and rehabilitation of these important habitat-forming plants, which have experienced declines of global significance.

  5. 21 CFR 178.3300 - Corrosion inhibitors used for steel or tinplate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Corrosion inhibitors used for steel or tinplate... AIDS, AND SANITIZERS Certain Adjuvants and Production Aids § 178.3300 Corrosion inhibitors used for steel or tinplate. Corrosion inhibitors may be safely used for steel or tinplate intended for use in,...

  6. Changes in the quality of life of patients with end-stage renal disease treated with high-efficiency bicarbonate hemodialysis in Mexico.

    Science.gov (United States)

    De Icaza, E; Arredondo, A; Calderon, C; Hernandez, G

    1997-01-01

    In accordance with the epidemiological changes in Mexico, the results of this study are intended to contribute to the evaluation of the end-stage renal disease (ESRD) program of the health services in Mexico. We measured the quality of life of 21 ESRD patients before and after 6 months of exposure to treatment with high-efficiency hemodialysis with bicarbonate (HEHD/bicarbonate). We cross-sectionally assessed the Quality Adjusted Life Year (QALY) index and the biochemical status of the subject pool. The QALY score for patients undergoing HEHD/bicarbonate after 6 months was significantly higher than with the previous dialysis modality (0.95 and 0.74, respectively, p = 0.02). The marked similarities of the biochemical status variables indicated there was little or no effect in the improvement of the quality of life of patients. Dialysis modality likely exerts an important influence on the quality of life of chronic dialysis patients; thus we believe HEHD/bicarbonate does offer greater benefits than hemodialysis alone. Longitudinal studies are needed to better ascertain the effect of the case mix, the treatment approach, and the characteristics of the dialysis in relation to the improvement of the quality of life of ESRD patients.

  7. Effects of sodium bicarbonate on the end-tidal CO2, PaCO2, HCO3-, PH and cerebral blood flow

    International Nuclear Information System (INIS)

    To estimate the quantitative reactivity of cerebral blood flow (CBF), the effects of sodium bicarbonate on the end-tidal CO2, arterial partial pressure of CO2 (PaCO2), HCO3-, pH and CBF were examined. The CBF was measured by 133Xe inhalation method with ring type SPECT (HEADTOME). Activation study with sodium bicarbonate administration was performed after 30 minutes of resting study, and the reactivity of each parameters was investigated. The arterial HCO3- and pH increased with similar reactivity, but PaCO2, end-tidal CO2 and CBF in the non-injured hemisphere changed with irregular reactivity. The excellent correlation between PaCO2 and end-tidal CO2 was vanished by the administration of sodium bicarbonate. The reactivity of CBF did not correlate with reactivity of PaCO2 and end-tidal CO2, but correlated with arterial HCO3- and pH. Thus the measurement of arterial HCO3- and pH may be indispensable to estimate the CBF reactivity with the administration of sodium bicarbonate. (author)

  8. Changes in the quality of life of patients with end-stage renal disease treated with high-efficiency bicarbonate hemodialysis in Mexico.

    Science.gov (United States)

    De Icaza, E; Arredondo, A; Calderon, C; Hernandez, G

    1997-01-01

    In accordance with the epidemiological changes in Mexico, the results of this study are intended to contribute to the evaluation of the end-stage renal disease (ESRD) program of the health services in Mexico. We measured the quality of life of 21 ESRD patients before and after 6 months of exposure to treatment with high-efficiency hemodialysis with bicarbonate (HEHD/bicarbonate). We cross-sectionally assessed the Quality Adjusted Life Year (QALY) index and the biochemical status of the subject pool. The QALY score for patients undergoing HEHD/bicarbonate after 6 months was significantly higher than with the previous dialysis modality (0.95 and 0.74, respectively, p = 0.02). The marked similarities of the biochemical status variables indicated there was little or no effect in the improvement of the quality of life of patients. Dialysis modality likely exerts an important influence on the quality of life of chronic dialysis patients; thus we believe HEHD/bicarbonate does offer greater benefits than hemodialysis alone. Longitudinal studies are needed to better ascertain the effect of the case mix, the treatment approach, and the characteristics of the dialysis in relation to the improvement of the quality of life of ESRD patients. PMID:9044456

  9. [Gastric emptying and metabolic acidosis. II. Study, in an experimental model in rats, of gastric retention of a sodium bicarbonate solution].

    Science.gov (United States)

    Belangero, V M; Collares, E F

    1992-01-01

    The gastric emptying of a 0.25 M sodium bicarbonate solution was studied in rats with metabolic acidosis induced by a previous (6 hours) orogastric infusion of a 0.5 M ammonium chloride solution. Two control groups were used: one previously infused with 0.5 M sodium chloride and the other with water, in the same volume that further solutions. Every animal was fed with 2 ml/100 g of its weight of these solutions. The test meal (bicarbonate solution) was utilized containing 6 mg% red fenol as a marker. The gastric retentions were determined 6 hours after those first meals at 5, 10, 20 and 30 minutes. The results demonstrated that the gastric retentions of the bicarbonate solution were significantly lower in the acidotic group than that one of water group (at 20 minutes) and that one of the sodium chloride (at 10, 20 and 30 minutes). The data here presented suggest that metabolic acidosis accelerates the gastric emptying of a sodium bicarbonate solution. PMID:1339142

  10. Inhibitors of histone demethylases

    DEFF Research Database (Denmark)

    Lohse, Brian; Kristensen, Jesper L; Kristensen, Line H;

    2011-01-01

    Methylated lysines are important epigenetic marks. The enzymes involved in demethylation have recently been discovered and found to be involved in cancer development and progression. Despite the relative recent discovery of these enzymes a number of inhibitors have already appeared. Most of the i...

  11. Inhibitors of histone deacetylase

    DEFF Research Database (Denmark)

    2015-01-01

    The present invention relates to compounds of formula (I) or a pharmaceutically acceptable salt, hydrate, solvate, or prodrug thereof, wherein X1, X2, X3, X4, X5, W1, W2, W3, and W4 are as described. The present invention relates generally to inhibitors of histone deacetylase and to methods...

  12. Are inter-center differences in EMS-management and sodium-bicarbonate administration important for the outcome of CPR? The Cerebral Resuscitation Study Group.

    Science.gov (United States)

    Delooz, H H; Lewi, P J

    1989-01-01

    The hospital of Brugge relies on selection of the emergency calls and sends a Mobile Intensive Care Unit (MICU) whenever cardiac arrest (CA) is suspected. The University Hospital of Leuven does no selection of calls and responds to every emergency call by sending an ambulance with an advanced life support (ALS) trained nurse. The MICU is called when the ambulance crew recognizes the emergency to be a CA. The Leuven system is a so-called tiered system. Although MICU-response times are significantly longer in Leuven than in Brugge, no difference is found as to the success of CPCR. The immediate response to all emergency calls by specialized E.D. nurses (paramedic) capable of ALS, seems to make up for the difference in MICU-response times. The University Hospital of Jette has a higher success-rate for CPCR for in-hospital CA, than the University Hospitals of Leuven. Due to size and lay-out differences, the MICU-response times are shorter in Jette than in Leuven. Basic life support (BLS) provided by doctors and nurses present at the scene, does not seem to be able to compensate for longer MICU-arrival times. The introduction of semi-automatic or automatic defibrillators, to be used by the BLS trained medical and nursing personnel, might be able to make up for the longer MICU-intervention times. Inter-center differences were witnessed as far as the amount of sodium-bicarbonate infused during CPR. Within each group of total duration of CPR an inverse correlation exists between the amount of bicarbonate infused and the success rate of CPCR. Partial correlation between the bicarbonate infused and the survival with regaining of consciousness at 14 days post-CPR, with constant CPR-time, is statistically significant. This indicates that long-term CPCR success is inversely correlated with increasing amounts of sodium-bicarbonate infused. Short duration of CPR and low adrenaline dosage correlate with immediate and long-term success of CPR. On the contrary, low versus high

  13. Fungicides for organic cantaloupe production in Oklahoma: An initial assessment

    Science.gov (United States)

    Fungicides that are potentially useful in organic production were evaluated for foliar disease control in cantaloupe (Cucumis melo L. var. reticulates ’Israeli’) during 2009 at Lane, Oklahoma. Milstop (85% potassium bicarbonate), Neem oil, Bonide liquid copper (10% copper octanoate), Serenade (QST ...

  14. Process for the production of sodium carbonate anhydrate

    NARCIS (Netherlands)

    Oosterhof, H.; Van Rosmalen, G.M.; Witkamp, G.J.; De Graauw, J.

    2000-01-01

    The invention is directed to a process for the production of sodium carbonate-anhydrate having a bulk density of at least 800 kg/m<3>, said process comprising: providing a suspension of solid sodium carbonate and/or solid sodium bicarbonate and/or solid double salts at least comprising one of

  15. [JAK2 inhibitors].

    Science.gov (United States)

    Hernández Boluda, Juan Carlos; Gómez, Montse; Pérez, Ariadna

    2016-07-15

    Pharmacological inhibition of the kinase activity of JAK proteins can interfere with the signaling of immunomodulatory cytokines and block the constitutive activation of the JAK-STAT pathway that characterizes certain malignancies, including chronic myeloproliferative neoplasms. JAK inhibitors may, therefore, be useful to treat malignancies as well as inflammatory or immune disorders. Currently, the most significant advances have been made in the treatment of myelofibrosis, where these drugs may lead to a remarkable improvement in the control of hyperproliferative manifestations. However, available data suggest that this treatment is not curative of myelofibrosis. In general, JAK2 inhibition induces cytopaenias, with this being considered a class side-effect. By contrast, the extrahaematologic toxicity profile varies significantly among the different JAK inhibitors. At present, there are several clinical trials evaluating the combination of ruxolitinib with other drugs, in order to improve its therapeutic activity as well as reducing haematologic toxicity. PMID:27033437

  16. Alpha glucosidase inhibitors.

    Science.gov (United States)

    Kalra, Sanjay

    2014-04-01

    Alpha glucosidase inhibitors (AGIs) are a unique class of anti-diabetic drugs. Derived from bacteria, these oral drugs are enzyme inhibitors which do not have a pancreato -centred mechanism of action. Working to delay carbohydrate absorption in the gastrointestinal tract, they control postprandial hyperglycaemia and provide unquestioned cardiovascular benefit. Specially suited for a traditional Pakistani carbohydrate-rich diet, AGIs have been termed the 'untapped diamonds' of diabetology. The use of these oral antidiabetic drugs (OADs) that target pathophysiology in the early stages of type 2 diabetes, notably to reduce postprandial hyperglycaemia and hyperinsulinaemia will inevitably increase with time. This review describes the history of their development, mechanism of action, basic and clinical pharmacology, and suggests practical, evidence-based guidance for their optimal use. PMID:24864650

  17. Coagulation inhibitors in inflammation.

    Science.gov (United States)

    Esmon, C T

    2005-04-01

    Coagulation is triggered by inflammatory mediators in a number of ways. However, to prevent unwanted clot formation, several natural anticoagulant mechanisms exist, such as the antithrombin-heparin mechanism, the tissue factor pathway inhibitor mechanism and the protein C anticoagulant pathway. This review examines the ways in which these pathways are down-regulated by inflammation, thus limiting clot formation and decreasing the natural anti-inflammatory mechanisms that these pathways possess. PMID:15787615

  18. Osteocompatibility of Biofilm Inhibitors

    OpenAIRE

    Rawson, Monica; Haggard, Warren; Jennings, Jessica A.

    2014-01-01

    The demand for infection prevention therapies has led to the discovery of several biofilm inhibitors. These inhibiting signals are released by bacteria, fungi, or marine organisms to signal biofilm dispersal or disruption in Gram-positive, Gram-negative, and fungal microorganisms. The purpose of this study was to test the biocompatibility of five different naturally-produced biofilm chemical dispersal and inhibition signals with osteoblast-like cells: D-amino acids (D-AA), lysostaphin (LS), f...

  19. Na/K citrate versus sodium bicarbonate in prevention of contrast-induced nephropathy

    OpenAIRE

    Sameh Mohamed Abouzeid; Hossam E ElHossary

    2016-01-01

    Contrast-induced nephropathy (CIN) is one of the important complications of radiographic procedures, especially in patients with chronic kidney disease. It is also one of the common causes of acute kidney injury. The pathogenesis is postulated to be the effect of oxygen- free radicals and hyperosmolar stress on the renal medulla. It is reported that the production of superoxide is most active at acid environment. K/Na citrate is well known as a urine alkalini- zation medium, and this has been...

  20. Variations in short term products of inorganic carbon fixation in exponential and stationary phase cultures of Aphanocapsa 6308.

    Science.gov (United States)

    Weathers, P J; Allen, M M

    1978-03-01

    Aphanocapsa 6308 metabolizes both NaHCO3 and Na2CO3. The short term incorporation (5-s) metabolic pattern and the patterns of incorporation of bicarbonate for exponential versus stationary phase cultures differ, however. Cells were equilibrated for 10 min in air and distilled water prior to injection of either NaH14CO3 at pH 8.0, or Na214CO3 at pH 11.0. Hot ethanol extracts were analyzed via paper chromatography and autoradiography for products of CO2 fixation. At 5 s, malate (51.5%) predominates slightly as a primary bicarbonate fixation product over 3-phosphoglycerate (40.3%); 3-phosphoglycerate is the primary product of carbonate fixation. At 60 s, the carbonate and bicarbonate labelling patterns are similar. Cells in stationary phase fix in 5 s a greater proportion of bicarbonate into malate (36% vs. 14% for 3-phosphoglycerate) than do cells in exponential growth. Likewise, 60 s incorporations show a large amount of bicarbonate fixed into aspartate (30.9%) in stationary phase cells over that of exponential phase (11.6%). These data suggest an operative C4 pathway for purposes not related to carbohydrate synthesis but rather as compensation for the incomplete tricarboxylic acid cycle in cyanobacteria. The enhancement of both aspartate fixation and CO2 fixation into citrulline in stationary phase correlates with an increase in cyanophycin granule production which requires both aspartate and arginine. PMID:417691

  1. Polyphenolic Compounds as Pancreatic Lipase Inhibitors.

    Science.gov (United States)

    Buchholz, Tina; Melzig, Matthias F

    2015-07-01

    Obesity and its associated diseases such as diabetes mellitus and coronary heart diseases are a major challenge for our society. An important target for the treatment of obesity includes the development of inhibitors of nutrient digestion and absorption. Inhibition of pancreatic lipase and the associated reduction of lipid absorption is an attractive approach for the discovery of potent agents. Currently, the only clinically approved pharmacologic agent as pancreatic lipase inhibitor is Orlistat. However, its usage is compromised by unpleasant gastrointestinal adverse reactions (oily stools, oily spotting, flatulence). The use of botanical materials as a potential source of new drugs is of increasing importance and application. Natural products that are interesting for obesity treatment are generally considered to have less toxic and side effects than totally synthetic drugs. One of the most important sources of potential pancreatic lipase inhibitors represents the class of polyphenols. This article summarizes most studied subclasses of polyphenols including flavonoids, hydroxycinnamic acids, hydroxybenzoic acids and lignans with pancreatic lipase inhibitory effects. A structural comparison of potent inhibitors shows an increased inhibitory effect depending on number and position of phenolic hydroxyl groups, degree of polymerization and elimination of glycosylation during digestion. PMID:26132857

  2. Mechanism for high PCO2 in gastric juice: roles of bicarbonate secretion and CO2 diffusion.

    Science.gov (United States)

    Stevens, M H; Thirlby, R C; Feldman, M

    1987-10-01

    The partial pressure of CO2 (PCO2) in gastric juice often exceeds the PCO2 of blood. CO2 in gastric juice may originate from blood and enter luminal fluid by diffusion, or CO2 may be produced in the lumen of the stomach from the reaction of HCO3- and H+. Because CO2 production from HCO3- is dependent on acid (low pH), we suppressed acid secretion with intravenous cimetidine to estimate to what extent appearance of CO2 in luminal fluid is due to production from HCO3-. When denervated fundic pouches of dogs were distended with saline, the PCO2 of the solution increased to the PCO2 of blood in approximately 20 min, with the initial rate of appearance of CO2 in the pouch solution only minimally affected by cimetidine. Thereafter, PCO2 of luminal fluid continued to increase to 50-60 mmHg in the absence of cimetidine, whereas PCO2 of luminal fluid remained approximately equal to that of blood when cimetidine was infused (P less than 0.001, cimetidine vs. control). The mean pH in the pouch solution remained between 6.3 and 6.9 during cimetidine infusion but decreased to 4.75 without cimetidine (P less than 0.001). In additional experiments, an acidic solution with high PCO2 (242 +/- 3 mmHg) was infused into the fundic pouches. PCO2 in luminal fluid decreased rather slowly toward plasma PCO2, requiring 240 min for luminal fluid PCO2 to decrease to 56 +/- 2 mmHg. Thus the permeability of the gastric mucosa to luminal CO2 was relatively low.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3116857

  3. [Effect of treatments of hydrogen peroxide and sodium dithionite-citrate-bicarbonate on clay minerals of red earth sediments].

    Science.gov (United States)

    Li, Rong-Biao; Hong, Han-Lie; Yin, Ke; Wang, Chao-Wen; Gao, Wen-Peng; Han, Wen; Wu, Qing-Feng

    2013-04-01

    As classical procedures for pretreatment of soil sediments, hydrogen peroxide (H2O2) and sodium dithionite-citrate-bicarbonate (DCB) treatment methods are very important in removing the organic matter and iron oxides acting as cementing agents in the soils. However, both of these methods have less been focused on the effect on the clay minerals when separating. Here, we report the comparable methods between H2O2 and DCB to reveal their effect on clay minerals in red earth sediments using X-ray diffraction (XRD). The XRD results suggested that mineral particles can be totally decentralized by either H2O2 or DCB method in the soils and high purity clay minerals can be obtained by separating quartz and other impurities from clay minerals effectively. However, the XRD data were distorted by the DCB treatment owning to the cation exchange between Na+ and interlayer cation. On the contrary, the authentic data can be obtained by H2O2 treatment. Therefore, the H2O2 treatment seems to be a more appropriate method to obtain authentic information of clay mineralogy when separating of clay minerals from red earth sediments.

  4. pCO2 Reveals Arteriovenous Fistula Recirculation in Bicarbonate Hemodialysis (RecirCO2lation Test).

    Science.gov (United States)

    Marano, Marco; Borrelli, Silvio; Zamboli, Pasquale

    2016-01-01

    We propose arterial pCO2 as test to discover vascular access recirculation (VAR) in bicarbonate hemodialysis (HD). We selected 30 HD patients with a ascertained well-functioning arteriovenous fistula (Control). In these patients, we artificially created VAR through the reversion of HD lines (Reversed). Results of the arterial gas analysis were collected at the start of HD (baseline) and after 5 min. At baseline, no differences of pH, pCO2 and HCO3 were found between the 2 groups. At 5 min, pCO2 increased from 38.1 ± 3.3 to 47.2 ± 6.3 mm Hg (p 4.5 mm Hg showed sensitivity 86.7% and specificity 100% with positive predictive value (PPV) 100% and negative predictive value (NPV) 89%. A pCO2 value above 43 mm Hg at 5 min showed sensitivity 80%, specificity 90%, PPV 89%, NPV 82%. pCO2 increase >4.5 mm Hg and/or pCO2 at 5 min >43 mm Hg may accurately detect VAR. PMID:26528539

  5. Enhancing the [13C]bicarbonate signal in cardiac hyperpolarized [1‐13C]pyruvate MRS studies by infusion of glucose, insulin and potassium

    DEFF Research Database (Denmark)

    Lauritzen, Mette Hauge; Laustsen, Christoffer; Butt, Sadia Asghar;

    2013-01-01

    the myocardial glucose oxidation in the citric acid cycle, reflected as an increase in the [13C]bicarbonate signal in cardiac hyperpolarized [1‐13C]pyruvate MRS measurements in fasted rats. Two groups of rats were infused with two different doses of GIK and investigated by MRS after injection of hyperpolarized...... rats. The increased [13C]bicarbonate signal indicates an increased flux of pyruvate through the pyruvate dehydrogenase enzyme complex and an increase in myocardial glucose oxidation through the citric acid cycle. Copyright © 2013 John Wiley & Sons, Ltd....... fasting, the myocardial glucose oxidation is low and the fatty acid oxidation (β‐oxidation) is high, which complicates the interpretation of pyruvate metabolism with the technique. The aim of this study was to investigate whether the infusion of glucose, insulin and potassium (GIK) could increase...

  6. Effect of Oral Sodium Bicarbonate on Progression of Chronic Kidney Disease%口服碳酸氢钠对慢性肾病进程的影响

    Institute of Scientific and Technical Information of China (English)

    刘进; 梅丽凡

    2012-01-01

    目的 探讨口服碳酸氢钠能否延缓慢性肾病(chronic kidney disease,CKD)肾功能下降的速率.方法 110例CKD患者随机分为碳酸氢钠组或安慰剂组,分别口服碳酸氢钠或安慰剂治疗2年,估算治疗前后肾小球滤过-(eGFR)下降的速率,eGFR快速下降[>3 mL-min-1·(1.73 m)-2·y-1]和发展成终末期肾病(ESRD)患者人数[eGFR<10 mL·min-1·(1.73 m)-2]比.同时测量血清白蛋白和饮食蛋白摄入.结果 治疗2年后,与安慰剂组相比,碳酸氢钠组eGFR下降较慢(P<0.05),快速进展的患者少(P<0.05),发展成ESRD的患者也少(P<0.05).碳酸氢钠组营养参数明显改善.结论 碳酸氢钠可延缓CKD发展成ESRD的速率,且可改善CKD患者的营养状态.%OBJECTIVE To study whether orally administrated sodium bicarbonate slows the decline of renal function in chronic kidney disease (CKD). METHODS All of 110 patients with CKD were randomly divided into sodium bicarbonate group and placebo group, and received the treatment with sodium bicarbonate or placebo for 2 years. Decline rate of glomerular filtration rate (eGFR), the ratio of patients with rapid decline of eGFR[>3 mL·min-1(1.73 m)-2·y-1] developed to end stag renal disease(ESRD) [eGFR<10mL·min-1·(1.73 m)-2] were estimated before and after the treatment. Serum albumin and dielary protein intake were measured at the same time. RESULTS Compared with placebo group, decline in eGFR was slower in sodium bicarbonate group(P<0.05) after treatment of 2 years. Patients in bicarbonate group were significantly less than experience rapid progression(P<0.05). Fewer patients in bicarbonate group developed ESRD(P<0.05). Nutritional parameters improved significantly in bicarbonate group. CONCLUSION Bicarbonate slows the rate of progression of CKD to ESRD and it improves nutrition status among patients with CKD.

  7. A Cellular Model for Screening Neuronal Nitric Oxide Synthase Inhibitors

    OpenAIRE

    Fang, Jianguo; Silverman, Richard B.

    2009-01-01

    Nitric oxide synthase (NOS) inhibitors are potential drug candidates because it has been well demonstrated that excessive production of NO critically contributes to a range of diseases. Most inhibitors have been screened in vitro using recombinant enzymes, leading to the discovery of a variety of potent compounds. To make inhibition studies more physiologically relevant and bridge the gap between the in vitro assay and in vivo studies, we report here a cellular model for screening NOS inhibit...

  8. Calpain inhibitor nanocrystals prepared using Nano Spray Dryer B-90

    OpenAIRE

    Baba, Koichi; Nishida, Kohji

    2012-01-01

    The Nano Spray Dryer B-90 offers a new, simple, and alternative approach for the production of drug nanocrystals. Among attractive drugs, calpain inhibitor that inhibits programmed cell death ‘apoptosis’ is a candidate for curing apoptosis-mediated intractable diseases such as Alzheimer’s disease and Parkinson’s disease. In this study, the preparation of calpain inhibitor nanocrystals using Nano Spray Dryer B-90 was demonstrated. The particle sizes were controlled by means of selecting mesh a...

  9. Effects of an Ionophore Coccidiostat (Monensin or Salinomycin, Sodium or Potassium Bicarbonate, or Both, and Bacitracin Methylene Disalicylate in Broiler Chicken Diets

    Directory of Open Access Journals (Sweden)

    Hooge DM

    2000-01-01

    Full Text Available Peterson x Arbor Acres chicks were grown on used litter to 45 or 46 days of age in three pen trials. Coccidial inoculations were given by water at 14 days of age. Sodium bicarbonate (SBC; 0.20% or potassium bicarbonate (PBC; 0.14% was added to broiler chicken diets containing monensin (MON; 110 mg/kg or salinomycin (SAL; 66 mg/kg in Experiment 1. In Experiment 2, using SAL (55 mg/kg, three dietary bicarbonate treatments (SBC, 0.20%; PBC, 0.20%; or SBC + PBC 0.10% each were tested with or without BMD R (55 mg/kg. Diets differing in SAL, BMD R, and SBC levels were evaluated in Experiment 3. Beneficial interaction was found between ionophores and bicarbonates for mortality (lower when SBC or PBC and MON in Experiment 1. For main effects, in Experiment 1 PBC with MON or SAL improved body weight, feed conversion ratio and mortality. SAL improved weight, feed conversion ratio and mortality compared to MON. In Experiment 2, PBC with SAL improved weight, coccidial lesion score, feed conversion ratio and mortality across two levels of BMD R. The PBC and SBC were equally effective in Experiment 1, but PBC was about 0 to 40% as effective as SBC, depending on parameter in Experiment 2. Half levels of SBC plus PBC generally gave intermediate results between control and SBC. SBC with MON or SAL lowered mortalities, coccidial lesion scores, and feed conversion ratios (Experiments 1 and 2, and increased body weight (Experiment 2. In Experiment 3, BMD R in all feeds improved body weight and feed conversion versus in starter feed only, and SBC with SAL and BMD R improved all performance parameters.

  10. Bicarbonate-sensitive soluble and transmembrane adenylyl cyclases in peripheral chemoreceptors.

    Science.gov (United States)

    Nunes, Ana R; Holmes, Andrew P S; Sample, Vedangi; Kumar, Prem; Cann, Martin J; Monteiro, Emília C; Zhang, Jin; Gauda, Estelle B

    2013-08-15

    Stimulation of the carotid body (CB) chemoreceptors by hypercapnia triggers a reflex ventilatory response via a cascade of cellular events, which includes generation of cAMP. However, it is not known if molecular CO2/HCO3(-) and/or H(+) mediate this effect and how these molecules contribute to cAMP production. We previously reported that the CB highly expresses HCO3(-)-sensitive soluble adenylyl cyclase (sAC). In the present study we systematically characterize the role of sAC in the CB, comparing the effect of isohydric hypercapnia (IH) in cAMP generation through activation of sAC or transmembrane-adenylyl cyclase (tmAC). Pharmacological deactivation of sAC and tmAC decreased the CB cAMP content in normocapnia and IH with no differences between these two conditions. Changes from normocapnia to IH did not effect the degree of PKA activation and the carotid sinus nerve discharge frequency. sAC and tmAC are functional in CB but intracellular elevations in CO2/HCO3(-) in IH conditions on their own are insufficient to further activate these enzymes, suggesting that the hypercapnic response is dependent on secondary acidosis.

  11. A host defense mechanism involving CFTR-mediated bicarbonate secretion in bacterial prostatitis.

    Directory of Open Access Journals (Sweden)

    Chen Xie

    Full Text Available BACKGROUND: Prostatitis is associated with a characteristic increase in prostatic fluid pH; however, the underlying mechanism and its physiological significance have not been elucidated. METHODOLOGY/PRINCIPAL FINDINGS: In this study a primary culture of rat prostatic epithelial cells and a rat prostatitis model were used. Here we reported the involvement of CFTR, a cAMP-activated anion channel conducting both Cl(- and HCO(3(-, in mediating prostate HCO(3(- secretion and its possible role in bacterial killing. Upon Escherichia coli (E. coli-LPS challenge, the expression of CFTR and carbonic anhydrase II (CA II, along with several pro-inflammatory cytokines was up-regulated in the primary culture of rat prostate epithelial cells. Inhibiting CFTR function in vitro or in vivo resulted in reduced bacterial killing by prostate epithelial cells or the prostate. High HCO(3(- content (>50 mM, rather than alkaline pH, was found to be responsible for bacterial killing. The direct action of HCO(3(- on bacterial killing was confirmed by its ability to increase cAMP production and suppress bacterial initiation factors in E. coli. The relevance of the CFTR-mediated HCO(3(- secretion in humans was demonstrated by the upregulated expression of CFTR and CAII in human prostatitis tissues. CONCLUSIONS/SIGNIFICANCE: The CFTR and its mediated HCO(3(- secretion may be up-regulated in prostatitis as a host defense mechanism.

  12. Chelation: a fundamental mechanism of action of AGE inhibitors, AGE breakers, and other inhibitors of diabetes complications.

    Science.gov (United States)

    Nagai, Ryoji; Murray, David B; Metz, Thomas O; Baynes, John W

    2012-03-01

    This article outlines evidence that advanced glycation end product (AGE) inhibitors and breakers act primarily as chelators, inhibiting metal-catalyzed oxidation reactions that catalyze AGE formation. We then present evidence that chelation is the most likely mechanism by which ACE inhibitors, angiotensin receptor blockers, and aldose reductase inhibitors inhibit AGE formation in diabetes. Finally, we note several recent studies demonstrating therapeutic benefits of chelators for diabetic cardiovascular and renal disease. We conclude that chronic, low-dose chelation therapy deserves serious consideration as a clinical tool for prevention and treatment of diabetes complications.

  13. Inhibitors of lysosomal cysteine proteases

    Directory of Open Access Journals (Sweden)

    Lyanna O. L.

    2011-04-01

    Full Text Available The review is devoted to the inhibitors of cysteine proteinases which are believed to be very important in many biochemical processes of living organisms. They participate in the development and progression of numerous diseases that involve abnormal protein turnover. One of the main regulators of these proteinases is their specific inhibitors: cystatins. The aim of this review was to present current knowledge about endogenous inhibitors of lysosomal cysteine proteases and their synthetic analogs.

  14. Molecular similarity of MDR inhibitors

    OpenAIRE

    Simon Gibbons; Mire Zloh

    2004-01-01

    Abstract: The molecular similarity of multidrug resistance (MDR) inhibitors was evaluated using the point centred atom charge approach in an attempt to find some common features of structurally unrelated inhibitors. A series of inhibitors of bacterial MDR were studied and there is a high similarity between these in terms of their shape, presence and orientation of aromatic ring moieties. A comparison of the lipophilic properties of these molecules has also been conducted suggesting that this ...

  15. Central functions of bicarbonate in S-type anion channel activation and OST1 protein kinase in CO 2 signal transduction in guard cell

    KAUST Repository

    Xue, Shaowu

    2011-03-18

    Plants respond to elevated CO(2) via carbonic anhydrases that mediate stomatal closing, but little is known about the early signalling mechanisms following the initial CO(2) response. It remains unclear whether CO(2), HCO(3)(-) or a combination activates downstream signalling. Here, we demonstrate that bicarbonate functions as a small-molecule activator of SLAC1 anion channels in guard cells. Elevated intracellular [HCO(3)(-)](i) with low [CO(2)] and [H(+)] activated S-type anion currents, whereas low [HCO(3)(-)](i) at high [CO(2)] and [H(+)] did not. Bicarbonate enhanced the intracellular Ca(2+) sensitivity of S-type anion channel activation in wild-type and ht1-2 kinase mutant guard cells. ht1-2 mutant guard cells exhibited enhanced bicarbonate sensitivity of S-type anion channel activation. The OST1 protein kinase has been reported not to affect CO(2) signalling. Unexpectedly, OST1 loss-of-function alleles showed strongly impaired CO(2)-induced stomatal closing and HCO(3)(-) activation of anion channels. Moreover, PYR/RCAR abscisic acid (ABA) receptor mutants slowed but did not abolish CO(2)/HCO(3)(-) signalling, redefining the convergence point of CO(2) and ABA signalling. A new working model of the sequence of CO(2) signalling events in gas exchange regulation is presented.

  16. Detection of OXA-48-type carbapenemase-producing Enterobacteriaceae in diagnostic laboratories can be enhanced by addition of bicarbonates to cultivation media or reaction buffers.

    Science.gov (United States)

    Studentova, Vendula; Papagiannitsis, Costas C; Izdebski, Radoslaw; Pfeifer, Yvonne; Chudackova, Eva; Bergerova, Tamara; Gniadkowski, Marek; Hrabak, Jaroslav

    2015-03-01

    Carbapenemase-mediated resistance to carbapenems in Enterobacteriaceae has become the main challenge in the treatment and prevention of infections recently. The partially unnoticed spread of OXA-48-type carbapenemase producers is usually assigned to low minimum inhibitory concentrations (MICs) of carbapenems that OXA-48-producing isolates often display. Therefore, there is an urgent need of specific and sensitive methods for isolation and detection of OXA-48 producers in clinical microbiology diagnostics. The influence of bicarbonates on carbapenem MICs against carbapenemase-producing Enterobacteriaceae was tested. We also checked whether the addition of bicarbonates to liquid media supplemented with meropenem may facilitate the selective enrichment of various carbapenemase producers in cultures. Furthermore, the sensitivity of carbapenemase confirmation by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-TOF MS) and spectrophotometric hydrolysis assays upon the addition of NH4HCO3 was examined. The addition of NaHCO3 significantly increased MICs of ertapenem and meropenem for OXA-48 producers. Furthermore, liquid media supplemented with NaHCO3 and meropenem were reliable for the selective enrichment of carbapenemase producers. The presence of NH4HCO3 in buffers used in the spectrophotometric and MALDI-TOF MS carbapenemase detection increased the sensitivity of that assay. Our results demonstrate that bicarbonates in media or reaction buffers can enhance the sensitivity of screening methods and diagnostic tests for carbapenemase producers.

  17. Identification of Genes Conferring Tolerance to Lignocellulose-Derived Inhibitors by Functional Selections in Soil Metagenomes

    OpenAIRE

    Kevin J. Forsberg; Patel, Sanket; Witt, Evan; Wang, Bin; Ellison, Tyler D.; Dantas, Gautam

    2016-01-01

    The production of fuels or chemicals from lignocellulose currently requires thermochemical pretreatment to release fermentable sugars. These harsh conditions also generate numerous small-molecule inhibitors of microbial growth and fermentation, limiting production. We applied small-insert functional metagenomic selections to discover genes that confer microbial tolerance to these inhibitors, identifying both individual genes and general biological processes associated with tolerance to multip...

  18. ACE INHIBITORS: A COMPREHENSIVE REVIEW

    Directory of Open Access Journals (Sweden)

    Pradeep Kumar Arora* and Ashish Chauhan

    2013-02-01

    Full Text Available Hypertension is a chronic increase in blood pressure, characterized as primary and secondary hypertension. The disorder is associated with various risk factors like obesity, diabetes, age, lack of exercise etc. Hypertension is being treated since ancient times by Ayurvedic, Chinese and Unani medicine. Now various allopathic drugs are available which include diuretics, calcium channel blockers, α-blockers, β-blockers, vasodilators, central sympatholytics and ACE-inhibitors. Non-pharmacological treatments include weight reduction, dietary sodium reduction, increased potassium intake and reduction in alcohol consumption. ACE-inhibitors are widely used in the treatment of hypertension by inhibiting the angiotensin converting enzyme responsible for the conversion of angiotensin I to angiotensin II (responsible for vasoconstriction. Various structure activity relationship studies led to the synthesis of ACE-inhibitors, some are under clinical development. This comprehensive review gives various guidelines on classification of hypertension, hypertension therapy including ancient, pharmacological, non-pharmacological therapies, pharmacoeconomics, historical perspectives of ACE, renin, renin angiotensin system (circulating vs local RAS, mechanism of ACE inhibitors, and development of ACE inhibitors. Review also emphasizes on the recent advancements on ACE inhibitors including drugs in clinical trials, computational studies on ACE-inhibitors, peptidomimetics, dual, natural, multi-functional ACE inhibitors, and conformational requirements for ACE-inhibitors.

  19. Cost of care of haemophilia with inhibitors.

    Science.gov (United States)

    Di Minno, M N D; Di Minno, G; Di Capua, M; Cerbone, A M; Coppola, A

    2010-01-01

    In Western countries, the treatment of patients with inhibitors is presently the most challenging and serious issue in haemophilia management, direct costs of clotting factor concentrates accounting for >98% of the highest economic burden absorbed for the healthcare of patients in this setting. Being designed to address questions of resource allocation and effectiveness, decision models are the golden standard to reliably assess the overall economic implications of haemophilia with inhibitors in terms of mortality, bleeding-related morbidity, and severity of arthropathy. However, presently, most data analyses stem from retrospective short-term evaluations, that only allow for the analysis of direct health costs. In the setting of chronic diseases, the cost-utility analysis, that takes into account the beneficial effects of a given treatment/healthcare intervention in terms of health-related quality of life, is likely to be the most appropriate approach. To calculate net benefits, the quality adjusted life year, that significantly reflects such health gain, has to be compared with specific economic impacts. Differences in data sources, in medical practice and/or in healthcare systems and costs, imply that most current pharmacoeconomic analyses are confined to a narrow healthcare payer perspective. Long-term/lifetime prospective or observational studies, devoted to a careful definition of when to start a treatment; of regimens (dose and type of product) to employ, and of inhibitor population (children/adults, low-responding/high responding inhibitors) to study, are thus urgently needed to allow for newer insights, based on reliable data sources into resource allocation, effectiveness and cost-utility analysis in the treatment of haemophiliacs with inhibitors.

  20. Cost of care of haemophilia with inhibitors.

    Science.gov (United States)

    Di Minno, M N D; Di Minno, G; Di Capua, M; Cerbone, A M; Coppola, A

    2010-01-01

    In Western countries, the treatment of patients with inhibitors is presently the most challenging and serious issue in haemophilia management, direct costs of clotting factor concentrates accounting for >98% of the highest economic burden absorbed for the healthcare of patients in this setting. Being designed to address questions of resource allocation and effectiveness, decision models are the golden standard to reliably assess the overall economic implications of haemophilia with inhibitors in terms of mortality, bleeding-related morbidity, and severity of arthropathy. However, presently, most data analyses stem from retrospective short-term evaluations, that only allow for the analysis of direct health costs. In the setting of chronic diseases, the cost-utility analysis, that takes into account the beneficial effects of a given treatment/healthcare intervention in terms of health-related quality of life, is likely to be the most appropriate approach. To calculate net benefits, the quality adjusted life year, that significantly reflects such health gain, has to be compared with specific economic impacts. Differences in data sources, in medical practice and/or in healthcare systems and costs, imply that most current pharmacoeconomic analyses are confined to a narrow healthcare payer perspective. Long-term/lifetime prospective or observational studies, devoted to a careful definition of when to start a treatment; of regimens (dose and type of product) to employ, and of inhibitor population (children/adults, low-responding/high responding inhibitors) to study, are thus urgently needed to allow for newer insights, based on reliable data sources into resource allocation, effectiveness and cost-utility analysis in the treatment of haemophiliacs with inhibitors. PMID:19845772

  1. Carbonic anhydrase in Escherichia coli. A product of the cyn operon.

    Science.gov (United States)

    Guilloton, M B; Korte, J J; Lamblin, A F; Fuchs, J A; Anderson, P M

    1992-02-25

    The product of the cynT gene of the cyn operon in Escherichia coli has been identified as a carbonic anhydrase. The cyn operon also includes the gene cynS, encoding the enzyme cyanase. Cyanase catalyzes the reaction of cyanate with bicarbonate to give ammonia and carbon dioxide. The carbonic anhydrase was isolated from an Escherichia coli strain overexpressing the cynT gene and characterized. The purified enzyme was shown to contain 1 Zn2+/subunit (24 kDa) and was found to behave as an oligomer in solution; the presence of bicarbonate resulted in partial dissociation of the oligomeric enzyme. The kinetic properties of the enzyme are similar to those of carbonic anhydrases from other species, including inhibition by sulfonamides and cyanate. The amino acid sequence shows a high degree of identity with the sequences of two plant carbonic anhydrases. but not with animal and algal carbonic anhydrases. Since carbon dioxide formed in the bicarbonate-dependent decomposition of cyanate diffuses out of the cell faster than it would be hydrated to bicarbonate, the apparent function of the induced carbonic anhydrase is to catalyze hydration of carbon dioxide and thus prevent depletion of cellular bicarbonate.

  2. How Strong Is the Evidence for Sodium Bicarbonate to Prevent Contrast-Induced Acute Kidney Injury After Coronary Angiography and Percutaneous Coronary Intervention?

    Science.gov (United States)

    Dong, Yuhao; Zhang, Bin; Liang, Long; Lian, Zhouyang; Liu, Jing; Liang, Changhong; Zhang, Shuixing

    2016-01-01

    Abstract Hydration with sodium bicarbonate is one of the strategies to prevent contrast-induced acute kidney injury (CI-AKI). The purpose of this study was to determine how strong is the evidence for sodium bicarbonate to prevent CI-AKI after coronary angiography (CAG) and/or percutaneous coronary intervention (PCI). We conducted PubMed, EMBASE, and CENTRAL databases to search for randomized controlled trials (RCTs) comparing the efficacy of sodium bicarbonate with sodium chloride to prevent CI-AKI after CAG and/or PCI. Relative risk (RR), standardized mean difference (SMD), or weighted mean difference (WMD) with 95% confidence intervals (CIs) was calculated. Heterogeneity, publication bias, and study quality were evaluated, sensitivity analyses, cumulative analyses, and subgroup analyses were performed. The risk of random errors was assessed by trial sequential analysis (TSA). Sixteen RCTs (3537 patients) met the eligibility criteria. Hydration with sodium bicarbonate showed significant beneficial effects in preventing CI-AKI (RR 0.67; 95% CI: 0.47–0.96, P = 0.029), decreasing the change in serum creatinine (SCr) (SMD −0.31 95% CI: −0.55 to −0.07, P = 0.011) and estimated glomerular filtration rate (eGFR) (SMD −0.17 95% CI: −0.30 to −0.04, P = 0.013). But no significant differences were observed in the requirement for dialysis (RR 1.11; 95% CI: 0.60–2.07, P = 0.729), mortality (RR 0.71; 95% CI: 0.41–1.21, P = 0.204) and reducing the length of hospital stay (LHS) (WMD −1.47; 95% CI: −4.14 to 1.20, P = 0.279). The result of TSA on incidence of CI-AKI showed the required information size (RIS = 6614) was not reached and cumulative z curve did not cross TSA boundary. The result of TSA on the requirement for dialysis and mortality demonstrated the required information sizes (RIS = 170,510 and 19,516, respectively) were not reached, and the cumulative z-curve did not cross any boundaries. The evidence that sodium

  3. Discovery and Rational Design of Natural-Product-Derived 2-Phenyl-3,4-dihydro-2H-benzo[f]chromen-3-amine Analogs as Novel and Potent Dipeptidyl Peptidase 4 (DPP-4) Inhibitors for the Treatment of Type 2 Diabetes.

    Science.gov (United States)

    Li, Shiliang; Xu, Hongling; Cui, Shichao; Wu, Fangshu; Zhang, Youli; Su, Mingbo; Gong, Yinghui; Qiu, Shaobing; Jiao, Qian; Qin, Chun; Shan, Jiwei; Zhang, Ming; Wang, Jiawei; Yin, Qiao; Xu, Minghao; Liu, Xiaofeng; Wang, Rui; Zhu, Lili; Li, Jia; Xu, Yufang; Jiang, Hualiang; Zhao, Zhenjiang; Li, Jingya; Li, Honglin

    2016-07-28

    Starting from the lead isodaphnetin, a natural product inhibitor of DPP-4 discovered through a target fishing docking based approach, a series of novel 2-phenyl-3,4-dihydro-2H-benzo[f]chromen-3-amine derivatives as potent DPP-4 inhibitors are rationally designed utilizing highly efficient 3D molecular similarity based scaffold hopping as well as electrostatic complementary methods. Those ingenious drug design strategies bring us approximate 7400-fold boost in potency. Compounds 22a and 24a are the most potent ones (IC50 ≈ 2.0 nM) with good pharmacokinetic profiles. Compound 22a demonstrated stable pharmacological effect. A 3 mg/kg oral dose provided >80% inhibition of DPP-4 activity within 24 h, which is comparable to the performance of the long-acting control omarigliptin. Moreover, the efficacy of 22a in improving the glucose tolerance is also comparable with omarigliptin. In this study, not only promising DPP-4 inhibitors as long acting antidiabetic that are clinically on demand are identified, but the target fish docking and medicinal chemistry strategies were successfully implemented.

  4. 来源于天然产物的α-葡萄糖苷酶抑制剂筛选研究进展概述%An Overview on Progressive Research of Screening for A--Glucosidase Inhibitors from Natural Products

    Institute of Scientific and Technical Information of China (English)

    郭凤霞; 曾阳; 陈振宁

    2012-01-01

    α-葡萄糖苷酶抑制剂是一种具有糖结构的新型抗糖尿病药物,它通过与α-葡萄糖苷酶发生竞争性抑制作用而达到降低餐后血糖的目的.目前以天然植物和药物为来源的α-葡萄糖苷酶抑制剂研究较多,现对以天然植物为来源的α-葡萄糖苷酶抑制剂的筛选国内外研究进展进行综述.%A--Glucosidase Inhibitor, as a new anti--diabetic medicine with a sugar--structure, reduces blood sugar after dinner by producing the competitive inhibitional effect with A--Glucosidase. Now, more researches have been made on A--Glucosidase inhibitors frp natural plants and drugs, so the paper starts to make an overview on progressive research of screening for a--glueosidase inhibitors from natural products.

  5. The impact of seawater saturation state and bicarbonate ion concentration on calcification by new recruits of two Atlantic corals

    Science.gov (United States)

    de Putron, S. J.; McCorkle, D. C.; Cohen, A. L.; Dillon, A. B.

    2011-06-01

    Rising concentrations of atmospheric CO2 are changing the carbonate chemistry of the oceans, a process known as ocean acidification (OA). Absorption of this CO2 by the surface oceans is increasing the amount of total dissolved inorganic carbon (DIC) and bicarbonate ion (HCO3 -) available for marine calcification yet is simultaneously lowering the seawater pH and carbonate ion concentration ([CO3 2-]), and thus the saturation state of seawater with respect to aragonite (Ωar). We investigated the relative importance of [HCO3 -] versus [CO3 2-] for early calcification by new recruits (primary polyps settled from zooxanthellate larvae) of two tropical coral species, Favia fragum and Porites astreoides. The polyps were reared over a range of Ωar values, which were manipulated by both acid-addition at constant pCO2 (decreased total [HCO3 -] and [CO3 2-]) and by pCO2 elevation at constant alkalinity (increased [HCO3 -], decreased [CO3 2-]). Calcification after 2 weeks was quantified by weighing the complete skeleton (corallite) accreted by each polyp over the course of the experiment. Both species exhibited the same negative response to decreasing [CO3 2-] whether Ωar was lowered by acid-addition or by pCO2 elevation—calcification did not follow total DIC or [HCO3 -]. Nevertheless, the calcification response to decreasing [CO3 2-] was nonlinear. A statistically significant decrease in calcification was only detected between Ωar = recruits was reduced by 22-37% per 1.0 decrease in Ωar. Our results differ from many previous studies that report a linear coral calcification response to OA, and from those showing that calcification increases with increasing [HCO3 -]. Clearly, the coral calcification response to OA is variable and complex. A deeper understanding of the biomineralization mechanisms and environmental conditions underlying these variable responses is needed to support informed predictions about future OA impacts on corals and coral reefs.

  6. Alternative therapies for the management of inhibitors.

    Science.gov (United States)

    Shima, M; Lillicrap, D; Kruse-Jarres, R

    2016-07-01

    The development of inhibitors to factor VIII (FVIII) or factor IX (FIX) remains a major treatment complication encountered in the treatment of haemophilia. Not all patients with even the same severity and genotype develop inhibitors suggesting an underlying mechanism of tolerance against FVIII- or FIX-related immunity. One mechanism may be central tolerance observed in patients in whom the FVIII mutation enables some production of the protein. The other is a peripheral tolerance mechanism which may be evident in patients with null mutation. Recently, recombinant porcine FVIII (rpFVIII, Obixur, OBI-1, BAX801) has been developed for the haemostatic treatment of both congenital haemophilia with inhibitor (CHAWI) and acquired haemophilia A (AHA). In 28 subjects with AHA with life-/limb-threatening bleeding, rpFVIII reduced or stopped bleeding in all patients within 24 h. The cross-reactivity of anti-human FVIII antibodies to rpFVIII remains around 30-50%. Recently, new therapeutics based on the quite novel concepts have been developed and clinical studies are ongoing. These are humanized asymmetric antibody mimicking FVIIIa function by maintaining a suitable interaction between FIXa and FX (Emicizumab, ACE910), and small interfering RNAs (siRNA, ALN-AT3) suppress liver production of AT through post-transcriptional gene silencing and a humanized anti-TFPI monoclonal antibody (Concizumab). Their main advantages are longer half-life, subcutaneous applicability and efficacy irrespective of the presence of inhibitors which will make it easier to initiate more effective treatment especially early childhood. PMID:27405674

  7. Inhibitor development in haemophilia according to concentrate. Four-year results from the European HAemophilia Safety Surveillance (EUHASS) project

    NARCIS (Netherlands)

    Fischer, Kathelijn; Lassila, Riita; Peyvandi, Flora; Calizzani, Gabriele; Gatt, Alex; Lambert, Thierry; Windyga, Jerzy; Iorio, Alfonso; Gilman, Estelle; Makris, Michael

    2015-01-01

    Inhibitor development represents the most serious side effect of haemophilia treatment. Any difference in risk of inhibitor formation depending on the product used might be of clinical relevance. It was this study's objective to assess inhibitor development according to clotting factor concentrate i

  8. Effect of calmodulin inhibitor on NO production and iNOS expression induced by LPS/IFN-γin RAW264.7 cells%CaM抑制剂对LPS/IFN-γ诱导的RAW264.7细胞NO生成及iNOS表达的影响

    Institute of Scientific and Technical Information of China (English)

    袁小媚; 雷寒; 柳青; 夏勇; 马康华

    2011-01-01

    Objective To investigate the effect of calmodulin (CaM) inhibitor on nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression induced by lipopolysaccharide (LPS) and/or interferon-γ (IFN-γ) in mouse RAW264.7 macrophage cells, and to study the anti-inflammation mechanism of CaM inhibitor. Methods An inflammatory response model was established using RAW264.7 cells induced by LPS and/or IFN-γ. CaM inhibitors N-(6-aminohexyl)-5-chloro-l-naphthalenesulfonamide (W-7) and triflu operazine (TFP) were used to pre-treat RAW264.7 cells to evaluate the effects of the CaM inhibitors. NO con centration was measured with Griess Reagent Kit. Target protein and mRNA expression was tested by Western blot and RT-PCR. Results In RAW264.7 cells induced by LPS or IFN-γ CaM inhibitors W-7 and TFP sig nificantly blocked NO production ( P < 0. 01 ) and protein and mRNA expression of iNOS ( P < 0. 01 ). In RAW264.7 cells induced by LPS and IFN-γ, W-7 and TFP remarkably prevented IKBα degradation (P < 0. 01 ) and phospho-IKK and phospho-STAT1 protein expression ( P < 0. 01 ). Conclusion CaM inhibitors W-7 and TFP can inhibit LPS/IFN-γ-induced NO production and iNOS protein and mRNA expression in RAW264.7 cells, probably by the mechanism of suppressing IKBα degradation and phospho-IKK and phospho- STAT1 protein expression. The anti-inflammatory effects of CaM inhibitors may be associated with NF-KB and JAK-STAT1 signaling pathways.%目的 观察钙调蛋白(Calmodulin,CaM)抑制剂对脂多糖/干扰素γ(LPS/IFN-γ)诱导的RAW264.7细胞一氧化氮(NO)的生成及诱生型一氧化氮合酶(iNOS)表达的作用及其可能的作用机制.方法 采用LPS/IFN-γ诱导RAW264.7巨噬细胞建立细胞炎症反应模型,钙调蛋白抑制剂(W-7,TFP)预处理细胞后,采用Griess试剂法测定NO释放量;采用Western blot法测定目的 蛋白的表达;采用反转录聚合酶链反应法(RT-PCR)分析iNOS mRNA表达的变化.结果 CaM抑制剂

  9. Selection criteria for corrosion inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Webb, L.; Boivin, J. [Cormetrics, Calgary, AB (Canada)

    2008-07-01

    The use of a corrosion inhibitor is the primary method to control internal corrosion of pipelines and to reduce costly failures. This presentation discussed the selection criteria for corrosion inhibitors. The selection process requires a detailed analysis of system chemistry; modeling flow regime; and laboratory testing protocols that challenge the inhibitor under conditions analogous to the field. The nature of corrosion inhibitors and inhibitor requirements were described. Physical factors were also presented. These included viscosity and pour point; stability; density; effect on elastomers and other materials; emulsion tendency; foaming tendency; gunking; polymerization/sludging; and reaction with gases and liquids. Other topics that were discussed included compatibility; solubility; partitioning; environmental effects; and selection requirements. Film tenacity was described in terms of corrosivity; water chemistry; and flow. The presentation concluded with a discussion of performance testing and wheel testing. figs.

  10. PLANT PROTEASE INHIBITORS: STRATEGY FOR PEST CONTROL IN CROPS

    Directory of Open Access Journals (Sweden)

    R.S.DHANDE1 N.J.CHIKHALE2

    2014-11-01

    Full Text Available Proteinase inhibitors (PIs are naturally occurring proteins in living organisms and are able to inhibit & control the activity of proteases. PIs are a diverse group of proteins that share a common biochemical activity. The role of plant proteinase inhibitors was investigated by Mickel and Standish in 1947 when they observed the insects larvae were unable to develop normally on soybean products. Subsequently, the soybean trypsin inhibitors were found to be lethal to the flour beetle larvae, Tribolium confusum (Lipke et. al., 1954. Now there are diverse examples of protease inhibitors active against many insect species both in vitro (Pannetier et. al., 1997; Koiwa et. al., 1998 and in vivo (Urwin et. al., 1997; Vain et. al., 1998 bioassays.

  11. Model for metabolic resistance against ALS inhibitors

    Directory of Open Access Journals (Sweden)

    Richter, Otto

    2014-02-01

    Full Text Available Due to herbicide selection pressure metabolic resistance has evolved in many weed species. In this paper we analyse the interaction between the branched chain amino acid (BBC pathway and detoxifying pathways for herbicide breakdown. The four phase detoxification pathway of herbicides comprising the action of P450, GST, glycosyltransferase and ABC transporter is modelled by a system of coupled enzyme kinetic reactions represented by nonlinear differential equations. The herbicide under consideration inhibits the enzyme ALS, which is the key enzyme for the biosynthesis of branched amino acids. For the kinetics of ALS a Monod approach is employed with a binding site for the inhibitor. Synthetic and detoxification pathways are coupled. The model is used to study the production of branched amino acids under the action of ALS inhibitors for different structures and modes of action of the detoxification pathway. The model is capable of generating typical dose response curves and their shift in dependence of the activity pattern of the enzymes of the detoxification pathway of the inhibitor.

  12. The hunt for HIV-1 integrase inhibitors.

    Science.gov (United States)

    Lataillade, Max; Kozal, Michael J

    2006-07-01

    Currently, there are three distinct mechanistic classes of antiretrovirals: inhibitors of the HIV- 1 reverse transcriptase and protease enzymes and inhibitors of HIV entry, including receptor and coreceptor binding and cell fusion. A new drug class that inhibits the HIV-1 integrase enzyme (IN) is in development and may soon be available in the clinic. IN is an attractive drug target because it is essential for a stable and productive HIV-1 infection and there is no mammalian homologue of IN. Inhibitors of integrase enzyme (INI) block the integration of viral double-stranded DNA into the host cell's chromosomal DNA. HIV-1 integration has many potential steps that can be inhibited and several new compounds that target specific integration steps have been identified by drug developers. Recently, two INIs, GS-9137 and MK-0518, demonstrated promising early clinical trial results and have been advanced into later stage trials. In this review, we describe how IN facilitates HIV-1 integration, the needed enzyme cofactors, and the resultant byproducts created during integration. Furthermore, we review the different INIs under development, their mechanism of actions, site of IN inhibition, potency, resistance patterns, and discuss the early clinical trial results. PMID:16839248

  13. Scale Inhibition of Green Inhibitor Polyepoxysuccinic Sodium

    Institute of Scientific and Technical Information of China (English)

    Feng Hui-xia; Wang Yi; Yu Shu-rong; Liang Bao-feng

    2004-01-01

    Polyepoxysuccinic acid (PESA) is the green water treatment agents recognized all over the world[1-3]. It is found that when PESA is used alone, it had good scale inhibition. PESA should be included in the category of green scale inhibitor.PESA is synthesized with maleicanhydride in the presence of catalysts. The effect on scale-in-hibiting property of the product from amount and feed times of catalyst, the reaction temperature, the reaction time were investigated. The optimum reaction conditions are as follows:n(maleic anhydride):n(Ca(OH)2):n(NaOH)=1:0.05-0.2:0.5, reaction temperature 95C, reaction time 4h.In all the references about PESA, PESA is researched as a kind of highly effective scale inhibitor or chelate. In this paper, the performance of scale inhibition of PESA is evaluated by scale static inhibitor.The results are shown in Figture1.It is evident from our experimental data (Figture1) that when inhibition for CaCO3.With the increase of PESA dosage, scale inhibition increases. When dosage is more than 6mg/L, inhibition efficiency is over 50%. The formulas give scale inhibition efficiency more than 95% at 12mg/L of total dosage.

  14. Cinnoline derivatives as human neutrophil elastase inhibitors.

    Science.gov (United States)

    Giovannoni, Maria Paola; Schepetkin, Igor A; Crocetti, Letizia; Ciciani, Giovanna; Cilibrizzi, Agostino; Guerrini, Gabriella; Khlebnikov, Andrei I; Quinn, Mark T; Vergelli, Claudia

    2016-08-01

    Compounds that can effectively inhibit the proteolytic activity of human neutrophil elastase (HNE) represent promising therapeutics for treatment of inflammatory diseases. We present here the synthesis, structure-activity relationship analysis, and biological evaluation of a new series of HNE inhibitors with a cinnoline scaffold. These compounds exhibited HNE inhibitory activity but had lower potency compared to N-benzoylindazoles previously reported by us. On the other hand, they exhibited increased stability in aqueous solution. The most potent compound, 18a, had a good balance between HNE inhibitory activity (IC50 value = 56 nM) and chemical stability (t1/2 = 114 min). Analysis of reaction kinetics revealed that these cinnoline derivatives were reversible competitive inhibitors of HNE. Furthermore, molecular docking studies of the active products into the HNE binding site revealed two types of HNE inhibitors: molecules with cinnolin-4(1H)-one scaffold, which were attacked by the HNE Ser195 hydroxyl group at the amido moiety, and cinnoline derivatives containing an ester function at C-4, which is the point of attack of Ser195. PMID:26194018

  15. The hunt for HIV-1 integrase inhibitors.

    Science.gov (United States)

    Lataillade, Max; Kozal, Michael J

    2006-07-01

    Currently, there are three distinct mechanistic classes of antiretrovirals: inhibitors of the HIV- 1 reverse transcriptase and protease enzymes and inhibitors of HIV entry, including receptor and coreceptor binding and cell fusion. A new drug class that inhibits the HIV-1 integrase enzyme (IN) is in development and may soon be available in the clinic. IN is an attractive drug target because it is essential for a stable and productive HIV-1 infection and there is no mammalian homologue of IN. Inhibitors of integrase enzyme (INI) block the integration of viral double-stranded DNA into the host cell's chromosomal DNA. HIV-1 integration has many potential steps that can be inhibited and several new compounds that target specific integration steps have been identified by drug developers. Recently, two INIs, GS-9137 and MK-0518, demonstrated promising early clinical trial results and have been advanced into later stage trials. In this review, we describe how IN facilitates HIV-1 integration, the needed enzyme cofactors, and the resultant byproducts created during integration. Furthermore, we review the different INIs under development, their mechanism of actions, site of IN inhibition, potency, resistance patterns, and discuss the early clinical trial results.

  16. Therapeutic potential of an orally effective small molecule inhibitor of plasminogen activator inhibitor for asthma.

    Science.gov (United States)

    Liu, Rui-Ming; Eldridge, Stephanie; Watanabe, Nobuo; Deshane, Jessy; Kuo, Hui-Chien; Jiang, Chunsun; Wang, Yong; Liu, Gang; Schwiebert, Lisa; Miyata, Toshio; Thannickal, Victor J

    2016-02-15

    Asthma is one of the most common respiratory diseases. Although progress has been made in our understanding of airway pathology and many drugs are available to relieve asthma symptoms, there is no cure for chronic asthma. Plasminogen activator inhibitor 1 (PAI-1), a primary inhibitor of tissue-type and urokinase-type plasminogen activators, has pleiotropic functions besides suppression of fibrinolysis. In this study, we show that administration of TM5275, an orally effective small-molecule PAI-1 inhibitor, 25 days after ovalbumin (OVA) sensitization-challenge, significantly ameliorated airway hyperresponsiveness in an OVA-induced chronic asthma model. Furthermore, we show that TM5275 administration significantly attenuated OVA-induced infiltration of inflammatory cells (neutrophils, eosinophils, and monocytes), the increase in the levels of OVA-specific IgE and Th2 cytokines (IL-4 and IL-5), the production of mucin in the airways, and airway subepithelial fibrosis. Together, the results suggest that the PAI-1 inhibitor TM5275 may have therapeutic potential for asthma through suppressing eosinophilic allergic response and ameliorating airway remodeling. PMID:26702150

  17. Comparative transcriptional profiling of Bacillus cereus sensu lato strains during growth in CO2-bicarbonate and aerobic atmospheres.

    Directory of Open Access Journals (Sweden)

    Karla D Passalacqua

    Full Text Available BACKGROUND: Bacillus species are spore-forming bacteria that are ubiquitous in the environment and display a range of virulent and avirulent phenotypes. This range is particularly evident in the Bacillus cereus sensu lato group; where closely related strains cause anthrax, food-borne illnesses, and pneumonia, but can also be non-pathogenic. Although much of this phenotypic range can be attributed to the presence or absence of a few key virulence factors, there are other virulence-associated loci that are conserved throughout the B. cereus group, and we hypothesized that these genes may be regulated differently in pathogenic and non-pathogenic strains. METHODOLOGY/PRINCIPAL FINDINGS: Here we report transcriptional profiles of three closely related but phenotypically unique members of the Bacillus cereus group--a pneumonia-causing B. cereus strain (G9241, an attenuated strain of B. anthracis (Sterne 34F(2, and an avirulent B. cereus strain (10987--during exponential growth in two distinct atmospheric environments: 14% CO(2/bicarbonate and ambient air. We show that the disease-causing Bacillus strains undergo more distinctive transcriptional changes between the two environments, and that the expression of plasmid-encoded virulence genes was increased exclusively in the CO(2 environment. We observed a core of conserved metabolic genes that were differentially expressed in all three strains in both conditions. Additionally, the expression profiles of putative virulence genes in G9241 suggest that this strain, unlike Bacillus anthracis, may regulate gene expression with both PlcR and AtxA transcriptional regulators, each acting in a different environment. CONCLUSIONS/SIGNIFICANCE: We have shown that homologous and even identical genes within the genomes of three closely related members of the B. cereus sensu lato group are in some instances regulated very differently, and that these differences can have important implications for virulence. This study

  18. A synergistic effect in controlling plum postharvest diseases occurs by applying UV-C light to sodium bicarbonate treated fruit.

    Science.gov (United States)

    D'Hallewin, G; Cubaiu, L; Ladu, G; Venditti, T

    2013-01-01

    The effectiveness of ultraviolet-C light (UV-C; 254 nm) alone at 0, 3, 6 and 12 kJm(-2), or combined with 0.0 or 0.5% (w7v) sodium bicarbonate (SBC), to control plum (Prunus domestica cv Stanley) postharvest decay caused by Penicillium expansum L. and Botrytis cinerea was investigated. First, fruit was sanitized and in one experiment plums were artificially wound-inoculated 24 h before treatments and afterwards kept at 25 degrees C with 90% RH for 7 days. In the second experiment, treatments were applied before fruit was spray-contaminated with conidia and then stored for 4 weeks at 5 degrees C and 90% RH (storage conditions). In both experiments, the highest degree of decay caused by the two pathogens was monitored when fruit stayed untreated (control), and a negligible reduction was achieved by treating with the sole salt or with a 3 kJm(-2) UV-C light. Compared to control (89 +/- 3% decay), the treatment of wound-inoculated fruit with 6 kJm(-2) provided a 35 and 38% reduction of P. expansum and B. cinerea decay, respectively. Meanwhile, 12 kJm(-2) provided an additional decrease of 25 and 27%, respectively. In both experiments, the best control of decay was attained when treatments with SBC and UV-C light were combined and the efficacy depended upon the sequence of application. Synergistic effects were found by applying the salt before UV-C light. When 6 or 12 kJm(-2) were employed following the 2% SBC treatment, no disease symptoms developed for either pathogens in both experiments. The same combination with 3 kJm(-2) resulted in a nearly 5 fold increase of efficacy compared to the sole light treatment. The combined treatments controlled the two pathogens to valuable levels and, since no quality losses were observed during storage, they could be considered as a suitable approach to contain postharvest losses of this fruit.

  19. Measurement of energy expenditure in overweight men and women using [C-14]-bicarbonate-urea before and after weight loss

    International Nuclear Information System (INIS)

    Full text: Many studies have demonstrated significant declines in 24-hour energy expenditure (TEE) measured by whole body calorimetry with either the process of weight loss or the maintenance of reduced body weight. The aims of this study were to determine the effect of weight loss and two weeks of weight maintenance on TEE using [14C]-bicarbonate-urea, Eleven subjects (6 males, 5 females), mean (±SE) age 50 ± 3 years, BMI 34.1 ± 2.1 kg/m2 and body fat 38.7 ± 3% were studied before and after a decrease in body weight of > 8% over a period of 8 weeks, followed by two weeks of weight maintenance. Weight loss was induced using the combination of Modifast and one small meal a day (∼3.34 MJ/day). Body composition (DEXA), resting energy expenditure (REE) and the thermic effect of a 2.7 MJ test meal (TEF) were measured in addition to TEE at week 2 and again at week 12. Diet was assessed using diaries and physical activity energy expenditure (PAEE) was calculated from the equation: 0.9 x TEE-REE, which assumes that 10% of TEE is accounted for by the TEE. Body weight decreased by 11.8 ± 1.0% from week 2 to 10, and remained stable thereafter. Total fat mass, abdominal fat mass and lean mass decreased by 19.7 ± 1.8%, 21.8 ± 2.3% and 6.0 ± 1.1 % respectively. At week 12, REE decreased by 5.7 ± 1.3% (p < 0.002). The decreases in TEF (13.3 ± 13.7%), PAEE (31 ± 57.5%) and TEE (0.18 + 3.68%) were not significant. There was a significant relationship between the change in REE and overall body weight (p < 0.026) but not lean mass. It is concluded that in free-living subjects, after weight loss and two weeks of weight maintenance, REE but not TEE decreases, although there is substantial variability between individuals.Copyright (2002) The Australian and New Zealand Society of Nuclear Medicine Inc

  20. Aromatic inhibitors derived from ammonia-pretreated lignocellulose hinder bacterial ethanologenesis by activating regulatory circuits controlling inhibitor efflux and detoxification

    Directory of Open Access Journals (Sweden)

    David H. Keating

    2014-08-01

    Full Text Available Efficient microbial conversion of lignocellulosic hydrolysates to biofuels is a key barrier to the economically viable deployment of lignocellulosic biofuels. A chief contributor to this barrier is the impact on microbial processes and energy metabolism of lignocellulose-derived inhibitors, including phenolic carboxylates, phenolic amides (for ammonia-pretreated biomass, phenolic aldehydes, and furfurals. To understand the bacterial pathways induced by inhibitors present in ammonia-pretreated biomass hydrolysates, which are less well studied than acid-pretreated biomass hydrolysates, we developed and exploited synthetic mimics of ammonia-pretreated corn stover hydrolysate (ACSH. To determine regulatory responses to the inhibitors normally present in ACSH, we measured transcript and protein levels in an Escherichia coli ethanologen using RNA-seq and quantitative proteomics during fermentation to ethanol of synthetic hydrolysates containing or lacking the inhibitors. Our study identified four major regulators mediating these responses, the MarA/SoxS/Rob network, AaeR, FrmR, and YqhC. Induction of these regulons was correlated with a reduced rate of ethanol production, buildup of pyruvate, depletion of ATP and NAD(PH, and an inhibition of xylose conversion. The aromatic aldehyde inhibitor 5-hydroxymethylfurfural appeared to be reduced to its alcohol form by the ethanologen during fermentation whereas phenolic acid and amide inhibitors were not metabolized. Together, our findings establish that the major regulatory responses to lignocellulose-derived inhibitors are mediated by transcriptional rather than translational regulators, suggest that energy consumed for inhibitor efflux and detoxification may limit biofuel production, and identify a network of regulators for future synthetic biology efforts.

  1. Green Inhibitors for Corrosion Protection of Metals and Alloys: An Overview

    OpenAIRE

    B E Amitha Rani; Basu, Bharathi Bai J.

    2012-01-01

    Corrosion control of metals is of technical, economical, environmental, and aesthetical importance. The use of inhibitors is one of the best options of protecting metals and alloys against corrosion. The environmental toxicity of organic corrosion inhibitors has prompted the search for green corrosion inhibitors as they are biodegradable, do not contain heavy metals or other toxic compounds. As in addition to being environmentally friendly and ecologically acceptable, plant products are inexp...

  2. Inhibitors of the AAA+ Chaperone p97

    Directory of Open Access Journals (Sweden)

    Eli Chapman

    2015-02-01

    Full Text Available It is remarkable that a pathway as ubiquitous as protein quality control can be targeted to treat cancer. Bortezomib, an inhibitor of the proteasome, was first approved by the US Food and Drug Administration (FDA more than 10 years ago to treat refractory myeloma and later extended to lymphoma. Its use has increased the survival rate of myeloma patients by as much as three years. This success was followed with the recent accelerated approval of the natural product derived proteasome inhibitor carfilzomib (Kyprolis®, which is used to treat patients with bortezomib-resistant multiple myeloma. The success of these two drugs has validated protein quality control as a viable target to fight select cancers, but begs the question why are proteasome inhibitors limited to lymphoma and myeloma? More recently, these limitations have encouraged the search for additional targets within the protein quality control system that might offer heightened cancer cell specificity, enhanced clinical utility, a lower rate of resistance, reduced toxicity, and mitigated side effects. One promising target is p97, an ATPase associated with various cellular activities (AAA+ chaperone. p97 figures prominently in protein quality control as well as serving a variety of other cellular functions associated with cancer. More than a decade ago, it was determined that up-regulation of p97 in many forms of cancer correlates with a poor clinical outcome. Since these initial discoveries, a mechanistic explanation for this observation has been partially illuminated, but details are lacking. Understandably, given this clinical correlation, myriad roles within the cell, and its importance in protein quality control, p97 has emerged as a potential therapeutic target. This review provides an overview of efforts towards the discovery of small molecule inhibitors of p97, offering a synopsis of efforts that parallel the excellent reviews that currently exist on p97 structure, function, and

  3. Purification and sequence analysis of two rat tissue inhibitors of metalloproteinases

    Science.gov (United States)

    Roswit, W. T.; McCourt, D. W.; Partridge, N. C.; Jeffrey, J. J.

    1992-01-01

    Two protein inhibitors of metalloproteinases (TIMP) were isolated from medium conditioned by the clonal rat osteosarcoma line UMR 106-01. Initial purification of both a 30-kDa inhibitor and a 20-kDa inhibitor was accomplished using heparin-Sepharose chromatography with dextran sulfate elution followed by DEAE-Sepharose and CM-Sepharose chromatography. Purification of the 20-kDa inhibitor to homogeneity was completed with reverse-phase high-performance liquid chromatography. The 20-kDa inhibitor was identified as rat TIMP-2. The 30-kDa inhibitor, although not purified to homogeneity, was identified as rat TIMP-1. Amino terminal amino acid sequence analysis of the 30-kDa inhibitor demonstrated 86% identity to human TIMP-1 for the first 22 amino acids while the sequence of the 20-kDa inhibitor was identical to that of human TIMP-2 for the first 22 residues. Treatment with peptide:N-glycosidase F indicated that the 30-kDa rat inhibitor is glycosylated while the 20-kDa inhibitor is apparently unglycosylated. Inhibition of both rat and human interstitial collagenase by rat TIMP-2 was stoichiometric, with a 1:1 molar ratio required for complete inhibition. Exposure of UMR 106-01 cells to 10(-7) M parathyroid hormone resulted in approximately a 40% increase in total inhibitor production over basal levels.

  4. Acute toxicity of sodium bicarbonate, a major component of coal bed natural gas produced waters, to 13 aquatic species as defined in the laboratory

    Science.gov (United States)

    Harper, David D.; Farag, Aida M.; Skaar, Don

    2014-01-01

    Water produced during coal bed natural gas (CBNG) extraction in the Powder River Structural Basin of Wyoming and Montana (USA) may contain concentrations of sodium bicarbonate (NaHCO3) of more than 3000 mg/L. The authors evaluated the acute toxicity of NaHCO3, also expressed as bicarbonate (HCO3−), to 13 aquatic organisms. Of the 13 species tested, 7 had a median lethal concentration (LC50) less than 2000 mg/L NaHCO3, or 1300 mg/L HCO3−. The most sensitive species were Ceriodaphnia dubia, freshwater mussels (Lampsilis siliquoidea), pallid sturgeon (Scaphirhynchus albus), and shovelnose sturgeon (Scaphirhynchus platorynchus). The respective LC50s were 989 mg/L, 1120 mg/L, 1249 mg/L, and 1430 mg/L NaHCO3, or 699 mg/L, 844 mg/L, 831 mg/L, and 1038 mg/L HCO3−. Age affected the sensitivity of fathead minnows, even within life stage. Two days posthatch, fathead minnows were more sensitive to NaHCO3 and HCO3− compared with 4-d-old fish, even though fish up to 14 d old are commonly used for toxicity evaluations. The authors recommend that ion toxicity exposures be conducted with organisms less than 24 h posthatch to ensure that experiments document the most sensitive stage of development. The results of the present study, along with historical and current research regarding the toxicity of bicarbonate, may be useful to establish regulatory standards for HCO3−.

  5. Density functional theory studies on theelectronic, structural, phonon dynamicaland thermo-stability properties of bicarbonates MHCO3, M D Li, Na, K

    Energy Technology Data Exchange (ETDEWEB)

    Duan, Yuhua; Zhang, Bo; Sorescu, Dan C.; Johnson, Karl; Majzoub, Eric H; Luebke, David R.

    2012-07-01

    The structural, electronic, phonon dispersion and thermodynamic properties of MHCO3 (M D Li, Na, K) solids were investigated using density functional theory. The calculated bulk properties for both their ambient and the high-pressure phases are in good agreement with available experimental measurements. Solid phase LiHCO3 has not yet been observed experimentally. We have predicted several possible crystal structures for LiHCO3 using crystallographic database searching and prototype electrostatic ground state modeling. Our total energy and phonon free energy .FPH/ calculations predict that LiHCO3 will be stable under suitable conditions of temperature and partial pressures of CO2 and H2O. Our calculations indicate that the HCO 3 groups in LiHCO3 and NaHCO3 form an infinite chain structure through O H O hydrogen bonds. In contrast, the HCO 3 anions form dimers, .HCO 3 /2, connected through double hydrogen bonds in all phases of KHCO3. Based on density functional perturbation theory, the Born effective charge tensor of each atom type was obtained for all phases of the bicarbonates. Their phonon dispersions with the longitudinal optical–transverse optical splitting were also investigated. Based on lattice phonon dynamics study, the infrared spectra and the thermodynamic properties of these bicarbonates were obtained. Over the temperature range 0–900 K, the FPH and the entropies (S) of MHCO3 (M D Li, Na, K) systems vary as FPH.LiHCO3/ > FPH.NaHCO3/ > FPH.KHCO3/ and S.KHCO3/ > S.NaHCO3/ > S.LiHCO3/, respectively, in agreement with the available experimental data. Analysis of the predicted thermodynamics of the CO2 capture reactions indicates that the carbonate/bicarbonate transition reactions for Na and K could be used for CO2 capture technology, in agreement with experiments.

  6. Deletion of the anion exchanger Slc26a4 (pendrin) decreases apical Cl−/HCO3− exchanger activity and impairs bicarbonate secretion in kidney collecting duct

    OpenAIRE

    Amlal, Hassane; Petrovic, Snezana; Xu, Jie; Wang, Zhaohui; Sun, Xuming; Barone, Sharon; Soleimani, Manoocher

    2010-01-01

    The anion exchanger Pendrin, which is encoded by SLC26A4 (human)/Slc26a4 (mouse) gene, is localized on the apical membrane of non-acid-secreting intercalated (IC) cells in the kidney cortical collecting duct (CCD). To examine its role in the mediation of bicarbonate secretion in vivo and the apical Cl−/HCO3− exchanger in the kidney CCD, mice with genetic deletion of pendrin were generated. The mutant mice show the complete absence of pendrin expression in their kidneys as assessed by Northern...

  7. Manganese(II) catalyzes the bicarbonate-dependent oxidation of amino acids by hydrogen peroxide and the amino acid-facilitated dismutation of hydrogen peroxide.

    OpenAIRE

    Berlett, B S; Chock, P B; Yim, M B; Stadtman, E. R.

    1990-01-01

    In bicarbonate/CO2 buffer, Mn(II) and Fe(II) catalyze the oxidation of amino acids by H2O2 and the dismutation of H2O2. As the Mn(II)/Fe(II) ratio is increased, the yield of carbonyl compounds per mole of leucine oxidized is essentially constant, but the ratio of alpha-ketoisocaproate to isovaleraldehyde formed increases, and the fraction of H2O2 converted to O2 increases. In the absence of Fe(II), the rate of Mn(II)-catalyzed leucine oxidation is directly proportional to the H2O2, Mn(II), an...

  8. Evaluating the effects of caffeine and sodium bicarbonate, ingested individually or in combination, and a taste-matched placebo on high-intensity cycling capacity in healthy males.

    Science.gov (United States)

    Higgins, Matthew F; Wilson, Susie; Hill, Cameron; Price, Mike J; Duncan, Mike; Tallis, Jason

    2016-04-01

    This study evaluated the effects of ingesting sodium bicarbonate (NaHCO3) or caffeine individually or in combination on high-intensity cycling capacity. In a counterbalanced, crossover design, 13 healthy, noncycling trained males (age: 21 ± 3 years, height: 178 ± 6 cm, body mass: 76 ± 12 kg, peak power output (Wpeak): 230 ± 34 W, peak oxygen uptake: 46 ± 8 mL·kg(-1)·min(-1)) performed a graded incremental exercise test, 2 familiarisation trials, and 4 experimental trials. Trials consisted of cycling to volitional exhaustion at 100% Wpeak (TLIM) 60 min after ingesting a solution containing either (i) 0.3 g·kg(-1) body mass sodium bicarbonate (BIC), (ii) 5 mg·kg(-1) body mass caffeine plus 0.1 g·kg(-1) body mass sodium chloride (CAF), (iii) 0.3 g·kg(-1) body mass sodium bicarbonate plus 5 mg·kg(-1) body mass caffeine (BIC-CAF), or (iv) 0.1 g·kg(-1) body mass sodium chloride (PLA). Experimental solutions were administered double-blind. Pre-exercise, at the end of exercise, and 5-min postexercise blood pH, base excess, and bicarbonate ion concentration ([HCO3(-)]) were significantly elevated for BIC and BIC-CAF compared with CAF and PLA. TLIM (median; interquartile range) was significantly greater for CAF (399; 350-415 s; P = 0.039; r = 0.6) and BIC-CAF (367; 333-402 s; P = 0.028; r = 0.6) compared with BIC (313: 284-448 s) although not compared with PLA (358; 290-433 s; P = 0.249, r = 0.3 and P = 0.099 and r = 0.5, respectively). There were no differences between PLA and BIC (P = 0.196; r = 0.4) or between CAF and BIC-CAF (P = 0.753; r = 0.1). Relatively large inter- and intra-individual variation was observed when comparing treatments and therefore an individual approach to supplementation appears warranted. PMID:26988768

  9. Chelation: A Fundamental Mechanism of Action of AGE Inhibitors, AGE Breakers, and Other Inhibitors of Diabetes Complications

    Energy Technology Data Exchange (ETDEWEB)

    Nagai, Rhoji; Murray, David B.; Metz, Thomas O.; Baynes, John

    2012-03-01

    Advanced glycation or glycoxidation end-products (AGE) increase in tissue proteins with age, and their rate of accumulation is increased in diabetes, nephropathy and inflammatory diseases. AGE inhibitors include a range of compounds that are proposed to act by trapping carbonyl and dicarbonyl intermediates in AGE formation. However, some among the newer generation of AGE inhibitors lack reactive functional groups that would trap reaction intermediates, indicating an alternative mechanism of action. We propose that AGE inhibitors function primarily as chelators, inhibiting metal-catalyzed oxidation reactions. The AGE-inhibitory activity of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers is also consistent with their chelating activity. Finally, compounds described as AGE breakers, or their hydrolysis products, also have strong chelating activity, suggesting that these compounds also act through their chelating activity. We conclude that chelation is the common, and perhaps the primary, mechanism of action of AGE inhibitors and breakers, and that chronic, mild chelation therapy should prove useful in treatment of diabetes and age-related diseases characterized by oxidative stress, inflammation and increased chemical modification of tissue proteins by advanced glycoxidation and lipoxidation end-products.

  10. Synthesis of Lysine Methyltransferase Inhibitors

    Directory of Open Access Journals (Sweden)

    Tao eYe

    2015-07-01

    Full Text Available Lysine methyltransferase which catalyze methylation of histone and nonhistone proteins, play a crucial role in diverse biological processes and has emerged as a promising target for the development of various human diseases, including cancer, inflammation, and psychiatric disorders. However, inhibiting Lysine methyltransferases selectively has presented many challenges to medicinal chemists. During the past decade, lysine methyltransferase inhibitors covering many different structural classes have been designed and developed. In this review, we describe the development of selective, small-molecule inhibitors of lysine methyltransferases with an emphasis on their discovery and chemical synthesis. We highlight the current state of lysine methyltransferase inhibitors and discuss future directions and opportunities for lysine methyltransferase inhibitor discovery.

  11. [Pharmacology of bone resorption inhibitor].

    Science.gov (United States)

    Menuki, Kunitaka; Sakai, Akinori

    2015-10-01

    Currently, bone resorption inhibitor is mainly used for osteoporosis. A number of these agents have been developed. These pharmacological action are various. Bisphosphonate inhibit functions of the osteoclasts by inducing apoptosis. On the one hand, RANK-ligand inhibitor and selective estrogen receptor modulator inhibit formation of osteoclasts. It is important to understand these pharmacological action for the selection of the appropriate medicine. PMID:26529923

  12. Benzoquinones as inhibitors of botulinum neurotoxin serotype A.

    Science.gov (United States)

    Bremer, Paul T; Hixon, Mark S; Janda, Kim D

    2014-08-01

    Although botulinum neurotoxin serotype A (BoNT/A) is known for its use in cosmetics, it causes a potentially fatal illness, botulism, and can be used as a bioterror weapon. Many compounds have been developed that inhibit the BoNTA zinc-metalloprotease light chain (LC), however, none of these inhibitors have advanced to clinical trials. In this study, a fragment-based approach was implemented to develop novel covalent inhibitors of BoNT/A LC. First, electrophilic fragments were screened against BoNT/A LC, and benzoquinone (BQ) derivatives were found to be active. In kinetic studies, BQ compounds acted as irreversible inhibitors that presumably covalently modify cysteine 165 of BoNT/A LC. Although most BQ derivatives were highly reactive toward glutathione in vitro, a few compounds such as natural product naphthazarin displayed low thiol reactivity and good BoNT/A inhibition. In order to increase the potency of the BQ fragment, computational docking studies were employed to elucidate a scaffold that could bind to sites adjacent to Cys165 while positioning a BQ fragment at Cys165 for covalent modification; 2-amino-N-arylacetamides met these criteria and when linked to BQ displayed at least a 20-fold increase in activity to low μM IC₅₀ values. Unlike BQ alone, the linked-BQ compounds demonstrated only weak irreversible inhibition and therefore acted mainly as non-covalent inhibitors. Further kinetic studies revealed a mutual exclusivity of BQ covalent inactivation and competitive inhibitor binding to sites adjacent to Cys165, refuting the viability of the current strategy for developing more potent irreversible BoNT/A inhibitors. The highlights of this study include the discovery of BQ compounds as irreversible BoNT/A inhibitors and the rational design of low μM IC50 competitive inhibitors that depend on the BQ moiety for activity. PMID:24984937

  13. Ximelagatran: direct thrombin inhibitor

    Directory of Open Access Journals (Sweden)

    Shir-Jing Ho

    2006-03-01

    -major orthopedic surgery. It has also been shown to be more effective than aspirin alone for prevention of recurrent major cardiovascular events in patients with recent myocardial infarction.Keywords: Ximelagatran, direct thrombin inhibitor, oral anticoagulants, thromboprophylaxis

  14. Entry and exit pathways of CO2 in rat liver mitochondria respiring in a bicarbonate buffer system.

    Science.gov (United States)

    Balboni, E; Lehninger, A L

    1986-03-15

    The dynamics and pathways of CO2 movements across the membranes of mitochondria respiring in vitro in a CO2/HCO-3 buffer at concentrations close to that in intact rat tissues were continuously monitored with a gas-permeable CO2-sensitive electrode. O2 uptake and pH changes were monitored simultaneously. Factors affecting CO2 entry were examined under conditions in which CO2 uptake was coupled to electrophoretic influx of K+ (in the presence of valinomycin) or Ca2+. The role of mitochondrial carbonic anhydrase (EC 4.2.1.1) in CO2 entry was evaluated by comparison of CO2 uptake by rat liver mitochondria, which possess carbonic anhydrase, versus rat heart mitochondria, which lack carbonic anhydrase. Such studies showed that matrix carbonic anhydrase activity is essential for rapid net uptake of CO2 with K+ or Ca2+. Studies with acetazolamide (Diamox), a potent inhibitor of carbonic anhydrase, confirmed the requirement of matrix carbonic anhydrase for net CO2 uptake. It was shown that at pH 7.2 the major species leaving respiring mitochondria is dissolved CO2, rather than HCO-3 or H2CO3 suggested by earlier reports. Efflux of endogenous CO2/HCO-3 is significantly inhibited by inhibitors of the dicarboxylate and tricarboxylate transport systems of the rat liver inner membrane. The possibility that these anion carriers mediate outward transport of HCO-3 is discussed.

  15. Entry and exit pathways of CO2 in rat liver mitochondria respiring in a bicarbonate buffer system.

    Science.gov (United States)

    Balboni, E; Lehninger, A L

    1986-03-15

    The dynamics and pathways of CO2 movements across the membranes of mitochondria respiring in vitro in a CO2/HCO-3 buffer at concentrations close to that in intact rat tissues were continuously monitored with a gas-permeable CO2-sensitive electrode. O2 uptake and pH changes were monitored simultaneously. Factors affecting CO2 entry were examined under conditions in which CO2 uptake was coupled to electrophoretic influx of K+ (in the presence of valinomycin) or Ca2+. The role of mitochondrial carbonic anhydrase (EC 4.2.1.1) in CO2 entry was evaluated by comparison of CO2 uptake by rat liver mitochondria, which possess carbonic anhydrase, versus rat heart mitochondria, which lack carbonic anhydrase. Such studies showed that matrix carbonic anhydrase activity is essential for rapid net uptake of CO2 with K+ or Ca2+. Studies with acetazolamide (Diamox), a potent inhibitor of carbonic anhydrase, confirmed the requirement of matrix carbonic anhydrase for net CO2 uptake. It was shown that at pH 7.2 the major species leaving respiring mitochondria is dissolved CO2, rather than HCO-3 or H2CO3 suggested by earlier reports. Efflux of endogenous CO2/HCO-3 is significantly inhibited by inhibitors of the dicarboxylate and tricarboxylate transport systems of the rat liver inner membrane. The possibility that these anion carriers mediate outward transport of HCO-3 is discussed. PMID:3081508

  16. Systemic reduction of rice blast by inhibitors of antioxidant enzymes

    Science.gov (United States)

    Systemic acquired disease resistance (SAR) of plants may result from an oxidative burst in their tissues caused by both increased production of ROS and decreased antioxidant activity, in particular, enzymatic. Here we tested whether the exogenous inhibitors of superoxide dismutase (SOD) and catalase...

  17. Influences of Temperature and pH Value on the Corrosion Behaviors of X80 Pipeline Steel in Carbonate/Bicarbonate Buffer Solution

    Institute of Scientific and Technical Information of China (English)

    LI,Jin-Bo; ZUO,Jian-E

    2008-01-01

    The joint effect of temperature and pH value on the corrosion behavior of X80 steel in carbonate/bicarbonate buffer solution was detected by cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS) and Mott-Schottky analysis. The results show that an unstable corrosion film will be formed on the X80 steel surface in low pH value solutions, and a better protective corrosion film can be formed on the X80 steel surface in high pH value solutions. On the whole, the corrosion film resistance and transfer resistance increase with the increment of pH value, and decrease with increase of solution temperature, which indicates that the protective effect of the corrosion film on X80 steel is enhanced with increasing pH value and decreasing the solution temperature. The corrosion film formed on X80 steel surface in carbonate/bicarbonate buffer solution has an n-type semi-conductive character, and the donor density decreases with increasing the pH value, and increases with increasing the solution temperature. The flat-band potential and pH value have a linear relationship with a positive slope.

  18. A study of X100 pipeline steel passivation in mildly alkaline bicarbonate solutions using electrochemical impedance spectroscopy under potentiodynamic conditions and Mott-Schottky

    Science.gov (United States)

    Gadala, Ibrahim M.; Alfantazi, Akram

    2015-12-01

    The key steps involved in X100 pipeline steel passivation in bicarbonate-based simulated soil solutions from the pre-passive to transpassive potential regions have been analyzed here using a step-wise anodizing-electrochemical impedance spectroscopy (EIS) routine. Pre-passive steps involve parallel dissolution-adsorption in early stages followed by clear diffusion-adsorption control shortly before iron hydroxide formation. Aggressive NS4 chlorides/sulfate promote steel dissolution whilst inhibiting diffusion in pre-passive steps. Diffusive and adsorptive effects remain during iron hydroxide formation, but withdraw shortly thereafter during its removal and the development of the stable iron carbonate passive layer. Passive layer protectiveness is evaluated using EIS fitting, current density analysis, and correlations with semiconductive parameters, consistently revealing improved robustness in colder, bicarbonate-rich, chloride/sulfate-free conditions. Ferrous oxide formation at higher potentials results in markedly lower impedances with disordered behavior, and the involvement of the iron(III) valence state is observed in Mott-Schottky tests exclusively for 75 °C conditions.

  19. Case Reports That Illustrate the Efficacy of SGLT2 Inhibitors in the Type 1 Diabetic Patient

    OpenAIRE

    Bell, David S. H.

    2015-01-01

    SGLT2 inhibitors are only approved for use in adults with type 2 diabetes. However, because SGLT2 inhibitors have a mechanism of action that does not require the presence of endogenous insulin, these drugs should also be efficacious in type 1 diabetes where endogenous insulin production is greatly reduced or absent. Herein, I present five cases which illustrate the benefits of utilizing an SGLT2 inhibitor with type 1 diabetes. In these cases the use of SGLT2 inhibitors resulted not only in...

  20. One case of sodium bicarbonate-induced allergy and the review of literatures%口服碳酸氢钠过敏1例报告并文献复习

    Institute of Scientific and Technical Information of China (English)

    李怡辉; 卓莉; 李文歌

    2014-01-01

    碳酸氢钠为临床上常用的药物,其不良反应较少,过敏反应罕有报道,本文报告1例在应用碳酸氢钠后出现药物过敏患者的临床症状、处理方法及过程,并查阅相关文献进行总结,为临床安全应用碳酸氢钠提供参考。%Sodium bicarbonate is commonly used in clinical, the adverse effect is rarely, drug allergic were more rarely reported. We report a case of clinical symptoms after application of sodium bicarbonate, processing methods and procedures of the relevant literature to summarize, in order to provide a preference of clinical safe use of sodium bicarbonate.